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Cholinergic basal forebrain (CBF) signaling exhibits multiple timescales of activity with classic slow signals related to brain and behavioral states and fast, phasic signals reflecting behavioral events, including movement, reinforcement and sensory-evoked responses. However, it remains unknown whether sensory cholinergic signals target the sensory cortex and how they relate to local functional topography. Here we used simultaneous two-channel, two-photon imaging of CBF axons and auditory cortical neurons to reveal that CBF axons send a robust, nonhabituating and stimulus-specific sensory signal to the auditory cortex. Individual axon segments exhibited heterogeneous but stable tuning to auditory stimuli allowing stimulus identity to be decoded from population activity. However, CBF axons displayed no tonotopy and their frequency tuning was uncoupled from that of nearby cortical neurons. Chemogenetic suppression revealed the auditory thalamus as a major source of auditory information to the CBF. Finally, slow fluctuations in cholinergic activity modulated the fast, sensory-evoked signals in the same axons, suggesting that a multiplexed combination of fast and slow signals is projected from the CBF to the auditory cortex. Taken together, our work demonstrates a noncanonical function of the CBF as a parallel channel for state-dependent sensory signaling to the sensory cortex that provides repeated representations of a broad range of sound stimuli at all points on the tonotopic map.
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Pyramidal cell types drive functionally distinct cortical activity patterns during decision-making
Abstract Understanding how cortical circuits generate complex behavior requires investigating the cell types that comprise them. Functional differences across pyramidal neuron (PyN) types have been observed within cortical areas, but it is not known whether these local differences extend throughout the cortex, nor whether additional differences emerge when larger-scale dynamics are considered. We used genetic and retrograde labeling to target pyramidal tract, intratelencephalic and corticostriatal projection neurons and measured their cortex-wide activity. Each PyN type drove unique neural dynamics, both at the local and cortex-wide scales. Cortical activity and optogenetic inactivation during an auditory decision task revealed distinct functional roles. All PyNs in parietal cortex were recruited during perception of the auditory stimulus, but, surprisingly, pyramidal tract neurons had the largest causal role. In frontal cortex, all PyNs were required for accurate choices but showed distinct choice tuning. Our results reveal that rich, cell-type-specific cortical dynamics shape perceptual decisions.
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- Award ID(s):
- 1950621
- PAR ID:
- 10620768
- Publisher / Repository:
- Springer Science
- Date Published:
- Journal Name:
- Nature Neuroscience
- ISSN:
- 1097-6256
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s41593-022-01245-9
