Interactions between limbic, thalamo-striatal-cortical, and central autonomic pathways during epileptic seizure...

We used immunocytochemistry to determine the regional and temporal distribution of Fos protein expression in awake and unrestrained rats after a unilateral stereotaxic microinjection of a cholinergic agonist, carbachol, in the thalamic ventroposterolateral and reticular nuclei, previously shown to cause limbic and generalized convulsive seizures. The microinjection of carbachol elicits behavioral alterations including immobilization, staring, facial and jaw clonus, rearing, and falling, followed by recurrent generalized convulsive seizures, and a pattern of c-fos expression throughout the brain. In addition to the hypothalamic paraventricular and supraoptic nuclei, the initial induction of c-fos expression was observed as early as 15 minutes after the carbachol microinjection, in the piriform and entorhinal cortices, the thalamic paraventricular, the supramammilary, the lateral parabrachial nuclei, and the central gray. From 30 minutes to 2 hours, corresponding to the occurrence of motor expression of limbic and recurrent generalized convulsive seizures, Fos immunoreactivity was seen in a number of functionally related brain regions including the hippocampus, the amygdala, and the anterior thalamic nucleus (limbic system); the thalamus, the basal ganglia, and the cortex (thalamo-striatal-cortical system); and the hypothalamus, the central nucleus of the amygdala, the pons, and the medulla (central autonomic system). On the basis of the present results showing regional and temporal c-fos expression and well known neuroanatomical connections, we have constructed a neural network relating the limbic, thalamo-striatal-cortical, and central autonomic systems. This analysis provides, for the first time, neuronal circuits and pathways relating epilepsy-elicited behavioral expression of convulsive seizures and adaptive homeostatic responses and could serve as a basis for studying central autonomic regulation during epileptic disorders.