Neurosci 302: Membrane Biophysics & Synaptic Transmission

Cells of the Nervous System

• The nervous system consists of two primary cell types: neurons and glia (supporting cells). Neurons are specialized cells responsible for transmitting information throughout the body, while glial cells provide critical support functions to maintain neuronal health and efficiency in communication.

• The major types of glial cells include:

• Astrocytes: These star-shaped cells play a vital role in the maintenance and regulation of the blood-brain barrier, provide nutrient support to neurons, and help maintain extracellular ion balance.

• Oligodendrocytes: Responsible for the formation of myelin sheaths in the central nervous system (CNS), which insulate neuronal axons and significantly increase the speed of electrical signal conduction.

• Microglia: These immune cells of the central nervous system act as the brain's first line of defense, continuously monitoring the environment for signs of infection and injury, and clearing debris through phagocytosis.

Today's Goals

1. Membrane Potential: Understand the concept of membrane potential and its role in neuronal signaling.

2. System Components: Identify different components of the nervous system and their functions.

3. Definitions: Familiarize with key terminology related to neuronal function.

4. Techniques: Learn about various techniques used to measure membrane potentials and ionic currents within axons.

1. Membrane Potential

• Structure of the Cell Membrane:

• The cell membrane is primarily composed of a phospholipid bilayer that selectively permits the passage of certain ions and molecules.

• Key components include:

  • Channel Proteins: Integral membrane proteins that create a pathway for specific ions to pass through; they can be voltage-gated or ligand-gated.

  • Receptor Proteins: Molecules that bind specific neurotransmitters or hormones, potentially triggering a cellular response or channel opening.

  • Ion Pumps: Active transport proteins that utilize ATP to move ions against their concentration gradient, essential for maintaining the ion distribution necessary for action potential generation (e.g., the Na+/K+ pump which expels three Na+ ions in exchange for two K+ ions).

• Ions:

• Charged particles that play a crucial role in establishing and altering the membrane potential, generating current within the neuron.

• The most common ions involved in neuronal signaling include:

  • Na+ (Sodium)

  • K+ (Potassium)

  • Cl- (Chloride)

  • Proteins (A-): Negatively charged proteins that contribute to the overall charge balance within the cell.

• Membrane Potential Definition:

• This refers to the voltage difference across the membrane, crucial for the propagation of electrical signals. At rest, the typical membrane potential is around -70 mV, with the inside of the cell being more negatively charged compared to the outside.

2. Factors Determining Membrane Potential

• Ion Concentration Differences:

• Ion concentration gradients, established by active transport mechanisms such as the Na+/K+ pump, create unequal distributions of ions on either side of the membrane, which drive the development of membrane potential.

• Additionally, the permeability of the membrane influences membrane potential; for instance, K+ ions are more permeable than Na+, leading to a more negative resting potential due to K+ efflux.

• Active Transporters:

• These proteins are responsible for perpetuating the ionic gradients necessary for action potentials and spontaneous neuronal activity.

3. Measuring Voltage and Current

• Controlled Environment Techniques:

• Recording sessions often require a Faraday cage to mitigate electromagnetic interference.

• Electrodes:

• Microelectrodes are utilized to measure electrical activity with high spatial resolution, thereby enabling detailed observations of neuron behavior.

• Electrophysiological Techniques:

• Techniques can be categorized as

  • In vivo: Involves recording electrical activity from live animals or tissues.

  • Ex vivo: Used in dissected or cultured tissue to understand specific physiological processes.

  • Intracellular & Extracellular Recordings: These methods provide insights into action potentials and synaptic activities by measuring voltage changes inside or outside of cells.

Patch Clamp Techniques

• Types of Patch Clamps:

• Cell Attached Recording: Measures currents from individual ion channels while maintaining the physical connection to the cell.

• Whole Cell Recording: This technique disrupts the cell membrane to allow for chemical interventions and measurements of total current/voltage across the cell.

• Inside-out and Outside-out Recording: Techniques that expose the internal or external aspects of ion channels, allowing for detailed study of channel regulation and pharmacology.

Action Potential Overview

• Phases of Action Potential:

• Depolarization: Initiated by the influx of Na+ ions through voltage-gated sodium channels, leading to a rapid increase in membrane potential.

• Repolarization: Following the peak, K+ channels open, leading to K+ efflux, restoring the negative internal environment.

• Refractory Periods:

  • Absolute Refractory Period: A phase during which no new action potential can fire due to inactivation of Na+ channels.

  • Relative Refractory Period: A phase where a stronger than normal stimulus is required to initiate another action potential as some Na+ channels recover from inactivation.

Synaptic Transmission

• Chemical Synapses:

• Predominant in the nervous system, they involve neurotransmitters being released into the synaptic cleft and binding to receptors on postsynaptic neuron's membrane, triggering a response.

• Electrical Synapses:

• These are less common and allow direct electrical communication via gap junctions, facilitating rapid signal transmission and synchronization among neurons.

• Neurotransmitter Release Mechanism:

• The arrival of an action potential at the presynaptic terminal opens voltage-gated calcium channels. The ensuing calcium influx triggers the fusion of synaptic vesicles with the presynaptic membrane, releasing neurotransmitters into the synaptic cleft through exocytosis.

Postsynaptic Density

• This structure contains a complex of proteins, receptors, and signaling molecules that is crucial for organizing synaptic signaling, thereby ensuring efficient transmission and processing of signals at synapses. It includes scaffolding proteins like PSD-95, which are fundamental to forming receptor complexes and signaling pathways.

Integration at the Axon Hillock

• Neurons integrate local potentials (excitatory postsynaptic potentials - EPSPs, and inhibitory postsynaptic potentials - IPSPs) at the axon hillock.

• Types of Summation:

• Spatial Summation: Occurs when multiple synaptic inputs from various locations simultaneously influence the postsynaptic neuron.

• Temporal Summation: Involves rapid succession inputs from a single synapse affecting the postsynaptic neuron in close temporal proximity.

Conclusion

• A comprehensive understanding of the mechanisms governing membrane potential, action potentials, and synaptic transmission is fundamental to grasping how neurons communicate and process information within the broader context of the nervous system. The integrative processes occurring at the axon hillock determine the firing patterns of neurons, which are essential for the functioning of neural circuits and overall nervous system operation.