PDBIO 305 UNIT 2

Explain the concept of dual innervation.

• Both branches of the autonomic nervous system innervate most organs • Primary function of autonomic ns is to regulate and maintain homeostasis • At rest, both parasympathetic and sympathetic ns are working but para dominates • Some functions of the body require both parasympathetic and sympathetic ns working

Explain the role of the thalamus in relaying and interpreting sensory information.

• Diencephalon is the inner portion of the brain, consists of thalamus and hypothalamus • Thalamus is the relay station for sensory information • Screens out unimportant information • Filters and refines input before sending to the cerebral cortex • Interpretation center for sensory information • Modality (pain, heat, cold, touch pressure) of sensation is perceived here, but no location or intensity • Relay station for motor pathways from cerebral cortex

Define 'tonic' and 'phasic' and explain what is meant by receptor adaptation.

• Most receptors adapt to the stimulus- their response declines with the passage of time • Receptor adaptation is a decrease over time in the magnitude of the receptor potential in the presence of a constant stimulus • Tonic receptors (slowly adapting) show little adaptation, can function in signaling the intensity of a prolonged stimulus • Example- slowly adapting receptors include muscle stretch receptors that detect muscle length which detect pressure on the skin • Phasic receptors (rapidly adapting) adapt quickly, function best in detecting changes in stimulus intensity, rapidly adapting receptors respond at the onset of a stimulus then adapt • Examples include olfactory receptors

Identify the components of a reflex arc.

• Neural pathways for reflexes are known as reflex arches and are composed of 5 parts • A sensory receptor, an afferent neuron, an integration center, an efferent neuron and an effector organ • Similar to negative feedback

List nociceptor neurotransmitters.

• Pain is primarily a protective mechanism meant to bring a conscious awareness that tissue damage is happening • Storage of painful experiences in memory help us avoid potentially harmful events • Pain uses nociceptors • Substance P- activates ascending pathways that transmit nociceptive signals to high levels for further processing • Glutamate- major excitatory neurotransmitter • Activation of nociceptors leads to the perception of pain but also 1) autonomic responses like increased bp and heart rate, increase in blood epinephrine, etc. 2) emotional responses 3) a reflexive withdrawal from the stimulus

Explain the gate-control theory.

• States that somatic signals of non painful sources can inhibit signals of pain at the spinal level • Among the various interneurons within the spinal cord are ones that inhibit the second order neurons that transmit pain information • When these interneurons are active, the transmission of the pain signal is suppressed and the perception of pain is lessened • When information about a painful stimulus is being transmitted to the spinal cord by C fibers, the collaterals of these C fibers inhibit the activity of the inhibitory interneuron, this allows for the transmission to proceed to the second order neuron • The same inhibitory neuron is stimulated by collaterals from AB fibers associated with touch, pressure, or vibration • Therefore, if a non painful stimulus is applied with a painful stimulus, the collaterals from the AB fibers stimulate the inhibitory interneuron thus decreasing the transmission of pain signals

List the five glial cells and their functions/characteristics. Know where they are found

75-90% of the CNS is composed of glial cells: nonexcitable, 4 major types • 4 main types: Schwann cells, oligodendrocytes, microglia, and astrocytes. • All release growth factors and do maintenance • Astrocytes- most abundant, physically support the neurons, regulate the EE around the neurons AKA the blood brain barrier, direct formation of capillaries, guide growing neurons to the right destination, support regeneration of damaged axons, help maintain ion concentration • Schwann cells- form myelin sheaths in the PNS • Oligodendrocytes: form myelin sheaths in the CNS • Microglia: perform phagocytosis (immune defense), detect foreign matter, found in the CNS • Ependymal cells: neural stem cells, aid in production of CSF, found in CNS

Using an ion's equilibrium potential, describe the direction of the electoral driving force and the magnitude of the chemical driving force.

A cell at rest has a potential difference across its membrane such that the inside is negatively charged relative to the outside • Difference is called the resting membrane potential (Vm) because the cell is at rest (not receiving or transmitting any signals) • Resting membrane is approx. -70mV, described as the potential INSIDE the cell relative to the outside. Therefore, inside of neuron is 70x more negative compared to the outside • When a membrane potential exists, the unbalanced charges will accumulate in a thing layer along the membrane • Excess anions will line the intracellular side of the membrane while excess cations will line the extracellular surface of the membrane • Neurons communicate by generating electrical signals in the form of changes in mem. potent. • Any ion actively pumped across membrane is not at equil.- because 3 Na+ are pumped out per 2 K+ pumped out, Na+ are more highly concentrated outside the cell (this creates a chemical driving force to push Na+ ions in), we see the opposite in K+ Membrane Potential of a Cell Permeable to only K+ • Outside cell, there is a surplus of Na+ (balanced by Cl-) and inside there is a surplus of K+ • With a membrane only permeable to K+, the K+ move down their gradient out of the cell, they carry their positive charge out of the cell leaving the cell negatively charged. • This causes a negative membrane potential to develop • Once the membrane potential develops, two forces act on the K+ ions- a chemical force due to the gradient and an electrical force due to the membrane potential • The direction of chemical pushes K+ out of the cell while the electrical wants to pull the ions back into the cell (bring + to equalize the big - charge) • As more K+ leave, the electrical force gets bigger, as rate of membrane potential increases, the chemical force decreases • Once the electrical force has become strong enough to balance the chemical force, no move • This is equilibrium potential (Ek)- approx. -94mV Membrane Potential of a cell only permeable to Na+ • Na+ diffuses into the cell, as it moves, it carries its positive charge into the cell making the inside positive in relation to the outside- membrane potential is positive • As more Na+ diffuse in, an electrical force opposing this inward movement gets stronger • Na+ flows in until electrical force equals chemical force and we are at equilibrium potential • ENa- +60 mV Resting Membrane Potential of Neurons • Number of K+ ion channels EXCEEDS Na+, making it 25x more permeable to K+ to Na+ • Since K+ and Na+ are able to cross mem, they diffuse based on their concentration gradients • Since outward movement of K+ exceeds Na+, a net outward movement of positive charge occurs giving rise to a negative membrane potential • As this happens, the electrical force grows stronger to limit K+ out and Na+ in • When the flow of these ions becomes equal and opposite, we have resting membrane potential which is at about -70 mV 2 • As ions move, they tend to bring the membrane potential towards its respective equilibrium potential. However, neither ion can ever come to eqil. because the movement of one opposes the movement of another • Membrane is more permeable to K+ so we have a negative equilibrium potential • Leak channels allow for Na+ to leak in and K+ to leak out • Create membrane potential and slowly altar ion concentrations in the cell (raise Na+) • Na+/K+ pumps work in the cell membrane to ensure there is a concentration gradient for Na + into the cell and and K+ out of the cell • Because energy is required to sustain the resting state of a neuron, the cell is not in equilibrium but in a steady state

The Spinal Cord and spinal nerves

A cylinder of nerve tissue that's approximately 44 cm long • Continuous with brain, surrounded by vertebral columns, origin of 31 paris of spinal nerves • Spinal cord- 31 pairs of spinal nerves • 8 cervical- neck • 12 thoracic- chest • 5 lumbar - pelvic 1-coccygeal- tailbone • Cauda equina- thick bundle of nerve roots of lower vertebral canal • Dermatome- sensory region of skin, each dermatome is served by a spinal nerve

Describe the events that occur in the synaptic cleft in oder, starting with when the action potential reaches the axon terminal.

Almost all neurons transmit messages to other cells via chemical synapses • One neuron recreates a neurotransmitter in the extracellular fluid in response to an AP arrive in the axon terminal. NT binds to receptors on PM triggering the cell an electrical signal that may/may not initiate an AP • A neuron can form a synapse between another neuron or with effector cells in muscles/glan • These are effector organs and the synapse is called a neuroeffector junction • The presynaptic neuron us the one that transmits the signal to the postsynaptic neuron • the space between them is known as the synaptic cleft, movement in unidirectiona 1) Action potential depolarizes the presynaptic membrane 7 2) Voltage gated Ca++ channels open, Ca++ enters presynaptic axon terminal- Ca++ channels are the most abundant type in the axon terminal, when the channels are open, Ca is able to flow down its electrochemical gradient into the axon terminal, increase [Ca++] 3) Ca++ triggers exocytosis of NT- these NT are stored in vesicles, amount that diffuses depends on the [Ca++] which depends on the # of APs, diffuse rapidly across the cleft, 4) NT binds to a receptor on post-synaptic cellular membrane, this binding is brief and reversible, NT are quickly cleared to ensure new messages can be sent 5) Post-synaptic neuron responds due to signal transduction • Ca++ triggering exocytosis is the longest part of this process

Know the locations and functions of the control centers in the brainstem.

Cardiac center- medulla, controls heart rate and strength of contraction • Vasomotor center- medulla, controls blood pressure • Respiratory centers- medulla and pons, controls rate and depth of respiration • Digestive center- medulla, controls vomiting, swallowing, coughing, sneezing

Be able to describe what causes multiple sclerosis.

Caused by autoimmune attack of myelin • Scarring forms where the myelin is damaged • Inflammation causes degeneration of axons • Results in tingling, numbness, balance and coordination problems, and gradual paralysis. Synaptic Transmission

Describe the functions and circulation of CSF.

Cerebrospinal fluid- clear, watery fluid that bathes the CNS, similar in composition to plasma • CSF completely surrounds CNS and fills ventricles- circulates through them and central canal, then into the subarachnoid space at the 4th ventricle • Produced by ependymal cells of the choroid plexuses • Works to exchange nutrients with the interstitial fluid of the brain, cushions the brain, maintains the normal ions composition of neurons, removes waste, gets stuff from blood • Empties into the subarachnoid space into sinuses (venous blood) through arachnoid villi

Explain the role of the limbic system and how it affects incoming sensory information.

Collection of many areas of the brain- both parts of the diencephalon are apart of this • Include amygdala, hippocampus, fornix, etc. • Involved in your basic drives- primitive emotions • Associated with autonomic functions, motivation, aggression, learning, memory, emotions • Sensory information is relayed through the limbic system • All sensory information is routed through this system, everything you experience is colored by what you've experienced before

Understand what the absolute and relative refractory periods are and what causes them to occur.

During and immediately after an AP, membrane is less excitable than at rest • Refractory period- period of reduced excitability, divided into absolute refract. and relative • The absolute refractory period spans all of the depolarization phase plus most of the repolarization phase (1-2msec), no 2nd AP • Occurs because during rapid dipolar, the regenerative opening of Na+ channels will proceed to its conclusion and cannot be stopped by a second stimulus • Also, during the beginning of repolar, most of the Na+ inactivation gates are closed therefore, the channels are closed and incapable of another depolarization • Another depolarization cannot happen until the majority of Na+ channels have returned to resting state- this happens during repolarization • Relative refractory period- immediately after absolute period, 5-15 msec., possible to generate another AP but only in response to a stimulus stronger than that needed to reach threshold • Relative refectory due to increased permeability to K+ that continues beyond repolarization • Some Na+ inactivation gates may still be closed, especially early in relative refractory • How strong a stimulus must be is a matter of timing- early in the period takes a stronger stimulus than later • Refractory periods establish all-or-none property, the frequency with which an AP can be generated by a single neuron, and the unidirectional propagation along an axon • Information pertaining to stimulus intensity is encoded by changes in the frequency of APs • Because graded potentials last much longer than APs, stronger, longer lasting graded potentials may occur further apart or closer together. • Ex- if pain is super intense, the stimulus will last long enough and be strong enough to stimulate a second AP during the relative refractory period (overcome increased permeability to K+)

Know the Nernst equation and be able to calculate equilibrium potentials.

EI= RT/zF (ln [K+]B/[Na+]A, A and B stand for sides = (62/z-charge of ion)log([K+]ECF/[Na+]ICF • If the membrane is permeable to only one ion, the Nernst potential for that ion represents the total membrane potential

Be able to differentiate between polarization, depolarization, hyperpolarization, and repolarization.

Electrical signals occur in neurons via changes in membrane potential that take place when certain ion gated channels open or close in response to stimuli. • When the channels open/close, they affect the movement of that ion and change the memper • Channels generally at the end of afferent neurons, crucial for normal functioning • Changes in mem potent. are described based on the direction and change relative to the rest • Polarization- any state when the membrane potential is other than 0mV (usually at -70mV) • Because resting is a difference in potential across the mem, the men is polarized • Hyperpolarization- a change to a more negative value, membrane MORE polarized • Depolarization- change to a less negative or positive potential • Repolarization- membrane returns to the resting membrane potential after depolarization Explain significance of graded potential

Describe the differences between fast and slow pain.

Fast pain is perceived as a sharp prickling sensation that can be easily localized • Carried by small, myelinated A-delta fibers • Occurs first • Slow pain is poorly localized, transmitted by C fibers (unmyelinated), produces dull, aching, burning pain, persists for a longer time, more unpleasant

Identify the three major portions of the brain.

Forebrain- conscious though, memories, emotion, etc. take place • Includes Cerebrum, Diencephalon (thalamus, hypothalamus, corpus callosum, and PG) • Divided by corpus callosum, most superior part of the brain • Brain stem- includes thalamus, pons, medulla oblongata • Many involuntary and basic functions are controlled here • Cerebellum- in control over motor functions, coordination, and balance, mini brain in the back

Describe the difference between white and gray matter.

Gray matter- cell bodies, dendrites, and axon terminals, approx. 40% of the CNS and is the site of synaptic communication and neural integration • White matter- axons, constitutes approx. 60% of the CNS, white due to myelinated axons, specialized in rapid transmission of info to form APs

Explain how neurotransmitter is cleared from the synaptic cleft.

Neurotransmitters are cleared from the synaptic cleft by being degraded by enzymes, being actively transported back to the presynaptic neuron, or by diffusing away

Understand saltatory conduction is, how it occurs, including the role of nodes of Ranvier, myelination, Schwann cells, and oligodendrocytes.

Once an AP is initiated, it is propagated down the length of the axon from trigger zone to term • AP does not travel down but rather it sets up electrochemical gradients in the extracellular and intracellular fluids • Because the fluids have low resistance to current flow, positive charges move from the area where the membrane has been depolarized to the adjacent area (depolarizing it as well) • Current flows to adjacent areas of the axon's plasma membrane by conduction • First AP produced at the trigger zone produces a current that causes a second AP in the adjacent membrane, makes a third AP and so on until it reaches the axon terminal • Electric conduction is the process by which APs are propagated in unmyelinated axons • Called contiguous conduction- neurotransmitter causes membrane of axon hillock to become very permeable to Na+, Na+ rush in making the inside positive and the outside negative • + Ion currents change the potential to the threshold in the adjacent region of the axon • This causes a second AP- this process continues with one AP creating currents that create an AP for the neighbor until we get to the terminal • Diameter of axon determines how quickly current spreads- larger the diameter, less the resistance to longitudinal current flow • Currents can't travel back up stream and cause APs there because the membranes are still in refractory period -> ensures unidirectional movement of APs AP Propagation in Myelinated Axons • In axons sheathed with myelin (produced by schwann cells), the APs are propagated by saltatory conduction • Myelin provides high resistance to ion movement across the mem. but longitudinal resistance is low • Nodes of Ranvier are gaps in the myelin where the axon lacks insulation, is exposed to interstitial fluid, and has a HIGH concentration of voltage-gated channels • APs are produced at nodes- separation of change in the intracellular fluid causes current to flow from one node to the next • Currents move rapidly underneath myelin sheath but diminish as current leaks (no worry- remains strong enough to depolarize next area) • This "jumping" from node to node is the basis for the name, saltatory conduction • AP is propagated faster because it doesn't have to be regenerated at the myelinated section • Work 50x faster than unmyelinated fibers

Explain why the CNS receives/requires 15% of cardiac output.

Only accounts for 2% of your body weight but receives 15% of blood- due to the fact that CNS tissue has a high rate of metabolic activity compared to most body tissues • At resting, brain consumes 20% of all oxygen and 50% of all the glucose consumed • It receives all this blood through tons of blood vessels- its so dependent on its blood supply that just a few minutes can cause irreversible damage to CNS tissue • Reduction in blood flow causes deficits (stroke) • We need so much glucose because CNS stores little glycogen and they do not have access to fatty acids for energy- ultimately, it can only do aerobic metabolism so it always needs glu, O2

Explain presynaptic inhibition.

Presynaptic Inhibition is a mechanism by which the amount of neurotransmitter released by an individual synapse can be reduced, resulting of less excitation of the post-synaptic neuron. • Inhibition is due to less excitatory input • The release of inhibitory transmitter from terminal A opens Cl - and K+ channels on terminal B. In turn, this reduces the influx of Ca2+ through the voltage-gated channels on terminal A. This reduction of Ca2+ influx depresses the release or excitatory transmitter by terminal B at its synapse with the postsynaptic neuron C. • the 'inhibition' is targeted at specific types of input to a neuron, in contrast with the IPSP, which acts post-synapticially, and inhibits all activity in the neuron.

List the meninges and their identifying characteristics.

Protection of the brain from injury is provided by skull and vertebral column, meninges of the brain, CSF, and the BBB (chemical) • Meninges are three connective tissue membranes that separate the soft tissue of the CNS from the surrounding bone- include dura mater, arachnoid mater, and pia mater • Dura- outermost layer, closest to bone, hard and durable, fibrous tissue, leather-like • Arachnoid-weblike structure, no space between arachnoid and dura • Pia- immediately adjacent the CNS tissue, tender and kind, space between pia and arachnoid is called the subarachnoid space and is filled with CSF

Define modality.

Sensory receptors are specialized to detect a specific form of energy from environment • Energy form of a stimulus is called modality, ex- light waves, sound waves, pressure, temp • The modality to which a receptor best responds is called a stimulus. • Sufficiently strong 'inadequate' stimulus will induce the perception of the adequate stimulus

Describe the functions of the cerebellum.

Spinocerebellum- regulates muscle tone, coordination of skilled voluntary movements • Cerebrocerebellum- planning and initiation of voluntary activity • Verstibulocerebellum- maintenance of balance, control of eye movements

Explain the stretch reflex and withdraw reflex.

Stretch reflex- also known as the muscle spindle stretch reflex, ex: knee-jerk • Stretch reflex is the only known monosynaptic reflex in the body • Receptor- muscle spindle (specialized structure found in skeletal muscles that detects lengthening of the muscle) • Tapping the patellar tendon below the stretches the quadriceps muscle which excites muscle spindles in that muscle, triggering APs that can travel in afferent neutrons to the spinal cord (integration center). • Afferent neurons make direct excitatory synaptic connections with efferent neurons that innervate the quadriceps muscle stimulating the quadriceps to contract and the leg to jerk. • For extension to work effectively,the muscles causing extension (quads) should not be opposed by the actions that cause the leg to bend (hamstrings) • Afferent neurons from muscle spindles have collaterals that synapse with inhibitory interneurons innervating the motor neurons going to the hamstrings- this means that excitation of the quadriceps and inhabitation of the hamstrings are happening simultaneous • Withdraw reflex- when part of the body is subjected to painful stimulus, it withdraws from the stimulus automatically • Stepping on a tack activates nociceptors- respond to intense painful stimuli that are damaging to tissue • Afferent neurons from nociceptors transmit this information to the spinal cord where they have excitatory synapses at interneurons • Interneurons excite efferent neurons that cause withdrawal of the of the limb • For this to work, the muscles that cause withdrawal should be excited whereas muscles that oppose show be inhibited • This happens because branches of afferents activate inhibitory interneurons to the efferents innervating the quadriceps • Painful stimulus also triggers the crossed-extensor reflex- send signals to efferent neurons in opposite leg to trigger contraction of the extensor muscles and relaxation of the flexors • The same afferent neurons that activate the withdrawal reflex communicate with ascending pathways that send info to the brain that a painful stimulus has happened

Know which neurotransmitter is released at each synapse in the sympathetic and parasympathetic divisions.

Sym- acetylcholine and norepinephrine ->ACh is released by preganglionic neurons, nor is released by sympathetic post gang Para- ACh is released by pregang and postgang neurons Adrenal- pregang release ACh. Acts on endocrine cells in the adrenal medulla to stimulate the release of epinephrine • cholinergic- release ACh • adrenergic- release norepinephrine

Explain how agonists/antagonists would affect the ANS.

Sympathetic agonist- a drug that mimics the effect of norepinephrine • Sympathetic antagonist- drug that blocks the effect of norepinephrine • Parasympathetic agonist- drug that mimics the effect of ACh • Parasympathetic antagonist- drug that blocks the effect of ACh

Know how ACh and NE are removed from the synaptic cleft.

Synapse between efferent neuron and effector organ is called the neuroeffector junction • Synapses between autonomic postganglionic neurons and their effector organs differ from normal synapses because postganglionic neurons do not have discrete axon terminals • Instead, neurotransmitters are released from various swellings called varicosities • In these varicosities, NTs are synthesized and then stored in vesicles • The membrane of the axon contains voltage gated Na and K channels that support APs- also have Ca++ pumps that open when an AP reaches it • The mechanism for NT release is similar to mechanism in a normal axon terminal • AP arrives at varicosity and opens Ca++ channels, allows Ca to enter cytosol and stimulates the release of the NT by exocytosis • Because of different anatomy, an AP triggers the release of NTs from all the varicosities, because the distance between the varicosity and effector organ is greater, the NT bind on receptors throughout the organ

Explain temporal and spatial summation.

Temporal summation- adding together EPSP's or IPSP's generated by firing of the same presynaptic terminal at high frequency, same stimulus repeated • Spatial summation- adding together EPSP's or IPSP's generated by firing two or more presynaptic neurons simultaneously, multiple stimuli so they could be canceling each other

Describe endogenous analgesia and how NSAIDs relieve pain.

The Brain has an ability to block pain or to produce analgesia, through descending pathways that are apart of pain blocking endogenous analgesia systems • Stressful situations can activate an area of the midbrain which communicates with the medulla to activate neurons in the descending spinal cord to block transmission between nociceptors and second order neurons • Inhibitory interneurons form synapses with 2nd o neurons and the nociceptive afferent neuron • These inhibitory interneurons released endogenous opiate NTs like endorphins, enkephalins, and dynorphin • These bind to opioid receptors on the second order neuron and induce inhibitory postsynaptic potentials and bind to the nociceptive afferent neuron to prevent the release of substance P • Prostaglandins release from damaged tissue- greatly enhances receptor response to noxious stimuli (lower nociceptors threshold for activation). • Some pain relief can be achieved by inhibiting prostaglandin production

Describe how the blood-brain barrier is formed.

The exchange of oxygen, glucose, and other materials happens between blood and the cells in the CNS through capillaries which are composed of a single layer of endothelial cells • In the CNS, most hydrophobic molecules can diffuse across the membrane but movement or larger macromolecules through endocytosis does not happen • Movement of hydrophilic substances also is restricted because of the BBB • Blood brain barrier is a physical barrier that exists between the blood and the CSF, which is the interstitial fluid in the CNS • Existence of the barrier is due to the presence of tight junctions between the capillary endothelium- this eliminates pores • Astrocytes ensure that endothelium cells create tight junctions • Hydrophobic substances can diffuse across however, hydrophilic substances can only cross if they are transported (ions, carbs, aa, etc.) • BBB protects CNS from harmful substances (-ethanol)- all things have to come through mediated transport which is very strict, we see selective permeability • We can see what's in the CNS by doing a spinal tap of the CSF

Know what the "all-or-none" law states,

Threshold necessary for action potential corresponds to the level of depolarization needed to induce the sodium positive feedback loop • A depolarization less than threshold may open some Na+ but not enough of them to produce an inward flow of Na+ to combat the outward flow of K+ • A sub threshold stimulus provides no AP • A supra threshold stimulus (BIG) elicits AP • This AP is not stronger or bigger because APs are not graded • All or nothing principle- whether a membrane is depolarized to threshold or greater, the size of the resulting AP is the same; if the membrane is not depolarized to threshold,noAP • Level of depo reached at the peak of an AP depends not on strength of stimulus but on the relative strengths of the electrochemical gradients for Na+ and K+ and the relative permeabilities several times

Explain the signaling mechanism for each of the receptor types discussed.

Types of Cholinergic Receptors • Nicotinic Receptor • There are 4 subclasses, contains nicotine • Located in cell bodies and dendrites of sympathetic and parasympathetic postganglionic neurons, on chromaffin cells of the adrenal medulla, and on skeletal muscle cells • Signal transduction mechanisms of all subclasses are associated with channels that allow both sodium and potassium ions to move through them Pre Pre Sympathetic Parasympathetic ACh Post • When ACh binds to these receptors, the cation channels open allowing Na to diffuse in and K to move out Nicotinic receptors ACh • Since Na is further from equil, the flow of Na exceeds flow of K and the cell gets depolarized- nicotinic cholinergic receptors are associated with depolarization of the postsynaptic cell • Muscarinic Receptor Post Adrenergic Receptors Muscarinic receptors ACh NE • 5 subclasses, contains chemicals found in certain mushrooms • Found on effector organs on the parasympathetic NS, includes heart, smooth muscles Target Organ Target Organ • All subclasses are coupled to G proteins and second messengers- triggered by the binding of ACh, can be excitatory or inhibitory depending on the target cell Types of Adrenergic Receptors • Two major classes are alpha and beta receptors ,divided in to a1, a2, b1, b2, and b3 • Adrenergic receptors are coupled to G proteins that either activate or inhibit second messenger system • Binding of nor/epi to an a1 activates a G protein which activates phospholipase C, which then catalyses the conversion of different proteins which release calcium. This starts PKC to catalase the phosphorylation of a protein • Binding of nor/epi to a2 activates an inhibitory G protein which decreases the activity of cAMP • Binding of nor/epi to B receptors activates a G protein that increases the activity of cAMP • A have a greater affinity for norepinephrine than for epinephrine and a generally excitatory • B1 and B3 have equal affinities and tend to be excitatory • B2 have a greater affinity for epinephrine than norepinephrine, inhibitory response

Explain referred pain and phantom-limb pain.

• Activation of nociceptors in the viscera causes referred pain-pain detected on the body's surface- occurs because the second order neurons that receive input from visceral afferents also receive input from somatic afferents • Second order neurons receive input from multiple afferent neurons, Brain interprets signals based on past experience • Amputees experience pain in the missing limb- may be temporary or chronic • This is when second or third order pain neurons become hypersensitive and react to stimuli not intended for them

Define reflex.

• An autonomic, patterned response to a stimulus is called a reflex • Types- spinal or cranial, somatic or autonomic, innate or conditions, or monosynaptic or polysynaptic • Spinal or cranial- based on level of neural processing involved, highest level of integration happens in the spinal cord but cranial reflexes happen in the brain • Somatic or autonomic- depends on efferent division controls of the pathway- somatic involve signals sent via somatic neurons to skeletal muscle, autonomic signals are sent via autonomic neurons to smooth muscle, cardiac muscle, or glands • Innate or conditioned- innate = born with, conditioned= vary depending on person's experiences • Monosynaptic or poly- mono consists of two neurons and a single synapse, poly involves more than two neurons and multiple synapses.

Define equilibrium potential.

• An electrical potential (V) resulting from diffusion of ions through an ion selective mem • Due to differences in concentration and permeability of key ions

Be familiar with the basic anatomy of the ANS

• Autonomic nerve pathways consist of two efferent pathways containing two types of neurons • Neurons communicate with one another through synapses in the autonomic ganglia (perip) • Ganglia have axon terminals for preganglionic neurons and cell bodies and dendrites of postganglionic neurons • Neurons that travel from CNS to the ganglia are the presynaptic neurons • Neurons that travel from ganglia to effector are post ganglionic neurons • Generally a single pre ganglionic neuron synapses on several postganglionic neurons • Intrinsic neurons are found in ganglia- modulate the flow of information to the target organ Sympathetic NS • Preganglionic neurons arise from thoracic and lumbar regions of spinal cord • Pre/post ganglionic neurons are arranged in three ways: • Short axon preganglionic neuron, synapse in the sympathetic chain, long axon post ganglionic neuron • Long axon preganglionic neuron, synapse at adrenal medulla, release of catecholamines • Preganglionic neuron synapses at collateral ganglia, postganglionic neuron travels to target • Because sympathetic ganglia are connected (sympathetic chains) effects of activation are widespread and simultaneous • Endocrine aspect (release of catecholamines) contributes to this widespread effect • Collateral ganglia are not interconnected so effects are more targets and specific Parasympathetic NS • Preganglionic neurons arise from cranial nerves and sacral region • Long preganglionic fibers, ganglia near effector organs, and short postganglionic fibers

Discuss differences between the sympathetic and parasympathetic nervous systems.

• Autonomic nervous system innervates most effector organs and tissues including cardiac muscle, smooth muscle, visceral organs, glands, and adipose tissue • Called autonomic because functions occur at a subconscious level • The two branches are generally opposite in nature so their functions are opposed in a tissue • The parasympathetic ns is most active during resting conditions- it stimulates digestive system, inhibit the cardiovascular system, known as rest-and-digest • Sympathetic ns most active during excitation of physical acitvity, "fight or flight", heart rate increases blood flow shifts from gastrointestinal organs to skeletal and cardiac muscles and energy stores are mobilized

Explain what is meant by brain lateralization and describe in general functions controlled by the left and right hemispheres.

• Brain lateralization means that the brain is separated in two sides and that certain features are more dominant on one half than the other Left brain- controls the right side • in 90% of population, left brain is dominant for hand control • Left brain controls speech (broca's area), logic and analytical processing, math skills Right side of the brain controls the left side • Also generally associated with spatial orientation, creativity, face recognition, music, dream imagery, philosophy and intuition

Identify the lobes of the cerebrum and their functional characteristics.

• Cerebrum is the largest portion of the brain, has both white and gray matter • Layer of gray matter at the surface is called the cerebral cortex while the deep clusters of gray matter are called subcortical nuclei • Lobes of the cerebrum include: frontal lobe, temporal lobe, parietal lobe, and occipital • Frontal is responsible for premotor cortex and primary motor cortex • Initiates voluntary movement • Broca's area- speech formation • Prefrontal association area -> controls thoughts, personality, goal- directed behavior, restrain • The motor cortex is anterior the central sulcus. Different areas on the motor cortex control the motor function of different parts of the body. Bigger the area = wider the range of motor. • Parietal lobe- primary somatosensory cortex found here • Somesthetic sensations including touch, itch, temperature, and pain • Proprioception- awareness of muscle tension, joint, and limp positions • posterior the central sulcus is the sensory cortex- same deal as motor cortex • Occipital lobe- Primary visual cortex and visual association area • Association areas- involved in more complex processing that requires integrating different types of information. To make a decision, your brain must consolidate information from sensory systems and from memory. • Temporal lobe functions in primary auditory cortex, limbic association, and auditory association areas. Language comprehension also happens here.

Know what channels and changes in ion permeability are involved in its generation.

• Changes in permeability dependent on the opening and closing of voltage gated channels • Located primarily in the membranes of the axon hillock and axon • In myelinated axons, the channels are in great concentration at Nodes, on unmyelinated axons the channels are distributed evenly Voltage-gated Na+ Channel • The model for explaining actions of voltage-gated sodium channels involves two types of gates: activation gates (responsible for opening sodium during depolarization) and inactivation gates (responsible for closing during repolarization) • For sodium to be open, both gates must be open- they both open and close in response to changes in the membrane potential and based on the position of the two gates. • Three conformations include closed by capable of opening, open, and closed and incapable o. • Closed by capable- at rest, inactivation gate is open but the activation gate is closed, the channel is closed but it can be opened by a depolarizing stimulus • Open- on depolarization, activation gate opens and with both gates in their open position, the channel is open and Na+ move through channel into the cell, occurs during depolar • Closed and incapable- within approx. 1msec after initial stimulus to open the activation gate, the inactivation gate closes, response to depolarization, with inactivation gate closed and activation open, the channel is closed, remains closed until membrane potential returns to near resting potential- no second depolarization can happen, only after a depolarization • Opening of Na+ is a regenerative mechanism in that it opens more sodium gates by regenerating the stimulus. • Mechanism works by depolarization triggering the opening of a few Na+, this allows for movement of Na+ into the cell, which depolarizes the cell further, increasing sodium channels to open and so on- positive feedback loop • Level of depo. necessary to initiate the regenerative opening of Na+ channels is the threshold for initiating an action potential • Threshold occurs when the inward flux of Na+ exceeds the outward flux of K+ Voltage- gated K+ channels • Single gate that opens more slowly in response to depolarization • When the Na+ inactivation gates are closing (1-2msec after depolarization to threshold), the K + channels begin to open • The increased permeability to K+ coupled with the strong electrochemical gradient for K+ to move out of the cell increases the movement of K+ increases the movement of K+ out • This movement of + charge out repolarizes the cell • Part of a negative feedback look- as cell repolarizes, depolarizing stimulus weakens and K+ channels close Permeabilities • During the depol phase, Na+ permeabilities exceeds K+ and the MP approaches sodium equilibrium of 60+ mV As we repolarize, Na+ permeabilities decrease and K+ exceeds it

Define EPSP and IPSP and know how/why each occurs.

• EPSP- Excitatory Post-Synaptic Potential • Type of graded potential • Neurotransmitters can cause depolarization of the post neuron • Cation channels open and more Na+ move in than K+, cell more positive, moves out due to stronger electrochemical force • Cation channels are nonspecific- Na+ and K+ use these channels- Na+ has a much stronger driving source to get in that K+ has to get out • IPSP- Inhibitory Post-synaptic potential • Graded potential that is hyper polarizing • Opens a potassium channel! Potassium leaves and cell becomes farther away from threshold as the cell membrane becomes more negative • Makes it more difficult to get an action potential • GPSP- composite potential on the post synaptic metal segment membrane due to all EPSPs and IPSPs occurring at the same time. • Action potentials are generated in the in the initial segment of the axon when GPSPs initiate threshold potential

Explain significance of graded potential

• Graded potential- small changes in membrane potential that occur when ion channels open or close in response to a stimulus acting on a cell- stimuli could be sensory and and chemical • The magnitude of the change in membrane potential varies with the strength of stimulus (DP) • Can only travel from site of stimulation for a short distance because its size is decremental- the size of the membrane potential decreases as it moves along the membrane • Decremental because as it travels, some of the charge escapes in currents- the spread of voltage by passive charge movement is called electronic conduction • Can be depolarizations or hyperpolarizations • Direction of change depends on the particular neuron, the stimulus and the ion channels that open/close • Primary significance- determine whether a cell can generate an action potential • Graded potentials generate action potentials if they depolarize a neuron to a certain level of a membrane potential called the threshold- a critical value that must be met for AP • Graded polarizations that are depolarizing are called excitatory (opp- inhibitory) • Temporal summation- a stimulus is applied repeatedly in succession such that one graded potential doesn't dissipate before the next happens • Spatial summation- effects of stimuli from different sources occurring close together in sum

Explain the steps in creating a smooth and controlled movement.

• Involves 1) developing the idea to move, 2) putting together a program of motor commands to carry out the movement, 3) executing the movement by activating correct muscles at the correct time, and 4) constant feedback to ensure that the movement is carried out smoothly • Step 1- exerted by prefrontal cortex, association areas, basal nuclei, and limbic system • Idea is goal oriented, based on sensory input, memories, emotions, etc. • Step 2- involves primary motor cortex, prefrontal association areas and the premotor cortex • We must stimulate some muscles while inhibiting others • Program of motor commands myst be executed by sending commands through the efferent neuron innervating the muscle cell • these are motor neurons • Feedback is done by informing the spinocerebellum of planned motor command and making adjustments which sends info to skeletal muscles, which then sends info back to the spino

Describe the movement of an ion, given total membrane potential and the equilibrium potential for that ion.

• Larger [] means larger equilibrium potential because greater force is required to balance the larger chemical force • Electrical force goes in the direction opposite of the chemical force • Force into the cell is negative while force out of the cell is positive • K+ is chemically outward and electrically inward (-) • Na+ is chemically inward so electrical force is outward (+) (SEE CHARTS)

Understand how lidocaine (local anesthetic works).

• Lidocaine is injected near the nerves that control feeling in face, mouth, and tongue • The numbing effect is due to the ability of anesthetics to block the production of APs • They block the volt-gate Na+ channels- if these can't open, then an AP can't happen • AP are necessary in sensory neurons for communicating what's going on, brain left unaware • Analgesics block painful stimuli while anesthetics block all stimuli

Explain how changes in membrane permeability affect the electrochemical gradient and the total membrane potential.

• Membrane potential depends on relative permeabilities of the membranes to different ions • As the membrane's permeability increases for a specific ion, the resting equilibrium will move closer to that ion's equilibrium potential • The net electrochemical force on an ion tends to move that ion across the membrane in the direction that will move the membrane potential toward that ion's equilibrium potential • Na+ tends to bring the m.p. towards 60+ while K+ toward -94mV • When the membrane is more permeable to K+ ions to Na+, the inside of the cell is - • The strength of the electrochemical force is acting on a specific ion is is dp to to the difference between the membrane potential and the equilibrium potential for that ion • Thus, when we're at -70mV, Na+ experiences a much greater electrochemical force than K+

Know what an action potential is.

• Occur in membranes of excitable tissue (nerve/muscle) in response to graded potentials • During an AP, a large rapid depolarization occurs in which the polarity of the membrane actually reverses (it becomes positive for a bit) Explain how changes in membrane permeability affect the electrochemical gradient and the total membrane potential. • Membrane potential depends on relative permeabilities of the membranes to different ions • As the membrane's permeability increases for a specific ion, the resting equilibrium will move closer to that ion's equilibrium potential • The net electrochemical force on an ion tends to move that ion across the membrane in the direction that will move the membrane potential toward that ion's equilibrium potential • Na+ tends to bring the m.p. towards 60+ while K+ toward -94mV • When the membrane is more permeable to K+ ions to Na+, the inside of the cell is - • The strength of the electrochemical force is acting on a specific ion is is dp to to the difference between the membrane potential and the equilibrium potential for that ion • Thus, when we're at -70mV, Na+ experiences a much greater electrochemical force than K+ Action Potential- TUE Be able to differentiate between polarization, depolarization, hyperpolarization, and repolarization. Electrical signals occur in neurons via changes in membrane potential that take place when certain ion gated channels open or close in response to stimuli. • When the channels open/close, they affect the movement of that ion and change the memper • Channels generally at the end of afferent neurons, crucial for normal functioning • Changes in mem potent. are described based on the direction and change relative to the rest • Polarization- any state when the membrane potential is other than 0mV (usually at -70mV) • Because resting is a difference in potential across the mem, the men is polarized • Hyperpolarization- a change to a more negative value, membrane MORE polarized • Depolarization- change to a less negative or positive potential 4 • Once initiated, an action potential can be propagated long distances w/o a decrease in strength • Generation of AP based on the selective permeability of the plasma membrane and the Na+ and K+ electrochemical gradients- done by opening and closing gated ion channels 3 distinct phases 1) Rapid depolarization- membrane potential changes from -70 mV to +30 mV. Caused by a sudden and dramatic increase in permeability to Na+ plus an increase in the movement of Na+ down gradient, we are approaching Na's equilibrium potential 2) Repolarization- Mem potent returns to resting levels. Na+ permeability decreases rapidly reducing the inflow of Na+. K+ permeability increases and repolarizes. 3) After hyperpolarization- K+ remains elevated for a brief time after the membrane potent reaches the resting mem potent. Even more negative as it approaches K+ equil.

List 5 receptor types and their modalities.

• Photoreceptor- light, ex- retina • Mechanoreceptor- stretching or bending, ex- skin, organs, blood vessels • Thermoreceptor- heat or cold, ex- skin • Osmoreceptor- solute concentration, ex- brain, kidney, endocrine glands • Chemoreceptor- chemicals, ex- taste buds, olfactory tissue, blood vessels • Nociceptor- tissue damage, everywhere except the brain

Describe the role of the hypothalamus in homeostasis; list specific functions that it regulates.

• Regulates homeostasis • Serves as the link between the nervous system and the endocrine system • Releases tropic hormones in response to neural input • Contains satiety and hunger center • Contains thirst center • Contains thermoregulatory center • Generates and regulates circadian rhythm • Part of the limbic system • Coordinates body's response to stress

Explain how sensory intensity and localization are determined.

• Stimulus type is coded by the receptor and pathway activated when the stimulus is applied • Stimulus intensity is coded by frequency of APs and the number of receptors activated • Neurons either fire or don't fire- APs are all or nother • Intense sensory activation doesn't result in intense action potentials and intensity is coded by the frequency of APs or the number of afferent nerves activated • In frequency coding, a stronger stimulus results a larger graded potential • As long as the graded potential exceeds threshold, stronger depolarizations can overcome the relative refractory period and generate a second AP to come more quickly • In population coding, a stronger stimulus activates a great # of receptors- this increases frequency on afferent neuron or depolarization of increased number of afferent neurons • The coding of locations of tactile, proprioceptive, and visual stimuli is based on receptive fields • Precision of being able to locate stimulus is called acuity • Acuity depends on the size and number of receptive fields, the amount of overlap between the receptive fields, and lateral inhibition • localization is better in areas served by neurons with smaller receptive fields however, info from one afferent neuron does not alone provide precise localization • Localization is improved by overlapping of receptive fields (activates two or more neurons) • Lateral inhibition- stimulus that strongly excited receptors in a given location inhibits activity in the afferent pathways • If one afferent neuron is activated, the CNS inhibits the communication between afferent neurons in neighboring fields and their second-order neurons • This increases the strength of the one relative to the lateral neurons

Describe characteristics of substances that pass freely through the BBB and why.

• Substances that pass freely through the BBB are hydrophobic substances like gases • They can pass through because they can simply diffuse through the endothelium • Unlike hydrophilic (polarized) substances, they don't need to be transported through a medium- oxygen is needed in great abundance but things like glucose and ions need to be controlled more • We also want to keep toxins and bacteria out!

Know the divisions of the afferent nervous system.

• The PNS is divided into the afferent and efferent divisions • The afferent is subsequently divided by two stimuli- sensory and visceral • The afferent system works to transmit info from the periphery to the CNS, info is detected by sensory receptors • Visceral System • Visceral receptors- detect stimuli that arise in the body, include chemo/baro/ mechanoreceptors, we're not consciously aware of this stimuli • transmit information to the CNS by a class of afferent neurons known as visceral afferents • Sensory System • Sensory receptors- respond to specific types of stimuli in the external environment • Signals are transmitted to the cerebral cortex, reaches consciousness, and is perceived • Systems that allows us to perceive external environments include the somatosensory system (receptors in skin), proprioception (position of limbs), and special senses

Define sensory unit and receptive field.

• The specific neural pathways that transmit information pertaining to a particular modality are called labeled lines- each sensory modality follows it's line • Activation of a specific pathway causes perception of the associated modality, regardless of which stimulus actually activated it • The pathways for different modalities terminate in different sensory areas of the cerebral cortex • A sensory unit comprises a single afferent neuron and all the receptors associated with it • All the receptors associated with a given afferent neuron are of the same type and activation of the associated receptors may trigger APs in the afferent neuron • The area over which an adequate stimulus can produce a response is called the receptive field Pathway Receptors -> afferent neuron (first-order neuron) -> Spinal cord/brainstem -> Second order neuron -> Thalamus -> Third order neuron -> Cortex • The afferent neuron that transmits key information from the periphery to the CNS is called the first order neuron • Interneurons can branch off the first order to help sum converging inputs together • Some interneurons send info the hypo (second order), some then form synapses with third- order neurons that transmit that info into the cerebral cortex • Different sensory pathways travel through different areas of the thalamus and cortex • Receptive fields applies to second and higher order pathways

Calculate total membrane potential using the GHK equation.

• The total membrane potential is a composite of the individual Nernst potentials for each ion for which the membrane is permeable • The greater the permeability of the membrane to any one ion, the greater the contribution of the Nernst potential of that ion to the total membrane potential, called conductance (g) • If the membrane is impermeable to an ion, that ion does not influence the membrane potent. • Vm= ((Ek)(gK) + (ENa)(gNA)) / (gK + gNa) • Smaller conductance means that the membrane is slightly permeable to that smaller ion • Vm tells us the total membrane potential inside relative to outside • So if it's bigger than the resting potential, we know the membrane is a little more soluble to soluble to Na+. If it's smaller than resting potential, than we know its even more perm to K+