Generation of a whole-brain atlas for the cholinergic system and mesoscopic projectome analysis of basal forebrain cholinergic neurons

Abstract

The cholinergic system in the brain plays crucial roles in regulating sensory and motor functions as well as cognitive behaviors by modulating neuronal activity. Understanding the organization of the cholinergic system requires a complete map of cholinergic neurons and their axon arborizations throughout the entire brain at the level of single neurons. Here, we report a comprehensive whole-brain atlas of the cholinergic system originating from various cortical and subcortical regions of the mouse brain. Using genetically labeled cholinergic neurons together with whole-brain reconstruction of optical images at 2-μm resolution, we obtained quantification of the number and soma volume of cholinergic neurons in 22 brain areas. Furthermore, by reconstructing the complete axonal arbors of fluorescently labeled single neurons from a subregion of the basal forebrain at 1-μm resolution, we found that their projections to the forebrain and midbrain showed neuronal subgroups with distinct projection specificity and diverse arbor distribution within the same projection area. These results suggest the existence of distinct subtypes of cholinergic neurons that serve different regulatory functions in the brain and illustrate the usefulness of complete reconstruction of neuronal distribution and axon projections at the mesoscopic level.

In vivo ectopic Ngn1 and Neurod1 convert neonatal cochlear glial cells into spiral ganglion neurons

“…The “3xEGFP” refers to three DNA elements coding for different EGFPs: Emerald‐GFP (EmGFP), TagGFP2, and humanized Renilla‐GFP (hrGFP). These were connected via the 2A method, as described in one previous study . All mice were maintained according to guidelines of the IACUC of Institute of Neuroscience (ION), Chinese Academy of Sciences.…”

“…These were connected via the 2A method, as described in one previous study. 18 All mice were maintained according to guidelines of the IACUC of Institute of Neuroscience (ION), Chinese Academy of Sciences. Mice of either sex were used for the experiments.…”

Ultrafast immunostaining of organ-scale tissues for scalable proteomic phenotyping

“…Discrepancy between transgenic labeling and immunohistochemical labeling is widely recognized 28 , and there is a constant concerted effort to improve upon existing transgenic mouse lines for common targets [33][34][35] . To compare genetic labeling and eFLASH-mediated cell-type phenotyping approaches, we utilized transgenic mouse lines with two widely used transgene approaches: Cre-LoxP and BAC transgene 28,[36][37][38] .…”

Input dependent modulation of olfactory bulb activity by GABAergic basal forebrain projections

“…The olfactory system in mice is heavily innervated by centrifugal inputs from the BF with the majority of bulbopetal neurons located in the horizontal limb of the diagonal band of Broca (HDB) [21][22][23][24][25][26] .…”