Invited reviewHow inhibition influences seizure propagation

Inhibitory neuron behaviour is of fundamental importance to epileptic pathophysiology. When inhibition is compromised, such as by GABAergic blockade (Curtis et al., 1970; Connors, 1984; Traub and Miles, 1991) or by shifts in GABAergic reversal potential (Huberfeld et al., 2007), epileptiform discharges occur far more readily. Other studies have shown enhanced inhibition in vivo in the surrounding cortical territories associated with both focal pathological and physiological activity (Prince and Wilder, 1967; Dichter and Spencer, 1969a,b; Goldensohn and Salazar, 1986; Traub and Miles, 1991; Liang and Jones, 1997; Liang et al., 1998; Schwartz and Bonhoeffer, 2001). This gave rise to the concept of an “inhibitory restraint”. This concept can explain the often confusing anatomical reorganizations seen in chronically epileptic brains (Sloviter, 1987; Cossart et al., 2001), indicating which changes might be pro-epileptic, and which oppose the epileptic state. It also may explain key electrophysiological features of epileptic seizures. Here we describe current knowledge about the restraint, gleaned mainly from acute pharmacological experiments in animals, both in vivo and in vitro, and speculate how this may alter our understanding of human seizure activity in clinical practice.This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'.

► GABAergic inhibition plays a vital role regulating how activity flows through cortical networks. ► Surround (lateral) inhibition has been proposed as an important, anti-epileptic mechanism. ► Animal models have given us a clear picture of how such surround inhibition is manifest in cortex. ► Surround inhibition associated with focal ictal activity will create an ictal penumbra. ► Distinguishing the ictal focus from the penumbra will be critical for EEG seizure localization.