Introduction: Chemogenetic techniques, specifically the use of Designer Receptors
Exclusively Activated by Designer Drugs (DREADDs), have become invaluable tools in
neuroscience research. Yet, the understanding of how Gq- and Gicoupled DREADDs alter
local field potential (LFP) oscillations in vivo remains incomplete. Methods: This
study investigates the in vivo electrophysiological effects of DREADD actuation by
deschloroclozapine, on spontaneous firing rate and LFP oscillations recorded from
the anterior cingulate cortex in lightly anesthetized male rats. Results: Unexpectedly,
in response to the administration of deschloroclozapine, we observed inhibitory effects
with pan-neuronal hM3D(Gq) stimulation, and excitatory effects with pan-neuronal hM4D(Gi)
stimulation in a significant portion of neurons. These results emphasize the need
to account for indirect perturbation effects at the local neuronal network level in
vivo, particularly when not all neurons express the chemogenetic receptors uniformly.
In the current study, for instance, the majority of cells that were transduced with
both hM3D(Gq) and hM4D(Gi) were GABAergic. Moreover, we found that panneuronal cortical
chemogenetic modulation can profoundly alter oscillatory neuronal activity, presenting
a potential research tool or therapeutic strategy in several neuropsychiatric models
and diseases. Discussion: These findings help to optimize the use of chemogenetic
techniques in neuroscience research and open new possibilities for novel therapeutic
strategies.
