Sprouting in human temporal lobe epilepsy: excitatory pathways and axons of interneurons

Abstract

Changes of hippocampal GABAergic interneuronal circuits are known to play a central role in epileptogenesis. Fate of functionally different hippocampal interneuron types has been investigated in surgically removed hippocampi of therapy resistant human TLE patients. Perisomatic inhibitory cells containing parvalbumin are responsible for controlling the output of principal cells. Electron microscopic examination revealed that perisomatic innervation of the principal cells was preserved in both sclerotic and non-sclerotic samples, and the ratio of the initial segment synapses increased among the postsynaptic targets, which might give rise to an increased synchrony of granule cell firing. Calbindin-containing dendritic inhibitory cells are well preserved, and they terminate on other interneurons in larger proportion than in the control both in sclerotic and non-sclerotic cases. Substance P receptor-immunopositive cells possessed significantly larger numbers of dendritic branches in the epileptic CA1 region, and the synaptic input of their dendrites has notably increased, whereas the ratio of inhibitory and excitatory synaptic inputs has not changed. Our results suggest that an intense synaptic reorganization takes place in the epileptic hippocampus, including axonal sprouting of certain interneuron types, both in sclerotic and non-sclerotic tissue. Thus, axonal sprouting is a more general phenomenon of TLE than cell loss.