How 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'.
Institute of Neuroscience, Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. andytrev@gmail.com
Andrew J
AJ
Trevelyan
Catherine A
CA
Schevon
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D054351:Electrical Synapses / Q000502:physiology; D004594:Electrophysiology; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D007395:Interneurons / Q000502:physiology; D009415:Nerve Net / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology*; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid