35.2 How Neurons Communicate

Neuronal Communication

Neurons communicate through a combination of electrical and chemical signals. Understanding this process means knowing how neurons maintain their resting state, fire action potentials, transmit signals across synapses, and adapt their connections over time through plasticity.

Resting membrane potential significance

The resting membrane potential (RMP) is the electrical potential difference across the neuronal membrane when the neuron is not firing. It sits at roughly $-70 \text{ mV}$, meaning the inside of the neuron is more negative than the outside.

Two main mechanisms maintain the RMP:

• $K^+$ leak channels allow potassium ions to diffuse out of the cell down their concentration gradient. Because $K^+$ is positive and it's leaving, this makes the inside of the cell more negative.
• The $Na^+/K^+$ ATPase pump actively transports 3 $Na^+$ out and 2 $K^+$ in per cycle, consuming one ATP each time. This keeps sodium concentrated outside and potassium concentrated inside.

Why does the RMP matter for communication?

• It provides a stable baseline from which the neuron can fire. Without this charged-and-ready state, there's no signal to generate.
• It allows the neuron to respond rapidly to incoming stimuli by shifting its membrane potential.
• Small, local changes called graded potentials can add together (summation) near the axon hillock. If they push the membrane potential past threshold, an action potential fires.

Stages of action potential

An action potential is a rapid, all-or-nothing electrical signal that travels down the axon. Here are the stages in order:

1. Depolarization to threshold

   • A stimulus causes some voltage-gated $Na^+$ channels to open, letting $Na^+$ rush into the cell. The membrane potential becomes less negative.
   • If the potential reaches threshold (around $-55 \text{ mV}$), the action potential is triggered. Below threshold, nothing happens.
   • The axon hillock is typically where the action potential initiates because it has the highest density of voltage-gated ion channels.

2. Rising phase

   • Once threshold is reached, a positive feedback loop kicks in: more voltage-gated $Na^+$ channels open, causing a massive influx of $Na^+$.
   • The membrane potential shoots up to about $+40 \text{ mV}$, temporarily reversing the polarity of the membrane.

3. Falling phase (repolarization)

   • Voltage-gated $Na^+$ channels inactivate (they don't just close; they enter an inactivated state that prevents reopening). At the same time, voltage-gated $K^+$ channels open.
   • $K^+$ flows out of the cell, bringing the membrane potential back down toward rest.

4. Afterhyperpolarization (undershoot)

   • The voltage-gated $K^+$ channels are slow to close, so $K^+$ keeps leaving the cell briefly. This drives the membrane potential slightly below the RMP (more negative than $-70 \text{ mV}$).
   • During this period, the neuron enters a refractory period. In the absolute refractory period, no new action potential can fire regardless of stimulus strength (because $Na^+$ channels are inactivated). In the relative refractory period, a stronger-than-normal stimulus is needed.

Propagation along the axon:

• The influx of $Na^+$ at one spot creates local currents that depolarize the adjacent membrane to threshold, triggering the next action potential in a domino-like chain.
• In myelinated neurons, the myelin sheath insulates the axon, and action potentials only occur at gaps called nodes of Ranvier. The signal effectively jumps from node to node. This is called saltatory conduction, and it's much faster than continuous conduction in unmyelinated axons.

Chemical vs electrical synapses

Synapses are the junctions where neurons pass signals to other cells. The two types work very differently.

Chemical synapses:

• The presynaptic neuron releases neurotransmitters from synaptic vesicles into the synaptic cleft (the tiny gap between neurons).
• Neurotransmitters bind to receptors on the postsynaptic cell. The effect depends on the neurotransmitter and receptor type:
  • Excitatory neurotransmitters (e.g., glutamate) depolarize the postsynaptic membrane, making firing more likely.
  • Inhibitory neurotransmitters (e.g., GABA) hyperpolarize the postsynaptic membrane, making firing less likely.
• Transmission is unidirectional (pre → post) and has a slight synaptic delay because of the time needed for vesicle fusion, neurotransmitter diffusion, and receptor binding.
• Chemical synapses allow for signal modulation and integration. A single postsynaptic neuron can receive thousands of excitatory and inhibitory inputs and sum them together. Neuromodulators like dopamine can further fine-tune the signal.

Electrical synapses:

• Gap junctions directly connect the cytoplasm of adjacent cells, letting ions flow between them.
• Transmission is bidirectional and extremely fast, with virtually no synaptic delay.
• Found where speed and synchrony matter most, such as in cardiac muscle cells (keeping the heart beating in rhythm) and certain brain regions like the inferior olive.

The neuromuscular junction is a specialized chemical synapse between a motor neuron and a skeletal muscle fiber. Acetylcholine is the neurotransmitter here, and its binding triggers muscle contraction.

Synaptic plasticity in learning

Synaptic plasticity is the ability of synapses to strengthen or weaken over time based on activity. This is the cellular basis for how the brain learns and forms memories.

Long-term potentiation (LTP):

• A persistent increase in synaptic strength that occurs after repeated high-frequency stimulation of a synapse.
• The mechanism in many brain regions (especially the hippocampus) works like this:
  1. High-frequency stimulation strongly depolarizes the postsynaptic membrane.
  2. This relieves the $Mg^{2+}$ block on NMDA receptors, allowing $Ca^{2+}$ to flow in.
  3. The $Ca^{2+}$ influx triggers signaling cascades that insert additional AMPA receptors into the postsynaptic membrane.
  4. More AMPA receptors means the synapse responds more strongly to future glutamate release.
• LTP is strongly associated with learning and long-term memory formation.

Long-term depression (LTD):

• A persistent decrease in synaptic strength, typically following low-frequency stimulation.
• Involves the removal of AMPA receptors from the postsynaptic membrane through endocytosis (the cell pulls them back inside).
• LTD helps refine neural circuits, prevents synapses from becoming saturated, and may contribute to forgetting or overwriting old information.

What changes at the synapse during plasticity:

• Receptor changes: More or fewer AMPA/NMDA receptors at the postsynaptic membrane
• Presynaptic changes: Altered probability of neurotransmitter release and changes in vesicle pool size
• Structural changes: Growth or retraction of dendritic spines and formation of entirely new synaptic contacts

Together, LTP and LTD are considered the leading cellular mechanisms for how neural networks encode, store, and retrieve information. They allow the brain to adapt its wiring in response to experience, which is the foundation of learning.