Mouse fMRI with optogenetic silencing reveals neural interactions underlying resting-state fMRI

COEX 

Resting-state (RS) fMRI is a potent tool for mapping brain-wide functional connectivity (FC), yet its mechanism remains not fully understood. RS FC only partially corresponds to monosynaptic structural connectivity (SC) while exhibiting strong interhemispheric connections, implicating polysynaptic or indirect connectivity (Honey et al. 2009, Grandjean et al. 2017). However, a causal link between spontaneous neural interactions and FC has yet to be established. Optogenetic fMRI may resolve this question by mapping changes in neural activity induced by precise spatiotemporal neural manipulation (effective connectivity; EC). Notably, optogenetic activation of local excitatory neurons revealed predominantly ipsilateral connections resembling SC (Bauer et al. 2018, Kim et al. 2023). We hypothesized that this discrepancy arises because the upregulation of neural activity does not account for spontaneously occurring connectivity. To address this, we employed optogenetic silencing to assess ongoing interactions during RS. Our study investigated (de)activation patterns resulting from excitatory and inhibitory neuron-specific optogenetic EC and their relationship with SC and FC (Figure 1A).