Inhibitory Postsynaptic Potential (IPSP) | How Do Neurons Say 'Stop'?

An Inhibitory Postsynaptic Potential (IPSP) is a temporary change in the membrane potential of a postsynaptic neuron that makes it less likely to generate an action potential. The 'membrane potential' refers to the electrical charge difference across the neuron's membrane. In its resting state, a neuron maintains a negative charge inside relative to the outside. An IPSP makes this internal charge even more negative, a process called 'hyperpolarization'. This occurs when inhibitory neurotransmitters bind to receptors on the postsynaptic membrane, causing specific ion channels to open. Primarily, these are channels for chloride ions (Cl-), which carry a negative charge, or potassium ions (K+), which carry a positive charge. When Cl- channels open, negatively charged chloride ions flow into the neuron. When K+ channels open, positively charged potassium ions flow out of the neuron. Both events increase the negative charge inside the cell, moving the membrane potential further away from the 'threshold' required to fire an action potential. An 'action potential' is the electrical signal that neurons use to communicate. Therefore, an IPSP acts as a brake, reducing the neuron's probability of firing and passing on a message.

The primary inhibitory neurotransmitters in the central nervous system that generate IPSPs are Gamma-aminobutyric acid (GABA) and glycine. GABA is the most prevalent inhibitory neurotransmitter in the brain. It binds to two main types of receptors, GABA-A and GABA-B. GABA-A receptors are 'ionotropic', meaning when GABA binds to them, they directly open an integrated chloride (Cl-) ion channel, allowing Cl- to enter the cell and cause rapid hyperpolarization. Glycine serves a similar role but is more concentrated in the spinal cord and brainstem. Like GABA-A receptors, glycine receptors are ionotropic channels that permit Cl- to pass through. The precise action of these neurotransmitters is critical for balancing neuronal activity. Without this constant inhibitory signaling, neurons would fire uncontrollably, leading to a state of hyperexcitability. This balance is essential for almost all brain functions, from motor control to cognitive processing.

IPSPs and EPSPs are opposing forces that govern a neuron's decision to fire. While an IPSP hyperpolarizes the neuron (making it more negative) and inhibits firing, an Excitatory Postsynaptic Potential (EPSP) does the opposite. An EPSP 'depolarizes' the neuron, making its internal charge less negative and bringing it closer to the firing threshold. This is typically achieved by the influx of positively charged ions, such as sodium (Na+), through channels opened by excitatory neurotransmitters like glutamate. In essence, EPSPs are the 'go' signals, and IPSPs are the 'stop' signals in the nervous system.

A single neuron receives thousands of both inhibitory (IPSPs) and excitatory (EPSPs) inputs simultaneously. 'Summation' is the process by which the neuron integrates all these signals to determine its final output. There are two types: 'spatial summation,' where signals arriving at different locations on the neuron are added together, and 'temporal summation,' where signals arriving in quick succession at the same location are combined. If the total sum of EPSPs, minus the total sum of IPSPs, is sufficient to depolarize the membrane to its firing threshold, an action potential is generated. This integration process ensures that a neuron does not fire in response to trivial stimuli, allowing for complex information processing.

The precise balance between neuronal excitation (via EPSPs) and inhibition (via IPSPs) is fundamental for normal brain function. Disruption of this equilibrium is implicated in numerous neurological and psychiatric conditions. For instance, insufficient inhibition is a hallmark of epilepsy, a disorder characterized by seizures resulting from excessive, synchronized neuronal firing. This can be caused by dysfunctional GABA receptors or a reduced supply of GABA. Conversely, excessive inhibition can also be problematic, leading to conditions like cognitive impairment or sedation. Many therapeutic drugs work by modulating this balance. For example, benzodiazepines (e.g., Valium, Xanax) are a class of drugs used to treat anxiety and insomnia. They enhance the effect of GABA at the GABA-A receptor, increasing the frequency of chloride channel opening. This boosts the inhibitory signaling in the brain, producing a calming effect by reducing overall neuronal excitability.