Neurotransmission and Synaptic Mechanisms

  • Transmitters and Receptors

    • Ligand-gated receptors are specific to certain ligands; they can allow for excitatory postsynaptic potentials (EPSP) when they depolarize the membrane.
    • These occur at synaptic zones, where the axon hillock may influence action potentials.
  • Anterograde and Retrograde Transport

    • Movement of substances in neurons occurs via microtubules and neurofilaments:
    • Anterograde transport: Movement toward the axon terminal (e.g., neurotransmitters, proteins).
    • Retrograde transport: Movement back to the soma, facilitated by different motor proteins (e.g., kinesin for anterograde, dynein for retrograde).
  • Transport Rates

    • Slow transport: 0.1 to 5 mm/day, primarily for structural elements (e.g., neurofilaments, microfilaments as axons grow).
    • Fast axonal transport: Involves membrane vesicles, signaling molecules, neurotransmitters, and is continuous.
  • Neurotransmitter Receptors

    • Types:
    • Ionotropic receptors: Receptors that function as ion channels; ligand binding directly opens the channel (e.g., acetylcholine). No second messenger required, fast response (10-50 ms).
    • Metabotropic receptors: Separate receptor and channel; binding initiates a signaling cascade involving second messengers. Slower response, can operate pre or postsynaptically.
  • Neuromuscular Junction (NMJ)

    • Structure consists of a motor neuron terminal and the muscle fiber (motor end plate); features junctional folds for increased surface area and density of receptors (e.g., nicotinic acetylcholine receptors).
    • Action potential in the motor neuron results in the release of acetylcholine into the synaptic cleft, binding to receptors on the muscle fiber, allowing sodium influx and muscle contraction.
    • The mechanism of acetylcholine creation and secretion involves vesicle fusion in response to calcium influx; two binding sites on receptor must both be occupied for full activation.
  • Recording Techniques

    • Intracellular microelectrodes can be used to measure postsynaptic potential (PSP) signals in muscle cells.
    • Voltage clamp techniques allow researchers to analyze channel function and quantify currents during receptor activation.
    • Changes in membrane conductance due to ion flow (sodium in, potassium out) are observed during neurotransmission.
  • Excitatory and Inhibitory Synapses

    • Excitatory synapses lead to depolarization, making a postsynaptic action potential more likely (e.g., sodium influx).
    • Inhibitory synapses hyperpolarize the membrane (e.g., chloride influx or potassium efflux), reducing action potential likelihood.
    • Summation of excitatory inputs is required to reach threshold for firing; concurrent inhibitory signals can mitigate this effect.
  • Summation in Neurons

    • Temporal Summation: Quick succession of postsynaptic potentials can accumulate to reach the threshold.
    • Spatial Summation: Simultaneous input from multiple synapses can combine their effects to push the membrane potential up.
  • Key Points

    • For an action potential: Many EPSPs often need to occur, frequently through temporal and spatial summation, to counteract the influence of any inhibitory postsynaptic potentials (IPSPs).
    • The complexity of synaptic interactions (e.g., with approximately a thousand connections per neuron in the human brain) further emphasizes the importance of understanding both the electrical and biochemical signaling pathways involved in neuronal communication.