Neural Communication

Resting Membrane Potential

Neurons maintain an electrical charge difference across their membrane when inactive, known as the resting membrane potential (RMP).

• Typical value: –70 mV (inside is more negative).
• Created by the unequal distribution of ions and selective membrane permeability.

The Sodium–Potassium Pump

The Na⁺/K⁺ pump actively maintains RMP by exchanging ions:

• Pumps 3 Na⁺ out and 2 K⁺ in per cycle.
• Requires ATP.
• Sustains the negative interior crucial for signalling.

Post-Synaptic Potentials (PSPs)

Incoming signals produce small, graded voltage changes:

• EPSP (Excitatory Post-Synaptic Potential): depolarisation → neuron becomes less negative → increases firing probability.
• IPSP (Inhibitory Post-Synaptic Potential): hyperpolarisation → neuron becomes more negative → decreases firing probability.

Neurons integrate thousands of EPSPs and IPSPs.
If the summed depolarisation reaches threshold (~ –50 mV) at the axon hillock, an action potential fires.

Synaptic Transmission

Neurons communicate at synapses, which can be:

Electrical Synapses

• Direct ion flow through gap junctions.
• Fast, synchronising signals.

Chemical Synapses

• Most common.
• Use neurotransmitters, released into a synaptic cleft.

Steps of Chemical Transmission

1. Action potential arrives at terminal.
2. Voltage-gated Ca²⁺ channels open → Ca²⁺ enters.
3. Ca²⁺ triggers movement of neurotransmitter vesicles.
4. Vesicles fuse with membrane via SNARE proteins.
5. Neurotransmitters released by exocytosis.
6. They diffuse across synaptic cleft and bind receptors on postsynaptic neuron.

Termination of Neurotransmitter Action

• Reuptake via transporters (e.g., serotonin transporter).
• Enzymatic breakdown (e.g., AChE for acetylcholine).
• Repackaging into vesicles.

Neurotransmitters: Defining Features

A substance is considered a true neurotransmitter if:

1. Synthesised in the presynaptic neuron.
2. Stored in presynaptic terminals.
3. Released upon depolarisation (Ca²⁺ dependent).
4. Produces a postsynaptic effect via receptors.
5. Has an inactivation mechanism.
6. Exogenous application mimics natural effect.

Major Neurotransmitter Categories

Class	Examples	Notes
Amino acids	Glutamate, GABA, Glycine	Fast excitatory/inhibitory signalling
Acetylcholine (ACh)	—	Motor control, memory, REM sleep
Monoamines	Dopamine, Noradrenaline, Serotonin	Modulate mood, motivation, arousal
Peptides	Substance P, endorphins	Pain, reward, stress
Purines	ATP, adenosine	Neuromodulation
Lipids	Anandamide (endocannabinoid)	Appetite, mood regulation
Gases	Nitric oxide	Diffusible signals, unconventional NT

Neurotransmitter Synthesis & Storage

Peptides

• Synthesised in the soma.
• Packaged in large dense-core vesicles.
• Transported down axon.

Small-Molecule Neurotransmitters

(Amino acids, monoamines, ACh)

• Synthesised in axon terminals.
• Stored in small vesicles.

Major Neurotransmitters & Roles

Neurotransmitter	Primary Roles
Acetylcholine (ACh)	Memory, learning, attention, muscle activation
Dopamine (DA)	Reward, motivation, planning, movement
Noradrenaline (NA)	Arousal, attention, fight-or-flight
Serotonin (5-HT)	Emotion, cognition, appetite, sleep
Glutamate	Main excitatory NT; memory & LTP
GABA	Main inhibitory NT; stabilises neural activity
Norepinephrine	Stress response, vigilance

Amino Acid Neurotransmitters

Excitatory

• Glutamate
• Aspartate

Excess glutamate → excitotoxicity → neuronal death (glial cells regulate levels).

Inhibitory

• GABA
• Glycine

GABA is produced only in GABAergic neurons, often interneurons critical for inhibitory control.

Acetylcholine (ACh) System

Major Sources

• Nucleus basalis of Meynert
• Medial septal nucleus
• Mesopontine tegmentum
• Striatal interneurons

Synthesis

Acetyl-CoA + choline
→ (enzyme: choline acetyltransferase) →
ACh

Breakdown

ACh → choline + acetic acid
→ (enzyme: acetylcholine esterase)

Insecticides & nerve agents inhibit AChE, causing dangerous overstimulation and potential paralysis.

Monoamines

Types

• Catecholamines: dopamine, noradrenaline, adrenaline
• Indolamines: serotonin, melatonin
• Histamine is also a monoamine.

Where They’re Produced

• Dopamine: VTA & substantia nigra
• Noradrenaline: locus coeruleus
• Serotonin: dorsal raphe nuclei

Synthesis Pathways

Catecholamines:
Tyrosine → L-DOPA → dopamine → noradrenaline → adrenaline

Serotonin:
Tryptophan → 5-HTP → serotonin

Breakdown

Monoamine Oxidase (MAO) in mitochondria.
MAO inhibitors (MAOIs) prolong monoamine activity.

Receptors: Ionotropic vs Metabotropic

Ionotropic Receptors

• Ligand-gated ion channels
• Fast and short-lasting
• Example actions:
  • ACh or glutamate → Na⁺/Ca²⁺ influx → excitation
  • GABA → Cl⁻ influx → inhibition

Metabotropic Receptors

• G-protein coupled receptors (GPCRs)
• Slow, modulatory, long-lasting
• Allow signal amplification

Mechanism

1. NT binds receptor
2. G-protein activated
3. α, β, γ subunits dissociate
4. α subunit may:
   • Activate an enzyme → second messenger (cAMP, Ca²⁺)
   • Open/close ion channels indirectly

Inhibitory G-Proteins (Gi)

• Suppress second-messenger cascades
• Reduce over-excitation
• Important for neural stability

Complex Neural Signalling

Neurons receive simultaneous EPSPs and IPSPs across dendritic trees.
Outcome = net summation at axon hillock.

Autoreceptors on presynaptic terminals regulate neurotransmitter release by monitoring levels in the synapse.

Drug Effects on Receptors

• Agonists: mimic NT and activate receptors.
• Antagonists: block receptors and prevent activation.
• Drugs can act at any stage: synthesis, storage, release, receptor binding, reuptake, or breakdown.