12.5 Communication Between Neurons

Neurotransmitter Release and Reception

Communication between neurons happens at junctions called synapses. The process converts an electrical signal (the action potential) into a chemical signal (neurotransmitter release), then back into an electrical signal in the next neuron. Every step in this chain has to work correctly for the nervous system to function.

How neurotransmitter release works

Here's the sequence of events at a chemical synapse:

1. An action potential arrives at the axon terminal and depolarizes the presynaptic membrane.
2. Depolarization opens voltage-gated calcium channels in the terminal.
3. Calcium ions ($Ca^{2+}$) rush into the axon terminal down their concentration gradient.
4. The calcium influx causes synaptic vesicles (small membrane-bound sacs filled with neurotransmitter) to fuse with the presynaptic membrane.
5. Through exocytosis, neurotransmitters like acetylcholine or glutamate spill into the synaptic cleft, the narrow gap between the two neurons.

The calcium step is worth paying attention to. Calcium is the trigger for vesicle fusion. Without $Ca^{2+}$ entry, neurotransmitter release doesn't happen, even if the action potential arrives normally.

Receptor binding on the postsynaptic membrane

Once released, neurotransmitters diffuse across the synaptic cleft and bind to receptors on the postsynaptic neuron. There are two main receptor types:

• Ionotropic (ligand-gated) receptors are ion channels that open directly when a neurotransmitter binds. This allows ions like $Na^+$, $K^+$, or $Cl^-$ to flow through immediately. The response is fast.
• Metabotropic receptors don't open ion channels directly. Instead, neurotransmitter binding activates G proteins inside the cell, which trigger second messenger systems (like cAMP). These can modulate ion channels indirectly or alter gene expression. The response is slower but longer-lasting.

Clearing neurotransmitters from the synapse

The signal has to be turned off, or the postsynaptic neuron would be stimulated continuously. Three mechanisms handle this:

• Reuptake: Transporter proteins on the presynaptic neuron pump neurotransmitters back into the terminal for recycling.
• Enzymatic degradation: Enzymes in the synaptic cleft break down neurotransmitters. For example, acetylcholinesterase breaks down acetylcholine.
• Diffusion: Neurotransmitters simply drift away from the synapse and are no longer close enough to bind receptors.

Excitatory vs Inhibitory Postsynaptic Potentials

Not all synaptic signals push the postsynaptic neuron toward firing. Some make it more likely to fire, and others make it less likely. The difference comes down to which ions flow through the channels that open.

Excitatory postsynaptic potentials (EPSPs)

EPSPs depolarize the postsynaptic membrane, making the membrane potential more positive (closer to threshold).

• Neurotransmitters like glutamate open ligand-gated cation channels.
• $Na^+$ flows into the cell (this is the dominant effect), while $K^+$ flows out.
• The net result is depolarization because the sodium influx outweighs the potassium efflux.
• If enough depolarization occurs to reach threshold, the postsynaptic neuron fires an action potential.

Inhibitory postsynaptic potentials (IPSPs)

IPSPs hyperpolarize the postsynaptic membrane, making the membrane potential more negative (farther from threshold).

• Neurotransmitters like GABA and glycine open ligand-gated anion channels.
• $Cl^-$ flows into the cell, driving the membrane potential in the negative direction.
• This moves the membrane potential away from threshold, making it harder for the neuron to fire.

Spatial and temporal summation

A single EPSP is usually too small on its own to bring a neuron to threshold. The postsynaptic neuron has to combine inputs through summation.

Spatial summation combines signals from multiple synapses at the same time.

• Several presynaptic neurons fire simultaneously (or nearly so), each producing an EPSP at a different location on the postsynaptic neuron.
• These EPSPs add together. If their combined depolarization reaches threshold, the neuron fires.
• IPSPs from other synapses can cancel out some of those EPSPs, preventing the neuron from reaching threshold.

Temporal summation combines signals from one synapse firing repeatedly in quick succession.

• A single presynaptic neuron fires multiple times rapidly.
• Each EPSP builds on the previous one, but only if the next EPSP arrives before the first one fades back to resting potential.
• This stacking effect can push the membrane potential to threshold.

From summation to action potential

1. If the combined EPSPs (minus any IPSPs) bring the membrane at the axon hillock to threshold, an action potential is generated.
2. That action potential propagates down the axon to the next synapse, where the whole cycle of neurotransmitter release and reception starts again.
3. This integration process is how the nervous system weighs thousands of inputs on a single neuron and produces a coordinated output.

Neuronal Structure and Function

Basic structure of a neuron

• Cell body (soma): Contains the nucleus and most organelles. This is the metabolic center of the neuron.
• Dendrites: Branched extensions that receive incoming signals from other neurons. More branching means more synaptic connections.
• Axon: A single long projection that carries action potentials away from the cell body toward the next neuron or target cell.
  • Myelin sheath: A fatty insulating layer wrapped around some axons by glial cells. Myelin speeds up signal transmission by allowing the action potential to "jump" between gaps in the sheath (called nodes of Ranvier) through saltatory conduction.
• Axon terminal (synaptic bouton): The endpoint of the axon where synaptic vesicles are stored and neurotransmitters are released.

Signal transmission in neurons

• Graded potentials: Small, localized changes in membrane potential. Their strength varies with the intensity of the stimulus, and they decay over distance. EPSPs and IPSPs are both graded potentials.
• Action potentials: All-or-nothing electrical signals that propagate along the axon without losing strength. Once threshold is reached, the action potential fires at full amplitude every time.
• Refractory period: A brief window after an action potential during which the neuron cannot fire again (absolute refractory period) or requires a stronger-than-normal stimulus to fire (relative refractory period). This ensures the action potential travels in one direction down the axon.