Increased fMRI connectivity upon chemogenetic inhibition of the mouse prefrontal cortex

TY - JOUR

T1 - Increased fMRI connectivity upon chemogenetic inhibition of the mouse prefrontal cortex

AU - Rocchi, Federico

AU - Canella, Carola

AU - Noei, Shahryar

AU - Gutierrez-Barragan, Daniel

AU - Coletta, Ludovico

AU - Galbusera, Alberto

AU - Stuefer, Alexia

AU - Vassanelli, Stefano

AU - Pasqualetti, Massimo

AU - Iurilli, Giuliano

AU - Panzeri, Stefano

AU - Gozzi, Alessandro

N1 - © 2022. The Author(s).

PY - 2022/2/25

Y1 - 2022/2/25

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-022-28591-3

DO - 10.1038/s41467-022-28591-3

M3 - SCORING: Journal article

C2 - 35217677

VL - 13

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

M1 - 1056

ER -