FOS INDUCTION FOLLOWING SYSTEMIC KAINIC ACID - EARLY EXPRESSION IN HIPPOCAMPUS AND LATER WIDESPREAD EXPRESSION CORRELATED WITH SEIZURE

We determined the distribution of Fos protein expression in a model of generalised epilepsy caused by excessive neuronal excitation. Fos imm unoreactivity was mapped in forebrain in unrestrained rats, previously prepared with an indwelling venous catheter, after the intravenous ad ministration of kainic acid (10 mg/kg). We determined cerebral activat ion following various periods of exposure to kainic acid by using intr avenous administration of pentobarbitone to prevent further activation . Within a few minutes, kainic acid caused episodes of staring, sniffi ng, wet dog shakes, nodding and chewing. Fos induction occurred initia lly and simultaneously in hippocampus, subiculum, septum and entorhina l cortex as early as 9.5 min after kainate injection. After up to 40 m in of staring, sniffing, wet dog shakes, nodding and chewing, Fos indu ction was not further increased above levels present within the first 9.5 min. After 56 +/- 6 min a motor convulsion occurred, initially aff ecting the jaw, head and tail and variably extending to the forelimbs, trunk or hindlimbs. Following the convulsive event, additional Fos wa s expressed in hippocampus, thalamus, caudate-putamen and other subcor tical structures and in the cerebral cortex. Fos induction was sometim es asymmetric in entorhinal, visual, piriform, cingulum, parietal and frontal cortices and in amygdala and dorsal endopiriform area. Electro encephalographic recordings after a few minutes exposure to kainic aci d revealed an increased amplitude of fast frequencies in hippocampus w hich appeared to correlate with Fos induction in this structure. The f indings are generally consistent with the reported distribution and sl ow development of kainic acid-induced seizure activity using electroph ysiological and deoxyglucose methods. However, the Fos distribution su ggests that (i) hippocampal, possibly dentate, activation precedes sig nificant activation elsewhere, (ii) extensive involvement of other cer ebral structures and cerebral cortex occurs simultaneously and correla tes with motor seizures and (iii) brain structures can be recruited as ymmetrically. (C) 1997 IBRO.