Postsynaptic Mechanisms

Postsynaptic Mechanisms Lecture Notes

Overview of Postsynaptic Mechanisms

• Main Steps in Postsynaptic Mechanisms:

  1. Depolarization of the postsynaptic membrane.

  2. Opening of $Ca^{2+}$ channels leading to increased $Ca^{2+}$ concentration.

  3. Vesicle fusion and transmitter release.

  4. Binding of the transmitter to its receptor.

  5. Opening of ion channels in response to receptor activation.

• Key Concept: These steps occur in chemical synapses and differ from electrical synapses.

Electrical vs. Chemical Synapses

• Electrical synapse: Characterized by gap junctions.

  • Structure: Plasma membrane connections between cells enable direct electrical signaling.

  • Characteristics:

  • Bidirectional signaling, allowing for rapid communication.

  • Cannot change “signs” of signals.

• Why Chemical Synapses?

  • Are modifiable:

  • Long-Term Potentiation (LTP) increases efficacy.

  • Neuromodulators (e.g., hormones) alter synaptic transmission.

  • Dynamic and adaptable to varying stimuli.

  • They can be either excitatory or inhibitory, allowing for more complex signaling.

Neuromuscular Junction and Endplate Potentials (EPP)

• Location: Neuromuscular junction (NMJ).

  • Components:

  • Muscle fiber, synaptic cleft, presynaptic terminal, postsynaptic membrane (sarcolemma).

• Endplate Potential (EPP):

  • Reflects graded potential at the muscle fiber due to neurotransmitter release (e.g., acetylcholine).

  • Influenced by calcium (
    $[Ca^{2+}]$) influx through voltage-gated channels during action potentials.

Pools of Synaptic Vesicles

• Types of Vesicle Pools:

  1. Readily Releasable Pool (RRP):

  • Size: 1-2% of all vesicles.

  • Located in the active zone, they can be released in <1 second.

  1. Recycling Pool:

  • Size: 10-20% of vesicles.

  • Recycles vesicles within a few seconds.

  1. Reserve Pool:

  • Size: 80-90% of all vesicles, involved in longer-term replenishment.

  • Takes tens of seconds or minutes for vesicle release.

• Mechanisms of Vesicle Recycling:

  • Exocytosis, clathrin-coated vesicles, kiss-and-run mechanisms, and endocytosis.

Synaptic Activity: Facilitation and Depression

• Facilitation:

  • Increase in neurotransmitter release due to residual calcium after repeated stimulation.

  • Increases probability of release with subsequent action potentials due to lingering high $[Ca^{2+}]$ levels.

• Depression:

  • Occurs when stimulation leads to a decrease in neurotransmitter release due to vesicle depletion.

  • Short-term depression can happen after several action potentials.

Factors Influencing Postsynaptic Potentials (PSPs)

• Receptor Mechanisms:

  • Voltage-gated vs. Ligand-gated ion channels:

  • Voltage-gated channels respond to membrane depolarization.

  • Ligand-gated channels respond to neurotransmitter binding.

• **Equivalent Circuit for Ion Channels: **

  • Sodium (Na) Channels:
    $I<em>{Na} = g</em>{Na}(V, t) imes (V - E<em>{Na})$ where $g</em>{Na}(V,t) = m^3h$

  • Excitatory Channels:
    $I<em>{Exc} = g</em>{Exc}([L]) (V – E_{Exc})$
    where $[L]$ is concentration of ligand.

• Inhibitory Channels:
  $I<em>{inh} = g</em>{inh}([L]) imes (V - E_{inh})$

Time Course of Synaptic Currents

• Excitatory Postsynaptic Current (EPSC):

  • Measured in nanoamperes (nA) during voltage clamp experiments.

• Inhibitory Postsynaptic Current (IPSC):

  • Shows outward current under similar conditions.

• Factors Influencing Time Course:

  • Channel kinetics determine how long a channel remains open, impacting the time course for current.

  • Receptor interaction with transmitters affects opening and closing rates.

Neurotransmitter Dynamics

• Clearance Mechanisms:

  1. Diffusion from the synaptic cleft.

  2. Re-uptake by glial or presynaptic cells.

  3. Enzymatic degradation (e.g., acetylcholine esterase).

• Diverse Neurotransmitters and Their Receptors:

  • Amino acids: Glutamate, GABA, Aspartate, Glycine.

  • Monoamines: Norepinephrine, Dopamine, Serotonin.

  • Peptides: Vasopressin, Somatostatin, Neurotensin.

  • Acetylcholine and Nitric oxide also significant.

Glutamate Receptors

• AMPA and NMDA Receptors:

  • Often co-localized and involved in synaptic transmission.

  • AMPA receptors activate quickly and decay quickly, while NMDA receptors have slower kinetics and permit calcium ion influx.

• Hebbian Plasticity:

  • Proposed mechanism for the NMDA receptors’ role as candidates for synaptic strengthening during learning.

• Concentration of Magnesium (Mg²+):

  • Mg²+ block affects NMDA receptor activity, where higher Mg²+ concentrations inhibit neurotransmission until depolarization occurs.