Biopsych EXAM 1

Axo-axonic synapses

A synapse in which both the presnaptic and post elements are axons If presynap neuron increases amount of neurochem released, PRESYNAPTIC FACILITATION has occurred. If the presynap neuron decreases the amount of neurochem released by the target axon, PRESYNAPTIC INHIBITION has happened

Neuroscience

scientific study of the brain and NS, in health and in disease

Synaptic

"this structure participates in a network connecting these other structures to engage in this type of processing"

Animal Subject Guidelines

3Rs of animal research: -Reduce number of animals used -Replace use of animals with other options -Refine methods to ensure most human treatment possible Research should have clear scientific purpose Animals must have basic care and housing Cause as little pain and stress as possible

Ramon y Cajal

Argued that NS was made of separate independent cells. His concept was the Neuron Doctrine Used stain invented by Golgi to prove Golgi was incorrect

Trepanation

As long as 7000 years ago, people tried to cure others by drilling holes in the skull Hoped to release demons or relieve feelings of pressure

Network

Behavioral neuroscience: Behavioral neuroscience uses all previous forms of analysis from molecular up through the network to understand biological correlates of behavior. Biology can impact our behavior and behavior impacts bio

Brain's Blood Supply

Brain makes up 2% of body weight but target of 15-20% of the blood pumped by heart Brain served by CAROTID ARTERIES on either side of neck and VERTEBRAL ARTERIES that travel up through back of the skull. All the arteries circulate configuration and help lessen the damage to the brain that would result from blockage of a major artery

Evolution of NS

CHORDATES: animals with spinal columns and real brains Early brains differ from more advanced brains in both size and degree of convolution. Size of forebrain and cerebellum increased in more advanced chordate species True brains evolved relatively recently

CNS

CNS includes brain and spinal cord PNS contains all the nerves that exit the brain and spinal cord, carrying sensory and motor messages to and from the other parts of the body CNS tissue encased in bone, but tissue in PNS is not. CNS and PNS are almost similar, but there are some differences -CSF circulates around CNS but not within the PNS. Damage to CNS is considered permanent, but some recovery can occur in PNS Spinal Cord: -Spinal nerves exit between the bones of the vertebral column -Bones cushioned from one another with disks. -Spinal cord is in 31 segments. Close to brain there are 8 CERVICAL NERVES that serve neck and arms. 12 THORACIC NERVES which serves torso. 5 LUMBAR NERVES serving lower back and legs. 5 SACRAL NERVES serve back of legs and genitals. SINGLE COCCYGEAL NERVE -WHITE MATTER is made up of nerve fibers known as axons. Tissue looks white because of myelin which covers most human axons. Carries info to and from brain -GRAY MATTER consists of areas primarily made up of cell bodies -Neurons in DORSAL HORNS of the H receive sensory input and VENTRAL HORNS pass motor info on to muscles. Ventral horns participate in either voluntary movement or spinals REFLEXES -PATELLAR REFLEX (doc tapping on knee is one type of spinal reflex; managed by two diff types of neurons: one processes sensory info coming to the cord from muscle stretch receptors. it communicates with spinal motor neurons that respond to input by contracting muscle, causing the kick) -Spinal reflexes protect us from injury (WITHDRAWAL REFLEX: sensory neuron, motor, and interneuron) -Central pattern generators help us move rhythmically: ex, walking, hopping -Damage to spinal cord results in loss of sensation and voluntary movement Embryological Divisions of Brain: -Brain forms 3 bulges: HINDBRAIN (rhombencephalon), MIDBRAIN (mesencephalon), and FOREBRAIN (prosencephalon) -Hind and midbrain make up brainstem -Midbrain makes no further division BUT hindbrain divides into myelencephalon, or medulla, and the metencephalon, which has PONS AND CEREBELLUM -Forebrain divides into diencephalon and telencephalon Hindbrain: -Contains myelencephalon and metencephalon -THE MEDULLA (MYELENCEPHALON): Majority of all info passing to and from higher structure of the brain must pass through medulla. Medulla has number of NUCLEI suspended within the white matter of the medulla. Helps with vital functions. -Along midline of the upper medulla, we see caudal portion of a structure known as RETICULAR FORMATION. This is a complex collection of nuclei that runs along the midbrain of the brainstem from the medulla up into the midbrain. Plays important roles in regulation of consciousness and arousal -THE PONS AND CEREBELLUM (METENCEPHALON): Pons helps form connections between the medulla and higher brain centers as well as with cerebellum. The important nuclei found in this are the COCHLEAR NUCLEUS AND VESTIBULAR NUCLEUS. These are examples of cranial nerve nuclei. Cochlear receives info on sound and vestibular receives info about position and movement of head. Also helps keep balance. Pons also deals with REM. The RAPHE NUCLEI and LOECUS COERULEUS influence mood, arousal, aggression, appetite, and sleep -Cerebellum deals with movement, muscle tone, and balance. One of the first structures affected with consumption of alc. Contributes to motion sickness. Involved in executive function and emotional processing. Most theories propose a cerebellum that can use past experience to make corrections and automate behaviors, whether they involve motor systems or not Midbrain: -Also known as MESENCEPHALON has a dorsal or top half known as TECTUM and bottom half as TEGMENTUM. In midbrain, CSF is in small channel in the midline called CEREBRAL AQUADUCT. This separates tectum from tegmentum and links third and fourth ventricles. -PERIAQUEDUCTAL GRAY surrounds the cerebral aquaduct. Integrates autonomic, motor, and pain responses to environmetal stimuli. Especially important role in perception of pain. Helps regulate sleep and coordinates complex motor patterns, temp regulation, cardiovas and resp responses, sexual behavior, and peeing. Also important with maternal behavior. -Manages states of arousal: RED NUCLEUS AND SUBSTANTIA NIGRA. Degeneration of sub nigra happens in Parkinson's. Characterized by difficulties with movement and reward seeking behavior -INFERIOR COLLICULI involved with hearing; localization of sounds The Forebrain: -Contains many and most of the most advanced and most recently evolved structures of the brain -Has DIENCEPHALON and TELENCEPHALON. Diencephalon source of retina of the eye and also contains thalamus and hypothalamus. Telen has bulk of left and right CEREBRAL HEMISPHERES THALAMUS AND HYPOTHALAMUS: -Thalamus gets sensory input and regulatory input. Influences attention and consciousness. Damage to this results in coma and seizures. Participates in learning and memory -Hypothalamus is regulatory center. Regulates endocrine system and connected to PITUATARY GLAND where many hormones released. Directs autonomic NS which controls glands and organs BASAL GANGLIA: -Motor control -Includes CAUDATE NUCLEUS, PUTAMEN, GLOBUS PALLIDUS, SUBTHALAMIC NUCLEUS, NUCLEUS ACCUMBENS. Together known as CORPUS STRIATUM. -Degeneration of this produces disordered movement -Involved with forming and using implicit or unconscious memories (ex: walking around maze and trying to figure way out) LIMBIC SYSTEM: -Learning, motivated behavior, and emotion -HIPPOCAMPUS deals with learning and memory. Damage to this leads to anterograde amnesia (hard to make new longterm declaractive memories) -PARAHIPPOCAMPAL GYRUS fold of tissue near hippocampus. FORNIX is a fiber pathway connecting hippocampus with the MAMMILLARY BODIES of the diencephalon. All help in memory. -AMYGDALA helps connect stimuli to their emotional meanings. Also deals with fear and aggression. Damage to this leads to emotional calmness and inhibits organism's ability to respond appropriately to dangerous situations. Also responds to presence of reward. -CINGULATE CORTEX exerts cog influence over emotion. Example: Trying to manage PTSD. -SEPTAL AREA participates in reward. Lesions in this area lead to rage and attack. Stimulation leads to pleasure. CORTEX: -GYRI: hills of cortex -SULCI: valleys of cortex -FISSURE: large sulcus -Cortex wrinkly to increase surface area for cortical cells -Degree of convolution relates to how advanced a species is -6 distinct layers of cortex, labeled from outermost layer toward center of the brain -Layer I no cell bodies at all. Layers II and IV contain large numbers of small cells known as GRANULE CELLS. Layers III and V have large PYRAMIDAL CELLS. These layers provide most of the output from an area of cortex to other parts of the NS. Layer VI has many types of neurons which merge into the white matter that lies below cortical layers -Can divide functional areas of the cortex into three categories: SENSORY CORTEX, MOTOR CORTEX, and ASSOCIATION CORTEX LOCALIZATION OF FUNCTION IN THE CORTEX: -Two impt areas in frontal lobe are DORSOLATERAL PREFRONTAL CORTEX (attention, working memory behavior planning) and ORBITOFRONTAL CORTEX (impulse control and delayed gratification) -FRONTAL LOBOTOMIES: showed reductive in negative emotions -BROCA'S AREA: impt for speech production. -Left hemi of brain deals with logical thought and math -Right hemi emotional and intuitive BRAIN CIRCUITS AND CONNECTOME -Neurons behave in circuits. -Mapping of connectome major contemporary research initiative.

Imaging

CT: -Willhem Rontgen discovered xrays -CT may be useful for medical imaging -BUT can't distinguish difference between a living brain and a dead one -Give no info regarding activity levels in brain -Limits usefulness in helping answer questions about behavior PET: -Allows researchers to observe brain activity for first time -Don't give good info about brain structure -Combine radioactive tracers with wide variety of molecules, including oxygen, water neurochemicals, and drugs. -Researchers assigned red and yellow to areas of high activity and blue and green and black to low -A closely related procedure, SPECT is less expensive but gives less detail -For most research, PET AND SPECT have been replaced by fMRI -PET scan advantag: able to give info about levels of activity of certain neurochem in the brain MRI: -Uses magnets to align hydrogen atoms within a magnetic field. -Next, radio frequency pulses are directed at the part of the body to be imaged, producing "resonance" or spinning of the hydrogen atoms. -When RF pulses cease, the hydrogen atoms return to their natural alignment within the magnetic field -As atoms relax, each becomes a mini radio transmitter, emitting a characteristic pulse that is detected by the scanner -Each small area of tissue is assigned a VOXEL which is a 3D version of a pixel. The darkness or coloration of each voxel represents the level of pulse activity in an area fMRI: -Lets us correlate brain activity with the presentation of a stimulus, the presence of an emotional state, or performance of a certain task -Takes advantage of the fact that active neurons require more oxygen than less active neurons, and that variations in blood flow to a certain area will reflect this -Tracks blood flow: Hemoglobin has diff magnetic properties when combined with oxy or not. Signals from a voxel will change depending on on the oxygenation of the blood in that area, known as the Blood Oxygenation Level Dependent (BOLD) effect DTI: -Can map connectivity in the brain by tracking the movement of water in the fiber pathways of the NS -Can't tell us the direction of info flow

Stimulants

Caffeine: (most common stimulant) -Increases blood pressure and heart rate, improves concentration, and wards off sleepiness. Blocks off adenosine receptors, reducing the normal inhibitory activity of adenosine. Interference with normal adenosine activity in the basal ganglia produces improvements in reaction time. Also leads to increased release of dopamine in nucleus accumbens. -Caffeine crosses placenta easily and the fetus/breastfed newborn unable to metabolize caffeine, leading to reduced rates of growth. Caffeine produces withdrawal of headaches and fatigue. Caffeine reduces blood circulation to the brain, withdrawal and create severe headaches due to suddenly increased blow flow. -Caffeine use correlated with lower rates of Parkinson's in men. A Parkinson's like syndrome can be artificially produced by injecting mice with a toxin known as MPTP, which reduces dopamine levels in basal ganglia. If MPTP injections are preceded by caffeine, little or no drop in dopamine occurs. Nicotine: -Increases heart rate and blood pressure, promotes release of adrenaline into circulation, reduces fatigue, and heightens cog performance. In PNS, nicotine creates muscle relaxation. -About one third of all nicotine products sold in US is used by the 7% of ppl who are diagnosed with both psychological disorders and nicotine dependence. People with severe mental illness could be seeking to relieve their symptoms through the use of nicotine. Others suggest nicotine causes the illnesses, especially depression. Mental illness and vulnerability to nicotine dependence might be promoted by shared features of the cholinergic systems of the brain. -Has its primary effect as an agonist at the nicotinic cholinergic receptor. Nicotine's action on the cholinergic system arising in the basal forebrain, is probably responsible for increased alertness and cog performance. Stimulates cholinergic receptors in the ventral tegmental area which results in greater release of dopamine in the nucleus accumbens. This action on nucleus accumbens is likely source of addictive properties of nicotine. Symptoms of withdrawl: inability to concentrate and restlessness. Cocaine and Amphetamine: -Similar behavior effects to one another because both are powerful dopamine agonists. The most addictive drugs. At lower doses, these produce alertness, elevated mood, confidence, and a sense of well being. At higher doses, they produce symptoms similar to schizo. Users often experience hallucinations "bugs on skin", paranoid delusions. Users of meth 11x more likely to experience psychotic symptoms than nonusers. Can show repetitive motor behaviors, chewing movements or grinding teeth. Cocaine orginally used in Peru as mild stimulant and appetite suppressant. Amphetamine originally used a treatment for asthma. Modes of action for cocaine and amphe different. Both distort the action of dopamine transporters but do it differently. Amphetamine mimic dopamine, leading it to be captured and moved across the presynaptic membrane by dopamine transporters. Once inside neuron, amphetamine enters synaptic vesicles, pushing dopamine molecules out into the intracelllular fluid of the axon terminal. The presence of large amounts of dopamine outside of vesicles makes the transporters begin to work in reverse, pushing dopamine out of cell even in absence of any action potentials. With the transporters working in reverse and unable to retrieve the released dopamine, the molecules of dopamine become trapped in synaptic gap, stimulating receptors continuously. Cocaine is simpler. It blocks the transporters, keeping all previously released dopamine active in the synaptic gap Ecstasy (MDMA): -Synthetic relative of amphetamine. Increases heart rate, blood pressure, and body temp for 3-6 hours. In some cases, dehydration, exhaustion, hypothermia, convulsions, and death occur. MDMA produces increased sociability by stimulating the release of serotonin and the neurohormone oxytocin. -MDMA influences serotonin, norepinephrine, and dopamine transporters. Taken up by transporters causing them to reverse their action. Instead of removing the monoamines from the synaptic gap, they are pumped into the gap, where they become trapped. MDMA strongest effects in serotonergic systems but because it also increases dopamine activity, MDMA can create dependency. -Reseachers exploring use of MDMA for treating PTSD, social anxiety in autism, and axiety associated with life threatening illnesses

Neurochemical Release

Can be modified in response to the arrival of an action potential by drugs. Some drugs affect release by interacting with presynaptic autoreceptors. Others interact directly with the proteins responsible for exocytosis, which is the process responsible for the release of neurochem molecules into the synapse. METHAMPHETAMINE is a dopamine agonist. Initially these molecules are taken up by the dopamine transporters, Once inside axon terminal , it displaces dopamine in the vesicles. Some dopamine is deactivated by MAO but the higher concentration of dopamine in the intracellular fluid disturbs the actions of the transporters. Instead of moving dopamine from the synaptic gap back into the cell, the transporters reverse and start pumping dopamine into the gap, even in the absence of any action potentials. Because the transporters are malfunctioning, the released dopamine is trapped in the gap, where it can interact with postsynaptic receptors repeatedly. Other drugs act as antagonists by preventing release of chem messengers. Powerful toxins made by Clostridium botulinum bacteria prevent release of ACh at the neuromuscular junction and at synapses of the autonomic nervous system. The disease BOTULISM leads to paralysis and death.

PNS

Carries sensory info from body to spinal cord and brain and bring back to the body commands for appropriate responses. Contains 3 structural divisions: Cranial nerves, spinal nerves, and autonomic NS Cranial and spinal nerves makes up SOMATIC NS. This brings sensory input to the brain and spinal cord and returns commands to the muscles. AUTONOMIC NS controls actions of smooth muscles and many glands and organs. ENDOCRINE SYSTEM coordinate arousal, metabolism, growth, and sex by releasing chem messengers directly into bloodstream CRANIAL NERVES: -12 pairs that enter and exit the brain and give sensory and motor functions to the head, neck, and internal organs. SPINAL NERVES: -31 pairs. Give sensory and motor pathways to torso, arms, and legs. Each spinal nerve is a MIXED NERVE because it has a sensory (AFFERENT NERVE) and motor (EFFERENT NERVE) -Afferent nerves have both myelinated and unmyelinated fibers and efferent nerves are all myelinated AUTONOMIC NS: -Processes sensory and motor info to and from glands, organs, and smooth muscle. Sympathetic NS operates during times of arousal and prepares body for fight or flight reactions. Parasympathetic NS operates in times of rest and restoration. Enteric NS moves food through the gut and gives feedback to CNS -BIOFEEDBACK: People learn to control a number of autonomic processes, such as lowering blood pressure -Hypothalamus plays biggest role in managing this system. ENDOCRINE SYSTEM: -Consists of glands that release impt hormones into the blood that regulate arousal, growth, metabolism, and sex

Hippocrates

Correctly identified epilepsy as originating in the brain, although the most obvious outward signs of the disorder were muscular convulsions

Paul Broca

Correlated the damage he observed in patients with their behavior and concluded that language functions were localized in the brain

Action potential

DEPOLARIZATION: A change in a membrane potential in a more positive direction THRESHOLD: the level of depolarization in which an action potential is initiated Channels Open and Close During an Action Potential: -First consequence of reaching a cell's threshold is the opening of voltage-dependent sodium channels. Once sodium gates open, sodium is free to move into the cell and both diffusion and electrostatic pressure ensure it does so rapidly -At the peak of action potential, the inside of the neuron is now positively charged relative to the extra fluid, a complete reversal of the resting state -Once cell returns to resting level it HYPERPOLARIZES, becoming even more negative than when it was at rest. -Differences between the sodium and potassium voltage-dependent channels that are involved with action potentials. First, the sodium channels open very quickly whereas the potassium channels open very slowly. This difference accounts for the rapid rise in our recording of the action potential. Second, the sodium channels remain open briefly and are then inactivated until the cell nearly reaches its resting potential again. The potassium channels remain open longer, leading to hyperpolarization. Refractory Periods: -ABSOLUTE REFRACTORY PERIOD: the period in which an action potential will not occur in a certain location of an axon regardless of input -RELATIVE REFRACTORY PERIOD: the period following an action potential in which larger than normal input will produce a second action potential but in which normal input will be insufficient. Action Potential All or None: -The rate of neural firing can reflect sitmulus intensity. Large amount of stimulation produces rapid neural firing, whereas less intense input makes slower rates of firing. Max threshold of neural firing is 1000 action potentials per second. -In addition to firing rate, the number of active neurons can vary with stimulus intensity. Intense input will recruit action potentials from many neurons, wheras lower levels of stimulation will activate fewer neurons.

Causes of addiction

Damage to dopaminergic neurons will also reduce self-admin. Don't treat addiction in this manner because damaging these general reward circuits could deprive addicts of all pleasure permanently. Continued drug abuse reduces addicts' responses to normal environmental rewards. Addicts show a hyperactive response to stimuli associated with drug use such as the sight of drug paraphernalia. These changed might result from the ability of many types of drugs of abuse to disrupt plasticity in the nucleus accumbens. Changes in brain's reward system resulting from drug use overwhelm the impulse control system managed by the frontal lobes. A craving system involving the insula makes increased desire for the drug. Increased activity in the impulsive reward circuits of the brain coupled with less influence of the frontal executive circuits and increased desire sets the stage for a long term maintenance of compulsive, addictive behavior. Epigenetic explanations of addiction can also account for the roles of stress in adolescence and prenatal exposure to addictive drugs in increasing a person's risk for addiction.

Otto Loewi

Demonstrated chem signaling at the synapse

Charles Bell and Magendie

Demonstrated that info traveled in one direction, not two, within sensory and motor nerves

Helmholtz

Demonstrated that the mind had a physical basis by asking participants to push a button as soon as they felt a touch Participants reacted faster when their thigh was touched than when toe was touched because the more distant signal from the toe would take more time to reach the brain

Reuptake and Enzyme Degradation

Drugs that affect the deactivation of neurochemicals. Some of these drugs influence the reuptake of neurochem whereas others act on enzymes that break down released neurochem. Drugs that interfere with either reuptake or enzymatic degradation of chem messengers are usually powerful agonists. They promote the effects of neurochem by allowing more of the released substance to stay active in the synapse for a longer period of time. REUPTAKE INHIBITOR: substance that interferes with the transport of released neurotransmitter molecules back into the presynaptic terminal

Fritsch and Hitzig

Described how electrically stimulating the cortex of a rabbit and a dog produced movement on opposite side of the body

Frontal/Coronol Sections

Divide nervous system from front to back

Horizontal/transverse section

Divides brain from top to bottom

Computational neuroscience

Draws from computer science, electrical engineering, mathematics, and physics to produce models of the NS from the molecular up through behavioral levels of analysis Practical application of computational neuroscience is the use of neural decoding, or using neural activity to estimate what the brain is doing, in the dev of sophisticated prosthetic devices. Can use neural activity to figure out the brain's intentions to move in certain ways or perceive certain types of input as touch

Agonists and Antagonists

Drugs can boost or reduce activity of a neurochem. Drugs that enhance the activity of a neurochem are known as AGONISTS. Drugs that reduce the activity are ANTAGONISTS. The outcome of the action of an agonist or antagonist depends on the normal operation of a neurochem at a specific receptor. For ex, If a neurochem generally has an inhibitory effect on a postsynap neuron, the action of an agonist would increase the amount of this inhibitory effect. The action of an antagonist at this same receptor would result in less inhibition.

Admin of Drugs

Drugs have different effects on the nervous system depending on their method of admin. Your body has several mechanisms designed to protect against toxins. The AREA POSTREMA, located in the medulla, reacts to the presence of circulating toxins by initiating a vomiting reflex.

Recording

EEG: -Useful in study of sleep and epilepsy -Can be used to generate maps of activity, making it possible to pinpoint the source of abnormal activity -Can be used to follow patient withdrawal from drug or during coma -Can help diagnose disorders -Can create 3D map of brain activity Event-related Potentials (ERP): -Allows researchers to correlate the timing of activity of cortical neurons recorded through scalp electrodes with stimuli presented to participant -Helpful in cases where person's behavior does not provide a clear indication of whether a certain stimulus has been perceived -Allowed researchers to document the precise timing and localization of brain activity Magnetoencephalography MEG: -Records the brain's magnetic activity -Active neurons put out tiny magnetic fields -Advantage of recording magnetism rather than electrical activity from the brain relates to the interference of the skull bones and other tissues separating the brain from the electrodes. This prevents a large amount of the brain's electrical activity from being recorded using EEG -Recordings with this is much faster than fMRI and PET scans and gives moment by moment pictures of brain activity -Advantage of being silent and important technique for studying brain responses to sound -Uses SQUID that convert magnetic energy into electrical impulses that can be recorded and analyzed -Helps to localize cog functions and gives exact location of the source of abnormal electrical activity that characterizes a seizure Single-cell recording: -Assess activity of single neurons using tiny microelectrodes

Alcohol

Earliest drugs used by people. At lower doses, it dilates blood vessels, giving warm flushed feeling. It reduces anxiety, promotes assertiveness, and reduces behavioral inhibitions, causing people's behavior to be silly or fun. At higher doses assertiveness becomes aggression and disinhibition can lead to overtly risky behavior. Motor coordination drops. At very high doses, coma and death can result from suppression of respiration or asipiration of vomiting. Approx 8.5 percent of american adults meet criteria for dependence, including tolerance, withdrawal, inability to stop drinking and continued drinking in spite of sig probs. Heritability might explain 50 percent of individual differences in susceptibility to alc depedence. Alc initiates many changes to neurons. Membranes, ion channels, receptors, and enzymes all affected. Alc binds to acetylcholine, serotonin, GABA, and NMDA glutamate receptors. Alc creates main effects by acting as agonist at GABA-A receptor, which normally produces neural inhibition. Alc stimulates dopaminergic pathways which might explain the euphoric and addictive qualities of the drug. Alc's antagonism at the NMDA glutamate receptor might produce the characteristic memory problems associated with alc. Alc produces rapid tolerance. One source of tolerance is an increase in production of liver enzymes that eliminate alc from the system. Another source of tolerance is changes in receptor number and characteristics, especially at GABA-A receptor and NMDA glutamate receptor. These changes can create dramatic and life threatening withdrawal symptoms. The person will experience sweating nausea and vomiting, sleeplessness and anxiety. Sometimes hallucinations and seizures. Number of detrimental effects on health. Chronic us damages many parts of brain, including frontal lobe. Can lead indirectly to Korsakoff syndrome, in which ability to form new memories is impaired. Lack of dietary thiamine (vit B) common among alcs lead to damage of hippocampus. Binge drinking in teens particularly damaging especially to white matter in brain.

Movement of Ions

Electrical signals in an axon, or action potentials, result from the movement of ions across the membrane. DIFFUSION: tendency for molecules to distribute themselves equally within a medium such as air or water. Diffusion pressure moves molecules along a CONCENTRATION GRADIENT from areas of high concentration to areas of low concentration. ELECTROSTATIC PRESSURE: the force that moves molecules with like electrical charges apart and molecules with opp electrical charges together Diffusion is balanced by electrostatic pressure.

Eccles, Katz, Huxley, Hodgkin

Furthered understanding of neural communication

Neurotransmitters

Engage in wiring transmission by acting on neurons in their own immediate vicinity, generally at a synapse; On the post synaptic membrane, ion channels open when molecules of a neurotransmitter interact with either very fast ionotropic or somewhat slower metabotropic channels

Neuromodulators

Engaged in volume transmission, and differ from classical neurotransmitters. Rather than opening ion channels to depolarize or hyperpolarize a postsynaptic neuron, these influence more global functions, including attention and assessment of threat, saliency, novelty, and reward. They diffuse away from their site of release to influence diverse populations of neurons located at some distance from the releasing cells. Can remain in CSF for a long time during which they can continue to influence the activity of the CNS. These are restricted to interactions with metabotropic receptors. Produce slower and longer lasting changes in a neuron's metabolic processing. Target's G protein. Can interact with both pre and post synaptic cells.

Gavani and du Bois Reymond

Established electricity as mode of communication used by NS

Molecular

Explores NS at the level of the molecules that serve as its building block ; scientists attempt to understand the chemicals that build the system and make neural functioning possible

Ionic Composition of the Intracellular and Extra Fluids

Extracellular fluid: Large concentrations of sodium and chloride ions and a small concentration of potassium. This fluid is similar to seawater. Intracellular fluid: Large numbers of potassium ions and few sodium and choride ions. There are also large proteins in ion form that are negatively charged -The electrical environment inside neuron is more neg than on outside RESTING POTENTIAL: the measurement of the electrical charge across the neural membrane when the cell is not processing info

Types of Neurochemicals

Fall into three classes: small molecules, neuropeptides, gasotransmitters Small molecules can be further divided into AMINO ACIDS and amines. Neuropeptides are chains of amino acids Gases known as GASOTRANSMITTERS have been shown to influence adjacent neurons in ways similar to more classical chemical messengers DIFFERENCE BETWEEN SMALL MOLECULES AND NEUROPEPTIDES ------Small Mol -Synthesize in axon terminal -They recycle vesicles -For activation there is moderate action potential frequency -For deactivation they do reuptake or enzymatic degradation (Enzymatic deactivation occurs when an enzyme changes the structure of a neurotransmitter so that it is no longer recognized by the receptor.) -----Neuropep -They synthesize in cell body; requires transport -They don't recycle vesicles -For activation they need high action potential frequency -For deactivation, they diffuse away from the synapse or enzymatic degradation Many neurons release a small molecule along with a neuropeptide or a gasotransmitter The same neuron can release two small molecules in different locations

Descartes

Favored mind-body dualism The mind is neither physical nor accessible to study through the natural sciences. Views that animals as mechanical, not sentient human beings, experimented on animals

Generating Action Potential

First step is development of electrical signal (action potential). Signal generated first in initial segment of the neuron that is sending info, known as presynaptic neuron. Next, signal must be duplicated down length of axon. When action potential arrives at axon terminal, the process switches from electrical to chem signaling. The presynaptic neuron releases molecules of neurochem from its terminal. The neurochem molecules float across the synaptic gap to the waiting postsynaptic, or receiving neuron, or diffuse to other locations to interact with more distant neurons. It is then up to postsynaptic neuron to determine whether to send message along

Microscopic Methods

Florescent microscopy: Works by labeling a specimen with a certain fluorphore, a chem that emits light when excited by light. Downside is you have quickly because the light is not indefinite Electron microscopy: Uses beams of electrons rather than beams of visible light to illuminate specimen; Because electrons have shorter wavelengths than photons, resolution is improved. Lets us see features as small as a molecule. Disad: Can't be used on living cells Tissue to be studied must be prepared in series of steps: -Must be thin enough to allow light (or electrons) to pass through it -Fix the tissue by freezing, dehydrating, or treating with formalin -Once fixed, it is sliced or sectioned by a MICROTOME. Best stain to use is GOLGI STAIN to see detailed structural analysis of small number of single cells If want to identify clusters of cell bodies, the major bulk of the nerve cells, within a sample of tissue use NISSL STAIN MYELIN STAIN allows you to follow pathways carrying info from one part of the brain to another by staining the insulating material that covers many nerve fibers HORSERADISH PEROXIDASE if you know where a pathway ends but would like to discover its point of origin IMMUNOHISTOCHEMISTRY: Antibodies can be combined with variety of dyes to highlight certain proteins found in cells OPTICAL IMAGING allows researchers to construct a "see through brain"

John Hughlings Jackson

Founding of modern neuroscience Proposed that the NS system was organized as a hierarchy, with simpler processing carried out by lower levels of the brain, and more sophisticated processing by engaging our higher cortical executive functions When a person consumes alc however, the cortical inhibition might fail

Receptor Effects

Greatest number of drug interactions occur at receptor. In some cases, drugs are similar enough to chem composition to mimic the action of natural neurochems at the receptor site. In other cases, drugs can block synaptic activity by occupying a binding site on a receptor without activating the receptor. Finally, many receptors have many types of binding sites. Drugs that occupy one or more of these sites can indirectly influence the activity of the receptor. Both nicotine and muscarine are classified as cholinergic agonists. Other drugs like CURARE act by blocking nicotinic receptors. Because curare and snake venom occupy the nicotinic receptors located at the neuromuscular junction without breaking down or being released, ACh is unable to stimulate muscle fibers. Inactivation of the muscles of the diaphragm required for breathing, leads to paralysis and death. Number of important drugs exert influence on the GABA-A receptor. Although only one binding site is activated by GABA itself, there are 5 binding sites on the GABA receptor. Can be activate by BENZODIAZEPINES (tranquilizers), alcohol, and BARBITURATES, which are used as anesthesia and in control of seizures. Barb can single handedly activate the GABA-A receptor without any GABA present at all. Benzo and alc increase the receptor's response to GABA but only when they occupy binding sites at the same GABA is present. Because GABA has a hyperpolarizing or inhibitory effect on postsynaptic neurons, GABA agonists enhance inhibition. The combined action of alcohol, benzo, or barbs, at the same GABA-A receptors can make life threatening level of neural inhibition.

Neurochemical Storage

Interfering with the storage of a neurotransmitters in vesicles within a neuron. Ex: the drug RESERPINE, used to reduce blood pressure and psychosis, blocks the uptake of monoamines into synaptic vesicles. As a result, abnormally small quantities of monoamines are available for release in response to the arrival of action potentials. Reserpine's interference with the monoamine serotonin often results in depression.

Anton van Leeuwenhoek

Invented light microscope

LSD

LSD a schedule 1 drug. Chemically similar to serotonin and along with other hallucinogens, appears to act as an agonist at serotonergic autoreceptors in prefrontal cortex, locus coeruleus, and raphe nuclei. LSD produces tolerance but not withdrawal. Does not create addiction. Negative consequence is that it produces flashbacks in the form of intrusive and unwanted visual hallucinations which can continue long after use of the substance. The experience of continued flashbacks is referred to as hallucinogen persisting perception disorder (HPDD). HPPD might result from damage to inhibitory cortical neurons that possess serotonergic receptors and release GABA. Loss of these cells might contribute to a reduction in the signal to noise ratio of visual system, leading people to respond to signals that would normally be suppressed. Also suggested that increased excitatory input to the primary visual cortex is sufficient to make flashbacks. An inbalance between excitatory and inhibitory inputs to lower level of the visual system might give best explanantion for HPPD.

Behavioral

Looks at activity of NS in health and in cases of illness, injury, and psychological disorder

Biochem Methods

MICRODIALYSIS: Desirable to identify the chemicals that naturally exist in a certain location of the brain. Using implanted micropipettes, small amounts of extracellular fluid are filtered from the area of the brain surrounding the tip of the pipette for analysis Lets researchers identify which neurochemicals are active in a certain location as well as how much of these chem

Galen

Made careful dissections of animals. Believed erroneously that the ventricles played an important role in transmitting messages to and from the brain

Neuropeptides

Made in the neural cell body and must be transported to the axon terminal. It is possible to "run out of" neuropeptides during periods of active signaling. The often coexist in the same neuron with a small molecule messenger and are co-released to modify its effect. A single neuron can contain and release many different neuropeptides. All receptors for this are metabotropic. Deactivation of this in the synapse occurs through diffusion or enzymatic degradation and is a slow process. Among the neuropeptides are substance P which is involved in perception of pain and the endogenous morphines (endorphins), substances that act on the same receptors as opiods, such as heroin.

Protecting/Supplying NS

Meninges: -This is the three layers of membranes that protects brain -DURA MATER (outer layer), follows outline of skull bones -ARACHNOID LAYER, sticks close to outside of brain -PIA MATER (innermost layer), sticks close to outside of brain -Between arachnoid and pia mater is the SUBARACHNOID SPACE -These all cover brain and spinal cord -Brain's immune system communicates with the rest of the immune system Cerebrospinal Fluid: -Secreted in hollow spaces in the brain known as VENTRICLES -In lining of ventricles, the CHOROID PLEXUS changes material from the nearby blood supply into CSF -CSF circulates through the CENTRAL CANAL of the spinal cord and four ventricles in the brain: the two lateral ventricles, one in each hemi and the third and fourth ventricles in brainstem -Cerebral aquaduct connects third and fourth ventricle -Fourth ventricle continuous with central canal of spinal cord. Below this ventricle, there is small opening that allows CSF to flow into subarach space that surrounds both brain and spinal cord -CSF cushions brain, doesn't cause pressure on brain, circulates nutrients and removes waste, helps neurochemicals diffuse to more distant locations

Monism

Mind is result of brain activity, which can be studied scientifically.

Tiny to big picture

Molecular, Cellular, Synaptic, Network, Behavior (All computational)

Cannabis

Most common somewhat illegal substance Most people experience some excitation and mild euphoria, but others experience depression and social withdrawal. At higher doses can produce hallucinations. Has more than 50 psychoactive compounds known as cannabinoids. Implicated in many processes such as pain, appetite, movement, and learning. Most important cannabinoid is THC. THC makes some of its behavioral effects by serving as an agonist at receptors that are very similar to THC in chem composition. Two types have been identified: CB-1 and CB-2 that interact primarily with endogenous cannabinoids, ANANDAMIDE (sn-2) and 2-AG. Presence of cannabinoid receptors in the hippocampus and prefrontal cortex might explain why THC appears to have neg effects on memory formation, attention, and working memory. THC might also adversely influence hippocampal activity and memory by inhibiting glutamate release. Possible relationship between cannabis and development of psychosis. Ppl with schizo who do cannabis have worse outcomes than nonusers, as cannabis might exacerbate structural changes in the brain due to schizo. Both chronic, heavy cannabis users and patients with schizo show reduced volume in amygdala and hippocampus. Longitudinal studies show strong correlation between use and psychosis. Other people see the use as a risk for psychosis if they are predisposed toward psychosis. Others believe some ppl experience underlying, shared genetic risk leading to both heavy cannabis and psychosis

Edwin Smith Surgical papyrus

Oldest known med writing in history The author understood that paralysis and lack of sensation in the body resulted from NS damage; realized that NS damage couple not be fixed

Brain Stimulation

Most neurosurgery is conducted under local anesthesia; brain is numb and patient is conscious By stimulating an area of the exposed brain with a small amount of electricity and assessing any changes in behavior, surgeon can identify the area's functions Repeated transcraniel magnetic stimulation (rTMS): -Magnetic pulses delivered through a single coil of wire encased in plastic that is placed on scalp -Temporarily changes brain activity immediately below stimulation site -Shows promise in treatment of motor disease -Found to enhance memory and attention Optogenetics: -Use of molecules genetically inserted into certain neurons in the brain, which then allows neural function to be modified by light -Light can turn neurons on and off -Begins with identification of opsins, or light sensitive proteins, found in algae -Genetic material then modified to make opsin in only one certain type of cell. This is inserted into a virus which is then injected into brain of mouse -Virus infects many cells but the modifed genetic material ensure that only one type of cell will make the opsin protein

Glia and Neurons

NS made up of two types of cells: glia and neurons Glia have support functions for neurons Neuron is specialized to carry out the functions of info processing and communication Glia: -MACROGLIA are large glial cells and originate in ectoderm layer -MICROGLIA are small and originate in mesoderm layer -Macroglia have four types: astrocytes, ependymal cells, oligodendrocytes, and Schwann cells -EPENDYMAL CELLS line ventricles of the brain and the central canal of spinal cord -OLIGODENDROCYTES and SCHWANN CELLS supply the myelin covering that insulate nerve fibers known as axons -ASTROCYTES most common type. Primary function is that they provide structural matrix for the neurons. Helps transfer glucose and other nutrients to the neurons. They have ability to contact both blood vessels and SYNAPSE, or points of communication between two cells. -Astrocytes contribute to protective BLOOD-BRAIN BARRIER. This keeps most toxins circulating in the blood from entering the brain. -Astrocytes influence adjacent neurons and other astrocytes by releasing many excitatory and inhibitory neurochem released by neurons -Overactivation from astrocytes from injury, psychological disorders, lack of exercise, or poor diet can enhance sensations of pain and spread pain to other parts of the body. Damaged astrocytes release large quantities of glutamate, the brain's major excitatory neurochem. Too much kills neurons. -When CNS neurons are damaged, astrocytes form glial scars, or scar tissue that fills the area previously occupied by the now dead neurons and release chems that inhibit neural regrowth. Response of astro to injury is helpful in healing process, protecting cells from harmful chem, promoting healing of blood-brain barrier, and reducing inflammation. However, scarring interferes with repairing of damaged connections. -Ependymal cells line ventricles of the brain and the central canal of the spinal cord. It monitors quality of CSF and supplies underlying brain cells with proteins from CSF. Activation of stem cells might require signals from blood, CSF, and epen cells. These cells also act as firewall against viruses attacking the CNS. Malfunction of this might lead to hydrocephalus -Oligodendrocytes and Schwann cells provide myelin covering that insulates some nerve fibers or axons. Oligo form myelin in CNS and Schwann supply myelin in PNS. Oligo contribute to the structural stability of brain and spinal cord. A single one can myelinate axons from an avg of 15 diff neurons. Contrasting, one Schwann cell provides a single myelin segment on a peripheral axon. It takes large number of Schwann cells to myelinate a peripheral nerve. -Oligo and Schwann communicate with nearby axons by releasing EXOSOMES. These remove debris from a cell and also deliver substances, including genetic material, to other cells. In PNS, exosomes released by Schwann cells aid in regeneration of damaged axons. In CNS, they release oligo and support transport within neurons and protect them from damage. -Oligo and Schwann differ in reactions to injury. Schwann help guide the regrowth of damaged axons, whereas the oligo lack this capacity. -Microglia serve as brain's cleanup crew. Brain version of white blood cells or phagocytes. Travel to location of injury and digest the debris. Uncontrolled activation of micro can damage brain. Sometimes they will eat the healthy cell next to damage cells too. Play a role in removal of less active synapses, which is an important part of the wiring of the developing brain. By removing synapses in a weird way, micro could contribute to Alzheimer's which is characterized by synaptic loss.

Structure of Neurons

Neural membrane: -Made up of double layer of phospholipids, fatty molecules that contain phosphate. These fats don't dissolve in water -ION CHANNELS and ION PUMPS provide pores or channels through which certain IONS or electrically charged particles can move in or out of neuron -Ion channels allow ions to move passively without expenditure of energy -Ion pumps require energy -Both show ion selectivity -Some ion channels (VOLTAGE-DEPENDENT CHANNELS) open and close in response to the electrical status of adjacent areas of membrane -LIGAND-GATED CHANNELS open when they come in contact with certain chemicals -Two most important ion pumps in neurons are the SODIUM-POTASSIUM PUMP and CALCIUM PUMP. Sodium-potassium pumps help maintain the differences in chem composition between intra and extra fluid. They do "prisoner exchange" across neural membrane by sending 3 sodium ions out of cell while collecting 2 potassium ions from the extra environment. 20-40% of energy required by brain is used for this. Calc pumps perform similarly but don't collect another type of ion in exchange for the calc they pump out of cell. Neural Cytoskeleton: -Maintains shape of neuron -3 types of filament, or fiber, make up neural skeleton -MICROTUBULES are the largest of the three. Responsible for movement of various materials within the cell -ANTEROGRADE TRANSPORT: movement along the microtubules away from cell body -RETROGRADE TRANSPORT: movement toward cell body from the periphery -Microtubules implicated in dev of Alzheimer's -One characteristic of Alzheimer's is presence of neurofibrillary tangles consisting of a protein called TAU. In the disease, tau levels become elevated. In response, an affected neuron adds molecules of phosphate to the tau protein, which causes it to disconnect from the microtubules. The disconnected tau begins to form tangles, hindering the cell's ability to signal and maintain its structure. The neuron folds in on itself and collapses. -NEUROFILAMENT similar to structure of hair. Gives structural support. -Smallest fibers are MICROFILAMENTS and participates in changing the shape and length of these structures during development. Neural Cell Body: -Responsible for info processing and communication functions of the neuron -Mitochondria inherited from mother. Useful in tracking evolution. Complex structure and length of neurons pose special problems for mitochondria which are synthesized in the cell body but might be needed in an axon terminal many feet away. Disturbances in mito distribution and transport within neurons are suspected in many conditions including bipolar disorder Dendrites: -DENDRITIC SPINES are able to change shape based on activity occurring at the synapse, which contributes to learning and memory. Axon: -Neuron may have large numbers of dendrites but typically has one axon. -AXON HILLOCK: cone shaped segment of axon that lies at the junction of the axon and the cell body -ACTION POTENTIALS arise in INITIAL SEGMENT, or the portion of axon between the axon hillock and the first segment of myelin, and are then reproduced down the length of the axon -LOCAL CIRCUIT NEURONS: a neuron that communicates with neurons in its immediate vicinity -PROJECTION NEURONS: Neuron with very long axon that communicates with neurons in distant areas of the NS -COLLATERAL: one of the branches near the end of the axon closest to its targets -AXON TERMINAL: swelling at the tip of an axon collatoral specialized for the release of neurochem -AXON VARICOSITY: a swelling in an unmyelinated segment of axon containing mitochondria and in some case, synaptic vesicles -SYNAPTIC VESICLES: a small structure in the axon terminal that contains neurochem -Myelin advantages: Allows human axons to be smaller in diameter without sacrificing transmission speed. Reduces the energy requirements of neurons by decreasing the amount of work done by so-pot pumos. Myelin segments wrap tightly around axons that there is little to no need for ion channels under a myelin sheath. Contrast, an unmye axon has ion channels along entire length. During signaling, fewer ions move through the ion channels of a myelinated axon mem than through an unmye axon mem of the same length.

Identifying Neurochemicals

Neurochemicals are substances released by one cell that produces a reaction in a target cell. 1. The substance must be present within presynaptic cell 2. The substance is released in response to presynaptic depolarization 3. The substance interacts with specific receptors on postsynaptic cell

Cellular

Neuroscientists work hard to outline the structure, physiological properties, and functions of single cells found within the NS

Gasotransmitters

Nitric oxide (NO), Carbon monoxide (CO), Hydrogen sulfide (H2S) can transfer info from one cell to another. NO is a short living free radical produced by actions of the enzyme nitric oxide synthase (NOS). NO is a precursor for acid rain. NO is involved with neural communication, maintenance of blood pressure, and penile erection. NO activates second messengers within neurons, leading to probably roles in learning and memory, anxiety, and addiction. NO at high levels can have toxic effects on neurons. NO plays role in regulating communication between the thalamus and cerebral cortex, which influences amount of sensory input processed by the highest levels of the brain. Gaseous molecules dissolve in lipids so they diffuse through membranes without needing vesicles or a release mechanism. They act on receptors located within the cell rather than on receptors embedded in the membrane. Possible for them to travel through cell and influence its neighbors. They break down quickly without needing action of enzymes. They transfer info from postsynaptic neuron to the pre rather than other way around.

Propagating Action Potentials

Once a single action potential has been formed at the initial segment, the next step is PROPAGATION by which the signal reproduces itself down the length of the axon. This ability to reproduce the original signal ensures that the signal reaching the end of the axon is as strong as the signal formed at the axon hillock SALTATORY CONDUCTION: the movement of an action potential from node of Ranvier to node of Ranvier down the length of a myelinated axon -Drift of Na and K ions to adjacent segments of axon causes segments to reach threshold, triggering replication of the action potential -Existence of refractory period in the preceding segment prevents backwards propagaton

Sagittal section

Parallel to midline, allows side view of brain structures

Lesion

Primary purpose is to assess the probable function of an area ABLATION: deliberate lesions such as large areas of brain tissue being surgically removed Can be created by electrode heat killing small population of cells at the tip, chemicals killing specific neurons; both create permanent damage in brain Reversible type of lesions can be produced by cooling an area using a surgically implanted probe. When area is chilled, the neurons are unable to function. When unchilled, all good. Good for comparing before, during, and after of a temp lesion

Franz Josef Gall

Proposed idea that specific body parts are controlled by certain areas of the brain, called LOCALIZATION OF FUNCTION Elaborated by SPURZHEIM Proposed science of "phrenology" that maintained that the structure of people's skulls could be correlated with their individual personality characteristics and abilities Phrenologist could "read" a person's character by comparing the bumps on his skull to a bust showing the supposed location of each trait Both proposed modern view of the brain as organ of the mind

Resting Potential

Resting neural membrane allows potassium to cross freely. Resting potential in a neuron is so dependent on the movement of potassium, there is importance of controlling the concentration of potassium in the extracellular fluid If concentration of potassium increases in the extra fluid, the resting potential is wiped out. No signaling would occur Resting potential of neurons averages about -70mV. The interior of the cell is negatively charged relative to the exterior. An action potential is a reversal of this polarity.

Functional Variations in Neurons

SENSORY NEURONS: receive info from outside world and from within bodies MOTOR NEURONS: transmit commands from the CNS directly to muscles and glands INTERNEURON: vast majority. Acts as bridge between sensory and motor neurons

Neurohormones

Secreted by special neurons into the blood supply. Will interact with other cells that have specialized receptor sites to receive them. Many cells that produce neurohormones are located in the hypothalamus, the adrenal glands, and the enteric nervous system

The Small Molecules

Specific neurochemicals appear to play a vital role in neural signaling: -Acetylcholine, six monoamines, several amino acids, and the energy molecule ATP and its byproducts ACETYLCHOLINE first chem molecule to be discovered. Cholinergic neurons also manufacture the enzyme ACETYLCHOLINESTERASE (AChe). This is released into the synaptic gap, where it breaks down any ACh in that location. The choline resulting from the breakdown of ACh can then be recaptured by the presynaptic neuron and resynthesized into more ACh. ACh is the main neurotransmitter at the neuromuscular junction, the synapse between a neuron and a muscle fiber. Also important to the operation of the autonomic NS. Also form an important neuromodulation system in the brain. These cholinergic systems appear to participate in attention, wakefulness, learning, and memory Two major subtypes of cholinergic receptors: NICOTINIC RECEPTORS and MUSCARINIC RECEPTORS found in the NS. A nicotinic receptor responds to both ACh and to nicotine, whereas muscarinic receptor responds to both ACh and muscarine, a poisonous mushroom. Nicotinic receptors are fast ionotropic receptors. They are found at the neuromuscular junction, which is logical given the need for speed for muscle reaction. Muscarinic receptors are slower metabotropic receptors. They are found in heart muscle and other smooth muscle. CNS contains both nicotinic and muscarinic receptors but muscarinic are more common. Both found in autonomic NS. The six MONOAMINES divided into subgroups: CATECHOLAMINES (dopamine, norepinephrine, and epinephrine), the INDOLEAMINES (serotonin and melatonin), and histamine. All the monoamines are subject to reuptake from the synaptic gap following release. In axon terminal, monoamines that are not encased in vesicles are broken down by the action of the enzyme MONOAMINE OXIDASE (MAO). Outside neurons, catecholamines are broke down by the enzyme CATECHOL-O-METHYL-TRANSFERASE (COMT). Catecholamine synthesis begins with the amino acid tyrosine. All neurons with this also contain the enzyme tyrosine hydroxylase (TH). When TH acts on tyrosine, the end product is L-dopa. The production of dopamine requires additional step of L-dopa. Enzyme dopa decarboxylase acts on L-dopa to make dopamine. Dopamine is converted to NOREPINEPHRINE by action of dopamine hydroxylase (DBH). This last step takes place within synaptic vesicles. Finally the catecholamine EPINEPHRINE is made by the reaction between norepinephrine and the enzyme phenylethanolamine (PNMT). The synthesis of epinephrine is hard. Once norepinephrine is synthesized within synaptic vesicles, it must be released back into intracellular fluid, where it is converted by PNMT into epinephrine. The epinephrine is then transported back into vesicles. Dopamine systems are involved with movement as well as with motivated behaviors and the processing of reward. Disruptions of dopamine function are suspected of playing a role in schizophrenia and ADHD. The first pathway is known as the MESOSTRIATAL PATHWAY or NIGROSTRIATAL PATHWAY. Originating in the substantia nigra of the midbrain and proceeds in a dorsal direction to communicate with the caudate nucleus and putamen of the basal ganglia. Has approx 80% of the brain's dopamine and participates in motor planning and voluntary motor activity. It is damaged in Parkinson's disease. Second major pathway is the MESOLIMBIC PATHWAY, arising in the ventral tegmuntum of the midbrain and projects to the nucleus accumbens. This pathway responds to many types of rewards. A MESOCORTICAL PATHWAY connects the ventral tegmentum of the midbrain to areas of the prefrontal cortex and participates in executive functions and planning. Disruption of these systems appear to be involved in schizo. Increased activity in dopaminergic neurons projecting from the midbrain to the limbic system coupled with a decrease in activity in dopaminergic neurons projecting from the midbrain to the cortex might be responsible for some of the symptoms observed in psychological disorder. Two other dopaminergic pathways originate in hypothalamus. The paraventricular dopamine system connects the hypothalamus to the thalamus and to sympathetic neurons in the spinal cord, helping to coordinate motivated behaviors such as appetite, sex, and thirst. A second hypothalamic dopaminergic pathway connects to the pituatary gland and controls milk production in mammals. Multiple receptor subtypes exist for dopamine, labeled D1-D5. These are grouped into two categories. One class includes the D1 and D5 receptors and the other class includes the remaining D2, D3, and D4 receptors. All of these are metabotropic. First class makes excitation while the second class makes inhibition. First class found in hippocampus and hypothalamus while second found in frontal lobes of cortex, thalamus, and brain stem. Neurons releasing epinephrine is adrenergic and those releasing norepinephrine as noradrenergic. Epinephrine deals with adrenaline rush. Norepinephrine increases arousal and vigilance. Receptor types that respond to either norepinephrine or epinephrine are classified as a or B receptors. All of these are metabotropic. Indoleamines, including SEROTONIN and melatonin (synthesis of serotonin begins with TRYPTOPHAN. Two chem reactions are required to convert trytophan into serotonin. The first is the action of the enzyme tryptophan hydroxylase, which converts tryp to 5 HTP. Second, the 5-HTP is converted to serotonin by the action of the enzyme 5-HTP decarboxylase. 95% of the body's serotonergic neurons are located in the enteric nervous system. Most located in raphe nuclei of the brainstem. These deal with appetite, sleep, mood, dominance, and aggression. Serotonin pathways influence our motivation to consume carbs, leading with experimentation with reuptake blockers to treat obesity. Mood disorders such as depression are often treated with medications that increase activity of serotonin. Low levels of serotonin activity are associated not just with depressed mood but also with lower social rank, increased risk taking, and aggression. Melatonin is synthesized from serotonin. Serotonin is converted into L-acetylserotonin through the action of serotonin N-acetyletransferase and acetyl-CoA. L-acetylserotonin is then converted into melatonin through methylation of the hydroxl group by hydroxyindole O-methyltransferase and S-adenosyl methionine. Most melatonin is made by pineal gland, which lies outside blood-brain barrier. Histamine results from action of histidine decarboxylase on the amino acid L-histidine. Most histamine is released by immune system cells and blood cells, but also serves as neuromodulator in the brain. All his released in adult brain is made in the tuberomamillary nucleus (TMN) of the hypothalamus. Correlated with wakefull. After ACh and monoamines, the next category of small molecules is the amino acids. 3 significant ones: GLUTAMATE, GAMMA-AMINOBUTYRIC ACID (GABA) and GLYCINE. Glutamate and glycine used to build other proteins. Glutamate most common excitatory neurochemical in CNS, used by as many as 90 percent of the synapses in the human body. Glutamate is synthesized from a-ketoglutarate in the mitochondria. Once released, glutamate is taken up quickly by both neurons and astrocytes. The synaptic area must be cleared of excess glutamate because extended action of glutamate on neurons can be toxic. Only a tiny amount of the brain's glutamate, .01 percent, is found in the extracellular fluid. Some ppl appear oversensitive to MSG. Glutamate receptors can be either ionotropic or metatropic. The three ionotropic glutamate receptors are the NMDA receptor, the AMPA receptor, and the kainate receptor. Both the AMPA receptor, which is the most common, and the kainate receptor control a sodium channel. When these receptors bind molecules of glutamate, a sodium channel opens and an EPSP is produced. The NMDA receptor method is weird. NMDA receptors are both voltage-dependent and ligand-dependent. They will not open unless glutamate is present AND the postsynaptic membrane in their vicinity is depolarized at the same time. At the typical negative resting potentials of the postsynaptic neuron, the ion channels of NMDA receptors are blocked by magnesium ions. Because NMDA and AMPA receptors are usually found near one another on the same post synaptic membrane, sodium moving through a nearby AMPA receptor will depolarize the postsynaptic cell. When the membrane becomes sufficiently depolarized, the magesium ions will be ejected from the NMDA receptor, allowing it to open in response to the binding of glutamate. NMDA receptors allow both positively charged sodium and calcium ions to enter cell which depolarizes it. Normally an ion channel lets in one singly type of ion, not two. Once inside, calcium activates enzyme sequences that result in strucutral and biochemical changes. Because of calcium's ability to trigger lasting changes in neurons, the NMDA receptor is thought to participate in functions like long term mem. Action of calcium upon entering the cell is also responsible for the toxicity of excess glutamate levels. As more glutamate stimulates the NMDA receptors, more calcium enters neurons. The resulting excess enzyme activity can digest and kill the affected neuron. This might be responsible for damage following strokes and brain diseases. GABA serves as major inhibitory neurochemical of the CNS. It is synthesized from glutamate through action of the enzyme glutamatic acid decarboxylase (GAD). Three types of GABA receptors GABA-A, GABA-B, and GABA-C. GABA-A and GABA-C receptors are ionotropic postsynaptic chloride channels, which allow negatively charged chloride ions to enter the cell. GABA-B receptors are metabotropic potassium channels which allow positively charged potassium ions to leave the cell. Hyperpolarization can happen whenever negative ions enter the cell or when positive ions leave the cell. Glycine acts directly as an inhibitory neurochem by opening ionotropic chloride receptors. These receptors are blocked by the poision strychnine. Strychnine kills an organism by presenting the diaphragm muscles from relaxing. Glycine is synthesized when the enzyme serine transhydroxymethylase acts on serine in mitochondria. It is removed from the synaptic gap by reuptake Glycine is typically inhibitory, but it also plays an excitatory role in conjunction with glutamate at the NMDA receptor. It produces the lower body temp typical of sleep. This is a promise of treatment of insomnia. ATP and its byproduct ADENOSINE are neuromodulators in the CNS and in connection between autonomic neurons and the vas deferens, bladder, heart, and gut. Adenosine results from breakdown of ATP. As adenosine levels in the extracellular fluid rise, three type of metabotropic receptors are activated. A1 inhibits the release of glutamate, acetylcholine, norepinephrine, serotonin, and dopamine. A2 facilitates the release of glutamate and acetylcholine while inhibiting the release of GABA. As a result, adenosine modulates a wide variety of functions, including the excitability of neurons and the coordination of neural networks. The overall effect of high adenosine levels in the brain is inhibitory.

Opiods

Substances that interact with endorphin receptors (MORPHINE and CODEINE). Heroin is synthesized from morphine. OPIATES have med purposes including pain management, cough suppression, and treatment of diarrhea. 85% of all heroin originating from Afghan. Most frequently abused opioids is Oxycontin, used by 8% of high schoolers. Introduction of new formula of it had drop in abuse to 30% but this drop was accompanied by a doubling in heroin use by same population. -At low doses, produces euphoria, pain relief, lack of anxiety, muscle relaxation, and sleep. Higher doses produces a lot of euphoria or rush. With even higher doses, opioids depress respiration leading to death. -Three metabotropic receptors: mu, delta, and kappa receptors bind with opioids. Fourth receptor ORL 1. Neuropeptides produced within the body: ENDORPHINS. Two additional neuropeptides were discovered after: enkephalins and dinorphin. Endorphins interact with mu receptors, enkephalins with delta receptors, and dynorphin with kappa receptors. Most analgesic opioids show strongest affinity for mu receptor. Why would we have naturally occuring substances similar to opiates? The natural opiates probs help us escape emergency situations in spite of extreme pain. -Produce most of their effects by acting presynaptically to inhibit neurotransmitter release. They do so by inhibiting the entry of calcium into the presynaptic terminal, by enhancing the outward movement of potassium, which shortens duration of action potentials, and by interacting with normal enzyme cascades within neurons. -One of the indirect consequences of their binding to opioid receptors is to increase dopamine activity. They bind with mu receptors on cells that release GABA in the nucleus accumbens. These cells typically act to inhibit the release of dopamine. Under influence of the presynaptic inhibition made by the opioids, however, these cells release less GABA, which disinhibits the release of dopamine. Increased dopamine release in the nucleus accumbens rapidly creates dependence.

Production of Neurochemicals

Substances that promote increased production act as agonists and substances that interfere with production are antagonists. Simplest way to boost rate of neurochemical synthesis is to provide larger quantities of the basic building blocks, or precursors. Drugs can also exert antagonistic effects by interfering with the synthesis pathways of neurochemicals.

Camillo Golgi

Supported concept that NS was a vast interconnected network of continuous fibers

Synapse

The birth and propagation of the action potential within the presynaptic neuron makes up first half of neural communication Second half begins when the action potential reaches the axon terminal and the message must cross the synaptic gap to the adjacent postsynaptic neuron Synapses take on of two forms: GAP JUNCTIONS- a type of synapse in which a neuron directly affects an adjacent neuron through the movement of ions from one cell to another CHEMICAL SYNAPSE- a type of synapse in which messages are transmitted from one neuron to another by neurochem Gap Junctions: -Speed of transmission is nearly instataneous -Method of transmission is direct movement of ions from one cell to the other -Type of message is excitatory only -Type of cells involved; requires large presynaptic neuron to influence small postsynaptic neurons Chemical synapse: -Speed of transmission is up to several miliseconds -Method of transmission is release of neurochem -Type of message is excitatory or inhibitory -Type of Cells involved; small presynaptic neurons can influence large postsynaptic neurons Advantage of chemical synapses is that they provide greater variety of messages. Another advantage is that a very small presynaptic neuron using chemical messengers can still influence large postsynap neurons

Tolerance and Withdrawal

Tolerance effects can happen due to changes in enzymes and changes in receptor density, and learning. Not all effects of the same drug show equal levels of tolerance. Withdrawal effects are the opposite of the effects caused by the discontinued drug. Withdrawal from a sedative will become agitated, whereas a person withdrawing from a stimulant will become lethargic.

Genetic Methods

Twin studies: -CONCORDANCE RATE: type of statistical probability. EX: if one identical twin has bipolar disorder, there is as much as 90% chance other twin will have it Adoption studies: -HERITABILITY: amount that a trait varies in a population due to genetics, is still influenced by environment -Interpretation of adopt studies are controversial because adopt families are quite similar to one another because of screening process they undergo before adoption Genetic screens: -GENETIC SCREEN: Checking correlation between geno and phenotypes -FORWARD genetic screen is used to identify genes that seem important in development of phenotype. Researcher locates phenotypical trait of interest and attempts to find the genes necessary for showing that trait -REVERSE genetic screen involves testing one gene at a time. First select gene and then observe which phenotypical changes occur in absence. -KNOCKOUT GENES take the place of normal genes but fail to produce specific protein. With this method, researchers can assess roles of certain genes and the proteins they encode

Chemical Synapses

Two types: WIRING TRANSMISSION- Process in which chemicals diffuse from one cell to impact an adjacent cell or cells through private, highly localized cells VOLUME TRANSMISSION: Process in which neurochem diffuse through the extra fluid and CSF to influence cells located some distance away from the releasing cell Signaling at chem synapse happens in two steps. First step: release of neurochem by a presynaptic cell. Second step: reaction of a postsynaptic cell to neurochem Neurochemical Release: -In response to arrival of an action potential at a terminal, a new type of voltage-dependent channel will open. This time, voltage-dependent calcium channels. Amount of neurochem released is reflection of the amount of calc that enters the presynaptic neuron. Large influx of calc triggers large release of neurochem -Ca is found more in extra than intra fluid. Open in response to arrival of depolarizing action potential. -Before release, neurochem are stored in synaptic vesicles. Vesicles are anchored by special proteins near release sites on the presynaptic membrane. Process by which these vesicles release their contents is known as EXOCYTOSIS. This happens in two ways: first a synaptic vesicle can completely merge with the axon terminal membrane, releasing its entire contents into synaptic gap. Second, vesicles might be able to release some content through a small pore without losing their shape, "kiss and run" -Following exocytosis, neuron must prepare for arrival of next action potential. Ca pumps return Ca to extra fluid. -Embedded within the presynap membrane are special protein structures known as AUTORECEPTORS. These bind some of the neurochem released by the presynap neuron, giving feedback to the presynap neuron about its own level of activity Neurochem bind to postsynap receptor sites: -On the postsynap side of the synapse, we find new types of proteins embedded in the postsynap cell membrane called RECEPTORS. The receptors are characterized by RECOGNITION MOLECULES that respond to only certain neurochem. -2 major types: IONOTROPIC RECEPTOR-the recognition site is located on the channel protein. This is fast. Allow ions to move in or out of cell. As soon as receptor captures molecules of neurochem (ligands) the ion channel changes its configuration and opens to allow ions through membrane. These one-step receptors are capable of very fast reactions to neurochem. METABOTROPIC RECEPTORS- a protein structure embedded in postsynaptic membrane containing a recognition site and G protein. Neurochem binding to these receptors don't directly open ion channels. G PROTEIN is a protein found on the intra side of a metobotropic receptor that separates in response to the binding of a neurochem and travels to adjacent areas of the cell to affect ion channels or second messengers. Met receptors slower to respond. Met receptors can last much longer than those produced by iono. Met gives possibility of greater variety of responses to the binding of neurochem. Iono only affects small local part of a cell, a met receptor can have wide ranging and many influences within a cell due to its ability to activate a variety of second messengers. Termination of Chem Signal: -Necessary to end first message before starting second synaptic message. Neurochem deactivated in three diff ways: First method is diffusion away from synapse. Second method, neurochem molecules are deactivated by enzymes in synaptic gap. Third process, REUPTAKE, (a process for ending the action of neurochem in the synaptic gap in which the presynap membrane recaptures the molecules of neurochem), the presynap mem uses its own set of receptors known as TRANSPORTERS to recapture mol of neurochem and return them to interior of the axon terminal. Reuptake spares the cell the extra step of reconstructing the molecules out of component parts. Postsynap Potentials: -When molecules of neurochem bind to postsynap receptors, they can produce one of two outcomes. -One outcome is excitation, increases the likelihood that the postsynap cell will generate an action potential. The other outcome, inhibition, decreases the likelihood that cell will fire. -Excitation results from depolarization of the postsynap membrane, known as EXCITATORY POSTSYNAPTIC POTENTIAL (EPSP). Results from opening of ligand-gated rather than voltage-dependent sodium channels in the postsynap mem. There is signaling between neurons. -INHIBITORY POSTSYNAP POTENTIAL (IPSP) is signaling between neurons. Graded hyperpolarization of depolarization. Ligand-gated potassium or chloride channels. Neural Integration: -The determination of whether to fire an action potential, based on the summation of inputs to a neuron. -Located in axon hillock of postsynap cell body. -Drifting positive and neg currents converge at the axon hillock -If sufficient depolarization occurs at the axon hillock, the postsynap cell will generate action potential -SPATIAL SUMMATION: Neural integration in which the combined inputs from many synapses converge on the axon hillock, whereas an action potential will result if threshold is reached -TEMPORAL SUMMATION: Neural integration in which excitation from one active synapse is sufficient to initiate the formation of an action potential

Structural Variations in Neurons

Unipolar: -Single branch extending from body -Typical in invertebrae NS -In vertebrates, these are found in sensory system -Involved with somatosenses. Extends short distance from the cell body and then splits into two branches -Located near spinal cord, with processes extending to skin, muscle, organs, and glands Bipolar: -A neuron with two branches extending from the cell body: one axon and one dendrite -Important role in sensory system, including retina of eye. -Impt to assessing and performing the complex social behaviors -Loss of this might result in lack of empathy, social awareness, and self-control -Also located in anterior cingulate cortesx Multipolar: -Located in cerebral cortex (participates in movement and cognition), cerebellum (participates in movement), spinal cord, with axons extending to muscles and glands (carries commands to muscles and glands)

Neuraxis

an imaginary line that runs the length of the spinal cord to the front of the brain

Treatment of Addiction

Withdrawal from exposure to addictive drugs makes further changes in the nucleus accumbens, this time involving glutamate signaling. Drug seeking among addicts might be inhibited usings meds that target glutamate activity in the nucleus accumbens. Methadone prevents withdrawal symptoms yet it doesn't produce the major psychological effects of heroin. Alcoholics are treated with disulfiram, or Antabuse, which interferes with the activity of the enzyme ALDH in metabolizing alc. This creates unpleasant symptoms when alc is consumed. Vaccinations have also been made for this. They work by stimulating the immune system to bind molecules of the problem drug, preventing or delaying its movement across the blood brain barrier into the brain. Ethical and practical problems because an adolescent vaccinated against effects of nicotine might use higher doses to overcome it. Environmental factors can cause addiction too. Vietnam vets used heroin overseas more than when they were back home.

Charles Sherrington

coined the term synapse Conducted research on reflexes and the motor systems of the brain

Midsagittal section

divides the body into equal left and right parts

Greeks scholors...

proposed brain was the organ of sensation