Cell-type specific deletions of Neuroligin 2 reveal a vital role of synaptic excitation-inhibition balance

Longley, C. M.; Xu, X.; Messier, J. E.; Cai, Z.-L.; Park, J. W.; Chen, H.; Reznik, D. L.; Jadi, M. P.; Xue, M.

doi:10.1101/2022.09.23.509267

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bioRxiv · 10.1101/2022.09.23.509267

Cell-type specific deletions of Neuroligin 2 reveal a vital role of synaptic excitation-inhibition balance

Longley, C. M.·Xu, X.·Messier, J. E.·Cai, Z.-L.·Park, J. W.·Chen, H.·Reznik, D. L.·Jadi, M. P.·Xue, M.

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Abstract

Synaptic excitation (E) and inhibition (I) stay relatively proportional to each other over different spatiotemporal scales, orchestrating neuronal activity in the brain. This proportionality, referred to as E-I balance, is thought to be critical for neuronal functions because its disruption was observed in many neurological disorders. However, the causal evidence demonstrating its significance is scarce. Here we show that deleting Neuroligin-2 (Nlgn2), a postsynaptic adhesion molecule at inhibitory synapses, from mouse glutamatergic or GABAergic neurons reduces inhibition cell-autonomously without affecting excitation, thereby disrupting E-I balance and causing lethality. In contrast, deleting Nlgn2 constitutively or simultaneously from both glutamatergic and GABAergic neurons results in viable mice. A neural network model shows that reducing inhibition in either neuronal type is detrimental to network activity, but in both types partially re-establishes E-I balance and activity. Together, our results provide evidence for an essential role of E-I balance in brain functions and organism survival.

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Longley, C. M., Xu, X., Messier, J. E., Cai, Z.-L., Park, J. W., Chen, H., Reznik, D. L., Jadi, M. P., Xue, M.. 2022-09-24. Cell-type specific deletions of Neuroligin 2 reveal a vital role of synaptic excitation-inhibition balance. https://doi.org/10.1101/2022.09.23.509267

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