L3: Neurotransmitters and changes in membrane potential

Small Molecule, Rapidly Acting Transmitters

Transmitter class that causes fast, acute responses in neurons; synthesized in the presynaptic terminal and stored in vesicles.

Neuromodulators

A subset of transmitters that typically act via metabotropic receptors and produce slower, metabolic effects.

Excitatory or Inhibitory Effect

The effect of a neurotransmitter depends on the receptor it binds to; it can either excite or inhibit the postsynaptic neuron.

Class I Neurotransmitter

Acetylcholine (ACh) – primary neurotransmitter at the neuromuscular junction.

Class II Neurotransmitters (Amines)

Includes norepinephrine, epinephrine, dopamine, serotonin, melatonin, histamine; involved in mood, reward, arousal, and autonomic functions.

Dopamine

Produced in the substantia nigra; involved in movement and reward; affected in Parkinson's disease and increased by cocaine.

Serotonin

Regulates mood; targeted by SSRIs.

Melatonin

Regulates sleep-wake cycle.

Histamine

Involved in wakefulness and immune responses.

Class III Neurotransmitters (Amino Acids)

Includes glutamate (excitatory), GABA (inhibitory), glycine (inhibitory in spinal cord), aspartate (excitatory).

GABA

Primary inhibitory neurotransmitter in the CNS; GABA-T and GABA-E types linked to infections and spasms.

Class IV Transmitters (Neuromodulators)

Includes ATP, arachidonic acid, nitric oxide, carbon monoxide – modulate neuronal activity.

Nitric Oxide (NO)

Gaseous neuromodulator; synthesized on demand, diffuses across membranes, modifies intracellular processes.

Synthesis and Recycling of ACh

ACh is synthesized from choline and acetyl-CoA, broken down by acetylcholinesterase, and choline is recycled.

Neurotransmitter Clearance Mechanisms

Includes diffusion, reuptake by transporters, and enzymatic degradation.

Types of Synaptic Transmitters

Two main types: small-molecule rapidly acting transmitters and neuropeptides.

Neuropeptides

Larger, more potent, synthesized in neuronal cell bodies, transported via axonal streaming, long-lasting effects.

Neuropeptide Examples

Include hypothalamic-releasing hormones, pituitary peptides, gut-brain peptides, and hormones from other tissues.

Synaptic Transmission Timing

Small-molecule transmitters act within milliseconds; neuropeptides act over seconds to years.

Vesicle Recycling

Vesicle membranes fuse with presynaptic membrane, then recycle in seconds to minutes.

Ionotropic Receptors

Ligand-gated ion channels that mediate fast synaptic responses.

Metabotropic Receptors

G-protein-coupled receptors that trigger slower, prolonged effects.

Cation Channels

Allow Na+, Ca2+, K+; lead to depolarization and excitation.

Anion Channels

Allow Cl-; lead to hyperpolarization and inhibition.

EPSP

Excitatory postsynaptic potential; depolarizes the membrane.

IPSP

Inhibitory postsynaptic potential; hyperpolarizes the membrane.

Subthreshold Stimulus

Stimulus that causes depolarization but does not reach threshold.

Suprathreshold Stimulus

Stimulus strong enough to reach threshold and trigger an AP.

Resting Membrane Potential (RMP)

Baseline electrical potential (~ -70 mV) of a neuron.

Depolarization

Membrane becomes less negative; leads to excitation.

Hyperpolarization

Membrane becomes more negative; leads to inhibition.

Graded Potential

Localized potential changes; variable amplitude; decremental; arise in dendrites or soma.

Action Potential (AP)

All-or-none signal; arises at axon hillock; propagates along the axon; same amplitude.

Voltage-Gated Channels

Open in response to membrane potential changes; key in AP generation.

Ligand-Gated Channels

Open in response to neurotransmitter binding; common in graded potentials.

Summation (GP only)

Graded potentials can summate temporally or spatially to reach threshold.

Temporal Summation

Successive inputs from one synapse; can build up to trigger an AP.

Spatial Summation

Simultaneous inputs from multiple synapses; combined effect can reach threshold.

Propagation

Only action potentials propagate; graded potentials do not.

Refractory Period (AP only)

Time during which a neuron cannot fire again; ensures unidirectional propagation.

EPSP Timing

Na+ influx for 1–2 ms; depolarization lasts ~15 ms before RMP is restored.

IPSP Timing

Cl- influx or K+ efflux for 1–2 ms; hyperpolarization lasts ~15 ms before RMP returns.

Prolonged Synaptic Effects

Caused by neuropeptides; modulate genes, receptor numbers, and ion channels.

Neurotransmitter Reuptake

Recycling mechanism where transporters return NTs or their breakdown products to the presynaptic neuron.

Choline Acetyltransferase (ChAT)

Enzyme that synthesizes acetylcholine from choline and acetyl-CoA.

Substantia Nigra

Midbrain region that produces dopamine; degeneration leads to Parkinson's disease.

Cocaine

Blocks dopamine reuptake, increasing dopamine in the synaptic cleft.

SSRIs

Selective serotonin reuptake inhibitors; increase serotonin levels by preventing its reabsorption.

NO Signaling Mechanism

NO diffuses into target cells and activates guanylate cyclase, increasing cGMP.

Neuromodulator Function

Alters gene expression, enzyme activity, or receptor sensitivity to modulate long-term neuronal activity.