SPREAD OF EXCITATION IN CHRONICALLY LESIONED MOUSE HIPPOCAMPUS DETERMINED BY LASER-SCANNING MICROSCOPY

Fast optical recordings by means of laser scanning microscopy in conju nction with a voltage-sensitive dye (RH 414) were performed to monitor the spatiotemporal spread of neuronal activity in CA3/CA4-lesioned C5 7BL6 mouse hippocampal slices prepared approximately 3 months after in tracerebroventricular kainic acid (KA) injection. The aim of our study was to assess the effects of a circumscribed neuronal loss on the pro pagation of electrical activity along the trisynaptic hippocampal circ uit. Both in physiological bathing solution and in bicuculline (10 mu M), hilar stimulation failed to activate the downstream pathway, so th at, under these conditions, the chronically disinhibited CA1 region ap peared to be effectively isolated from burst activity arising upstream ; however, epileptiform discharges evoked in zero Mg2+ solution were r eliably transmitted from the dentate gyrus to the CA1 region. That the se bursts were indeed spreading across the lesion, and not along newly formed connections (e.g., between dentate gyrus and CA1), was confirm ed by acute transection experiments of the Schaffer collateral/commiss ural pathway, which completely abolished translesional burst propagati on, The fact that the surviving CA3-CA1 connections are unable to trig ger epileptiform bursts after suppression of GABAergic inhibition sugg ests that the lesioned region might serve as a filter that shields hyp erexcitable CA1 neurons from epileptic activity arising upstream, in p articular from chronically disinhibited granule cells of the dentate g yrus. An impaired GABAergic inhibition will thus only have minor facil itating effects on seizure propagation in the hippocampus of CA3-lesio ned animals. (C) 1998 Academic Press.