Increased fMRI connectivity upon chemogenetic inhibition of the mouse prefrontal cortex

Federico Rocchi, Carola Canella, Shahryar Noei, Daniel Gutierrez-Barragan, Ludovico Coletta, Alberto Galbusera, Alexia Stuefer, Stefano Vassanelli, Massimo Pasqualetti, Giuliano Iurilli, Stefano Panzeri () and Alessandro Gozzi ()
Additional contact information
Federico Rocchi: Istituto Italiano di Tecnologia
Carola Canella: Istituto Italiano di Tecnologia
Shahryar Noei: University of Trento
Daniel Gutierrez-Barragan: Istituto Italiano di Tecnologia
Ludovico Coletta: Istituto Italiano di Tecnologia
Alberto Galbusera: Istituto Italiano di Tecnologia
Alexia Stuefer: Istituto Italiano di Tecnologia
Stefano Vassanelli: University of Padova
Massimo Pasqualetti: Istituto Italiano di Tecnologia
Giuliano Iurilli: Istituto Italiano di Tecnologia
Stefano Panzeri: Istituto Italiano di Tecnologia
Alessandro Gozzi: Istituto Italiano di Tecnologia

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract While shaped and constrained by axonal connections, fMRI-based functional connectivity reorganizes in response to varying interareal input or pathological perturbations. However, the causal contribution of regional brain activity to whole-brain fMRI network organization remains unclear. Here we combine neural manipulations, resting-state fMRI and in vivo electrophysiology to probe how inactivation of a cortical node causally affects brain-wide fMRI coupling in the mouse. We find that chronic inhibition of the medial prefrontal cortex (PFC) via overexpression of a potassium channel increases fMRI connectivity between the inhibited area and its direct thalamo-cortical targets. Acute chemogenetic inhibition of the PFC produces analogous patterns of fMRI overconnectivity. Using in vivo electrophysiology, we find that chemogenetic inhibition of the PFC enhances low frequency (0.1–4 Hz) oscillatory power via suppression of neural firing not phase-locked to slow rhythms, resulting in increased slow and δ band coherence between areas that exhibit fMRI overconnectivity. These results provide causal evidence that cortical inactivation can counterintuitively increase fMRI connectivity via enhanced, less-localized slow oscillatory processes.

Date: 2022
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DOI: 10.1038/s41467-022-28591-3

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