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  3. The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation

The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation

  • bioRxiv. 2023 Sep 15:2023.06.21.545778. doi: 10.1101/2023.06.21.545778.
Catherine Elorette 1,  Atsushi Fujimoto 1,  Frederic M Stoll 1,  Satoka H Fujimoto 1,  Lazar Fleysher 2,  Niranjana Bienkowska 1,  Brian E Russ 1 3 4,  Peter H Rudebeck 1
Affiliations

Affiliations

  • 1 Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029.
  • 2 BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029.
  • 3 Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY 10962.
  • 4 Department of Psychiatry, New York University at Langone, One, 8, Park Ave, New York, NY 10016.
PMID: 37745436 DOI: 10.1101/2023.06.21.545778
Abstract

Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations of fronto-limbic circuits. Understanding the relationship between rs-FC and neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by designer drugs (DREADDs) into the macaque amygdala and activated them with a highly selective and potent DREADD agonist, deschloroclozapine. We evaluated the causal effect of activating the DREADD receptors on rs-FC and neural activity within circuits connecting amygdala and frontal cortex. Interestingly, activating the inhibitory DREADD increased rs-FC between amygdala and ventrolateral prefrontal cortex. Neurophysiological recordings revealed that the DREADD-induced increase in fMRI rs-FC was associated with increased local field potential coherency in the alpha band (6.5-14.5Hz) between amygdala and ventrolateral prefrontal cortex. Thus, our multi-disciplinary approach reveals the specific signature of neuronal activity that underlies rs-FC in fronto-limbic circuits.

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