Origin, Early Commitment, Migratory Routes, and Destination of Cannabinoid Type 1 Receptor-Containing Interneurons

It is now well established that inhibitory interneurons of the cerebral cortex display large diversity, but where each subclass originates and how they acquire final position and physiological characteristics is only begin to be elucidated. Recent studies indicate that the phenotypes of many forebrain interneurons are specified in the ganglionic eminence (GE) at the time of their origin. However, developmental history of cannabinoid type 1 receptor (CB1) positive (+) interneurons is not known. Here, we focus on the origin and migratory routs of prospective CB1/cholecystokinin (CCK)+ and CB1/reelin/calretinin+ gamma-aminobutyric acid (GABA)-ergic hippocampal interneurons. We have used variety of markers and a combination of methods, including immunocytochemistry at light and electron microscopic level, and in utero electroporation, to identify a subpopulation of CB1+ cells at the time of their origin in the caudal GE and pallial-subpallial boundary at the 11th-12th embryonic days. We have followed their migration, first radially to the marginal zone, then tangentially in the lateral-to-medial direction within the dorsal telencephalon, before they reach their final destination in the hippocampus proper and the dentate gyrus where they differentiate into CB1/CCK+ or CB1/reelin/calretinin+ GABAergic interneurons. Thus, the specific subclasses of CB1+ inhibitory interneurons, similar to the projection neurons, are determined at the time and place of last cell division and follow their own complex migratory pattern to the final positions.