Electrical Signals in Neurons and Synaptic Transmission

Electrical Signals in Neurons

• Nerve impulse = Action potential (AP): electro-chemical signal used for long-distance sensory, motor & integrative communication.
• Conducts in peripheral nerves and within brain/spinal cord → basis for “thought.”
• Max somatic conduction speed ≈ 280\;\text{mph} \;(\approx 125\;\text{m·s}^{-1}).

Membrane Potentials

• Ion concentration difference across plasma membrane ⇒ voltage (measured in mV).
• Inside of neuron: negative; outside: positive.
• Creates electrical potential energy – “opposites attract.”
• Analogy: charged membrane behaves like a tiny biological battery.

Resting Membrane Potential (RMP)

There is more potassium (K+) inside the neuron than (Na+), and more sodium (Na+) outside the neuron than (K+).

• Defined as the voltage difference across the neuron’s membrane when at rest, typically around -70 mV.
• Result of uneven distribution of ions, primarily sodium (Na+) and potassium (K+).
• Maintained by the sodium-potassium pump, which actively transports Na+ out and K+ into the cell.

• Typically around -70 mV, maintained by the sodium-potassium pump which moves Na+ ions out and K+ ions in, helping to establish an electrochemical gradient.

• Polarized baseline ≈ -70\;\text{mV} when neuron not firing.
• Maintained by two protein systems:
• Gated ion channels – close at rest, reopen after AP to re-establish RMP.
• Sodium–Potassium pump (Na⁺/K⁺-ATPase) – active transport exchanging 3\,\text{Na}^+ out/ 2\,\text{K}^+ in per ATP → restores ionic gradient so next AP can fire.

Action Potential (All-or-None Event)

• Self-propagating electrical fluctuation along the membrane.
• Sequence of events

Polarized phase: membrane at -70\;\text{mV}.
Adequate stimulus applied.
Threshold reached ≈ -55\;\text{mV}.
Voltage-gated Na⁺ channels open → Na⁺ rushes in (depolarization).
At peak, Na⁺ channels inactivate; K⁺ channels open + Na⁺/K⁺ pump starts.
K⁺ exits cell → repolarization; slight hyperpolarization may follow.
RMP restored.
• Refractory periods
• Absolute: second AP impossible no matter stimulus strength.
• Relative: second AP possible but requires stronger-than-normal stimulus.

Propagation of the Action Potential

• AP travels from soma → axon terminals (synaptic bulbs).
• Two conduction modes (Text p.419):
• Continuous – step-by-step depolarization in unmyelinated axons.
• Saltatory – AP "leaps" node to node (Nodes of Ranvier) in myelinated axons (much faster).
• Factors affecting speed
• Degree of myelination ↑ myelin ⇒ ↑ speed.
• Axon diameter ↑ diameter ⇒ ↓ resistance ⇒ ↑ speed.

Signal Transmission at Synapses

Synapse Structure

• Presynaptic neuron – sends signal.
• Synaptic bulb/knob – terminal end containing neurotransmitter vesicles.
• Synaptic cleft – extracellular gap between cells.
• Postsynaptic membrane – contains receptor proteins.

Chemical Synaptic Mechanism (Text Fig 19-12)

AP arrives at presynaptic bulb.
Voltage-gated Ca²⁺ channels open → Ca²⁺ influx.
Ca²⁺ triggers exocytosis of neurotransmitter (NT) into cleft.
NT diffuses & binds receptors on postsynaptic membrane.
Binding produces graded potential:
• EPSP (excitatory) – depolarizes; pushes toward threshold (“GO”).
• IPSP (inhibitory) – hyperpolarizes; moves away from threshold (“STOP”).

Removal of Neurotransmitter (Text Fig 19-13)

• Necessary to prevent indefinite stimulation.

Diffusion away into interstitial fluid.
Enzymatic degradation (e.g., acetylcholinesterase destroys ACh at NMJ).
Re-uptake by presynaptic neuron (basis for many antidepressants – Box 19-2).

Neurotransmitters (Small-Molecule & Peptide)

• Acetylcholine (ACh)
- Excitatory at skeletal NMJ; inhibitory at cardiac muscle.

Amines (mainly CNS)
- Serotonin – sensory perception, thermoregulation, mood, appetite, sleep.
- Dopamine – emotion, reward/addiction, motor tone regulation.
- Norepinephrine – arousal, alertness, and mood regulation.
- Glutamate – primary excitatory neurotransmitter in the CNS, vital for synaptic plasticity and cognition.
- GABA (gamma-aminobutyric acid) – primary inhibitory neurotransmitter, plays a key role in regulating neuronal excitability.
- Epinephrine & Norepinephrine – arousal, dreaming, mood; NE = primary autonomic NT.
  • Amino Acids – most abundant in CNS/PNS synaptic vesicles (e.g., glutamate, GABA, glycine).
  Other small molecules
  • Nitric Oxide (NO) – gaseous; causes vasodilation & smooth muscle relaxation.
  • Neuropeptides
  • Enkephalins & Endorphins – endogenous opioids; analgesic.
  • Substance P – enhances pain perception.

Synapses, Learning & Memory (Text pp.423-424)

• Memories stored by facilitation or inhibition of synaptic transmission.
• Short-term (sec–min): transient changes in NT release probability at presynaptic terminals.
• Long-term (months–years): structural remodeling – new dendrites/axons, additional receptors, altered protein synthesis.
• Neural networks become “hard-wired” through repeated activation (Hebbian principle: "cells that fire together wire together").

Disorders of Nerve Signaling

Conduction Disorders

• Demyelinating diseases (e.g., Multiple Sclerosis) – slowed/blocked APs.
• Mechanical/chemical nerve damage – trauma, toxins.
• Cerebrovascular accidents (stroke) – reduced blood, glucose & O_2 → neuronal death.

Synaptic Disorders

• Myasthenia gravis – autoimmune antibodies block ACh receptors at skeletal NMJ → muscle weakness.
• Autism Spectrum Disorder – complex synaptic signaling irregularities (exact mechanisms under study).

Practical & Ethical Notes

• Pharmacology: drugs targeting NT removal (SSRIs, MAO inhibitors) alter mood & cognition.
• Clinical diagnostics: nerve conduction velocity tests assess myelination integrity.
• Neuroethics: long-term potentiation research raises questions about memory enhancement or manipulation.

Key Numbers & Equations

• RMP \approx -70\;\text{mV} ; Threshold \approx -55\;\text{mV}.
• Na⁺/K⁺ pump ratio 3\,\text{Na}^+{\text{out}} : 2\,\text{K}^+{\text{in}} per ATP.
• Maximum human somatic axon conduction velocity \approx 125\;\text{m·s}^{-1} (≈ 280\;\text{mph}).