Abstracts

Hypothalamic hamartomas (HH) are rare subcortical lesions associated with gelastic seizures and precocious puberty. The mechanisms underlying HH-induced epileptogenesis are unknown. Recent advances in the surgical treatment of HH have led to dramatic resolution of seizures in many cases, and have also provided viable tissue specimens for detailed cellular electrophysiological studies. Whole cell recordings were performed in neurons from 350 [mu]M HH slices prepared immediately following surgical resection. Half of the neurons exhibited spontaneous repetitive firing, SRF (N=23; resting membrane potential [RMP], -53.9 [plusmn] 0.9 mV; input resistance ([italic]R[sub]N[/sub][/italic]), 950 [plusmn]165 M[Omega]); the remaining quiescent cells had normal neuronal properties (RMP, -67.1 [plusmn] 1.70 mV; [italic]R[sub]N[/sub][/italic]: 583.3 [plusmn] 103 M[Omega]). SRF was consistently observed in small size neurons (8-10 [mu]m) contained within clusters of cells. In contrast, quiescent neurons were generally larger (N=23; 16-24 [mu]m) and were identified outside of neuronal clusters. No significant differences in either action potential amplitude or threshold were seen between these two groups of cells. To test whether SRF was related to a change in excitatory or inhibitory postsynaptic transmission, we applied either the GABA[sub]A[/sub] blocker, bicuculline methiodide (BMI, 300 [mu][Mu]) or the ionotropic glutamate receptor antagonist, kynurenic acid (KYN, 1 mM). SRF was not altered by BMI or KYN. On the other hand, both the sodium channel blocker, tetrodotoxin (1 [mu][Mu]) and the L-type calcium channel blocker, nimodipine (1 [mu][Mu]) consistently blocked SRF. These data suggest that neurons clustered in HH slices may contribute to the generation of gelastic seizures, and support prior observations indicating the intrinsic epileptogenicity of this lesion. (Supported by Barrow Neurological Institute Foundation and NIH K02 NS 044846 (JMR).)