How Neurons Communicate

Nerve Impulse Transmission within a Neuron: Resting Potential

The resting potential of a neuron is controlled by the difference in total charge between the inside and outside of the cell.

Learning Objectives

Explain the formation of the resting potential in neurons

Key Takeaways

Key Points

  • When the neuronal membrane is at rest, the resting potential is negative due to the accumulation of more sodium ions outside the cell than potassium ions inside the cell.
  • Potassium ions diffuse out of the cell at a much faster rate than sodium ions diffuse into the cell because neurons have many more potassium leakage channels than sodium leakage channels.
  • Sodium-potassium pumps move two potassium ions inside the cell as three sodium ions are pumped out to maintain the negatively-charged membrane inside the cell; this helps maintain the resting potential.

Key Terms

  • ion channel: a protein complex or single protein that penetrates a cell membrane and catalyzes the passage of specific ions through that membrane
  • membrane potential: the difference in electrical potential across the enclosing membrane of a cell
  • resting potential: the nearly latent membrane potential of inactive cells

Nerve Impulse Transmission within a Neuron

For the nervous system to function, neurons must be able to send and receive signals. These signals are possible because each neuron has a charged cellular membrane (a voltage difference between the inside and the outside). The charge of this membrane can change in response to neurotransmitter molecules released from other neurons and environmental stimuli. Any voltage is a difference in electric potential between two points; for example, the separation of positive and negative electric charges on opposite sides of a resistive barrier. To understand how neurons communicate, one must first understand the basis of charged membranes and the baseline or ‘resting’ membrane charge.

Neuronal Charged Membranes

The lipid bilayer membrane that surrounds a neuron is impermeable to charged molecules or ions. To enter or exit the neuron, ions must pass through special proteins called ion channels that span the membrane. Ion channels have different configurations: open, closed, and inactive. Some ion channels need to be activated in order to open and allow ions to pass into or out of the cell. These ion channels are sensitive to the environment and can change their shape accordingly. Ion channels that change their structure in response to voltage changes are called voltage-gated ion channels. Voltage-gated ion channels regulate the relative concentrations of different ions inside and outside the cell. The difference in total charge between the inside and outside of the cell is called the membrane potential.

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Ion channel configurations: Voltage-gated ion channels are closed at the resting potential and open in response to changes in membrane voltage. After activation, they become inactivated for a brief period and will no longer open in response to a signal.

Resting Membrane Potential

For quiescent cells, the relatively-static membrane potential is known as the resting membrane potential. The resting membrane potential is at equilibrium since it relies on the constant expenditure of energy for its maintenance. It is dominated by the ionic species in the system that has the greatest conductance across the membrane. For most cells, this is potassium. As potassium is also the ion with the most-negative equilibrium potential, usually the resting potential can be no more negative than the potassium equilibrium potential.

A neuron at rest is negatively charged because the inside of a cell is approximately 70 millivolts more negative than the outside (−70 mV); this number varies by neuron type and by species. This voltage is called the resting membrane potential and is caused by differences in the concentrations of ions inside and outside the cell. If the membrane were equally permeable to all ions, each type of ion would flow across the membrane and the system would reach equilibrium. Because ions cannot simply cross the membrane at will, there are different concentrations of several ions inside and outside the cell. The difference in the number of positively-charged potassium ions (K+) inside and outside the cell dominates the resting membrane potential. When the membrane is at rest, K+ ions accumulate inside the cell due to a net movement with the concentration gradient. The negative resting membrane potential is created and maintained by increasing the concentration of cations outside the cell (in the extracellular fluid) relative to inside the cell (in the cytoplasm). The negative charge within the cell is created by the cell membrane being more permeable to K+ movement than Na+ movement.

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Membrane potential: The (a) resting membrane potential is a result of different concentrations of Na+ and K+ ions inside and outside the cell. A nerve impulse causes Na+ to enter the cell, resulting in (b) depolarization. At the peak action potential, K+ channels open and the cell becomes (c) hyperpolarized.

In neurons, potassium ions (K+) are maintained at high concentrations within the cell, while sodium ions (Na+) are maintained at high concentrations outside of the cell. The cell possesses potassium and sodium leakage channels that allow the two cations to diffuse down their concentration gradient. However, the neurons have far more potassium leakage channels than sodium leakage channels. Therefore, potassium diffuses out of the cell at a much faster rate than sodium leaks in. More cations leaving the cell than entering it causes the interior of the cell to be negatively charged relative to the outside of the cell. The actions of the sodium-potassium pump help to maintain the resting potential, once it is established. Recall that sodium-potassium pumps bring two K+ ions into the cell while removing three Na+ ions per ATP consumed. As more cations are expelled from the cell than are taken in, the inside of the cell remains negatively charged relative to the extracellular fluid.

Nerve Impulse Transmission within a Neuron: Action Potential

Signals are transmitted from neuron to neuron via an action potential, when the axon membrane rapidly depolarizes and repolarizes.

Learning Objectives

Explain the formation of the action potential in neurons

Key Takeaways

Key Points

  • Action potentials are formed when a stimulus causes the cell membrane to depolarize past the threshold of excitation, causing all sodium ion channels to open.
  • When the potassium ion channels are opened and sodium ion channels are closed, the cell membrane becomes hyperpolarized as potassium ions leave the cell; the cell cannot fire during this refractory period.
  • The action potential travels down the axon as the membrane of the axon depolarizes and repolarizes.
  • Myelin insulates the axon to prevent leakage of the current as it travels down the axon.
  • Nodes of Ranvier are gaps in the myelin along the axons; they contain sodium and potassium ion channels, allowing the action potential to travel quickly down the axon by jumping from one node to the next.

Key Terms

  • action potential: a short term change in the electrical potential that travels along a cell
  • depolarization: a decrease in the difference in voltage between the inside and outside of the neuron
  • hyperpolarize: to increase the polarity of something, especially the polarity across a biological membrane
  • node of Ranvier: a small constriction in the myelin sheath of axons
  • saltatory conduction: the process of regenerating the action potential at each node of Ranvier

Action Potential

A neuron can receive input from other neurons via a chemical called a neurotransmitter. If this input is strong enough, the neuron will pass the signal to downstream neurons. Transmission of a signal within a neuron (in one direction only, from dendrite to axon terminal) is carried out by the opening and closing of voltage-gated ion channels, which cause a brief reversal of the resting membrane potential to create an action potential. As an action potential travels down the axon, the polarity changes across the membrane. Once the signal reaches the axon terminal, it stimulates other neurons.

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Formation of an action potential: The formation of an action potential can be divided into five steps. (1) A stimulus from a sensory cell or another neuron causes the target cell to depolarize toward the threshold potential. (2) If the threshold of excitation is reached, all Na+ channels open and the membrane depolarizes. (3) At the peak action potential, K+ channels open and K+ begins to leave the cell. At the same time, Na+ channels close. (4) The membrane becomes hyperpolarized as K+ ions continue to leave the cell. The hyperpolarized membrane is in a refractory period and cannot fire. (5) The K+ channels close and the Na+/K+ transporter restores the resting potential.

Depolarization and the Action Potential

When neurotransmitter molecules bind to receptors located on a neuron’s dendrites, voltage-gated ion channels open. At excitatory synapses, positive ions flood the interior of the neuron and depolarize the membrane, decreasing the difference in voltage between the inside and outside of the neuron. A stimulus from a sensory cell or another neuron depolarizes the target neuron to its threshold potential (-55 mV), and Na+ channels in the axon hillock open, starting an action potential. Once the sodium channels open, the neuron completely depolarizes to a membrane potential of about +40 mV. The action potential travels down the neuron as Na+ channels open.

Hyperpolarization and Return to Resting Potential

Action potentials are considered an “all-or nothing” event. Once the threshold potential is reached, the neuron completely depolarizes. As soon as depolarization is complete, the cell “resets” its membrane voltage back to the resting potential. The Na+ channels close, beginning the neuron’s refractory period. At the same time, voltage-gated K+ channels open, allowing K+ to leave the cell. As K+ ions leave the cell, the membrane potential once again becomes negative. The diffusion of K+ out of the cell hyperpolarizes the cell, making the membrane potential more negative than the cell’s normal resting potential. At this point, the sodium channels return to their resting state, ready to open again if the membrane potential again exceeds the threshold potential. Eventually, the extra K+ ions diffuse out of the cell through the potassium leakage channels, bringing the cell from its hyperpolarized state back to its resting membrane potential.

Myelin and Propagation of the Action Potential

For an action potential to communicate information to another neuron, it must travel along the axon and reach the axon terminals where it can initiate neurotransmitter release. The speed of conduction of an action potential along an axon is influenced by both the diameter of the axon and the axon’s resistance to current leak. Myelin acts as an insulator that prevents current from leaving the axon, increasing the speed of action potential conduction. Diseases like multiple sclerosis cause degeneration of the myelin, which slows action potential conduction because axon areas are no longer insulated so the current leaks.

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Action potential travel along a neuronal axon: The action potential is conducted down the axon as the axon membrane depolarizes, then repolarizes.

A node of Ranvier is a natural gap in the myelin sheath along the axon. These unmyelinated spaces are about one micrometer long and contain voltage gated Na+ and K+ channels. The flow of ions through these channels, particularly the Na+ channels, regenerates the action potential over and over again along the axon. Action potential “jumps” from one node to the next in saltatory conduction. If nodes of Ranvier were not present along an axon, the action potential would propagate very slowly; Na+ and K+ channels would have to continuously regenerate action potentials at every point along the axon. Nodes of Ranvier also save energy for the neuron since the channels only need to be present at the nodes and not along the entire axon.

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Nodes of Ranvier: Nodes of Ranvier are gaps in myelin coverage along axons. Nodes contain voltage-gated K+ and Na+ channels. Action potentials travel down the axon by jumping from one node to the next.

Synaptic Transmission

Synaptic transmission is a chemical event which is involved in the transmission of the impulse via release, diffusion, receptor binding of neurotransmitter molecules and unidirectional communication between neurons.

Learning Objectives

Describe the process of synaptic transmission

Key Takeaways

Key Points

  • In a chemical synapse, the pre and post synaptic membranes are separated by a synaptic cleft, a fluid filled space.
  • The chemical event is involved in the transmission of the impulse via release, diffusion, receptor binding of neurotransmitter molecules and unidirectional communication between neurons.
  • The neurotransmitter termination can occur in three ways – reuptake, enzymatic degradation in the cleft and diffusion.

Synaptic Transmission

In a chemical synapse, the pre and post synaptic membranes are separated by a synaptic cleft, a fluid filled space. The chemical event is involved in the transmission of the impulse via release, diffusion, receptor binding of neurotransmitter molecules and unidirectional communication between neurons.

Chemical Synapse

Neurotransmission at a chemical synapse begins with the arrival of an action potential at the presynaptic axon terminal. When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated Na+ channels. Na+ ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated Ca2+ channels to open. Calcium ions entering the cell initiate a signaling cascade. A calcium sensing protein binds calcium and interacts with SNARE proteins. These SNARE proteins are involved in the membrane fusion. The synaptic vesicles fuse with the presynaptic axon terminal membrane and empty their contents by exocytosis into the synaptic cleft. Calcium is quickly removed from the terminal.

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Synaptic vesicles inside a neuron: This pseudocolored image taken with a scanning electron microscope shows an axon terminal that was broken open to reveal synaptic vesicles (blue and orange) inside the neuron.

Fusion of a vesicle with the presynaptic membrane causes neurotransmitters to be released into the synaptic cleft. The neurotransmitter diffuses across the synaptic cleft, binding to receptor proteins on the postsynaptic membrane.

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Communication at a chemical synapse: Communication at chemical synapses requires release of neurotransmitters. When the presynaptic membrane is depolarized, voltage-gated Ca2+ channels open and allow Ca2+ to enter the cell. The calcium entry causes synaptic vesicles to fuse with the membrane and release neurotransmitter molecules into the synaptic cleft. The neurotransmitter diffuses across the synaptic cleft and binds to ligand-gated ion channels in the postsynaptic membrane, resulting in a localized depolarization or hyperpolarization of the postsynaptic neuron.

The binding of a specific neurotransmitter causes particular ion channels, in this case ligand-gated channels, on the postsynaptic membrane to open. The binding of a neurotransmitter to its receptor is reversible. As long as it is bound to a post synaptic receptor, a neurotransmitter continues to affect membrane potential. The effects of the neurotransmitter generally lasts few milliseconds before being terminated. The neurotransmitter termination can occur in three ways. First, reuptake by astrocytes or presynaptic terminal where the neurotransmitter is stored or destroyed by enzymes. Second, degradation by enzymes in the synaptic cleft such as acetylcholinesterase. Third, diffusion of the neurotransmitter as it moves away from the synapse.

Signal Summation

Signal summation occurs when impulses add together to reach the threshold of excitation to fire a neuron.

Learning Objectives

Describe signal summation

Key Takeaways

Key Points

  • Simultaneous impulses may add together from different places on the neuron to reach the threshold of excitation during spatial summation.
  • When individual impulses cannot reach the threshold of excitation on their own, they can can add up at the same location on the neuron over a short time; this is known as temporal summation.
  • The action potential of a neuron is fired only when the net change of excitatory and inhibitory impulses is non-zero.

Key Terms

  • temporal summation: the effect when impulses received at the same place on the neuron add up
  • spatial summation: the effect when simultaneous impulses received at different places on the neuron add up to fire the neuron
  • axon hillock: the specialized part of the soma of a neuron that is connected to the axon and where impulses are added together

Signal Summation

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Signal summation at the axon hillock: A single neuron can receive both excitatory and inhibitory inputs from multiple neurons. All these inputs are added together at the axon hillock. If the EPSPs are strong enough to overcome the IPSPs and reach the threshold of excitation, the neuron will fire.

Each neuron connects with numerous other neurons, often receiving multiple impulses from them. Sometimes, a single excitatory postsynaptic potential (EPSP) is strong enough to induce an action potential in the postsynaptic neuron, but often multiple presynaptic inputs must create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential. Summation, either spatial or temporal, is the addition of these impulses at the axon hillock. Together, synaptic summation and the threshold for excitation act as a filter so that random “noise” in the system is not transmitted as important information.

One neuron often has input from many presynaptic neurons, whether excitatory or inhibitory; therefore, inhibitory postsynaptic potentials (IPSPs) can cancel out EPSPs and vice versa. The net change in postsynaptic membrane voltage determines whether the postsynaptic cell has reached its threshold of excitation needed to fire an action potential. If the neuron only receives excitatory impulses, it will also generate an action potential. However, if the neuron receives as many inhibitory as excitatory impulses, the inhibition cancels out the excitation and the nerve impulse will stop there. Spatial summation means that the effects of impulses received at different places on the neuron add up so that the neuron may fire when such impulses are received simultaneously, even if each impulse on its own would not be sufficient to cause firing. Temporal summation means that the effects of impulses received at the same place can add up if the impulses are received in close temporal succession. Thus, the neuron may fire when multiple impulses are received, even if each impulse on its own would not be sufficient to cause firing.

Synaptic Plasticity

Synapses experience plasticity by strengthening or weakening over time.

Learning Objectives

Distinguish between long-term potentiation and long-term depression

Key Takeaways

Key Points

  • Short-term synaptic enhancement occurs when the amount of available neurotransmitter is increased, while short-term synaptic depression occurs when the amount of vesicles with neurotransmitters is decreased.
  • Synapses are strengthened in long-term potentiation (LTP) when AMPA receptors (which bind to negatively-charged glutamate) are increased, allowing more calcium ions to enter the cell, causing a higher excitatory response.
  • Long-term depression (LTD) occurs when the AMPA receptors are decreased, which decreases the amount of calcium ions entering the cell, weakening the synaptic response to the release of neurotransmitters.
  • The strengthening and weakening of synapses over time controls learning and memory in the brain.

Key Terms

  • long-term potentiation: a long-lasting (hours in vitro, weeks to months in vivo) increase, typically in amplitude, of the response of a postsynaptic neuron to a particular pattern of stimuli from a presynaptic neuron
  • long-term depression: a long-term weakening of a synaptic connection
  • plasticity: the property of neuron that allows it to be strengthened or weakened

Synaptic Plasticity

Synaptic plasticity is the strengthening or weakening of synapses over time in response to increases or decreases in their activity. Plastic change also results from the alteration of the number of receptors located on a synapse. Synaptic plasticity is the basis of learning and memory, enabling a flexible, functioning nervous system. Synaptic plasticity can be either short-term (synaptic enhancement or synaptic depression) or long-term. Two processes in particular, long-term potentiation (LTP) and long-term depression (LTD), are important forms of synaptic plasticity that occur in synapses in the hippocampus: a brain region involved in storing memories.

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Long-term potentiation and depression: Calcium entry through postsynaptic NMDA receptors can initiate two different forms of synaptic plasticity: long-term potentiation (LTP) and long-term depression (LTD). LTP arises when a single synapse is repeatedly stimulated. This stimulation causes a calcium- and CaMKII-dependent cellular cascade, which results in the insertion of more AMPA receptors into the postsynaptic membrane. The next time glutamate is released from the presynaptic cell, it will bind to both NMDA and the newly-inserted AMPA receptors, thus depolarizing the membrane more efficiently. LTD occurs when few glutamate molecules bind to NMDA receptors at a synapse (due to a low firing rate of the presynaptic neuron). The calcium that does flow through NMDA receptors initiates a different calcineurin and protein phosphatase 1-dependent cascade, which results in the endocytosis of AMPA receptors. This makes the postsynaptic neuron less responsive to glutamate released from the presynaptic neuron.

Short-term Synaptic Enhancement and Depression

Short-term synaptic plasticity acts on a timescale of tens of milliseconds to a few minutes. Short-term synaptic enhancement results from more synaptic terminals releasing transmitters in response to presynaptic action potentials. Synapses will strengthen for a short time because of either an increase in size of the readily- releasable pool of packaged transmitter or an increase in the amount of packaged transmitter released in response to each action potential. Depletion of these readily-releasable vesicles causes synaptic fatigue. Short-term synaptic depression can also arise from post-synaptic processes and from feedback activation of presynaptic receptors.

Long-term Potentiation (LTP)

Long-term potentiation (LTP) is a persistent strengthening of a synaptic connection, which can last for minutes or hours. LTP is based on the Hebbian principle: “cells that fire together wire together. ” There are various mechanisms, none fully understood, behind the synaptic strengthening seen with LTP.

One known mechanism involves a type of postsynaptic glutamate receptor: NMDA (N-Methyl-D-aspartate) receptors. These receptors are normally blocked by magnesium ions. However, when the postsynaptic neuron is depolarized by multiple presynaptic inputs in quick succession (either from one neuron or multiple neurons), the magnesium ions are forced out and Ca2+ ions pass into the postsynaptic cell. Next, Ca2+ ions entering the cell initiate a signaling cascade that causes a different type of glutamate receptor, AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, to be inserted into the postsynaptic membrane. Activated AMPA receptors allow positive ions to enter the cell.

Therefore, the next time glutamate is released from the presynaptic membrane, it will have a larger excitatory effect (EPSP) on the postsynaptic cell because the binding of glutamate to these AMPA receptors will allow more positive ions into the cell. The insertion of additional AMPA receptors strengthens the synapse so that the postsynaptic neuron is more likely to fire in response to presynaptic neurotransmitter release. Some drugs co-opt the LTP pathway; this synaptic strengthening can lead to addiction.

Long-term Depression (LTD)

Long-term depression (LTD) is essentially the reverse of LTP: it is a long-term weakening of a synaptic connection. One mechanism known to cause LTD also involves AMPA receptors. In this situation, calcium that enters through NMDA receptors initiates a different signaling cascade, which results in the removal of AMPA receptors from the postsynaptic membrane. With the decrease in AMPA receptors in the membrane, the postsynaptic neuron is less responsive to the glutamate released from the presynaptic neuron. While it may seem counterintuitive, LTD may be just as important for learning and memory as LTP. The weakening and pruning of unused synapses trims unimportant connections, leaving only the salient connections strengthened by long-term potentiation.