AUTHOR=Duan Jingjing , Pandey Saurabh , Li Tianming , Castellano David , Gu Xinglong , Li Jun , Tian Qingjun , Lu Wei 

TITLE=Genetic Deletion of GABAA Receptors Reveals Distinct Requirements of Neurotransmitter Receptors for GABAergic and Glutamatergic Synapse Development

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=13

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00217

DOI=10.3389/fncel.2019.00217

ISSN=1662-5102

ABSTRACT=<p>In the adult brain GABA<sub>A</sub> receptors (GABA<sub>A</sub>Rs) mediate the majority of synaptic inhibition that provides inhibitory balance to excitatory drive and controls neuronal output. In the immature brain GABA<sub>A</sub>R signaling is critical for neuronal development. However, the cell-autonomous role of GABA<sub>A</sub>Rs in synapse development remains largely unknown. We have employed the CRISPR-CAS9 technology to genetically eliminate GABA<sub>A</sub>Rs in individual hippocampal neurons and examined GABAergic and glutamatergic synapses. We found that development of GABAergic synapses, but not glutamatergic synapses, critically depends on GABA<sub>A</sub>Rs. By combining different genetic approaches, we have also removed GABA<sub>A</sub>Rs and two ionotropic glutamate receptors, AMPA receptors (AMPARs) and NMDA receptors (NMDARs), in single neurons and discovered a striking dichotomy. Indeed, while development of glutamatergic synapses and spines does not require signaling mediated by these receptors, inhibitory synapse formation is crucially dependent on them. Our data reveal a critical cell-autonomous role of GABA<sub>A</sub>Rs in inhibitory synaptogenesis and demonstrate distinct molecular mechanisms for development of inhibitory and excitatory synapses.</p>