Synaptic Transmission Notes

Synaptic Transmission

Lecture Objectives

  • Explain the different types of synapses (chemical, electrical).

  • Describe in detail how an electrical signal (action potential) is transmitted from one neuron to another by a chemical synapse.

  • Explain how a synaptic potential may generate an action potential in the postsynaptic neuron, and that this may be an Excitatory (EPSP) or Inhibitory Post-Synaptic Potential (IPSP).

Outline

  • Electrical vs. chemical synapses.

  • Mechanisms of chemical synaptic transmission.

  • Types of post-synaptic potentials.

Synaptic Transmission

  • A synapse is the junction between neurons or between a neuron and an effector.

  • Electrical Synapse: Gap junctions connect cells and allow the transfer of information to synchronize the activity of a group of cells.

  • Chemical Synapse: One-way transfer of information from a presynaptic neuron to a postsynaptic neuron. The lecture focuses on chemical synapses.

Neural Pathways and Synapses

  • Specific brain pathways are activated (e.g., dorsal column pathway, corticospinal pathway).

  • These pathways are composed of a series of neurons.

  • Neurons communicate via specialized sites called synapses.

  • Information transfer to and from the brain occurs through these pathways.

Communication Between Neurons

  • Communication between neurons is referred to as synaptic transmission.

  • Synaptic transmission may be either:

    • Electrical via connexons.

    • Chemical, mediated by neurotransmitters.

Electrical Synapse Details

  • Gap junctions connect the cytoplasm of two neurons.

  • Ions can flow directly through connexon channels.

  • Connexons are made of connexin proteins.

  • Electrical synapses synchronize activity of interconnected neurons.

  • Distance between membranes: 3.5 nm

  • Gap junction channel diameter: 20 nm

Chemical Synapse Details

  • Chemical synapses use neurotransmitters to transmit signals from one neuron to another.

  • Types of connections:

    • Axoaxonic (axon to axon)

    • Axodendritic (axon to dendrite)

    • Axosomatic (axon to cell body)

Mechanisms of Chemical Synaptic Transmission

  1. Transmitter Synthesis and Storage:

    • Neurotransmitter is synthesized and then stored in vesicles.

  2. Action Potential Arrival:

    • An action potential invades the presynaptic terminal.

  3. Depolarization and Calcium Influx:

    • Depolarization of the presynaptic terminal causes opening of voltage-gated Ca^{2+} channels.

  4. Calcium's Role:

    • Influx of Ca^{2+} through channels.

    • Ca^{2+} causes vesicles to fuse with the presynaptic membrane.

  5. Neurotransmitter Release:

    • Transmitter is released into the synaptic cleft via exocytosis.

  6. Receptor Binding:

    • Transmitter binds to receptor molecules in the postsynaptic membrane.

  7. Postsynaptic Current:

    • Opening or closing of postsynaptic channels.

    • Postsynaptic current flow.

  8. Postsynaptic Potential:

    • Postsynaptic current causes excitatory or inhibitory postsynaptic potential that changes the excitability of the postsynaptic cell.

  9. Neurotransmitter Removal:

    • Removal of neurotransmitter by glial uptake or enzymatic degradation.

Events at the Chemical Synapse: Synaptic Transmission

  1. AP Arrives: Action potential arrives at the synaptic bouton.

  2. Depolarization: Depolarizes synaptic bouton.

  3. Calcium Channels Open: Depolarization opens voltage-gated Ca^{2+} channels. The intracellular/extracellular Ca^{2+} concentration gradient means Ca^{2+} moves into the terminal.

  4. Vesicle Fusion: Ca^{2+} influx triggers synaptic vesicle (SV) fusion. Ca^{2+} sensing proteins are activated on the SV membrane and presynaptic neuron membrane, resulting in fusion.

  5. Neurotransmitter Release: Neurotransmitter is released from synaptic vesicles.

  6. Receptor Activation: Activates receptors on the postsynaptic cell.

  7. Neurotransmitter Clearance: Neurotransmitter diffuses or is cleared from the synaptic cleft.

Key Components at the Synapse

  • Synaptic vesicles contain neurotransmitter.

  • Synaptic vesicles are localized to the active zone.

  • Voltage-gated Ca^{2+} channels are present in the presynaptic terminal.

  • There is a space between the presynaptic terminal and postsynaptic cell called the synaptic cleft.

  • Receptors are localized to the postsynaptic density of the postsynaptic neuron.

Tetrodotoxin (TTX)

  • Puffer fish contain tetrodotoxin (TTX).

  • TTX blocks sodium channels, so no action potential is generated.

Synaptic Inputs onto Dendrites

  • Dendrites contain microtubule-associated protein 2 (MAP2).

  • Synapses contain synaptic vesicle protein called synaptotagmin.

  • Communication is unidirectional.

  • There can be 1000’s of synapses, both excitatory and inhibitory, on a single neuron.

Neurotransmitters Regulate Ion Channels

  1. Directly (Ligand-Gated Ion Channel Receptors):

    • The receptor is part of the ion channel complex.

    • Neurotransmitter binding changes the permeability of the ion channel.

    • Allows fast postsynaptic potentials (10-100 ms duration).

  2. Indirectly (G Protein-Coupled Ion Channel Receptors):

    • The receptor complex is separate from the ion channel.

    • Allows slow postsynaptic potentials (100ms - 2s).

    • Plays a major role in overall modulation.

One Neurotransmitter, Different Effects

  • One neurotransmitter can act on different receptors/channels.

  • The receptor type determines the response of the cell.

  • Example: Acetylcholine (ACh)

    • Nicotinic receptors: e.g., skeletal muscle cells

      • Directly ligand-gated channel.

      • Opened by ACh binding.

      • Receptor permeable to Na^{+} (influx) and K^{+} (efflux).

      • Main effect is increased Na^{+} influx.

      • Fast Excitatory Post Synaptic Potential (EPSP) results.

    • Muscarinic receptors: e.g., smooth muscle cells

      • Indirectly gated channel linked to a K^{+} leak channel that is open to K^{+} at rest.

      • Closed by ACh binding.

      • G protein closes K^{+} channel and decreases permeability to K^{+}.

      • Main effect is decreased K^{+} efflux.

      • Slow EPSP results.

Receptor (Synaptic) Potentials

  • Receptor Potentials are triggered by synaptic transmission

  • Excitatory postsynaptic potentials (EPSP): A depolarizing postsynaptic potential.

  • Inhibitory postsynaptic potentials (IPSP): A hyperpolarizing postsynaptic potential.

  • A postsynaptic neuron can receive many signals at once.

Additional Resources

  • Lisman JE, Raghavachari S, Tsien RW. The sequence of events that underlie quantal transmission at central glutamatergic synapses. Nature Review Neuroscience (2007), 8: 451-465.

  • Ryan TJ & Grant SGN. The origin and evolution of synapses. Nature Review Neuroscience (2009), 10: 701-712.