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:
Presynaptic action potential -> Neurotransmitter release.
Activation of postsynaptic receptors.
Ion movement leads to current flow across the membrane.
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.