Lecture 1 Nervous System and Neuronal Excitability

What are the two major structural divisions of the nervous system?

Central nervous system (CNS) and peripheral nervous system (PNS).

What structures make up the CNS?

Brain and spinal cord.

What structures make up the PNS?

All nerves connecting to the CNS (cranial and spinal nerves).

Which PNS division brings sensory information into the CNS?

Afferent (sensory) division.

Which PNS division sends commands from the CNS to effectors?

Efferent (motor) division.

What are the two branches of the efferent division?

• Somatic nervous system

• autonomic nervous system.

What does the somatic nervous system control?

Skeletal muscle (voluntary) motor output.

Which three divisions compose the autonomic nervous system?

Sympathetic, parasympathetic, and enteric.

What is another term for an action potential?

AP, spike, nerve impulse, or conduction signal.

What is another term for the autonomic nervous system?

Visceral nervous system.

What is another term for an axon?

Nerve fiber.

What is axonal transport also called?

Axoplasmic flow.

List three synonyms for axon terminal.

Synaptic knob, synaptic bouton, presynaptic terminal.

What is the cytoplasm of an axon called?

Axoplasm.

What are two synonyms for cell body?

Soma, nerve cell body.

What is the axon’s cell membrane called?

Axolemma.

What are glial cells also called?

Neuroglia or glia.

What is another term for interneuron?

Association neuron.

What is the rough ER in neurons called?

Nissl substance/body.

What is another term for sensory neuron?

Afferent neuron.

What do dendrites do?

Receive incoming signals.

What does the axon do?

Carries outgoing information away from the soma.

Name the three functional neuron types.

Sensory (afferent), interneurons, and motor (efferent).

Where is the trigger zone that initiates action potentials?

At the axon hillock/initial segment.

What is the general role of glial cells?

Physical and biochemical support for neurons.

How many glia are there relative to neurons?

Roughly 10–50× more glia than neurons.

List the four major CNS glial cell types.

Astrocytes, oligodendrocytes, microglia, ependymal cells.

Key functions of astrocytes?

• most numerous

• Maintain blood-brain barrier

• regulate extracellular chemical environment

• guide neurons during development

• play role in synapse formation.

Function of oligodendrocytes?

Form and maintain CNS myelin sheaths.

Function of microglia?

Phagocytes that remove debris, damaged cells, pathogens.

Function of ependymal cells?

Produce and help circulate cerebrospinal fluid (CSF).

Which cell forms myelin in the PNS?

Schwann cell.

Which cell forms myelin in the CNS?

Oligodendrocyte.

Key functions of the myelin sheath?

• Electrical insulation (faster action potential conduction)

• Found in both CNS (oligodendrocyte) and PNS (schwann cells)

• makes up white matter

What are Nodes of Ranvier?

Gaps in the myelination where voltage-gated channels cluster; sites of AP regeneration.

• is a section of unmyelinated axon membrane between two Schwann cells

What does demyelination do to conduction?

Slows or blocks conduction due to current leak between nodes.

What tissue does myelin largely comprise in the CNS?

White matter.

What is a neuron’s typical resting membrane potential (RMP)?

About –70 mV.

Two determinants of RMP?

1. Ion concentration gradients

2. membrane permeability to those ions

Which ion most strongly sets RMP and why?

K⁺, because of abundant K⁺ leak channels (high resting permeability).

What does the Na⁺/K⁺ ATPase do per cycle?

Pumps 3 Na⁺ out and 2 K⁺ in using ATP.

Where is Na⁺ concentration highest?

Outside the cell (extracellular).

Where is K⁺ concentration highest?

Inside the cell (intracellular).

Where is Cl⁻ concentration highest?

Outside the cell (extracellular).

What are leak channels?

Channels that randomly alternate open/closed; set resting permeability.

What opens ligand-gated channels?

Binding of a chemical ligand (e.g., neurotransmitter).

What opens mechanically gated channels?

Mechanical stimuli like touch, pressure, stretch, vibration.

What opens voltage-gated channels?

Changes in membrane potential (voltage).

Threshold voltage: same or different among channels?

Varies by channel type.

What does the Nernst equation describe?

Equilibrium potential for a single ion given its concentration gradient.

What does the Goldman–Hodgkin–Katz (GHK) equation predict?

Membrane potential considering all permeant ions and their permeabilities.

Approximate EK+, ENa+, and ECl- in neurons?

K ≈ –90 mV;

Na ≈ +60 mV;

Cl ≈ –63 mV.

What happens in a K⁺-only permeable membrane?

K⁺ exits, inside becomes negative until E_ionK (~–90 mV) reached.

What happens in a Na⁺-only permeable membrane?

Na⁺ enters, inside becomes positive until E_ionNa (~+60 mV) reached.

What is a graded potential?

Local membrane potential change that varies in amplitude.

Where do graded potentials usually occur?

Dendrites and soma (cell body)

Do graded potentials decrement with distance?

Yes, they decrease as they spread from the origin.

Define depolarizing vs hyperpolarizing graded potentials.

• Depolarizing = less negative

  • makes the membrane potential less polarized

• hyperpolarizing = more negative.

  • makes the membrane potential more polarized

Two ways graded potentials sum?

Spatial (multiple inputs) and temporal (rapid successive inputs).

What is a subthreshold stimulus at the trigger zone?

Below threshold; does not initiate an action potential.

What is a suprathreshold stimulus at the trigger zone?

At/above threshold; initiates an action potential.

Are APs graded or all-or-none?

All-or-none events.

What opens first during AP depolarization?

Voltage-gated Na⁺ channels (activation gate opens rapidly).

What stops Na⁺ entry at the AP peak?

Na⁺ channel inactivation gate closes.

What drives repolarization of the AP?

Opening of voltage-gated K⁺ channels and K⁺ efflux.

Why is there after-hyperpolarization?

K⁺ channels close slowly, allowing extra K⁺ efflux.

What restores resting conditions after an AP?

Channel reset and Na⁺/K⁺ pump maintaining gradients.

List how action potential goes.

1. Resting membrane potential

2. depolarizing stimulus

3. membrane depolarizes to threshold. voltage-gated Na+ channel open quickly and Na+ enters the cell. Voltage-gated K+ channels begin to open slowly.

4. Rapid Na+ entry depolarizes cell.

5. Na+ channels close and slower K+ channels open

6. K+ moves from cell to extracellular fluid

7. K+ Channels remain open and additional K+ leaves cell, hyperpolarizing it. 

8. Voltage-gated K+ channels close, less K+ leaks out of the cell

9. Cell returns to resting ion permeability and resting membrane potential.

List how Voltage-Gated Na+ channels work.

1. at resting membrane potential, the activation gate closes the channel

2. depolarizing stimulus arrives at the channel. activation gate opens

3. with activation gate open, Na+ enters the cell

4. inactivation gate closes and Na+ entry stops

5. during repolarization caused by K+ leaving the cell, the two gates reset to their original positions

What prevents APs from traveling backward?

Refractory period of upstream Na⁺ channels.

Define absolute vs relative refractory period.

• Absolute: no AP possible

• Relative: stronger-than-normal stimulus needed.

How does myelin affect conduction?

Enables saltatory conduction; increases speed and efficiency.

Where are voltage-gated Na⁺ channels concentrated in myelinated axons?

At the Nodes of Ranvier.

Two main factors that increase conduction velocity (speed of action potential)?

• Larger axon diameter

  • Larger axons = faster

• Myelination

  • myelinated axons are faster

What causes current leak and slower conduction?

Low membrane resistance (unmyelinated segments, demyelination).

How is stimulus strength encoded in neurons?

By frequency of action potentials (and NT amount released).

How do weak vs strong stimuli affect transmitter release?

• Weak → little neurotransmitter

• Strong → more neurotransmitter released.

Effect of normokalemia on excitability?

Normal threshold

• subthreshold stimuli do not trigger APs.

• but a suprathreshold (above-threshold) stimulus will fire an action potential

Effect of hyperkalemia on excitability?

Membrane closer to threshold (-60mV instead of -70mV)→ increased excitability; subthreshold may trigger APs.

Effect of hypokalemia on excitability?

Membrane hyperpolarized (-80mV instead of -70mV) → decreased excitability; even strong stimuli may fail.

Primary signal type at most synapses?

Chemical; neurotransmitters cross synaptic cleft.

What ion triggers neurotransmitter vesicle exocytosis?

Ca²⁺ entering via voltage-gated Ca²⁺ channels.

List the five basic steps in chemical synaptic transmission.

1. AP arrives (depolarizes the axon terminal)

2. Ca²⁺ channels open (depolarization opens voltage gated Ca²⁺ channels) —> Ca²⁺ enters the cell

3. Calcium entry triggers exocytosis of synaptic vesicle contents

4. Neurotransmitter diffuses across the synaptic cleft and binds postsynaptic receptors.

5. Neurotransmitter binding initiates a response in the postsynaptic cell

Three ways neurotransmitter action is terminated.

• Reuptake into axon/glia

• enzymatic breakdown

• diffusion out of cleft.

Name the seven structural classes of neurocrines.

Acetylcholine (ACh), amines, amino acids, purines, gases, peptides, lipids.

What is acetylcholine synthesized from?

Choline and acetyl-CoA.

How is ACh cleared from the synaptic cleft?

Rapid hydrolysis (broken down) by acetylcholinesterase; choline recycled (to axon terminal and used to make more ACh)

Which amines derive from tyrosine?

• Dopamine,

• norepinephrine (secreted by noradrenergic neurons),

• epinephrine.

From which amino acid is serotonin synthesized?

Tryptophan.

From which amino acid is histamine synthesized?

Histidine.

List major amino acid neurotransmitters and their general actions.

• Glutamate: excitatory —> CNS

• Aspartate: excitatory —> brain

• GABA: inhibitory (brain)

• glycine: inhibitory —> (spinal cord).

Give examples of purine, gas, peptide, and lipid transmitters.

• Purines: ATP/AMP;

• Gases: NO/CO;

• Peptides: Substance P and opiod peptides;

• Lipids: eicosanoids

Two types of cholinergic receptors and their properties.

• Nicotinic on skeletal muscle, in PNS and CNS

  • monovalent cation channels —> Na+ and K+

• Muscarinic in CNS and PNS (metabotropic, linked G-protein).

Where are nicotinic receptors prominent?

Skeletal muscle NMJ, CNS, and PNS.

What are adrenergic receptor families and coupling?

Alpha and beta; both are G-protein–coupled receptors.

What is an EPSP?

Excitatory postsynaptic potential: depolarizing graded potential.

• more likely to shoot an action potential

What is an IPSP?

Inhibitory postsynaptic potential: hyperpolarizing graded potential.

• less likely to fire an action potential

Outcome when EPSPs + IPSPs reach threshold at the trigger zone?

An action potential is fired.

What is neuronal divergence?

One neuron influences multiple targets.

What is neuronal convergence?

Many presynaptic neurons synapse onto one postsynaptic neuron.