Synaptic Transmission: Types, Mechanisms, and Integration

Types of Synapses

Electrical Synapses

Electrical synapses allow direct, rapid transmission of signals between neurons via specialized connections called gap junctions.

• Gap junctions: Channels that permit direct ionic current transfer between adjacent neurons.

• Cytoplasmic continuity: The cytoplasm of connected neurons is continuous, allowing ions and small molecules to pass freely.

• Bidirectionality: Electrical synapses typically transmit signals in both directions.

• Occurrence: Rare in adult mammalian brains; more common during development and in invertebrates.

Chemical Synapses

Chemical synapses use neurotransmitters to transmit signals across a synaptic cleft, allowing for more complex and regulated communication.

• Action potential (AP): Depolarization at the presynaptic terminal opens voltage-gated Ca2+ channels.

• Calcium influx: Entry of Ca2+ triggers exocytosis of synaptic vesicles containing neurotransmitter (NT).

• Neurotransmitter diffusion: NT diffuses across the synaptic cleft (~20–40 nm) and binds to postsynaptic receptors, eliciting a response.

Timeline of Events (Chemical Synapse)

The sequence of events at a chemical synapse ensures precise and rapid communication between neurons.

• AP arrives at the presynaptic terminal.

• ~0.3 ms: Ca2+ channels open.

• ~0.5 ms: Ca2+ triggers vesicle fusion.

• ~0.4 ms: NT diffuses and binds to postsynaptic receptors.

• Postsynaptic response is nearly immediate (latency ~1–2 ms).

Synaptic Vesicle Lifecycle

Synaptic vesicles undergo a cycle of loading, docking, fusion, and recycling to maintain neurotransmission.

• NT synthesis: Neurotransmitters are synthesized and loaded into vesicles by transporters.

• Reserve pool: Vesicles stored in the cytoplasm.

• Docked/primed vesicles: Vesicles at the active zone, ready for release.

• Exocytosis: Triggered by Ca2+, sensed by synaptotagmin (a Ca2+ sensor).

• Reuptake: NT is taken up by presynaptic terminals or glial cells.

• Enzymatic breakdown: NT is degraded by enzymes (e.g., acetylcholine by acetylcholinesterase).

• Diffusion: NT diffuses away from the synaptic cleft.

• Pharmacological examples:

  • SSRIs: Inhibit serotonin (5-HT) reuptake, prolonging signaling.

  • Cocaine: Blocks dopamine reuptake, enhancing dopamine action.

Neurotransmitter Receptors

Neurotransmitter receptors mediate the effects of NTs on postsynaptic cells and are classified by structure and function.

• Neuron classification: Based on the NT released (e.g., cholinergic, glutamatergic, GABAergic).

Ionotropic Receptors

• Ligand-gated ion channels: Open in response to NT binding.

• Fast responses: Typically <100 ms.

• Direct ion flux: Common ions include Na+, K+, Cl-, Ca2+.

Metabotropic Receptors

• G-protein coupled: Activate intracellular signaling cascades.

• Slower responses: 100 ms to minutes.

• Second messengers: Amplify and diversify cellular responses.

Excitatory vs Inhibitory Transmission

Neurotransmitters can have excitatory or inhibitory effects on postsynaptic neurons, depending on the receptor and ion flow.

• Glutamate: Major excitatory NT in the CNS.

  • Ionotropic receptors: AMPA, Kainate, NMDA.

  • Metabotropic receptors: mGluRs (Groups I–III).

• GABA: Major inhibitory NT.

  • GABAA receptors: Ionotropic, permeable to Cl-.

• Acetylcholine: Excitatory at the neuromuscular junction.

• Monoamines: Dopamine (DA), norepinephrine (NE), serotonin (5-HT); act as neuromodulators affecting brain states.

• Neuropeptides: Diverse modulatory roles.

NMDA Receptors

NMDA receptors are a subtype of glutamate receptor with unique properties important for synaptic plasticity.

• Permeable to Na+, K+, and Ca2+.

• Reversal potential ($E_{rev}$) ≈ 0 mV (weighted average of $E_{Na}$ and $E_{K}$).

• Voltage-dependent Mg2+ block:

  • At hyperpolarized potentials, Mg2+ blocks the channel.

  • Depolarization relieves the block.

• Require both glutamate binding and depolarization (coincidence detection).

• Critical for synaptic plasticity (e.g., learning and memory).

GABAA Receptors

GABAA receptors mediate fast inhibitory transmission in the CNS.

• Permeable to Cl-.

• Chloride reversal potential ($E_{Cl}$) ≈ -70 mV.

• At rest ($V_{m}$ ≈ -70 mV): little driving force for Cl- movement.

• Shunting inhibition: Increases membrane conductance, reducing the effect of excitatory inputs without significant hyperpolarization.

• Provides strong inhibitory control over neuronal activity.

Synaptic Integration

Neurons integrate multiple synaptic inputs to determine whether to fire an action potential.

• Temporal summation: Multiple inputs at the same synapse in close succession.

• Spatial summation: Inputs from different synapses on dendrites summing together.