BS2015 – Block 4: Synaptic Physiology Study Notes

BS2015 – Block 4: Synaptic Physiology Study Notes

Introduction

  • Instructor: Dr. Volko Straub

  • Contact: vs64@le.ac.uk

  • Tools: Top Hat for sessions (Course Code: 982675)

Neuronal Function and Synapses

  • Neuronal Function Complexity:

    • Neurons can generate intrinsic activity.

    • Neurons receive inputs via synapses from other neurons.

    • They integrate received synaptic inputs.

    • Information is encoded in activity patterns.

    • Outputs are distributed to other neurons via synapses.

  • Integration of synaptic inputs along with intrinsic properties allows for complex information processing.

Purpose of Chemical Synapses

  • Information Transfer Between Cells:

    • Can achieve excitation, inhibition, or modulation.

    • Amplification of signals occurs.

    • Integration of multiple inputs is essential.

    • Plasticity supports learning and memory.

Synaptic Potentials & Synaptic Currents

  • Mechanism Overview:

    • Action potentials (AP) precede synaptic potentials (P SP).

    • Process:

    1. Presynaptic action potential -> Neurotransmitter release.

    2. Activation of postsynaptic receptors.

    3. Ion movement leads to current flow across the membrane.

    4. Change in membrane potential occurs.

  • The relationship: Post-Synaptic Current (PSC) leads to Post-Synaptic Potential (PSP), but PSC ≠ PSP.

Recording Post-Synaptic Potentials and Currents

  • Post-Synaptic Potentials:

    • Measured as the electrical potential difference across the membrane using intracellular and extracellular electrodes connected to a membrane potential amplifier.

  • Post-Synaptic Currents requires Voltage-Clamp Technique:

    • Measure the potential across the membrane and compare to command potential ($V_{command}$).

    • If the recorded potential deviates, current is injected to maintain homeostasis.

    • The injected current equals the synaptic current but is of opposite polarity.

Differences Between PSC and PSP

  • Post-synaptic potentials have longer duration changes than post-synaptic currents due to:

    • Neurotransmitter action leading to ion channel opening.

    • Initial reduction of membrane resistance ($R_m$) results in shorter time constant and faster rise time.

    • After neurotransmitter removal, ion channels close and resistance increases, slowing discharge.

Driving Force for Ion Movement

  • The driving force is calculated as the difference between resting membrane potential ($Vm$) and equilibrium potential for specific ions ($E{ion}$).

  • Amplitude Variability:

    • Postsynaptic potentials' amplitudes vary depending on the membrane potential.

    • Reversal potential can be determined by plotting PSP amplitude against resting membrane potential.

Neurotransmitter Classification

  • Synaptic Responses:

    • Excitatory Post-Synaptic Potential (EPSP): Associated with ionotropic receptors allowing Na+ and/or Ca++ influx.

    • Inhibitory Post-Synaptic Potential (IPSP): Linked to K+ efflux or Cl- influx leading to hyperpolarization.

  • Types of Neurotransmitters:

    • Acetylcholine, amino acids (glutamate and GABA), monoamines (serotonin, histamine, catecholamines), neuropeptides, and gases like nitric oxide.

Concentration Gradients and Membrane Potential

  • Ion Concentration Influence:

    • K+ concentration causes resting membrane to be about 50 times more permeable, pushing $Vm$ closer to $EK$.

  • Transmitter Functions:

    • EPSP Mechanism: Opens Na+/Ca++ channels leading to depolarization.

    • IPSP Mechanism: Opens K+/Cl- channels leading to hyperpolarization.

Chloride Channel Dynamics

  • Chloride channel behavior can be context-dependent:

    • ECl < Vm results in hyperpolarization through net influx.

    • ECl > Vm results in depolarization through net efflux.

  • Adult neurons vs. developmental stages show varied chloride concentrations affecting synaptic outcomes.

Ionic Basis of EPSPs and IPSPs

  • Cation influx leads to depolarization (Na+/Ca++ for EPSP).

  • Cation efflux or anion influx leads to hyperpolarization (Cl-/K+ for IPSP).

  • Ion selectivity is crucial in determining synaptic effects.

Summary of Synaptic Processes

  • Synaptic strengths can be influenced by:

    • Opening of specific ion channels based on the type of neurotransmitter.

    • Factors determining the excitatory or inhibitory nature of synapses, including ligand-gated channel properties.

    • Successful synaptic integration calls for interaction among excitatory and inhibitory inputs, crucial for neural processing.

Interaction of EPSPs and IPSPs

  • Synaptic integration allows neurons to process multiple inputs, determining overall neural activity and action potential generation.

  • Factors influencing this include synaptic potential timing, location, and channel selectivity.

‘Silent’ Postsynaptic Inhibition

  • Mechanism:

    • If synaptic reversal potential matches resting potential, ion channel activation may not produce current flow or membrane potential shift.

  • Implications: Inhibitory input can have significant effects on excitatory responses, potentially leading to decreased excitability in postsynaptic neurons.

Complexity of Neural Connectivity

  • The human brain’s complexity encompasses billions of neurons and trillions of synapses.

  • Significant interconnectivity facilitates extensive integration of synaptic signals for processing.

  • Data indicates both developmental and adult neurogenesis plays roles in connectivity and plasticity.

Temporal and Spatial Integration of Inputs

  • Neurons function as both temporal and spatial integrators

    • Spatial Summation: Multiple synaptic inputs activate simultaneously, impacting membrane potential.

    • Temporal Summation: Synaptic potentials summate over time, enhancing postsynaptic activity through rapid sequential actions.

  • The decay of postsynaptic potentials depends on time and distance, governed by membrane properties such as resistance and capacitance.

Synaptic Plasticity Mechanisms

  • Short-term changes in synaptic efficiency include paired-pulse facilitation and depression based on presynaptic activity adjustments.

  • Long-term potentiation (LTP) is significant for memory formation and involves sustained changes in synaptic strength.

    • Inductive Elements: Initial high-frequency stimulation leads to prolonged enhancement of synaptic responses, lasting from hours to years depending on biological context.

Conclusion

  • Mastery of synaptic physiology is key to understanding complex neural networks and behaviors, underlying cognitive functions and responses to stimuli.

  • Homework and practice through assessments will reinforce comprehension of these principles.