Abstract
Neuronal inhibition is essential for cognitive processes in the brain, but molecular mechanisms mediating activity - dependent regulation of inhibitory GABAergic interneurons remain unclear. Neuropsin proteolytically cleaved mature neuregulin 1 (NRG1) bound to extracellular glycosaminoglycans, liberating the soluble ligand, which activated its receptor, ErbB4. Processed NRG1 was directed to ErbB4 - and parvalbumin - expressing interneurons and subsequently activated GABAergic transmission. Neuropsin- knockout mice exhibited disruption of the excitation- inhibition balance (E/I balance) and impairments in long- term potentiation, both of which are essential in processing and storing information, reversed by application of the NRG1 ligand moiety. These results suggest that neuropsin regulates GABAergic interneurons through NRG1 - ErbB4 signaling during network activity and reveal mechanisms linking neuropsin/NRG1/ErbB4 signaling with network balance control that may be altered in patients with schizophrenia.
