Abstract
Kindling is a model in which fleeting changes of neuronal activity produce a lifelong modification of neuronal structure and function in the mature nervous system. Immediate-early genes (IEGs) such as c-fos have been implicated as a causal link in the chain of molecular events coupling fleeting pathologic activity to lasting hyperexcitability. Identification of the brain structures exhibiting IEG expression during the evolution of kindling is necessary to guide investigations of the phenotypic consequences. We used in situ hybridization histochemistry to identify the structures exhibiting expression of multiple IEGs during the evolution of amygdala kindling and compared this to the pattern following angular bundle kindling. The principal findings included that: (1) generalized limbic and clonic motor (class 5) kindled seizures evoked by stimulation of one amygdala induced the expression of IEGs in a small subset of limbic structures with remarkable symmetry between the two hemispheres; (2) the anatomic extent of seizure-evoked expression of c-fos mRNA expanded progressively following focal limbic and motor (classes 0-3) seizures during the development of amygdala kindling; c-fos mRNA was detected first ipsilaterally in AM, ACO, and PC and with higher-class seizures in hippocampal formation and homologous structures contralaterally, and (3) class 5 seizures evoked by stimulation of two different sites in the limbic system (amygdala or angular bundle) induced IEG expression in distinct but partially overlapping anatomic structures. We propose that synaptic activation of glutamate receptors contributes to the expression of these diverse IEGs throughout the forebrain. The findings provide a constellation of anatomic structures in which to investigate the structural and functional consequences of IEG expression.