What Are Excitatory and Inhibitory Signals? EPSP vs. IPSP

What Are Excitatory and Inhibitory Signals?

Introduction

Neurons constantly receive signals from other cells. Some signals make a neuron more likely to generate an action potential, while others make it less likely.

These are called excitatory signals and inhibitory signals. The brain needs both types to transmit information while keeping neural activity controlled and organized.

An excitatory signal increases the likelihood that a neuron will fire an action potential, while an inhibitory signal decreases that likelihood. Excitatory inputs commonly produce excitatory postsynaptic potentials (EPSPs), whereas inhibitory inputs commonly produce inhibitory postsynaptic potentials (IPSPs).

What Are Excitatory and Inhibitory Signals?

Excitatory and inhibitory signals are electrical changes produced in a receiving cell after neurotransmitters bind to its receptors.

At a typical chemical synapse:

1. A neurotransmitter is released from the presynaptic neuron.
2. It crosses the synaptic cleft.
3. It binds to receptors on the postsynaptic cell.
4. The receptors alter ion flow across the cell membrane.
5. The resulting electrical change makes an action potential more or less likely.

This electrical change is called a postsynaptic potential.

Unlike an action potential, a postsynaptic potential is graded. It can vary in size depending on how much neurotransmitter is released, which receptors are activated, and how the ions move across the membrane.

What Is an Excitatory Signal?

An excitatory signal makes the postsynaptic neuron more likely to fire.

The electrical response it produces is called an excitatory postsynaptic potential, or EPSP.

At many excitatory synapses, receptor activation allows positively charged ions, especially sodium, to enter the receiving neuron. This commonly causes depolarization, meaning the membrane potential becomes less negative.

Depolarization moves the membrane potential closer to the threshold for generating an action potential.

However, an EPSP does not guarantee that the neuron will fire. A single EPSP is often too small to reach threshold by itself.

What Is an Inhibitory Signal?

An inhibitory signal makes the postsynaptic neuron less likely to fire.

The resulting response is called an inhibitory postsynaptic potential, or IPSP.

Inhibition commonly occurs when receptor activation:

• Allows chloride ions to move through the membrane
• Allows potassium ions to leave the cell
• Stabilizes the membrane below the action-potential threshold
• Reduces the effect of simultaneous excitatory input

An IPSP may make the membrane potential more negative, a change called hyperpolarization. However, inhibition does not always require substantial hyperpolarization. It can also work by stabilizing the membrane and making excitatory input less effective.[1]

EPSPs and IPSPs Compared

Feature	EPSP	IPSP
Full name	Excitatory postsynaptic potential	Inhibitory postsynaptic potential
Effect on firing	Makes an action potential more likely	Makes an action potential less likely
Common voltage change	Depolarization	Hyperpolarization or membrane stabilization
Common ion movement	Positive ions enter the cell	Chloride movement or potassium exit
Typical transmitter in the brain	Glutamate	GABA
Main role	Promotes neural activity	Limits and controls neural activity

These descriptions represent common patterns. The actual effect depends on the receptor, the ions it conducts, and the ion concentrations inside and outside the receiving cell.[1,2]

Which Neurotransmitters Produce Excitatory Signals?

Glutamate

Glutamate is the principal excitatory neurotransmitter in the vertebrate central nervous system.

When glutamate activates certain receptors, positively charged ions can enter the postsynaptic neuron. This commonly produces an EPSP and moves the neuron closer to its action-potential threshold.

Glutamate does not act through only one receptor. Different glutamate receptors can produce different cellular effects. These receptor types are discussed separately in What Are Neural Receptors?

Acetylcholine

Acetylcholine can produce excitation at some synapses. For example, it produces an excitatory response at the connection between a motor neuron and skeletal muscle.

In the nervous system, however, acetylcholine may have different effects depending on the receptor and target cell. It should not be classified as universally excitatory.

Which Neurotransmitters Produce Inhibitory Signals?

GABA

Gamma-aminobutyric acid, or GABA, is the principal inhibitory neurotransmitter in much of the mature vertebrate brain.

GABA commonly activates receptors that increase chloride conductance or indirectly increase potassium conductance. These effects reduce the likelihood that the postsynaptic neuron will generate an action potential.

Glycine

Glycine is another important inhibitory neurotransmitter. It is especially prominent in the spinal cord and brainstem.

Glycine receptors commonly open chloride channels, helping to limit the activity of the receiving neuron.[3]

Is a Neurotransmitter Always Excitatory or Inhibitory?

No. A neurotransmitter’s effect is not determined by its name alone.

The response depends on:

• The receptor activated by the neurotransmitter
• The ion channels connected to that receptor
• The concentration of ions inside and outside the cell
• The electrical state of the postsynaptic neuron

For example, acetylcholine can be excitatory at one type of receptor and inhibitory at another. Glutamate is predominantly excitatory in the brain, while GABA is predominantly inhibitory in the mature brain, but these are general patterns rather than rules without exceptions.[2]

It is therefore more accurate to describe a particular synaptic response as excitatory or inhibitory.

How Do These Signals Affect Neuronal Firing?

Neurons usually receive both excitatory and inhibitory inputs. Excitatory inputs move the membrane potential toward threshold, while inhibitory inputs reduce or control that movement.

How neurons combine these signals is explained in How Do Neurons Combine Excitatory and Inhibitory Signals?

Why Does the Brain Need Both Types of Signals?

Excitation allows information to spread through neural pathways. Inhibition controls when, where, and how strongly that activity occurs.

Together, excitatory and inhibitory signals help the nervous system:

• Select appropriate responses
• Control the timing of neuronal firing
• Filter unnecessary information
• Refine sensory signals
• Coordinate movements
• Prevent neural activity from spreading without control
• Organize communication within neural circuits

Inhibition is therefore not simply the absence of activity. It is an active part of neural information processing.

The wider relationship between excitation and inhibition within neural networks is discussed in What Is Excitation–Inhibition Balance in the Brain?

Clinical Relevance

Disruption of excitatory or inhibitory signaling can contribute to abnormal neural activity. Seizures, for example, may involve changes in synaptic transmission, ion channels, brain structure, metabolism, or neural networks. They cannot be explained by excitation or inhibition alone.

Common Misunderstandings

An Excitatory Signal Always Makes a Neuron Fire

An EPSP only increases the probability of firing. It may not be strong enough to bring the neuron to threshold.

An Inhibitory Signal Completely Turns a Neuron Off

An inhibitory signal reduces the likelihood or changes the timing of firing. The neuron may still fire if other inputs are sufficiently strong.

Every Inhibitory Signal Hyperpolarizes the Neuron

Many inhibitory responses cause hyperpolarization, but some mainly stabilize the membrane or weaken the effect of excitatory input.

Every Neurotransmitter Has One Fixed Effect

The same neurotransmitter can produce different responses through different receptors. The receptor and postsynaptic conditions determine the final effect.

• Excitatory signals make an action potential more likely.
• Inhibitory signals make an action potential less likely.
• Excitatory and inhibitory inputs commonly produce EPSPs and IPSPs.
• Glutamate is the main excitatory transmitter in much of the brain.
• GABA is the main inhibitory transmitter in much of the mature brain.
• The effect of a neurotransmitter depends on its receptor and the receiving cell.

Related Articles

• How Do Neurons Communicate?
• What Are Neural Receptors and How Do They Work?
• What Is a Neural Circuit?
• How Do Neurons Combine Excitatory and Inhibitory Signals?
• What Is Excitation–Inhibition Balance in the Brain?

References

1. Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Excitatory and Inhibitory Postsynaptic Potentials. In: Neuroscience. 2nd ed. Sinauer Associates; 2001. NCBI Bookshelf
2. Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neurotransmitter Receptors and Their Effects. In: Neuroscience. 2nd ed. Sinauer Associates; 2001. NCBI Bookshelf
3. Siegel GJ, Agranoff BW, Albers RW, et al., editors. Synaptic Transmission. In: Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th ed. Lippincott-Raven; 1999. NCBI Bookshelf