The assembly of specific neuronal circuits relies on the expression of complementary molecular programs in presynaptic and postsynaptic neurons. In the cerebral cortex, the tyrosine kinase receptor ErbB4 is critical for the wiring of specific populations of GABAergic interneurons, in which it paradoxically regulates both the formation of inhibitory synapses as well as the development of excitatory synapses received by these cells. Here we found that Nrg1 and Nrg3, two members of the neuregulin family of trophic factors, respectively regulate the inhibitory outputs and excitatory inputs of interneurons in the mouse cerebral cortex. The differential role of Nrg1 and Nrg3 in this process is not due to their receptor-binding EGF-like domain, but rather to their distinctive subcellular localization within pyramidal cells. Our study reveals a novel strategy for the assembly of cortical circuits that involves the differential subcellular sorting of family-related synaptic proteins.
- Oscar Marín
- Beatriz Rico
- Oscar Marín
- Beatriz Rico
- Oscar Marín
- David Exposito-Alonso
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals in accordance with European regulations, and Home Office personal and project licenses (PPL 0808-2004-2019, PPL PD025E9BC-2019-2024) under the UK Animals (Scientific Procedures) 1986 Act. The experiments performed in this study, have been designed to follow the 3R's rules whenever possible.
- Nils Brose, Max Planck Institute of Experimental Medicine, Germany
- Received: March 17, 2020
- Accepted: December 14, 2020
- Accepted Manuscript published: December 15, 2020 (version 1)
? 2020, Exposito-Alonso et al.
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