Cell-type specific optogenetic fMRI on basal forebrain reveals functional network basis of behavioral preference

Abstract

The basal forebrain (BF) is a complex structure that plays key roles in regulating various brain functions. However, it remains unclear how cholinergic and non-cholinergic BF neurons modulate large-scale functional networks and their relevance in intrinsic and extrinsic behaviors. With optimized awake mouse optogenetic fMRI approach, we revealed optogenetic stimulations of four BF neuron types evoked distinct cell-type specific whole-brain BOLD activations, which could attribute to BF-originated low dimensional structural networks. Additionally, optogenetic activation of VGLUT2, ChAT and PV neurons in BF modulated the preference of locomotion, exploration and grooming, respectively. Furthermore, we uncovered the functional network basis of the above BF-modulated behavioral preference, through a decoding model linking the BF-modulated BOLD activations, low dimensional structural networks, and behavioral preference. To summarize, we decoded functional network basis of differential behavioral preference with cell-type specific optogenetic fMRI on BF, and provided an avenue for investigating mouse behaviors from a whole-brain view.