BSC2085 Test 3

What is the difference between a neurotransmitter and a neuromodulator?

*** Characteristics of neuromodulators: • Typically are neuropeptids(small peptide chains) that bind to the postsynaptic receptor to activate cytoplasmic enzymes. • Effects are long term, slow to appear • Responses involve multiple steps, intermediary compounds • Affect presynaptic membrane, postsynaptic membrane, or both • Released alone or with a neurotransmitter o Can alter either the rate of neurotransmitter release or the response of a postsynaptic neuron to specific neurotransmitters

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**Action potential An electrical impulse produced by graded potential Propagates along surface of axon to synapse ***Synaptic activity Releases neurotransmitters at presynaptic membrane Produces graded potentials in postsynaptic membrane I **Information processing Response (integration of stimuli) of postsynaptic cell

Passive Forces acting Across the Plasma Membrane

**Chemical gradients Concentration gradients (chemical gradient) of ions (Na+, K+) **Electrical gradients Separate charges of positive and negative ions Result in potential difference

Summary of Neurons and Neuroglia

**Neurons perform: All communication, information processing, and control functions of the nervous system **Neuroglia preserve: Physical and biochemical structure of neural tissue **Neuroglia are essential to: Survival and function of neurons

Five Main Membrane Processes in Neural Activities

**Resting potential The transmembrane potential of resting cell **Graded potential Temporary, localized change in resting potential Caused by stimulus to the cell

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**Temporal Summation Rapid, repeated stimuli at one synapse **Spatial Summation Many stimuli, arrive at multiple synapses

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**The resting state **Opening sodium channel produces graded potential. Events include: Resting membrane exposed to chemical Sodium channel opens Sodium ions enter the cell Transmembrane potential rises Depolarization occurs

Synaptic Delay

*A synaptic delay of 0.2-0.5 msec occurs between: Arrival of action potential at synaptic terminal And effect on postsynaptic membrane *Fewer synapses mean faster response *Reflexes may involve only one synapse

Effects of graded potentials

---At cell dendrites or cell bodies **Trigger specific cell functions **For example, exocytosis of glandular secretions ---At motor end plate Release ACh into synaptic cleft

Serotonin inhibtory

-A CNS neurotransmitter -Affects attention and emotional states -Decreased serotonin production may be responsible for some cases of severe chronic depression Treated with Selective Serotonin Repiptake Inhibitors SSRI

Dopamine both

-A CNS neurotransmitter -May be excitatory or inhibitory -Damage to neurons that produce dopamine results in rigidness characteristic of Parkinson's disease Cocaine inhibits dopamine removal from the synapse, increases postsynaptic effect and feeling of "high"

Opioids

-neuromodulators in the CNS -Bind to the same receptors as opium or morphine -Relieve pain=Inhibits the release of neurotransmitter SUBSTANCE P(neuropeptide) at synapse that relay pain sensations. Four Classes of Opioids *Endorphins *Enkephalins *Endomorphins *Dynorphins - most potent pain-relieving effect of the opiods and even more powerful than morphine

Events at a Cholinergic Synapse

1.Action potential arrives, depolarizes synaptic terminal 2.Calcium ions enter synaptic terminal, trigger exocytosis of ACh 3.ACh binds to receptors, depolarizes postsynaptic membrane 4.ACh removed by AChE •AChE breaks ACh into acetate and choline

Three Mechanisms that Neurotransmitters and Neuromodulators Work

1.Direct effects on membrane channels For example, ACh, glycine, aspartate 2.Indirect effects via G proteins (second messenger system involving cAMP) For example, E, NE, dopamine, histamine, GABA 3.Indirect effects via intracellular enzymes For example, lipid-soluble gases (NO, CO)

Three layers of the meninges

1.Dura mater - inner fibrous layer (meningeal layer), outer fibrous layer (endosteal layer) fused with periosteum. Venous sinuses found between the two 2.Arachnoid mater - covers the brain, subarachnoid space located between arachnoid and pia mater 3.Pia mater - attaches to brain surface by astrocytes

Four Types of Neuroglia in the CNS

1.Ependymal cells Cells with highly branched processes; contact neuroglia directly 2.Astrocytes Large cell bodies with many processes 3.Oligodendrocytes Smaller cell bodies with fewer processes 4.Microglia Smallest and least numerous neuroglia with many fine-branched processes

Three largest dural folds

1.Falx cerebri - Projects between the cerebral hemispheres 2.Tentorium cerebelli - Separates cerebellum and cerebrum 3.Falx cerebelli - Divides cerebellar hemispheres below the tentorium cerebelli

PNS

1.Fragmentation of axono and myelin occurs in distal stump 2.Schwann cells for cord, grow into and cut, and unite stumps. Macrophages engulf degenerating axon and myelin. 3.Axon sends buds into network of Schwann cells and then starts growing along cord of Schwann cells. 4.Axon continues to grow into distal stump and is enclosed by Schwann cells.

Four Breaks in the BBB

1.Portions of hypothalamus • Secrete hypothalamic hormones 2.Posterior lobe of pituitary gland • Secretes hormones ADH and oxytocin 3. Pineal gland • Pineal secretions 4.Choroid plexus • Where special ependymal cells maintain blood-CSF barrier

Neuroglia of the Peripheral Nervous System

1.Satellite cells Also called amphicytes Surround ganglia (Masses of neuron cell bodies in the PNS) Regulate environment around neuron 2.Schwann cells Also called neurilemma cells Form myelin sheath (neurilemma) around peripheral axons One Schwann cell sheaths one segment of axon

Four basic characteristics of graded potentials

1.The transmembrane potential is most changed at the site of stimulation, and the effect decreases with distance 2.The effect spreads passively, due to local currents

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3.The graded change in transmembrane potential may involve either depolarization or hyperpolarization **The properties and distribution of the membrane channels involved determine the nature of the change **For example, in a resting membrane, the opening of sodium channels causes depolarization, whereas the opening of potassium channels causes hyperpolarization 4.The stronger the stimulus, the greater the change in the transmembrane potential and the larger the area affected

Inhibition

A neuron that receives many IPSPs Is inhibited from producing an action potential Because the stimulation needed to reach threshold is increased

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Absolute Refractory Period Sodium channels are open or inactivated No action potential possible Relative Refractory Period Membrane potential almost normal Very large stimulus can initiate action potential

Saltatory Propagation

Action potential along myelinated axon Faster and uses less energy than continuous propagation Myelin insulates axon, prevents continuous propagation Local current "jumps" from node to node Depolarization occurs only at nodes

Synaptic Activity

Action potentials (nerve impulses) Are transmitted from presynaptic neuron to postsynaptic neuron (or other postsynaptic cell) across a synapse

All-or-none principle

An action potential is either triggered, or not If a stimulus exceeds threshold amount, an action potential is generated. The action potential is the same no matter how large the stimulus

Cholinergic Synapses

Any synapse that releases Ach. Located at: All neuromuscular junctions with skeletal muscle fibers Many synapses in CNS All neuron-to-neuron synapses in PNS All neuromuscular and neuroglandular junctions of ANS parasympathetic division

Graded Potentials (local potentials)

Are changes in transmembrane potential that cannot spread far from site of stimulation Includes any stimulus that opens a gated channel which produces a graded potential

Chemical Synapses

Are found in most synapses between neurons and all synapses between neurons and other cells Cells not in direct contact Action potential may or may not be propagated to postsynaptic cell, depending on: Amount of neurotransmitter released Sensitivity of postsynaptic cell

Electrical Synapses

Are locked together at gap junctions (connexons) Allow ions to pass between cells Produce continuous local current and action potential propagation Are found in areas of brain, eye, ciliary ganglia

The Resting Potential

At the normal resting potential, these passive and active mechanisms are in balance The resting potential varies widely with the type of cell A typical neuron has a resting potential of approximately -70 mV

Information Processing

At the simplest level (individual neurons) --Many dendrites receive neurotransmitter messages simultaneously, some excitatory, some inhibitory --NET EFFECT on axon hillock determines if action potential is produced Therefore, a change in transmembrane potential that determines whether or not action potentials are generated is the simplest form of information processing

The Resting Potential

Because the plasma membrane is highly permeable to potassium ions: The electrochemical gradient for sodium ions is very large, but the membrane's permeability to these ions is very low The sodium-potassium exchange pump ejects 3 Na+ ions for every 2 K+ ions that it brings into the cell It serves to stabilize the resting potential when the ratio of Na+ entry to K+ loss through passive channels is 3:2

Transmembrane Potential Exists Across Plasma Membrane

Because: Cytosol and extracellular fluid have different chemical/ionic balance The plasma membrane is selectively permeable **Transmembrane Potential Changes with plasma membrane permeability in response to chemical or physical stimuli

Other Neurotransmitters

Biogenic amines Amino acids Neuropeptides Dissolved gases

What happens if there is bleeding between the meningeal layers?

Blood will collect here, create pressure on nerve tissue and brain, and potientially cause brain damage.

Embryological Development

Brain starts as a hollow neural tube Neural tube enlarges into three primary brain vesicles **Prosencephalon- Becomes the telenchephalon and diecephalon **Mesencephalon **Rhombencephalon- becames the metencephalon and myelencephalon

NOTE

Choline is reabsorded by the synaptic terminal to form more ACh while the acetate is absorbed by postsynaptic cell or other cells/tissues

Three States of Gated Channels

Closed, but capable of opening Open (activated) Closed, not capable of opening (inactivated)

Cerebrum

Controls higher mental functions Divided into left and right cerebral hemispheres Surface layer of gray matter (neural/cerebral cortex) Folded surface increases surface area Elevated ridges (gyri/gyrus) Shallow depressions (sulci/sulcus) Deep grooves (fissures)

Continous and saltatory propagation

Different becasue continous is unmylinated axons, affects only one segment of an axon at a time which makes it slower than saltatory. Saltatory moves action potential along myelinated axons faster and uses less energy, Myelin insultate axons which prevents continous propagation.

Which neurotransmitters work by which mechanism?

Direct effects=ACh Indirect= NE dopamine, GABA Indirect=NO, CO

Cerebrovascular Disease

Disorders interfere with blood circulation to brain Stroke or cerebrovascular accident (CVA) Shuts off blood to portion of brain Neurons die

Electrical Currents and Resistance

Electrical current Movement of charges to eliminate potential difference Resistance The amount of current a membrane restricts

Two Types of Synapses

Electrical synapses - Direct physical contact between cells Chemical synapses - Signal transmitted across a gap by chemical neurotransmitters

Norepinephrine (NE) Stimulator

Excitatory and depolarizing effect Widely distributed in brain (CNS) and portions of ANS

Two Classes of Neurotransmitters

Excitatory neurotransmitters Cause depolarization of postsynaptic membranes Inhibitory neurotransmitters Cause hyperpolarization of postsynaptic membranes

Dural Folds

Folded inner layer of dura mater Extend into cranial cavity Stabilize and support brain Contain collecting veins (dural sinuses)

The Electrochemical Gradient

For a particular ion (Na+, K+), the electrochemical gradient is: The sum of chemical and electrical forces acting on the ion across a plasma membrane This is a form of potential energy

Ependymal Cells

Form epithelium called ependyma Line central canal of spinal cord and ventricles of brain Secrete cerebrospinal fluid (CSF) Have cilia or microvilli that circulate CSF Monitor CSF Contain stem cells for repair

Blood-CSF Barrier

Formed by special ependymal cells Surrounds capillaries of choroid plexus Limits movement of compounds transferred Allows chemical composition of blood and CSF to differ

Rate of Generation of Action Potentials

Frequency of action potentials depends on degree of depolarization above threshold Holding membrane above threshold level **Has same effect as a second, larger stimulus **Reduces relative refractory period

Gamma Aminobutyric Acid (GABA) inhibit

Generally inhibitory effect Functions in CNS not well understood GABA release may reduce anxiety. (some antiaxiey drugs enhance this effort

Postsynaptic Potentials

Graded potentials developed in a postsynaptic cell In response to neurotransmitters ****Two Types of Postsynaptic Potentials ---Excitatory postsynaptic potential (EPSP) Graded depolarization of postsynaptic membrane ---Inhibitory postsynaptic potential (IPSP) Graded hyperpolarization of postsynaptic membrane

Summary on Information Processing

Information is relayed in the form of action potentials In general, the degree of sensory stimulation or the strength of the motor response is proportional to the frequency of action potentials The neurotransmitters released at a synapse may have either excitatory or inhibitory effects The effect on the axon's initial segment reflects a summation of the stimuli that arrive at any moment The frequency of generation of action potentials is an indication of the degree of sustained depolarization at the axon hillock

Frequency of Action Potentials

Information received by a postsynaptic cell may be simply the frequency of action potentials received

Initiating Action Potential

Initial stimulus A graded depolarization of axon hillock large enough (10 to 15 mV) to change resting potential (-70 mV) to threshold level of voltage-gated sodium channels (-60 to -55 mV)

Dura mater

Inner fibrous layer (meningeal layer) Outer fibrous layer (endosteal layer) fused to periosteum Venous sinuses between two layers

Oligodendrocytes

Involved in myelination of axons Produces Myelin that insulates axons, functions to: Increase speed of action potentials Make nerves appear white Wrapping of axon is not complete, there are gaps (nodes) Nodes (also called nodes of Ranvier) Internodes - myelinated segments of axon

Axon Diameter and Propagation Speed

Ion movement is related to cytoplasm concentration Axon diameter affects action potential speed The larger the diameter, the lower the resistance

Direct Effects

Ionotropic effects - alters ion movements through the plasma membrane Open/close gated ion channels

Indirect Effects - Intracellular Receptors

Lipid-soluble gases (NO, CO) - can diffuse across the plasma membrane(by simple diffusion) Bind to enzymes in brain cells to alter cell activity

Diencephalon

Located under cerebrum and cerebellum Links cerebrum with brain stem Divisions of the diencephalon Left and right thalamus - Relays and processes sensory information Hypothalamus - Involved in hormone production, autonomic function, emotion. Connected to the pituitary gland (hypophysis is a major endocrine gland connecting nervous and endocrine glands) by infundibulum.

Astrocytes

Maintain blood-brain barrier (isolates CNS) Create three-dimensional framework for CNS Repair damaged neural tissue Guide neuron development Control interstitial environment

Nerve Regeneration in CNS limited by

Many more axons likely to be involved Astrocytes that: Release chemicals that block growth Produce scar tissue

Microglia

Migrate through neural tissue Clean up cellular debris, waste products, and pathogens

Depolarization

Movement of Na+ through channel Produces local current Depolarizes nearby plasma membrane (graded potential) Note: change in potential is proportional to stimulus

Type A Fibers

Myelinated Large diameter High speed (140 m/sec) Carry rapid information to/from CNS For example, position, balance, touch, and motor impulses

Type B Fibers

Myelinated Medium diameter Medium speed (18 m/sec) Carry intermediate signals For example, sensory information, peripheral effectors

White matter

Myelination causes nervous tissue to appear white. Regions of CNS with many myelinated nerves

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Neuromodulators Can alter either the rate of neurotransmitter release or the response of a postsynaptic neuron to specific neurotransmitters Neurons May be facilitated or inhibited by extracellular chemicals other than neurotransmitters or neuromodulators

Summation of EPSPs and IPSPs

Neuromodulators and hormones Can change membrane sensitivity to neurotransmitters Shifting balance between EPSPs and IPSPs

Important Neurotransmitters Other than acetylcholine

Norepinephrine (NE) Biogenic Dopamine biogenic Serotonin biogenic Gamma aminobutyric acid (GABA) amino acid

Synaptic Fatigue

Occurs when neurotransmitter cannot recycle fast enough to meet demands of intense stimuli ---formation of new ACh from recycled choline is not fast enough to meet demand Synapse inactive until ACh is replenished

The Effect of a Neurotransmitter

On a postsynaptic membrane Depends on the receptor, NOT on the neurotransmitter For example, acetylcholine (ACh) Usually promotes action potentials

Chemically Gated Channels

Open in presence of specific chemicals (e.g., ACh) at a binding site Found on neuron cell body and dendrites

Brain Protection and Support

Physical Protection of the Brain - three forms of physical protection: --Bones of the cranium ---Cranial meninges --Cerebrospinal fluid *Biochemical Isolation Blood-brain barrier

The Brain Stem

Processes information between spinal cord and cerebrum or cerebellum. Includes: Midbrain (mesencephalon) - Processes sight, sound, and associated reflexes. Maintains consciousness Pons - Connects cerebellum to brain stem, is involved in somatic and visceral motor control Medulla oblongata - connects brain to spinal cord, relays info and regulates autonomic functions

Action Potentials

Propagated changes in transmembrane potential Affect an entire excitable membrane Link graded potentials at cell body with motor end plate actions

Propagation of Action Potentials

Propagation Moves action potentials generated in axon hillock along entire length of axon to the axon terminals Two methods of propagating action potentials ***Continuous propagation (unmyelinated axons) ***Saltatory propagation (myelinated axons)

The Cranial Meninges

Protect the brain from cranial trauma, are continuous with spinal meninges

Voltage-gated Channels

Respond to changes in transmembrane potential Have activation gates (open) and inactivation gates (close) Characteristic of excitable membrane Found in neural axons, skeletal muscle sarcolemma, cardiac muscle

Mechanically Gated Channels

Respond to membrane distortion Found in sensory receptors (touch, pressure, vibration)

Hyperpolarization

Result of opening a potassium channel Opposite effect of opening a sodium channel Positive ions move out, not into cell

Cerebellum

Second largest part of brain Coordinates repetitive body movements Two hemispheres Covered with cerebellar cortex

Active Forces across the Membrane

Sodium-potassium ATPase (exchange pump) Powered by ATP, it carries 3 Na+ out and 2 K+ in Balances passive forces of diffusion Maintains resting potential (-70 mV)

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Step 1: Depolarization to threshold Graded potential reaches axon hillock to depolarize it to threshold Step 2: Activation of Na channels Voltage gated Na+ channels cause rapid depolarization Na+ ions rush into cytoplasm Inner membrane changes from negative to positive

Four Steps in the Generation of Action Potentials

Step 1: Depolarization to threshold Step 2: Activation of Na channels Step 3: Inactivation of Na channels and activation of K channels Step 4: Return to normal permeability

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Step 3: Inactivation of Nachannels and activation of K channels At +30 mV Inactivation gates close (Na channel inactivation) K channels open Repolarization begins Step 4: Return to normal permeability K+ channels begin to close when membrane reaches normal resting potential (-70 mV) K+ channels finish closing when membrane is hyperpolarized to -90 mV Transmembrane potential returns to resting level Action potential is over

Blood Supply to the Brain

Supplies nutrients and oxygen to brain Delivered by internal carotid arteries and vertebral arteries Removed from dural sinuses by internal jugular veins

Five Secondary Brain Vesicles

Telencephalon - Becomes cerebrum Diencephalon - remains as diencephalon Mesencephalon - remains as midbrain Metencephalon - Forms cerebellum and pons Myelencephalon - Becomes medulla oblongata

What type of sensory information relies on fast action potential velocities?

The most important information (vision, balance, motor commands). It is carried by large-diameter, myelinated axons (type A).

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The response of a postsynaptic neuron to the activation of a presynaptic neuron can be altered by: The presence of neuromodulators or other chemicals that cause facilitation or inhibition at the synapse Activity under way at other synapses affecting the postsynaptic cell Modification of the rate of neurotransmitter release through presynaptic facilitation or presynaptic inhibition

The Refractory Period

The time period from beginning of action potential to return to resting state during which membrane will not respond normally to additional stimuli

Chemical and electrical gradients

They're important because...transmembrane potential rises or falls in response to temporary changes in membrane permeability from opening or closing specific membrane channels

The Transmembrane Potential

Three important concepts -The extracellular fluid (ECF) and intracellular fluid (cytosol) differ greatly in ionic composition Concentration gradient of ions (Na+, K+) -Cells have selectively permeable membranes -Membrane permeability varies by ion

Summation

To trigger an action potential One EPSP is not enough EPSPs (and IPSPs) combine through summation **Temporal summation **Spatial summation

Three Groups of Axons

Type A fibers Type B fibers Type C fibers These groups are classified by: Diameter Myelination Speed of action potentials

Type C Fibers

Unmyelinated Small diameter Slow speed (1 m/sec) Carry slower information For example, involuntary muscle, gland controls

Gray matter

Unmyelinated areas of CNS Nissel bodies(in dense areas of RER and Ribosomes) make neural tissue appear grey.

Neural Responses to Injuries in the PNS

Wallerian degeneration Axon distal to injury site degenerates Macrophages migrate into area and remove debris Schwann cells form path for new growth Wrap new axon in myelin

Indirect Effects - G Proteins

Work through second messengers Enzyme complex that binds GTP Link between neurotransmitter (first messenger) and second messenger Activate enzyme adenylate cyclase (enzyme that converts ATP to cyclic AMP) The second messenger cyclic-AMP (cAMP) can open membrane channels

The Brain

a large, delicate mass of neural tissue Containing internal passageways and chambers filled with cerebrospinal fluid Each of the major brain regions has specific functions Ascending from the medulla oblongata to the cerebrum, brain functions become more complex and variable Conscious thought and intelligence - produced in the neural cortex of the cerebral hemispheres

Multiple sclerosis (MS)

demyelination disease affecting CNS axons (vision, speech, balance, motor coordination affected). 1/3 of cases it is progressive. Treatment of corticosteroids and interferon to slow disease progression.

Diphtheria

disease caused by toxin from bacterial infection. Damages Schwann cells and destroys PNS myelin sheath. Can lead to fatal paralysis. Rare since there is a vaccine

Guillain-Barre syndrome

virus triggers the autoimmune disorder causing demyelination of peripheral nerves. Sensation of weakness or tingling of legs that spreads to arms. Progression of disease leads to paralysis (diaphragm also affected). Most fully recover, but some continue to have residual weakness.

What is the function of the blood brain barrier (BBB)? How is it maintained?

• Blood-Brain Barrier (BBB) • Isolates CNS neural tissue from general circulation • Formed by network of tight junctions Between endothelial cells of CNS capillaries • Lipid-soluble compounds (O2, CO2), steroids, and prostaglandins can bypass through endothelial cells Diffuse into interstitial fluid of brain and spinal cord • Astrocytes control blood-brain barrier by: Releasing chemicals that control permeability of endothelium

What is the function of cerebrospinal fluid (CSF)? What produces it and how is it circulated through the brain?

• Cerebrospinal Fluid (CSF) produced by Choroid plexus (about 500 ml/day). Choroid plexus consists of: • Specialized ependymal cells and capillaries. The cells: 1. Secrete CSF into ventricles 2. Remove waste products from CSF 3. Adjust composition of CSF

Cerebrospinal Fluid (CSF) circulates:

• From choroid plexus through ventricles • To central canal of spinal cord • Into subarachnoid space via two lateral apertures and one median aperture around the brain, spinal cord, and cauda equina

What are some diseases or toxins that may alter neuron function by affecting the neuroglia?

• Toxins and disease may alter neuron function by affecting myelination. • Heavy-metal poisoning - chronic exposure to heavy metals can damage neuroglia and lead to demyelination and cause axons to irreversibly deteriorate

How are the ventricles of the brain arranged

• Ventricles of the Brain • Each cerebral hemisphere contains one large lateral ventricle Separated by a thin medial partition (septum pellucidum) • Third ventricle - Ventricle of the diencephalon Lateral ventricles communicate with third ventricle via interventricular foramen • Fourth ventricle - Connected to the third ventricle via narrow canal in midbrain called the cerebral aqueduct The ventricle extends into medulla oblongata Becomes continuous with central canal of the spinal cord

How does having more than one synapse affect the speed of reflexes?

•Fewer synapses mean faster response •Reflexes may involve only one synapse

Continuous Propagation

•Of action potentials along an unmyelinated axon •Affects one segment of axon at a time •Steps in propagation: Step 1: Action potential in segment 1 Depolarizes membrane to +30 mV Local current Step 2: Depolarizes second segment to threshold Second segment develops action potential Step 3: First segment enters refractory period Step 4: Local current depolarizes next segment Cycle repeats •Action potential travels in one direction (1 m/sec) - Why?