Chandelier cells and epilepsy

Abstract

The main goal of this article is to review certain aspects of the circuitry of the human cerebral cortex that may be particularly relevant for the development, maintenance or spread of seizures. There are a number of different structural abnormalities that are commonly found in the cortex of epileptic patients, but these abnormalities do not appear to be intrinsically epileptogenic, since some patients displaying them are epileptic (after variable delays) whereas others are not. Therefore, cortical circuits in an affected brain may undergo a series of changes that finally cause epilepsy. In this article, it is proposed that the chandelier cell, which is considered to be the most powerful cortical GABAergic inhibitory interneuron, is probably a key component of cortical circuits in the establishment of human intractable temporal lobe epilepsy. These cells (among other types) have been found to be lost or reduced at epileptic foci in both experimental animals and epileptic patients. A hypothesis is presented by which the normal variability in the number of interneurons might explain the predisposition of some individuals to develop epilepsy more than others as a result of a lesion or other precipitating factors that lead to loss of neurons. The sources of GABAergic input on dendrites and somata of cortical pyramidal cells originate from many and diverse types of interneurons but, at the level of the axon initial segment of these cells, all synapses come from a few chandelier cells (five or less). Loss of one class of interneurons ending on soma and dendrites might have relatively little impact on the inhibitory control of the pyramidal cell. However, if chandelier cells were affected, it would have serious consequences for the inhibitory control of the pyramidal cells. Evidence suggests that the loss of chandelier cells may be nonspecific and that when this occurs epilepsy may develop. Therefore, these cells might represent a key component in the aetiology of human temporal lobe epilepsy.