Glial cells undergo rapid changes following acute chemogenetic manipulation of cortical layer 5 projection neurons

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2024年10月9日

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Auguste Vadisiute,
Elise Meijer,
Rajeevan Narayanan Therpurakal,
Marissa Mueller,
Florina Szabó,
Fernando Messore,
Alfonsas Jursenas,
Oliver Bredemeyer,
Lukas B. Krone,
Ed Mann,
Vladyslav Vyazovskiy,
Anna Hoerder-Suabedissen,
Zoltán Molnár

摘要

Bidirectional communication between neurons and glial cells is crucial to establishing and maintaining normal brain function. Some of these interactions are activity-dependent, yet it remains largely unexplored how acute changes in neuronal activity affect glial-to-neuron and neuron-to-glial dynamics. Here, we use excitatory and inhibitory designer receptors exclusively activated by designer drugs (DREADD) to study the effects of acute chemogenetic manipulations of a subpopulation of layer 5 cortical projection and dentate gyrus neurons in adult (Rbp4^Cre) mouse brains. We show that acute chemogenetic neuronal activation reduces synaptic density, and increases microglia and astrocyte reactivity, but does not affect parvalbumin (PV+) neurons, only perineuronal nets (PNN). Conversely, acute silencing increases synaptic density and decreases glial reactivity. We show fast glial response upon clozapine-N-oxide (CNO) administration in cortical and subcortical regions. Together, our work provides evidence of fast, activity-dependent, bidirectional interactions between neurons and glial cells.