1College of Pharmaceutical Sciences, Brain Institute, Capital Medical University, Beijing 100069, China 
2State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China 
3Department of Neurosurgery, Epilepsy Center, Sanbo Brain Hospital of Capital Medical University, Beijing Key Laboratory of Epilepsy, Epilepsy Institution, Beijing Institute for Brain Disorders, Beijing 100093, China 
4Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou 501260, China

Abstract 

Inhibitory GABAergic interneurons are fundamental elements of cortical circuits and play critical roles in shaping network activity. Dysfunction of interneurons can lead to various brain disorders, including epilepsy, schizophrenia, and anxiety. Based on the electrophysiological properties, cell morphology, and molecular identity, interneurons could be classified into various subgroups. In this study, we investigated the density and laminar distribution of different interneuron types and the co-expression of molecular markers in epileptic human cortex. We found that parvalbumin (PV) and somatostatin (SST) neurons were distributed in all cortical layers except layer I, while tyrosine hydroxylase (TH) and neuropeptide Y (NPY) were abundant in the deep layers and white matter. Cholecystokinin (CCK) neurons showed a high density in layers IV and VI. Neurons with these markers constituted ~7.2% (PV), 2.6% (SST), 0.5% (TH), 0.5% (NPY), and 4.4% (CCK) of the gray-matter neuron population. Double- and triple-labeling revealed that NPY neurons were also SST-immunoreactive (97.7%), and TH neurons were more likely to express SST (34.2%) than PV (14.6%). A subpopulation of CCK neurons (28.0%) also expressed PV, but none contained SST. Together, these results revealed the density and distribution patterns of different interneuron populations and the overlap between molecular markers in epileptic human cortex.

Keywords

Interneuron; Epilepsy; Human cortex; Cell type; Immunostaining; Parvalbumin; Somatostatin; Tyrosine hydroxylase; Neuropeptide Y; Cholecystokinin

[SpringerLink]