Susceptibility to kindling and neuronal connections of the anterior claustrum.

The claustrum has been implicated in the kindling of generalized seizures from limbic sites. We examined the susceptibility of the anterior claustrum itself to kindling and correlated this with an anatomical investigation of its afferent and efferent connections. Electrical stimulation of the anterior claustrum resulted in a pattern of rapid kindling with two distinct phases. Early kindling involved extremely rapid progression to bilaterally generalized seizures of short duration. With repeated daily kindling stimulations, early-phase generalized seizures abruptly became more elaborate and prolonged, resembling limbic-type seizures as triggered from the amygdala. We suggest that the rapid rate of kindling from the anterior claustrum is an indication that the claustrum is functionally close to the mechanisms of seizure generalization. In support of our hypothesis, we found significant afferent, efferent, and often reciprocal connections between the anterior claustrum and areas that have been implicated in the generation of generalized seizures, including frontal and motor cortex, limbic cortex, amygdala, and endopiriform nucleus. Additional connections were found with various other structures, including olfactory areas, nucleus accumbens, midline thalamus, and brainstem nuclei including the substantia nigra and the dorsal raphe nucleus. The anatomical connections of the anterior claustrum are consistent with its very high susceptibility to kindling and support the view that the claustrum is part of a forebrain network of structures participating in the generalization of seizures.