A novel approach to map induced activation of neuronal networks using chemogenetics and functional neuroimaging in rats: A proof-of-concept study on the mesocorticolimbic system

NeuroImage
T J M RoelofsRick M Dijkhuizen

Abstract

Linking neural circuit activation at whole-brain level to neuronal activity at cellular level remains one of the major challenges in neuroscience research. We set up a novel functional neuroimaging approach to map global effects of locally induced activation of specific midbrain projection neurons using chemogenetics (Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-technology) combined with pharmacological magnetic resonance imaging (phMRI) in the rat mesocorticolimbic system. Chemogenetic activation of DREADD-targeted mesolimbic or mesocortical pathways, i.e. projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc) or medial prefrontal cortex (mPFC), respectively, induced significant blood oxygenation level-dependent (BOLD) responses in areas with DREADD expression, but also in remote defined neural circuitry without DREADD expression. The time-course of brain activation corresponded with the behavioral output measure, i.e. locomotor (hyper)activity, in the mesolimbic pathway-targeted group. Chemogenetic activation specifically increased neuronal activity, whereas functional connectivity assessed with resting state functional MRI (rs-fMRI) remained stable. Positive and negative BOLD...Continue Reading

Citations

Oct 31, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Milou StraathofWillem M Otte
Mar 1, 2019·Pharmacological Reviews·Annika Højrup RunegaardUlrik Gether
May 23, 2018·Disease Models & Mechanisms·Mazen Asaad, Jin Hyung Lee
Feb 11, 2020·Frontiers in Neuroinformatics·Francesca MandinoJoanes Grandjean
Jan 7, 2019·NeuroImage·Zhe HanZhifeng Liang
Aug 28, 2020·IScience·Lore M PeetersGeorgios A Keliris
Apr 25, 2021·Trends in Neurosciences·Anne-Noël SamahaTerry E Robinson
Dec 4, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jingwei SongMichael Michaelides

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