Molecular Neuroscience II

Molecular Neuroscience Overview

  • Focus on molecules that regulate and control excitation and inhibition in the nervous system.

  • Electrical activity in the brain is essential for understanding practical measurements.

  • Emphasizes the importance of understanding molecular operations underlying observed phenomena in practicals.

Resting Membrane Potential

  • Sodium-Potassium ATPase: Pumps 3 sodium ions out and 2 potassium ions in, creating uneven ion distribution.

  • Resting membrane potential is largely maintained by the leaky flux of potassium ions (positive charged ions) from inside to outside, leaving a net negative charge inside the cell.

  • Concentration details in mammalian neurons:

    • Sodium: 142 mM (outside) vs. 10 mM (inside)

    • Potassium: Inverse distribution with more inside.

    • Chloride (Cl-): Higher outside than inside; influx reduces neuronal excitability.

Calcium's Role

  • Calcium ions (Ca2+) are present in much lower concentrations inside (1-2 mM) than outside (2 mM).

  • The significant diffusion gradient promotes Ca2+ influx, crucial for various cellular processes.

  • Essential to control intracellular calcium levels to prevent pathological consequences.

Neuronal Excitation and Inhibition

  • To excite a neuron: open channels that allow positive ions to influx.

  • To inhibit a neuron: can either bring in negative charges (like Cl-) or allow positive charges to exit (like K+).

  • Action potentials are driven by these ionic movements across the membrane through specific ion channels.

Intercellular Communication

Electrical Synapses

  • Gap Junctions: Allow direct electrical connections between adjacent neurons, facilitating rapid communication.

  • Important for synchronization of neuronal activity, especially in invertebrates.

Chemical Synapses

  • Characterized by a small gap (30 nm) between pre- and postsynaptic neurons.

  • Involves neurotransmitter release from presynaptic vesicles, binding to postsynaptic receptors influencing downstream electrical activity.

  • Synaptic Vesicles: Contain neurotransmitters; released through exocytosis triggered by calcium influx.

  • Communication involves complex enzymatic reactions, receptor interactions, and neurotransmitter dynamics.

Mechanism of Neurotransmission

  1. Presynaptic Action Potential: Triggers the opening of voltage-gated Na+ and K+ channels.

  2. Calcium Channels: Recognize depolarization and allow Ca2+ influx, critical for neurotransmitter release.

  3. Calcium-Sensing Proteins (e.g., Synaptic Tag): React to calcium influx, facilitating membrane fusion of vesicles containing neurotransmitters.

  4. Ion Channel Receptors: Postsynaptic receptors can be voltage-gated or ligand-gated and dictate whether the signal is excitatory or inhibitory.

    • Excitatory Response: When cations flow in and depolarize the membrane.

    • Inhibitory Response: When anions like Cl- flow in and hyperpolarize the membrane.

Feedback Mechanisms

  • Reuptake: Transporters on presynaptic cells or surrounding glia take neurotransmitters back into the cell, effectively terminating the signal.

  • Important for recycling neurotransmitters and ensuring proper neural communication.

  • Dependence on vesicle availability to ensure neurotransmitter release is efficient and regulated.

Key Concepts

  • Understand the actions of sodium (Na+), potassium (K+), and calcium (Ca2+) in bringing about excitability in neurons.

  • Familiarity with the distinction between electrical and chemical synapses enhances understanding of neural circuits and functions.

  • Integration of molecular mechanisms in neurotransmission is crucial for overall brain functionality, influencing behaviours and interactions.