Nervous System Physiology
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Questions and Answers

What is the primary role of acetylcholine at the neuromuscular junction?

  • Facilitating the fusion of vesicles with the muscle membrane
  • Degrading neurotransmitters in the synaptic space
  • Triggering muscle contraction by binding to receptors (correct)
  • Inhibiting the action potential in the muscle fiber

    • Which structure increases the surface area for acetylcholine action at the neuromuscular junction?

  • Motor end plate
  • Nerve terminals
  • Synaptic vesicles
  • Subneural clefts (correct)

    • What happens when calcium channels open at the nerve terminal during an action potential?

  • Calcium ions bind to receptors on the muscle fiber, initiating contraction
  • Calcium ions leave the nerve terminal, inhibiting neurotransmitter release
  • Calcium ions destroy acetylcholine in the synaptic space
  • Calcium ions enter the nerve terminal, leading to neurotransmitter exocytosis (correct)

    • What is the function of acetylcholinesterase in the synaptic space?

    <p>To destroy acetylcholine after it has acted on the muscle fiber</p> Signup and view all the answers

    What distinguishes the neuromuscular junction from other types of synapses?

    <p>It is characterized by the presence of myelinated nerve fibers</p> Signup and view all the answers

    What role does Na+ play in the postsynaptic muscle fiber membrane when acetylcholine binds to its receptor?

    <p>It causes an influx leading to end plate potential.</p> Signup and view all the answers

    How is acetylcholine primarily removed from the synaptic space?

    <p>By destruction through acetylcholinesterase.</p> Signup and view all the answers

    What happens if the end plate potential exceeds the threshold?

    <p>A self-regenerative action potential develops.</p> Signup and view all the answers

    Which of the following neurotransmitters is considered excitatory and is responsible for a significant number of synapses in the CNS?

    <p>Glutamate</p> Signup and view all the answers

    What occurs when botulinum toxin is present at the neuromuscular junction?

    <p>Decreased quantity of acetylcholine release.</p> Signup and view all the answers

    What types of transporters are responsible for the uptake of glutamate?

    <p>Excitatory amino acid transporters and vesicular glutamate transporters.</p> Signup and view all the answers

    What type of receptors does glutamate act on, which can form ligand-gated ion channels?

    <p>Ionotropic receptors.</p> Signup and view all the answers

    Which neurotransmitter is primarily involved in muscle contraction at the neuromuscular junction?

    <p>Acetylcholine</p> Signup and view all the answers

    What effect do NMDA receptors have on membrane permeability?

    <p>Increase permeability to Ca2+, Na+, and K+</p> Signup and view all the answers

    Which co-agonist is required along with glutamate for the activation of NMDA receptors?

    <p>Glycine</p> Signup and view all the answers

    What condition leads to glutamate toxicity through NMDA receptors?

    <p>Ischemia and excessive calcium influx</p> Signup and view all the answers

    What is the primary function of acetylcholine at the neuromuscular junction?

    <p>Induce excitatory postsynaptic potentials</p> Signup and view all the answers

    What is the role of acetylcholinesterase in synaptic transmission?

    <p>To rapidly degrade acetylcholine in the synaptic cleft</p> Signup and view all the answers

    How do nicotinic receptors (nAChR) influence ion movement?

    <p>They open Na+ and K+ channels upon activation</p> Signup and view all the answers

    During spatial summation, what mainly contributes to the increase in postsynaptic potentials?

    <p>Multiple simultaneous synaptic inputs from different locations</p> Signup and view all the answers

    Which neurotransmitter has both excitatory and inhibitory effects depending on the context?

    <p>Acetylcholine</p> Signup and view all the answers

    What are the main functions of the nervous system?

    <p>To pick up signals, conduct them to CNS, and integrate these signals</p> Signup and view all the answers

    Which of the following is NOT a function associated with the nervous system?

    <p>Regulation of metabolic rate</p> Signup and view all the answers

    How many cells are typically categorized as neurons in the human brain?

    <p>100 billion</p> Signup and view all the answers

    What role do the ion channels play in action potential generation?

    <p>They facilitate the rapid change of membrane potential</p> Signup and view all the answers

    Which part of the nervous system is involved in integrating signals for immediate or delayed responses?

    <p>Central Nervous System</p> Signup and view all the answers

    What is the primary role of calcium ions (Ca++) at the nerve terminal during the secretion of acetylcholine?

    <p>To trigger the exocytosis of synaptic vesicles</p> Signup and view all the answers

    Which structure at the neuromuscular junction is primarily responsible for synthesizing acetylcholine?

    <p>Nerve terminal</p> Signup and view all the answers

    What occurs immediately after the action potential triggers the opening of voltage-gated calcium channels at the nerve terminal?

    <p>Calcium ions enter the nerve terminal</p> Signup and view all the answers

    What structure increases the surface area for synaptic transmission at the neuromuscular junction?

    <p>Motor end plate</p> Signup and view all the answers

    How is acetylcholine primarily cleared from the synaptic space after its release?

    <p>Enzymatic degradation by cholinesterase</p> Signup and view all the answers

    Which receptor type is coupled to Gi alpha and primarily leads to the inhibition of cAMP formation?

    <p>D2 receptors</p> Signup and view all the answers

    What is the physiological effect of activation of α1 adrenergic receptors?

    <p>Open ion channels through phospholipase C</p> Signup and view all the answers

    Which neurotransmitter is primarily associated with the control of mood, sleep wake cycle, and feeding?

    <p>Serotonin</p> Signup and view all the answers

    What role does the serotonin transporter (SERT) play in serotonin function?

    <p>It reuptakes released serotonin.</p> Signup and view all the answers

    Which mechanism clears serotonin from the synaptic space?

    <p>Reuptake via serotonin transporter (SERT)</p> Signup and view all the answers

    Which dopamine receptor activation is associated with excitation through the opening of Na channels?

    <p>D1-like activation</p> Signup and view all the answers

    What is a primary function of norepinephrine in the central nervous system?

    <p>Regulating mood and anxiety</p> Signup and view all the answers

    What is the effect of selective serotonin reuptake inhibitors (SSRIs)?

    <p>Inhibit serotonin reuptake</p> Signup and view all the answers

    What initiates the release of neurotransmitters from the presynaptic terminal?

    <p>Local depolarization of the membrane</p> Signup and view all the answers

    Which molecule does calcium bind to in order to facilitate the release of neurotransmitters?

    <p>Synaptotagmin</p> Signup and view all the answers

    What is the role of synapsin I in neurotransmitter release?

    <p>Cages the vesicles to prevent release</p> Signup and view all the answers

    What results from the binding of calcium to the calmodulin complex?

    <p>Activation of protein kinase to phosphorylate synapsin I</p> Signup and view all the answers

    Which protein complex is responsible for pulling the vesicle closer to the presynaptic membrane?

    <p>SNARE proteins</p> Signup and view all the answers

    What mechanism releases neurotransmitters into the synaptic cleft?

    <p>Exocytosis of vesicles containing neurotransmitters</p> Signup and view all the answers

    What occurs immediately after an action potential reaches the axon terminal?

    <p>Vesicles filled with neurotransmitter fuse with the presynaptic membrane</p> Signup and view all the answers

    What effect does the diffusion of neurotransmitters into the synaptic cleft have?

    <p>It binds to receptors on the postsynaptic membrane resulting in synaptic potentials.</p> Signup and view all the answers

    What result follows when acetylcholine binds to nicotinic receptors on the postsynaptic muscle membrane?

    <p>An influx of Na+ leading to end plate potential</p> Signup and view all the answers

    How is most of the acetylcholine removed from the synaptic space?

    <p>By the action of acetylcholinesterase</p> Signup and view all the answers

    What effect does botulinum toxin have on the release of neurotransmitters?

    <p>It inhibits the release of acetylcholine</p> Signup and view all the answers

    Which type of neurotransmitter is responsible for approximately 75% of excitatory synapses in the CNS?

    <p>Glutamate</p> Signup and view all the answers

    What do ionotropic receptors for glutamate primarily form?

    <p>Ligand-gated ion channels</p> Signup and view all the answers

    Which two subclasses are included in glutamate transporters?

    <p>EAATs and VGLUTs</p> Signup and view all the answers

    What occurs if the end plate potential does not reach the required threshold?

    <p>No action potential is developed</p> Signup and view all the answers

    What triggers the self-regenerative action potential in muscle fibers?

    <p>A threshold-exceeding end plate potential</p> Signup and view all the answers

    What initiates the NMDA-receptor-dependent long-term potentiation (LTP)?

    <p>Sufficient depolarization that expels Mg2+ from the NMDA receptor</p> Signup and view all the answers

    What is the effect of low-frequency stimulation on the postsynaptic cell?

    <p>It activates protein phosphatases, leading to long-term depression</p> Signup and view all the answers

    Which reflex is primarily controlled at the spinal cord level of the CNS?

    <p>Walking movements</p> Signup and view all the answers

    Which structure is part of the subcortical level of the CNS?

    <p>Cerebellum</p> Signup and view all the answers

    What is a major function of the cerebral cortex?

    <p>Thought processes and motor function modulation</p> Signup and view all the answers

    Which of the following activities is NOT controlled by the lower brain level of the CNS?

    <p>Conscious decision-making</p> Signup and view all the answers

    What is the role of the spinal cord in the CNS?

    <p>It serves as a conduit for signals to and from peripheral organs</p> Signup and view all the answers

    Which statement correctly describes long-term depression (LTD)?

    <p>It reduces synaptic strength through selective activation of protein phosphatases</p> Signup and view all the answers

    Study Notes

    Nervous System Physiology

    • Nervous system is responsible for picking up signals from internal and external environments.
    • It conducts these signals to the CNS.
    • It integrates the signals to form responses like thoughts, senses, movements, and balance.
    • Functions of the nervous system include sensory system, motor system, limbic system(behavior and motivation), sleep-wakefulness, thinking and thoughts, planning, learning, memory, intelligence, and consciousness.
    • Neurons are 100 billion in the brain, and 100 trillion cells in the body.
    • The defining characteristic of neurons is electrical excitability – the ability to produce action potentials (impulses) in response to stimuli.

    Neurons- Cell Body

    • The soma is the metabolic center of the neuron.
    • It integrates signals.
    • The nucleus contains genetic material and prominent nucleolus (high synthetic activity)
    • Nissl bodies are rough endoplasmic reticulum and free ribosomes for protein synthesis. They are involved in the replacement of neuronal cellular components during growth and repair.
    • Neurofilaments (neurofibrils) are bundles of intermediate filaments, giving the cell shape and support.
    • Microtubules are involved in moving materials within the cell.

    Neurons- Dendrites

    • Dendrites receive messages from other neurons.
    • They are short, tapering, and highly branched structures.
    • Dendrites are the input portion of the neuron.

    Neurons- Axon

    • Axons carry information away from the cell body, and are the longest part of the neuron.
    • Impulses arise at the junction of the axon hillock and initial segment.
    • Swollen tips (synaptic end bulbs) contain vesicles filled with neurotransmitters.
    • Axon endings have fine processes called axon terminals.
    • Cytoplasm is called axoplasm.
    • Plasma membrane is called axolemma.
    • Axon collaterals emerge from the axon.

    Axonal Transport

    • Cell bodies are the location for most protein synthesis (e.g., neurotransmitters & repair proteins).
    • Axons or axon terminals require proteins
    • (1) Slow axonal flow: Axoplasm moves only anterograde direction (away from cell body) at 1-5 mm/day. This replenishes axoplasm in regenerating or maturing neurons.
    • (2) Fast axonal flow: Moves organelles and materials along the surface of microtubules at 200-400 mm per day. It transports material in both directions. Degenerating mitochondria is transported in the retrograde direction for recycling, and new mitochondria move down the axon.
    • Polypeptides packaged into vesicles are attached to the molecular motors (kinesin for anterograde movement and dynein for retrograde movement), which move them along microtubules.

    Glial Cells

    • Microglia act as phagocytes clearing away dead cells and protecting the CNS from disease by phagocytosis of microbes. At injured sites, they clear away debris.
    • Macroglia (astrocytes): Star-shaped with many processes, forming the blood-brain barrier, regulating nutrient concentrations, maintaining pH & [K+], taking up excess neurotransmitters, assisting in neuronal migration during brain development, and performing repairs (scar formation).
    • Oligodendroglia myelinate axons of the central nervous system (CNS).
    • Schwann cells myelinate axons of the peripheral nervous system (PNS).
    • Ependymal cells form epithelial membrane lining cerebral cavities that contain Cerebrospinal Fluid(CSF). They produce and circulate CSF.
    • Satellite cells are flat cells surrounding peripheral axons, supporting neurons in the peripheral nervous system (PNS).

    Nerve Action Potential

    • Nerve signals are transmitted by action potentials.
    • Action potentials are rapid changes in resting membrane potential that rapidly spread along the nerve fiber membrane.
    • At rest, before action potential begins, conductance for K+ is ~75 times more than that for Na+.
    • The membrane is polarized.
    • At the onset of action potential, Na channels become activated, Na conductance increases by 5000-fold, leading to Na influx, and membrane potential shifts rapidly in a positive direction(depolarization).
    • After depolarization, rapid diffusion of K+ efflux establishes the normal negative resting membrane potential (repolarization).

    Receptor Potential/Graded Potentials

    • When ion channels open with stimuli in receptors, receptor potentials are generated which are not all-or-none like action potentials.
    • If receptor potential rises above threshold, action potential occurs in nerve fiber.
    • As intensity of stimuli increases, the amplitude of receptor potential and consequently the frequency of action potential increase.
    • Examples of graded potentials include synaptic potentials (EPSP&IPSPs) and receptor potentials.

    Properties of Graded Potentials vs Action Potentials

    • Graded potentials can be depolarization or hyperpolarization while action potentials are only depolarization.
    • Graded potentials are initiated by stimuli, neurotransmitters, or spontaneously, but action potentials are initiated by graded potentials.
    • In graded potentials, amplitude varies with the size of the initiating event while in action potentials, it is independent.
    • Graded potentials can be summed over time and space, unlike action potentials which cannot be summed.
    • Graded potentials have no threshold while action potentials do.
    • Graded potentials have no refractory periods while action potentials do.
    • In graded potentials, amplitude decreases with distance, while in action potentials, it is conducted without decrement and amplified to a constant value at every point along the membrane.
    • Graded potentials are not all-or-none, while action potentials are all-or-none.

    Synapses

    • Synapses are junctions between neurons.
    • Types of synapses include electrical and chemical.
    • In electrical synapses, gap junctions conduct ions freely, synchronizing the electrical activity of large populations of neurons.
    • In chemical synapses, neurotransmitters transmit signals. The region belonging to the initiating neuron is called the presynaptic membrane, and the region belonging to the receiving neuron is called the postsynaptic membrane. The space in between is called the synaptic cleft.
    • There are three types of synapses: axo-dendritic, axo-somatic, and axo-axonic.

    Presynaptic Terminals

    • The synaptic gap is between the end of the axon and the postsynaptic membrane.
    • The synaptic cleft is 200-300 A°.
    • The presynaptic terminal has two internal structures: Transmitter vesicles that contain neurotransmitters, and mitochondria that provide ATP which is used for synthesizing neurotransmitters.

    Receptors for Neurotransmitter

    • Receptors for neurotransmitters are located on the postsynaptic membrane.
    • Some presynaptic neurons also have receptors for the transmitters they release,called autoreceptors.
    • Autoreceptors are often important in regulating the amount of transmitter released subsequently.

    Transmitter Release from Presynaptic Terminals

    • If an action potential depolarizes the presynaptic membrane, voltage-gated Ca++ channels open, causing Ca++ to flow into the axon terminal and [Ca++]i to increase.
    • Ca++ binding to calmodulin activates Ca-calmodulin dependent protein kinase (CaMK). CaMK phosphorylates synapsin I, uncaging vesicles, which become free .
    • Ca++ also binds to synaptotagin, promoting fusion of the vesicle with the presynaptic membrane.
    • SNARE proteins (synaptobrevin, Syntaxin 1, and SNAP 25 ) pull vesicles closer for transmitter release to be released to the synaptic cleft.

    The Sequence of events that lead to Postsynaptic Changes

    • Action potential arrives at the axon terminal
    • Depolarization opens voltage-gated Ca++ channels
    • Ca++ enters the presynaptic cell
    • Ca++ causes vesicles filled with neurotransmitter to migrate towards the presynaptic and merges with the presynaptic membrane
    • Neurotransmitter is released into the synaptic cleft by exocytosis.
    • Transmitter diffuses through synaptic cleft, binding to receptors in the postsynaptic membrane.
    • Synaptic potentials (EPSP or IPSPs) develop.

    Transmitter Substance

    • Receptor molecules on postsynaptic membrane have: Binding component that protrudes outward from the membrane; Ionophore component that passes through the membrane..
    • Receptor ionophore can be (1) An ion channel (ionotropic receptor) or (2) a second messenger activator (metabotropic receptor) causing prolonged postsynaptic excitation/inhibition.

    Excitatory or Inhibitory Receptors

    • Some receptors cause excitation of postsynaptic neuron (EPSP), opening of Na+ channels resulting in Na+ influx, depolarization (excitation).
    • Others cause inhibition of postsynaptic neuron (IPSP), opening of Cl− channels resulting in Cl− influx, repolarization (inhibition).

    Excitatory Postsynaptic Potential (EPSP)

    • Discharge of axon terminals causes release of excitatory neurotransmitter.
    • Nat moves into postsynaptic cell through receptor channels, depolarizing it to −45 mV (If reaching threshold it elicits action potentials (in the initial segment of the axon – axon hillock)).

    Inhibitory Postsynaptic Potential (IPSP)

    • Discharge of axon terminals causes release of inhibitor neurotransmitter.
    • Chloride ion moves into the interior through receptor channels.
    • This leads to hyperpolarizing potential (-70 mV) compared to resting (-65 mV).
    • Nernst potential for Cl–~−70 mV
    • K+ efflux also makes membrane potential more negative (Nernst potential for K+ ~−70−95 mV;).

    Summation in Neurons

    • EPSP due to fast neurotransmitters dies away in ~15 ms.
    • Neuropeptides can excite/inhibit postsynaptic neurons for msec to hours.
    • The strength is increased by the frequency of nerve impulses.
    • Simultaneous postsynaptic potentials from multiple terminals summate.
    • Repeated discharges from single terminals, if rapidly enough, summative.

    Neuromuscular Junction

    • The synapse between a motor neuron and a skeletal muscle fiber is called neuromuscular junction.
    • Skeletal muscle fibers are innervated by large, myelinated nerve fibers. Each fiber branches, stimulating 3–500 muscle fibers.
    • Each nerve ending makes a neuromuscular junction with the muscle fiber.
    • The postsynaptic region is called the motor end plate.

    Secretion of Acetylcholine by the Nerve Terminals

    • As an action potential spreads, voltage-gated Ca++ channels open, and Ca++ flows into the nerve terminal.
    • Vesicles fuse with the neural membrane and empty acetylcholine into the synaptic space by exocytosis.

    Acethylcholine on postsynaptic muscle fiber membrane

    • Acetylcholine binds to nicotinic acetylcholine receptors on the postsynaptic membrane.
    • Nicotinic receptors are permeable to Na+, K+, and possibly Ca++ inducing Na+ influx and creating a local positive potential change (end-plate potential).
    • If the end-plate potential exceeds threshold, a self-regenerative action potential develops and spreads along the muscle membrane, triggering muscle contraction.

    Destruction of Released Acetylcholine

    • Acetylcholine persists in the synaptic space to activate acetylcholine receptors.
    • It's rapidly removed by two means:
      • Most of the acetylcholine is destroyed by acetylcholinesterase.
      • A small amount diffuses out of the synaptic space.
    • Botulinum toxin decreases the quantity of acetylcholine release.

    Neurotransmitters (transmitters)& Receptors

    • Study of neurotransmitters and their receptors.
    • Examples of neurotransmitters include:
    • Acetylcholine, Norepinephrine, Serotonin, Dopamine, Histamine, GABA, Glycine.

    Catecholamines

    • Catecholamines include adrenaline, noradrenaline, and dopamine.
    • Norepinephrine synthesis begins in the axoplasm of the nerve ending and is completed inside the secretory vesicles.
    • Tyrosine hydroxylase is the rate-limiting enzyme in the synthesis of adrenaline, noradrenaline, and dopamine.

    Norepinephrine

    • Norepinephrine is secreted by nerve terminals (of adrenergic nerve fibers) in the axoplasm, but is completed inside the secretory vesicles. Tyrosine hydroxylase is the rate-limiting enzyme in the synthesis of noradrenaline, adrenaline, and dopamine.
    • Removal after secretion occurs by: re-uptake into nerve endings by an active transport (~65% of the secreted NE), diffusion away into the surrounding body fluids into blood (most remaining NE), and destruction by tissue enzymes(monoamine oxidase (MAO) found in nerve endings; catechol-O- methyl transferase ( COMPT), found in diffusely in all tissues).
    • Norepinephrine is found in the Locus ceruleus in pons (controls brain activity, wakefulness), and in postganglionic neurons of the sympathetic nervous system.
    • a-adrenergic receptors (α1, α2), β-adrenergic receptors (β1, β2), all affect by activating channels through second messenger systems, a1 affecting phospholipase C (PLC),resulting in [Ca++]i increase, a2 inactivating adenylate cyclase decreasing cAMP, and β1/β2 activating adenylate cyclase, and increasing cAMP activating protein kinase, and phosphorylating proteins, opening ion channels.

    Serotonin (5-HT)

    • Serotonin is secreted by nuclei originating in the median raphe of the brainstem, projecting to many brain and spinal cord areas (especially to the dorsal horns of spinal cord and hypothalamus).
    • Functions: mood control, anxiety, aggression, pain pathways inhibition, sexual behavior, feeding, sleep, memory, response to stress, cognition, locomotion, reward, and decision-making.
    • 7 families of 5HT receptors, including 5-HT1, 2, 3, 4, 5, 6, and 7, including ionotropic 5-HT3 and metabotropic 5-HT1-7 receptors.
    • Serotonin released into the synaptic space is cleared by two mechanisms: metabolism by MAO-A and reuptake by serotonin transporter (SERT).
    • Selective serotonin reuptake inhibitors (SSRIs) are used to treat mental disorders.

    Dopamine

    • Secreted by neurons originating in the substantia nigra; often with inhibitory effects.
    • Lack of dopamine in neurons can cause Parkinson's disease.
    • Dopamine pathways include: mesolimbic, nigrostriatal, mesocortical, and tuberoinfundibular tracts.
    • Dopamine receptors (D1, D5) are coupled to Gs alpha stimulating adenylate cyclase activity, resulting in cAMP formation (excitation or inhibition depending on the target ion channels).
    • Dopamine receptors (D2, D3, D4) are coupled to Gi alpha inhibiting cAMP formation (mostly inhibition of the target neuron).

    Histamine

    • Histamine axons originate from the posterior hypothalamus (tuberomammillary nucleus—TMN) and innervate most CNS regions.
    • Active solely during waking, histamine maintains wakefulness and attention.

    Glycine

    • Secreted mainly at synapses in the spinal cord, acting as an inhibitory transmitter.
    • Glycine is the smallest amino acid(20).
    • Glycine is blocked by strychnine.
    • A co-agonist with glutamate for NMDA receptors in the brain.
    • Tetanus toxin blocks GABA and glycine release.

    Gamma-Aminobutyric Acid (GABA)

    • Secreted by nerve terminals in the spinal cord, cerebellum, basal ganglia, and cortex.
    • Always causes inhibition.
    • Synthesized from glutamate using L-glutamic acid decarboxylase (GAD), with pyridoxal phosphate (active form of vitamin B6) as a cofactor.

    GABA receptors

    • Two types of GABA receptors: GABAa and GABAb.

    • GABAa receptors are ionotropic, conducting Cl− ions selectively.

    • GABAb receptors are metabotropic, linked via G-proteins to K channels.

    Review USMLE Questions

    • Includes questions on NMDA receptor activation by glutamate, dopamine receptor deficiency in Parkinson's disease, types of neurotransmitters, and autonomic actions.

    Organization of the Nervous System

    • Embryonic and adult brain regions, corresponding structures, and major levels of CNS function (spinal cord, lower brain, higher brain).

    Peripheral Nervous System

    • Contains somatic and visceral sensory and motor divisions.

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