Lecture Notes on Trafficking Neurotransmitters

Trafficking Neurotransmitters

Course: NEUR3600: Lecture 14
Date: Winter 2026, 02/11/2026

Overview of Trafficking Cycle

  • Definition: Trafficking cycle refers to the processes by which neurotransmitters (NT) are synthesized, stored, released, and recycled in the synaptic terminal.

  • Key components involved:

    • Glial cells, synaptic vesicles, presynaptic terminals, and postsynaptic receptors.

    • Involvement of ions, particularly calcium ions ($Ca^{2+}$).

Steps in the Trafficking Cycle

  1. Synthesis and Storage of Neurotransmitters

    • Neurotransmitter (NT) is synthesized and stored in vesicles.

    • Glial cell involvement in maintaining synaptic environment.

  2. Action Potential Invades Presynaptic Terminal

    • An action potential arrives at the presynaptic terminal, leading to:

      • Opening of voltage-gated $Ca^{2+}$ channels.

      • Influx of $Ca^{2+}$ into the presynaptic terminal.

  3. Vesicle Fusion

    • $Ca^{2+}$ ions trigger vesicles to fuse with the presynaptic membrane.

    • Result: Neurotransmitter is released into the synaptic cleft via exocytosis.

  4. Binding to Postsynaptic Receptors

    • Released neurotransmitters bind to receptor molecules on the postsynaptic membrane.

    • This binding results in the opening or closing of postsynaptic channels.

    • A postsynaptic current flows, creating either an excitatory or inhibitory postsynaptic potential (EPSP or IPSP) that alters the excitability of the postsynaptic cell.

  5. Removal of Neurotransmitter

    • Neurotransmitter is removed from the synaptic cleft through:

      • Glial uptake: Transport into glial cells.

      • Enzymatic degradation: Breakdown by specific enzymes.

Mechanisms of Exocytosis

  • Overview: The release of neurotransmitters from vesicles to the synaptic cleft is a complex process facilitated by various proteins and calcium ions.

  • Key Components:

    • Synapsin: Tethers vesicles in a reserve pool; displaced by CaMKII upon stimulation.

    • SNARE Complex Proteins:

      • Synaptobrevin: Vesicular protein that aids in the docking of the vesicle.

      • Syntaxin: Plasma membrane protein involved in vesicle fusion.

      • SNAP-25: Affects the interaction of SNARE proteins.

    • Synaptotagmin: Acts as a calcium sensor; triggers fusion of the vesicle when $Ca^{2+}$ concentration increases.

Mechanisms of Endocytosis

  • Definition: Endocytosis is the process of retrieving and recycling vesicles after neurotransmitter release.

Endocytosis Process

  1. Transmitter Loading:

    • Involves transporter proteins and a proton pump to load neurotransmitter into vesicles.

  2. Budding of Vesicles:

    • Vesicle formation begins with the action of proteins such as dynamin and clathrin which help in the pinching off of the vesicle from the membrane.

  3. Uncoating of Vesicles:

    • Clathrin and other proteins disassemble the coated vesicles, allowing for reuse.

    • Auxilin and Hsc-70 play roles in this uncoating process.

  4. Recycling and Restocking of Vesicles:

    • Synapsins: Help in the mobilization and recycling of vesicles.

    • Fast local recycling allows for efficient replenishment after neurotransmitter release.

Visual Aids and Figures

  • Important to understand the dynamics involved in neurotransmitter release, including the electron microscopy images depicting fusion events and vesicle dynamics.

Conclusion and Upcoming Topics

  • Reading Assignment for Next Class: Chapter 5: "Synaptic Transmission" (5.5-5.7)

    • Discussion on proteins involved in vesicle fusion and the roles of clathrin and dynamin in vesicle budding and pruning.

  • Prepare to elaborate on two key proteins for the next quiz: clathrin and dynamin.