Excitatory neurons sculpt GABAergic neuronal connectivity in the C. elegans motor circuit

Author:

Barbagallo Belinda1,Philbrook Alison1,Touroutine Denis1,Banerjee Navonil1,Oliver Devyn1,Lambert Christopher M.1,Francis Michael M.1

Affiliation:

1. Department of Neurobiology, University of Massachusetts Medical School, Worcester MA, 01605, USA

Abstract

Establishing and maintaining the appropriate number of GABA synapses is key for balancing excitation and inhibition in the nervous system, though we have only a limited understanding of the mechanisms controlling GABA circuit connectivity. Here, we show that disrupting cholinergic innervation of GABAergic neurons in the C. elegans motor circuit alters GABAergic neuron synaptic connectivity. These changes are accompanied by a reduced frequency and increased amplitude of GABAergic synaptic events. Acute genetic disruption in early development–during the integration of post-embryonic born GABAergic neurons into the circuit–produces irreversible effects on GABAergic synaptic connectivity that mimic those produced by chronic manipulations. In contrast, acute genetic disruption of cholinergic signaling in the adult circuit does not reproduce these effects. Our findings reveal that GABAergic signaling is regulated by cholinergic neuronal activity, likely through distinct mechanisms in the developing and mature nervous system.

Funder

National Institute of Neurological Disorders and Stroke

National Institute on Drug Abuse

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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