Axon terminals of GABAergic chandelier cells are lost at epileptic foci.

Axon terminals of chandelier cells were analyzed in monkeys with cortical focal epilepsy produced by alumina gel to determine if this type of GABAergic terminal is lost at epileptic foci. These terminals form a dense plexus with the axon initial segments of pyramidal neurons, especially those in layers II and III. Axon initial segments of pyramidal neurons were traced for at least 40 micron in serial thin sections and beyond this point were observed to become myelinated. In single sections, 10-15 axon terminals were found to form symmetric synapses throughout the entire length of the axon initial segments from nonepileptic preparations and were observed to synapse with only these structures and not adjacent dendrites or spines. In epileptic cortex, the axon initial segments of pyramidal neurons were apposed by glial profiles that contained clusters of filaments typical of reactive astrocytes. Only a few, small axon terminals were observed to form symmetric synapses with these axon initial segments. Thus, the chandelier cell axons appeared to degenerate in epileptic cortex. The highly strategic site of GABAergic inhibitory synapses on axon initial segments suggests that they exert a strong influence on the output of pyramidal cells. The near absence of these chandelier cell axons in epileptic foci most likely contributes to the hyperexcitability of neurons.