Synaptic Tranmission

Dr. DeBello, Fall 2024, Lectures 9-10

Synapse

• Connections between neurons and target cells, usually other neurons, that allows for communication, electrical or chemical

Electrical Synapses

• Permit direct ‘electrical coupling’ between two cells

• Protein tunnels build from connexin proteins allow for passive current flow from one cytosol to the next

  • These tunnels are much larger than ion channel pores

• Gap junction

• Cardiac cells are electrically coupled

Chemical Synapses

• Connection between neuron and another cell

• Neurotransmitter is released from the presynaptic terminal via calcium mediated exocytosis (aka excitation-secretion coupling)

• The mature brain relies mostly on chemical synapses

What are the steps that cause a chemical synapse to fire?

1. An action potential is propagated in presynaptic neuron

2. This opens voltage gated Ca²+ channels, allowing it to enter the synaptic knob

3. Neurotransmitters are released by exocytosis which was triggered by Ca²+ entering the synaptic knob

   1. The receptor that triggers exocytosis is low affinity- requires high concentration of Ca²+ ions to be activated

4. Neurotransmitters bind to ligand gated postsynaptic receptors

5. Binding opens specific ion channels in the subsynaptic membrane, creating a postsynaptic potential (PSP)

• This is a graded potential

Excitatory Postsynaptic Potential (EPSP)

• Depolarizing event that brings the membrane potential closer to threshold for firing an action potential

• Ionic selectivity of the postsynaptic neuron is often Na+

• Glutamate and acetylcholine are common excitatory neurotransmitters

Inhibitory Postsynaptic Potential (IPSP)

• Hyperpolarizing event that brings the membrane potential away from threshold for firing an action potential

• Ionic selectivity of postsynaptic receptor often Cl- vs K+

• GABA and glycine are common inhibitory neurotransmitters

Excitatory vs Inhibitory Neurotransmitters

• Chemical messengers are not inherently excitatory or inhibitory, the effect depends on the receptor identity

Ionotropic Receptor

• Receptor is the ion channel

• Fast synapses

• Ligand-gated channels

Metabotropic Receptor

• Receptor activates G-protein cascade which acts on a separate ion channel

• Slower and longer lasting

Reversal Potential

• Membrane potential when there is no net flow of ions into or out of the cell

Ionotropic Glutamate Receptor

• Permeable to both Na+ and K+

• Dominant charge is Na+ due to its larger net driving force in and around resting potential

• The result is depolarization

• The reversal potential is ~0mV which is well above threshold for firing a spike, therefore the effect is excitatory

  • EPSP

Ionotropic GABA Receptor

• Permeable to Cl-

• Reversal potential is ~-70mV which is below threshold for firing a spike, therefore the effect os inhibitory

  • IPSP

• Many metabotropic receptors activate K+ channels, the reversal potential is ~-90mV therefore the effect is inhibitory

At what values is there no net current flow?

• Equilibrium potential- ions

• Reversal potential- channels

Convergence

• Synaptic input of neurons onto one neuron

Divergence

• Synaptic output of one neuron onto many neurons

What does diffusion result in?

• Dilution

Spatiotemporal Summation

• PSPs added/ subtracted form each other when they occur close together in time and space

What do summed PSPs that reach threshold for firing do?

• Cause a spike to be fired from the axon hillock

• There is no undershoot because EPSPs are large and long lasting, the depolarization of them cancels out the hyperpolarization of delayed K+ channels deactivating