Basal forebrain cholinergic neurons (BFCNs) project throughout the cortex to regulate arousal, stimulus salience, plasticity, and learning. Although often treated as a monolithic structure, the basal forebrain features distinct connectivity along its rostrocaudal axis that could impart regional differences in BFCN processing. Here, we performed simultaneous bulk calcium imaging from rostral and caudal BFCNs over a one-month period of variable reinforcement learning in mice. BFCNs in both regions showed equivalently weak responses to unconditioned visual stimuli and anticipated rewards. Rostral BFCNs in the horizontal limb of the diagonal band were more responsive to reward omission, more accurately classified behavioral outcomes, and more closely tracked fluctuations in pupil-indexed global brain state. Caudal tail BFCNs in globus pallidus and substantia innominata were more responsive to unconditioned auditory stimuli, orofacial movements, aversive reinforcement, and showed robust associative plasticity for punishment-predicting cues. These results identify a functional topography that diversifies cholinergic modulatory signals broadcast to downstream brain regions.
Figure 1 - Source Data 1 contains the data for Figure 1D. All data generated or analyzed during this study are available on Mendeley Data (doi:10.17632/d8tjdxyjcm.2)
Data for: "A functional topography within the cholinergic basal forebrain for encoding sensory cues and behavioral reinforcement outcomes."Mendeley Data, doi: 10.17632/d8tjdxyjcm.2.
- Daniel B Polley
- Daniel B Polley
- Blaise Robert
- Blaise Robert
- Eyal Y Kimchi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All procedures were approved by the Massachusetts Eye and Ear Animal Care and Use Committee (protocol #10-03-006A) and followed the guidelines established by the National Institutes of Health for the care and use of laboratory animals.
- Martin Vinck, Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Germany
© 2021, Robert et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
An animal entering a new environment typically faces three challenges: explore the space for resources, memorize their locations, and navigate towards those targets as needed. Here we propose a neural algorithm that can solve all these problems and operates reliably in diverse and complex environments. At its core, the mechanism makes use of a behavioral module common to all motile animals, namely the ability to follow an odor to its source. We show how the brain can learn to generate internal “virtual odors” that guide the animal to any location of interest. This endotaxis algorithm can be implemented with a simple 3-layer neural circuit using only biologically realistic structures and learning rules. Several neural components of this scheme are found in brains from insects to humans. Nature may have evolved a general mechanism for search and navigation on the ancient backbone of chemotaxis.
Automatic leveraging of information in a hippocampal neuron database to generate mathematical models should help foster interactions between experimental and computational neuroscientists.