Cannabinoid receptor 1-labeled boutons in the sclerotic dentate gyrus of epileptic sea lions

Pathology in the dentate gyrus, including sclerosis, is a hallmark of temporal lobe epilepsy, and reduced inhibition to dentate granule cells may contribute to epileptogenesis. The perisomatic-targeting axonal boutons of parvalbumin-expressing interneurons decrease in proportion with granule cells in temporal lobe epilepsy. In contrast, dendrite-targeting axonal boutons of somatostatin-expressing interneurons sprout exuberantly in temporal lobe epilepsy. A third major class of GABAergic interneurons expresses cannabinoid receptor type 1 (CB1) on their terminal boutons, but there is conflicting evidence as to whether these boutons are increased or decreased in temporal lobe epilepsy. Naturally occurring temporal lobe epilepsy in California sea lions, with unilateral or bilateral sclerosis, offers the benefit of neuroanatomy and neuropathology akin to humans, but with the advantage that the entirety of both hippocampi from control and epileptic brains can be studied. Stereological quantification in the dentate gyrus revealed that sclerotic hippocampi from epileptic sea lions had fewer CB1-labeled boutons than controls. However, the reduction in the number of granule cells was greater, resulting in increased CB1-labeled boutons per granule cell in sclerotic hippocampi at temporal levels. This suggests that although CB1-expressing boutons are decreased in sclerotic dentate gyri, surviving cells have enhanced innervation from these boutons in epileptic sea lions.