Susceptibility to kindling and neuronal connections of the anterior claustrum

The claustrum has been implicated in the kindling of generalized seizures f rom 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 r apid kindling with two distinct phases. Early kindling involved extremely r apid progression to bilaterally generalized seizures of short duration. Wit h repeated daily kindling stimulations, early- phase generalized seizures a bruptly became more elaborate and prolonged, resembling limbic- type seizur es as triggered from the amygdala. We suggest that the rapid rate of kindli ng from the anterior claustrum is an indication that the claustrum is funct ionally 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 f rontal 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 anatomica l connections of the anterior claustrum are consistent with its very high s usceptibility to kindling and support the view that the claustrum is part o f a forebrain network of structures participating in the generalization of seizures.