PYSC 106 Lecture 4

Synapse and Neurotransmitter Release

  • Components of a Synapse

    • Presynaptic terminal

    • Postsynaptic terminal

    • Postsynaptic structures can include:

    • Dendrites

    • Soma

    • Axon

  • Neurotransmitter Release Process

    • Change in voltage along the presynaptic membrane triggers opening of voltage-gated calcium channels.

    • Calcium rushes into the presynaptic terminal.

    • Causes vesicles containing neurotransmitters to fuse with the presynaptic membrane.

    • Vesicles release their contents into the synaptic cleft.

  • Neurotransmitter Diffusion and Receptor Interaction

    • Released neurotransmitters diffuse across the synaptic cleft and bind to receptors on the postsynaptic membrane.

    • Types of Receptors:

    • Ion Channels:

      • e.g. AMPA receptors (for glutamate).

    • G-Protein Coupled Receptors (GPCRs):

      • e.g. NMDA receptors (require binding of multiple ligands).

AMPA and NMDA Receptors

  • AMPA Receptors

    • Ion channel receptor that mediates fast synaptic transmission.

    • Upon binding of glutamate, it opens to allow positive ions to flow into the postsynaptic neuron.

  • NMDA Receptors

    • Complex receptor that requires both glutamate and glycine to bind for activation.

    • Uses a magnesium block that prevents ion flow until membrane depolarization occurs, allowing excitation of the neuron.

    • Requires two events for activation:

    1. Binding of glutamate and glycine.

    2. Depolarization to remove the magnesium block.

  • Comparison of Postsynaptic Neurons

    • Neuron A: 2 AMPA receptors and 1 NMDA receptor.

    • Neuron B: 3 AMPA receptors and 1 NMDA receptor.

    • More AMPA receptors lead to higher initial depolarization in Neuron B due to more binding sites for glutamate.

Action Potential and Synaptic Responses

  • Process of Depolarization

    • AMPA receptors open first, allowing positive ions into the cell, leading to depolarization.

    • Higher AMPA activation increases the likelihood of reaching the action potential threshold.

    • NMDA receptors can allow for an additional influx of positive ions providing a further depolarization boost after AMPA activation.

Synaptic Plasticity and Receptor Regulation

  • Concept of Plasticity

    • Neurons adjust receptor levels based on past neurotransmitter activity, facilitating learning and memory.

    • Activity-Dependent Receptor Insertion:

    • More active synapses can lead to increased AMPA and NMDA receptor insertion to adapt to increased glutamate presence.

GABA as an Inhibitory Neurotransmitter

  • GABA Receptors

    • Types of GABA Receptors:

    • GABA A: Ion channel allowing chloride ions to enter the neuron.

    • GABA B: G-Protein coupled receptor.

    • Clinical implications:

    • Many drugs (e.g., alcohol, benzodiazepines) act on GABA receptors, enhancing their inhibitory effects.

Neurotransmitter Clearance Mechanisms

  • Primary Mechanisms of Neurotransmitter Clearance:

    1. Reuptake:

      • Specialized transporters remove neurotransmitters from the synapse back into the presynaptic neuron.

      • Example: Cocaine inhibits dopamine reuptake, increasing synaptic dopamine levels.

    2. Enzymatic Breakdown:

      • Enzymes degrade leftover neurotransmitters in the synaptic cleft (e.g., degradation of acetylcholine).

    3. Diffusion:

      • Neurotransmitters can diffuse away from the synaptic cleft.

Role of Glial Cells in the Central Nervous System

  • Types of Glial Cells:

    • Astrocytes: Provide structural support, transport nutrients and regulate neurotransmitter levels.

    • Oligodendrocytes: Form myelin sheaths around CNS axons for insulation and effective signal transmission.

    • Microglia: Act as immune cells in the CNS, removing debris and dead neurons.

Blood-Brain Barrier

  • Function of the Blood-Brain Barrier (BBB):

    • A selective barrier that restricts the passage of substances from the bloodstream into the brain, preserving neuronal health.

    • Facilitated by astrocytic end-feet that surround blood vessels.

Neurotransmitter Dynamics

  • Synthesis and Recycling:

    • Astrocytes help synthesize neurotransmitters (e.g., converting glutamate to glutamine, which can be reused by neurons).

  • Turnover of Receptors:

    • Receptors undergo recycling based on activity levels to maintain optimal synaptic signaling.

Final Notes

  • Understanding these processes is crucial for exploring neuronal communication, learning and memory mechanisms, and the effects of various pharmacological agents on brain function.