Sunday 13th November, 9:00-10:00
8:00- 12:00 - Dynamic Neurovascular and Activity Changes in the Brain (141)
Chemogenetic stimulation of oxytocinergic neurons dynamically modulates fMRI connectivity
C. Montani1, *A. Hayward1, D. Gutierrez-Barragan1, G. Morelli2, F. G. Alvino1, L. Coletta1,3, A. Galbusera1, M. Pasqualetti4, L. Cancedda2, A. Gozzi1
1) Functional Neuroimaging Lab., Inst. Italiano di Tecnologia, Rovereto, Italy; 2) Brain Develop. and Dis. Lab., Inst. Italiano di Tecnologia, Genoa, Italy; 3) CIMeC - Ctr. for Mind/Brain Sci., Univ. of Trento, Rovereto, Italy; 4) Unit of Cell and Developmental Biology, Dept. of Biol., Univ. of Pisa, Pisa, Italy
Presentation Number: 141.06
Presentation Time: Sun., Nov. 13, 2022 9:00 AM - 10:00 AM
Posterboard Number: TBD
Oxytocin (OXT) is a key modulator of complex socio-affective behaviors. However, the brain-wide networks endogenously modulated by OXT remain poorly understood.
Here, we combine chemogenetics and fMRI to map the topography and dynamics of brain networks engaged by endogenously-released OXT in the mammalian brain. To remotely stimulate endogenous OXT release, we crossed mice harboring a double-floxed DREADD activator hM3Dq with OXT-specific Cre-recombinase mice, leading to cell-type specific expression of hM3Dq in OXT-producing neurons. Stimulation of DREADD receptors with the selective JHU37160 actuator in OXT-hM3Dq mice produced physiologically-relevant release of OXT, an effect that was associated with increased grooming behavior as previously reported.
fMRI mapping of OXT-evoked activity in OXT-hM3Dq (n=20) vs. control (n=21) mice revealed sustained fMRI (cerebral blood volume) activation of parietal cortical areas, hypothalamus and dorsal hippocampal regions. These effects were associated with a dramatic reconfiguration of fMRI connectivity as assessed with resting state fMRI. Specifically, chemogenetic stimulation of OXT-producing neurons robustly increased functional connectivity between hypothalamic regions and prefrontal areas, and by inverse coupling between insular and amygdala regions of the rodent salience network, and between the hippocampus and fronto-cortical areas. Notably, these changes were paralleled by a distinct reorganization of the temporal structure of rsfMRI connectivity, with a robustly increased occurrence of dynamics states encompassing the rodent salience network, which were configured as network attractors.
Taken together, these results show that endogenous OXT can rapidly and robustly alter interareal communication between key components of the social brain via temporal re-organization of fMRI dynamics.