Journal Article

Surviving CA1 pyramidal cells receive intact perisomatic inhibitory input in the human epileptic hippocampus

L. Wittner, L. Erőss, S. Czirják, P. Halász, T. F. Freund and Zs. Maglóczky

in Brain

Published on behalf of The Guarantors of Brain

Volume 128, issue 1, pages 138-152
Published in print January 2005 | ISSN: 0006-8950
Published online November 2004 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awh339
Surviving CA1 pyramidal cells receive intact perisomatic inhibitory input in the human epileptic hippocampus

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Temporal lobe epilepsy (TLE) is known to be linked to an impaired balance of excitation and inhibition. Whether inhibition is decreased or preserved in the human epileptic hippocampus, beside the excess excitation, is still a debated question. In the present study, quantitative light and electron microscopy has been performed to analyse the distribution, morphology and input–output connections of parvalbumin (PV)-immunopositive interneurons, together with the entire perisomatic input of pyramidal cells, in the human control and epileptic CA1 region. Based on the degree of cell loss, the patients with therapy-resistant TLE formed four pathological groups. In the non-sclerotic CA1 region of TLE patients, where large numbers of pyramidal cells are preserved, the number of PV-immunopositive cell bodies decreased, whereas axon terminal staining, and the distribution of their postsynaptic targets was not altered. The synaptic coverage of CA1 pyramidal cell axon initial segments (AISs) remained unchanged in the epileptic tissue. The somatic inhibitory input is also preserved; it has been decreased only in the cases with patchy pyramidal cell loss in the CA1 region (control, 0.637; epileptic with mild cell loss, 0.642; epileptic with patchy cell loss, 0.424 μm synaptic length/100 μm soma perimeter). The strongly sclerotic epileptic CA1 region, where pyramidal cells can hardly be seen, contains a very small number of PV-immunopositive elements. Our results suggest that perisomatic inhibitory input is preserved in the epileptic CA1 region as long as pyramidal cells are present. Basket and axo-axonic cells survive in epilepsy if their original targets are present, although many of them lose their PV content or PV immunoreactivity. An efficient perisomatic inhibition is likely to take part in the generation of abnormal synchrony in the non-sclerotic epileptic CA1 region, and thus participate in the maintenance of epileptic seizures driven, for example, by hyperactive afferent input.

Keywords: perisomatic inhibition; GABA; basket cell; chandelier cell; selective vulnerability; AIS = axon initial segment; CA1–3 = regions of the cornu Ammonis; PV = parvalbumin; TLE = temporal lobe epilepsy

Journal Article.  9128 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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