Work

Chemogenetic silencing reveals presynaptic Gi/o protein-mediated inhibition of developing hippocampal synchrony in vivo

Year: 2024

Type: article

Abstract: Recent advances in understanding how neuronal activity shapes developing brain circuits increasingly rely on G i/o -dependent inhibitory chemogenetic tools (G i -DREADDs). However, their mechanisms of action and efficacy in neurons with immature G i/o signaling are elusive. Here, we express the G i -DREADD hM4Di in glutamatergic telencephalic neurons and analyze its impact on CA1 pyramidal neurons in neonatal mice. Using acousto-optic two-photon Ca 2+ imaging, we report that activation of hM4Di leads to a complete arrest of spontaneous synchrony in CA1 in vitro . We demonstrate that hM4Di does not cause somatic hyperpolarization or shunting but rather mediates presynaptic silencing of glutamatergic neurotransmission. In vivo , inhibition through hM4Di potently suppresses early sharp waves (eSPWs) and discontinuous oscillatory network activity in CA1 of head-fixed mice before eye opening. Our findings provide insights into the role of G i/o signaling in synchronized activity in the neonatal hippocampus and bear relevance for applying chemogenetic silencing at early developmental stages.

Source: iScience

DOI: 10.1016/j.isci.2024.110997

Authors: Jürgen Graf, Arash Samiee, Tom Flossmann, Knut Holthoff, Knut Kirmse

Institutions: Jena University Hospital, University of Würzburg

Language: English

Topic: Neuroscience and Neuropharmacology Research

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,150