Abstracts

RATIONALE: Factors which regulate the electrical stability of hippocampal networks are of great interest to epilepsy research. Hippocampal inhibitory interneurons show a wide diversity of morphological, physiological and pharmacological properties. This study was designed to determine if interneuronal diversity itself serves a stabilizing role in neuronal networks. METHODS: Multicompartmental models of various interneuronal principal cell circuits were constructed to study the influence of functional and anatomical diversity of interneurons on network stability. The interneuronal heterogeneity was varied by systematically altering the distribution of relevant anatomical or physiological parameters within the interneuronal populations. The stability of the network was determined by scanning the frequency of the incoming EPSPs from 0 to 1000 Hz, and measuring the output firing frequency of the principal cells. RESULTS: When interneurons were designed to be identical physiologically, increased anatomical diversity (in axonal targets along the axis of the principal cells) enhanced the ability of interneurons to suppress principal cell discharges in response to incoming excitation. In networks where the anatomical diversity of interneurons was kept constant, and the physiological parameters (e.g. spike frequency adaptation, resting membrane potential) were varied, heterogeneous interneuronal networks were again better at inhibiting principal cell discharges compared to anatomically identical but physiologically homogenous interneurons. CONCLUSIONS:These data show that interneuronal diversity strongly influences network stability, and suggest that changes in diversity during epileptogenesis may play important roles in the development of hyperexcitable states. Supported by the NIH (NS38580) to I.S. and by the Epilepsy Foundation of America to I.A.