Observational analysis detected changes to gaba and glutamate in mice, indicating the utility of mrs for chemogenetic studies.
Motivation: Excitatory designer receptors (DREADDs) may affect glutamatergic and GABAergic neural signaling. Measuring acute neurochemical changes resulting from DREADDs activation using magnetic resonance spectroscopy (MRS) would provide new capabilities for chemogenetic studies. Goal(s): We investigated the potential for MRS to detect changes to glutamate, GABA, and other neurochemicals following DREADDs activation in the dorsal striatum of mice. Approach: Mice expressing DREADDs in striatal interneurons completed an MRS session during which DREADDs were activated between two MRS acquisitions. Results: We detected significant differences in GABA, glutamate, glutamine, choline, and creatine concentrations following activation of the designer receptors. Sex differences were found. Impact: Our results suggest that magnetic resonance spectroscopy provides noninvasive measurement of changes to glutamate and GABA following acute chemogenetic activation. This presents new opportunities for the optimization of experiments and improved interpretation of results for studies utilizing chemogenetic techniques.
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Baetscher et al. (2025) studied this question.
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