Dissociation between hemodynamic and neurochemical responses during chemogenetic modulation of cortical circuits in rats
Abstract
Introduction: Chemogenetic tools such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) provide a powerful means to causally manipulate defined neuronal populations in vivo. While chemogenetic fMRI studies have consistently demonstrated robust hemodynamic responses following circuit perturbation, considerably less is known about the accompanying metabolic consequences. Functional magnetic resonance spectroscopy (fMRS) offers the potential to probe these neurochemical processes, yet the relationship between hemodynamic and metabolic responses remains poorly understood. Here, we combined chemogenetics, pharmacological fMRI (ph-fMRI), and proton magnetic resonance spectroscopy ( 1 H-MRS/fMRS) at 7 T to investigate the temporal evolution of metabolic and hemodynamic responses in the rat motor cortex.
Methods: Female Fischer rats received viral injections in the motor cortex to express either a pan-neuronal hM3D(Gq) DREADD construct (hSyn-hM3Dq) or an interneuron-targeted construct (hDlx-hM3Dq). Ph-fMRI, fMRS, and 1 H-MRS measurements were performed before, during, and following systemic administration of clozapine-N-oxide (CNO, 1 mg/kg). Functional MRS was acquired during the acute response phase (0–60 min post-injection), while conventional 1 H-MRS measurements were obtained at a delayed time point (70 min post-injection).
Results: Chemogenetic modulation produced robust and opposing hemodynamic responses. Pan-neuronal activation elicited focal positive…
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