Abstract
The basal forebrain cholinergic system (BFCS) robustly modulates many important behaviors, such as arousal, attention, learning and memory, through heavy projections to cortex and hippocampus. However, the presynaptic partners governing BFCS activity still remain poorly understood. Here, we utilized a recently developed rabies virus-based cell-type-specific retrograde tracing system to map the whole-brain afferent inputs of the BFCS. We found that the BFCS receives inputs from multiple cortical areas, such as orbital frontal cortex, motor cortex, and insular cortex, and that the BFCS also receives dense inputs from several subcortical nuclei related to motivation and stress, including lateral septum, central amygdala, paraventricular nucleus of hypothalamus, dorsal raphe, and parabrachial nucleus. Interestingly, we found that the BFCS receives inputs from the olfactory areas and the entorhinal–hippocampal system. These results greatly expand our knowledge about the connectivity of the mouse BFCS and provided important preliminary indications for future exploration of circuit function.
Highlights
Acetylcholine is very important for brain function and has the ability to reconfigure the brain network drastically (Bargmann, 2012)
We genetically targeted the basal forebrain cholinergic system (BFCS) based on a transgenic mouse line expressing Cre recombinase in cholinergic neurons (ChATCre mice) (Gong et al, 2007)
We carried out the immunostaining experiments to characterize the inputs from the orbitofrontal cortex (OFC) and piriform cortex (PC), and the results showed that the neurons in the OFC and PC that target the BFCS are not parvalbumin-positive neurons (Supplementary Figure S3)
Summary
Acetylcholine is very important for brain function and has the ability to reconfigure the brain network drastically (Bargmann, 2012). The basal forebrain cholinergic system (BFCS) has been related to brain states and believed to regulate several important behaviors, remarkably involving sleep, attention, decision making (Kilgard, 2003; Yeomans, 2012; Chubykin et al, 2013; Irmak and De Lecea, 2014; Shi et al, 2015). The dysfunction of BFCS is related to neurological disorders such as Alzheimer’s disease (AD) and schizophrenia (Cuello et al, 2010; Bohnen and Albin, 2011; Marra et al, 2012; Banuelos et al, 2013; Burke et al, 2013). BF nuclei show heterogeneous (Zaborszky et al, 2012). Different type of BF neurons have variable physiological properties and response dynamics to stimuli, representing their specific repertoire of afferent inputs (Hangya et al, 2015).
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