Week 2 Synapses

Introduction to Synapses

Welcome to a short presentation on synapses where we'll discuss nerve to nerve and nerve to muscle communication. Grab your lecture notes and let's explore synapses.

Learning Objectives

This presentation has four main learning objectives:

  1. To understand how neurotransmitters are released at synapses.

  2. To consider the different types of signalling at synapses.

  3. To understand the events that occur at a neuromuscular junction.

  4. To examine a disorder at the neuromuscular junction.

Reading material can be found in most university-level neuroscience textbooks. Information from this presentation was largely obtained from Sherwood's Human Physiology and Kandel's Principles of Neural Science.

What is a Synapse?

A synapse is an anatomically specialized space between two neurons at which the electrical activity in one neuron influences the electrical activity in the second neuron.

Components of a Synapse

As shown in the image:

  • Presynaptic Terminal: Where neurotransmitters are released.

  • Synaptic Cleft: The space between the neurons.

  • Postsynaptic Site: Where the neurotransmitter binds to specific receptors.

Synaptic Transmission Process

Synaptic transmission involves the processes of:

  • Exocytosis: Release of a chemical neurotransmitter.

  • Amplification: The action of one synapse can open thousands of ion channels in the postsynaptic membrane.

  • Reception: Binding of the transmitter to receptors on the postsynaptic cell.

Neurotransmitter Release by Exocytosis

The process starts with a synaptic vesicle loaded with a neurotransmitter:

  1. When an action potential reaches the terminal, it results in an influx of calcium through voltage-gated calcium channels.

  2. This influx causes the synaptic vesicle to fuse with the membrane and release its contents into the synaptic cleft.

  3. If neurotransmitters do not bind with receptors, they are recycled by endocytosis.

Changes in Membrane Potential

Synaptic communication involves generating a change in membrane potential within a postsynaptic cell.

  • Excitatory Postsynaptic Potential (EPSP): An increase in membrane potential. It occurs when a specific neurotransmitter:

    • Is released from the presynaptic terminal.

    • Binds to ion channels that are specific for sodium, allowing sodium to enter the cell.

    • The influx of sodium makes the membrane potential more positive, resulting in an EPSP.

  • Inhibitory Postsynaptic Potential (IPSP): A decrease in membrane potential. It happens when:

    • A specific neurotransmitter binds to ion channels that allow chloride ions to enter, making the membrane potential more negative, resulting in an IPSP.

Summation of Postsynaptic Potentials

  • EPSP Responses:

    • A single presynaptic input induces a small EPSP in a postsynaptic cell (shown in panel A).

    • Spatial Summation: Involvement of action potentials from two or more inputs summed to generate a larger EPSP.

    • Temporal Summation: Occurs when the same presynaptic input fires action potentials quickly enough for them to summate in time.

    • Both summations make it more likely that the depolarization reaches the threshold to produce an action potential in the postsynaptic cell.

Postsynaptic and Presynaptic Inhibition

  • Standard Inhibition: Postsynaptic inhibition where one input suppresses the effect of another.

  • Presynaptic Inhibition: Occurs through an axo-axonal synapse, selectively modifying the excitatory response from other presynaptic inputs.

Examples of Input Combinations

The figure shows a postsynaptic cell C responding to combined inputs from cells A (excitatory), B (inhibitory), and D (excitatory):

  • Input A alone produces an EPSP; combined with input B, the EPSP is suppressed, leading to no change in membrane potential. Other inputs, like D, remain unaffected by input B.

Neurotransmitter Types and Synaptic Transmission Speed

Different neurons in the brain release different neurotransmitters, and the speed of synaptic transmission varies widely.

  • Most neurons fall into one of three categories:

    1. Amino Acids: (e.g., glutamate, GABA, glycine) involved in fast synaptic transmission.

    2. Amines: (e.g., acetylcholine - ACh) generate fast excitatory responses, especially at neuromuscular junctions.

    3. Peptides: Contribute to slower synaptic transmission.

  • Slow synaptic transmission can last from 100 milliseconds to minutes and involves transmitters from all three categories.

Synaptic Receptors

Receptors are proteins within the cell membrane with specialized areas for binding the transmitter, producing a response in the target cell.
The two main types of receptors are:

  1. Ionotropic Receptors: Feature a central pore allowing ions to pass through when open.

  2. Metabotropic Receptors: Act on other structures generating additional reactions within the cell.

Glutamate’s Role in Synaptic Transmission

Most neurons in the central nervous system have both NMDA and AMPA receptors that bind to glutamate, generating an excitatory response when:

  • An action potential at the presynaptic terminal causes glutamate release.

  • Sodium influx through AMPA receptors, sodium and calcium through NMDA receptors, leads to an EPSP.

NMDA Receptor Activation

  • Activation requires special conditions:

    • Glutamate binding can open the channel, but it's blocked by magnesium at resting membrane potential.

    • Membrane depolarization must occur before glutamate binds to expel magnesium, allowing sodium and calcium to pass through.

Inhibition in the Nervous System

  • GABA is the major inhibitory neurotransmitter in the CNS, while glycine accounts for most of the rest. Both act on chloride channels.

  • Excessive or insufficient inhibition can lead to severe consequences, such as loss of consciousness or seizures.

  • The GABA receptor possesses binding sites for various chemicals, which can modify the effect of GABA without directly opening the channel.

G-Protein Coupled Receptors (GPCRs)

G-Protein receptors generate slowly acting but widespread effects in the CNS through:

  1. Binding of neurotransmitter to receptor.

  2. Activation of separate G proteins.

  3. Activation of other proteins influencing the postsynaptic cell.

Effects of Proteins

  • The proteins activated by G-Proteins can influence:

    • Ion channels.

    • Enzymes producing second messengers that diffuse throughout the cell.

Neuromuscular Junction (NMJ)

  • The image shows connections between motor neurons and skeletal muscle, known as the neuromuscular junction. Each muscle fiber has only one NMJ.

  • Action Potential Process: At the NMJ, the neurotransmitter is always acetylcholine (ACh), producing an EPSP in muscle fibers.

Steps of Neuromuscular Transmission

  1. An action potential in a motor neuron reaches the axon terminal.

  2. Voltage-gated calcium channels open, allowing calcium entry.

  3. Calcium triggers release of ACh by exocytosis.

  4. ACh diffuses across the synaptic cleft and binds receptors on the motor end plate of muscle cell membrane.

  5. Cation channels open, leading to sodium influx and potassium efflux.

  6. The end plate potential occurs, with local current flow between the depolarized end plate and adjacent membrane.

  7. Local current flow opens voltage-gated sodium channels in adjacent membrane.

  8. Sodium entry reduces potential to threshold, initiating an action potential in the muscle fiber.

  9. Acetylcholine is destroyed by acetylcholinesterase, ending the response.

Myasthenia Gravis

  • Myasthenia gravis affects about one in every twenty thousand people. This autoimmune disease leads to immunity against ACh-activated ion channels.

  • Resulting symptoms include muscle weakness and paralysis, particularly in facial and limb muscles.

  • Treatment with anti-cholinesterase drugs can temporarily improve muscle function by increasing ACh availability at the NMJ, as illustrated in images showing eyelid drooping improvement after administration.

Myasthenia Gravis Mechanism

  • Transmission across NMJ fails to reliably produce action potentials in muscle fibers.

  • Comparison:

    • Normal NMJ (Panel A): Individual end plate potentials exceed threshold, triggering muscle actions.

    • Myasthenic NMJ (Panel B): Reduced end plate potentials lead to some fibers reaching threshold while others do not, causing overall decreased and inconsistent muscle force.

  • Changes in NMJ in myasthenia gravis include:

    • Reduced number of ACh receptors.

    • Simplified synaptic folds.

    • Widened synaptic space.

    • Normal appearance of the nerve terminal, indicating that issues arise in the muscle fiber end plate region.

Key Points

  • Review the key points from this presentation and consult texts if needed for clarity.