Intrinsic Optical Signals and Electrographic Seizures in the Rat Limbic System

Authors: D'Arcangelo G.1; Tancredi V.1; Avoli M.2, 3

Source: Neurobiology of Disease, Volume 8, Number 6, December 2001 , pp. 993-1005(13)

Publisher: Academic Press

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Abstract:

We measured the intrinsic optical signals (IOSs) generated by rat hippocampus-entorhinal cortex (EC) slices in response to single shock electrical stimuli delivered in the EC deep layers during application of the convulsant drug 4-aminopyridine (50 muM). With field potential recordings the stimulus-induced responses had duration = 35 ± 6.3 s mean ± SEM, n = 7 slices) and characteristics resembling electrographic seizures. IOS changes reflecting an increase in light transmittance occurred in the EC and hippocampus following similar stimuli (n = 45). IOSs increased progressively to reach peak values 20–30 s after the stimulus and returned slowly to prestimulus values within 100 s, thus outlasting the field potential discharge. IOS changes initiated in the medial EC, near to the stimulation site, and spread to the lateral EC, the dentate, and the CA3/CA1 areas. IOS spread from EC to hippocampus was not seen after perforant path cut (n = 5). Moreover, field potential and IOS responses were markedly decreased by excitatory amino acid receptor antagonists (n = 12). The antiepileptic drugs topiramate (10–100 muM, n = 16) or lamotrigine (100–400 muM, n = 12) reduced the IOS changes in the EC and their spread to distant areas. These effects were reversible and dose-dependent (IC50 = 48 muM and 210 muM for topiramate and lamotrigine, respectively). Thus, in 4AP-treated hippocampus-EC slices, IOS changes accompany and outlast the field potential epileptiform responses, depend on glutamatergic transmission and are characterized by temporal and spatial distributions consistent with propagation through established anatomical pathways. We also propose that IOSs may represent a reliable tool for screening the effects of neuroactive compounds such as antiepileptic drugs. ©2001 Elsevier Science.

Language: English

Document Type: Research article

Affiliations: 1: Dipartimento di Neuroscienze, Università degli Studi di Roma ‘Tor Vergata’, Roma, 00173, Italy 2: Montreal Neurological Institute and Departments of Neurology and Neurosurgery and Physiology, McGill University, Montreal, Quebec, H3A 2B4, Canada 3: IRCCS Neuromed, 86077 Pozzilli, Isernia, Italy

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