Excitation-inhibition balance · Grey Matter

Excitation-inhibition balance is the way cortical circuits keep the excitatory drive a neuron receives matched by inhibition that arrives with it, so that the network can respond strongly to an input without tipping into runaway activity.

Excitation-inhibition balance. Excitation-inhibition balance is the way cortical circuits keep the excitatory drive a neuron receives matched by inhibition that arrives with it, so that the network can respond strongly to an input without tipping into runaway activity.

The cortex is built from recurrent excitation: pyramidal cells excite each other, and an excited group could in principle recruit its neighbours without end. What stops it is inhibition that tracks excitation. When an input arrives, it excites pyramidal cells and, a millisecond or two later, interneurons that inhibit those same cells; recordings show that the two currents rise and fall together, in proportion, across a wide range of input strengths. The result is a network that sits close to its firing threshold, responds quickly, and stays stable.

The balance is dynamic. It is held from moment to moment by the wiring (each input drives its own inhibition) and over hours and days by plasticity that adjusts synapses and intrinsic excitability to keep activity in a working range.

The ratio can be pushed. Neuromodulators such as noradrenaline from the locus coeruleus, sleep loss, metabolic state, and changes in ion concentrations move the operating point, raising or lowering how easily the tissue fires.

Losing it has two classic failure modes in this theme. Inhibition that falls behind lets activity become excessive and synchronous (a seizure); a collapse of the ion gradients themselves silences the tissue (spreading depression).

Balance is a description of averages. A single neuron receives a fluctuating mix, and much of what it computes lives in the brief moments when excitation leads inhibition.

A balanced cortex buys its sensitivity by sitting close to the edge.

It responds fast because it hovers near threshold, and for the same reason a small shift on either side changes its behaviour sharply.

Questions: How can a minority of GABA interneurons hold back a majority of excitatory cells? Each interneuron contacts many pyramidal cells, fires fast without tiring, and often synapses on the cell body or the start of the axon, where it has the most control over whether a spike is produced. Interneurons are driven by the same inputs as their targets, so inhibition arrives a millisecond or two after excitation and scales with it, which keeps the ratio of the two roughly constant. GABA-A inhibition also works by shunting: open chloride channels cancel excitatory currents even when the voltage barely moves. Interneurons make up roughly a fifth to a quarter of neocortical neurons in rodents and a larger share in humans. What do the tonic and phasic modes of the locus coeruleus do to the cortex? In the phasic mode, moderate background firing is punctuated by brief bursts locked to task-relevant events, and the noradrenaline released then sharpens cortical responses to exactly those events. In the high tonic mode, firing is steady and elevated, bursts fade, and behaviour becomes distractible and exploratory. The adaptive gain theory of Aston-Jones and Cohen proposes that the system switches between exploiting the current task and searching for alternatives this way. Because noradrenaline raises the gain and excitability of cortical circuits, sustained high tonic output also shifts the excitation-inhibition operating point toward easier firing. What is a cortical column, and how large is it? A cortical column is a vertical module running through the layers of the cortex, in which neurons share inputs and respond to related features, first described by Vernon Mountcastle in the 1950s. The word covers two scales: minicolumns, chains of cells about 50 micrometres across, and larger columns (macrocolumns) about 300 to 600 micrometres across, built from many minicolumns; the often-quoted figure of a millimetre is at the generous end. Each column contains pyramidal cells and inhibitory interneurons wired in a recurring microcircuit, so it is a natural unit in which to study the balance of excitation and inhibition. How sharp their boundaries are varies by area and species, and whether columns are a universal computational unit is debated. What is a neuronal avalanche, and what does its power law say about the cortex? An avalanche is a burst of activity that spreads across a group of recording sites and then stops, preceded and followed by quiet. In slices of rat cortex Beggs and Plenz found that avalanche sizes follow a power law with exponent about −3/2 and durations one with exponent about −2, the values expected for a branching process in which each active unit triggers on average exactly one other. That means activity is balanced at the edge between dying out and growing, which is the critical point. Since the balance of excitation and inhibition sets how many units each event recruits, weakening inhibition pushes avalanches toward large, runaway events and strengthening it makes them fizzle. What does it mean for a brain to have a seizure threshold, and what lowers it? The threshold is how hard a brain has to be pushed before excitation outruns inhibition and a seizure starts, so it is the excitation-inhibition balance seen from the side of its failure. Lasting causes lower it, such as mutations in ion channels, lost interneurons or a scar after injury, and that lasting lowering is what epilepsy means. Temporary triggers lower it for hours or days: sleep deprivation, fever, alcohol withdrawal, low blood sugar or sodium, and some medicines, and in diary studies of people with epilepsy, less sleep and more stress were each followed by more seizures. Why is synchrony, rather than just more firing, the signature of a seizure? A healthy cortex is busy but loosely coordinated: inhibition keeps each neuron's firing to brief, scattered windows, so neighbours rarely fire in lockstep. When inhibition falls behind excitation, a recruited group excites its neighbours faster than they can be held back, and the activity locks into a shared fast rhythm that pulls in more and more tissue. The international definition of a seizure names exactly this (abnormal excessive or synchronous neuronal activity), and synchrony is also what makes a seizure large on the EEG, because aligned currents add up while scattered ones cancel.