Increased Cannabinoid Receptor 1-Immunopositive Perisomatic Input of Principal Cells in Human Epileptic Patients in...

Drug-resistant epilepsy is often associated with a neurodevelopmental disorder, focal cortical dysplasia (FCD). As demonstrated by numerous studies, defects in perisomatic inhibition may play a role in the formation of seizures. In our previous study, we observed an increase in parvalbumin-immunopositive perisomatic input. It has been observed that other perisomatic inhibitory cells expressing cannabinoid receptor type-1 (CB1R) and containing cholecystokinin (CCK) sprout in epileptic hippocampi. Therefore, we have investigated whether CB1R-immunopositive innervation has also changed in FCD. FCDIIB surgical samples were compared to controls with short post-mortem delay. The perisomatic input contacting principal cells was examined by NeuN-CB1R double immunostaining. Quantification in 3D was performed using a confocal fluorescence microscope. The results show that the CB1R-immunopositive synaptic input of principal cells is significantly larger in FCD cases. This condition may be an adaptive response to abnormal activity, or it may be a pre-existing pathology that is exacerbated by seizures. The reorganisation of the perisomatic inhibitory system has the potential to further increase the seizure probability in both cases. It should be noted that alterations in both PV- and CCK-CB1R-expressing basket cells may be implicated in seizure generation.