scholarly journals Dynamic cholinergic tone in the basal forebrain reflects reward-seeking and reinforcement during olfactory behavior

2020 ◽  
Author(s):  
Elizabeth Hanson ◽  
Katie L Brandel-Ankrapp ◽  
Benjamin R Arenkiel

AbstractSensory perception underlies how we internalize and interact with the external world. In order to adapt to changing circumstances and interpret signals in a variety of contexts, sensation needs to be reliable, but perception of sensory input needs to be flexible. An important mediator of this flexibility is top-down regulation from the cholinergic basal forebrain. Basal forebrain projection neurons serve as pacemakers and gatekeepers for downstream neural networks, modulating circuit activity across diverse neuronal populations. This top-down control is necessary for sensory cue detection, learning, and memory, and is disproportionately disrupted in neurodegenerative diseases associated with cognitive decline. Intriguingly, cholinergic signaling acts locally within the basal forebrain to sculpt the activity of basal forebrain output neurons. To determine how local cholinergic signaling impacts basal forebrain output pathways that participate in top-down regulation, we sought to define the dynamics of cholinergic signaling within the basal forebrain during motivated behavior and learning. Towards this, we utilized fiber photometry and the genetically encoded acetylcholine indicator GAChR2.0 to define temporal patterns of cholinergic signaling in the basal forebrain during olfactory-guided, motivated behaviors and learning. We show that cholinergic signaling reliably increased during reward-seeking behaviors but was strongly suppressed by reward delivery in a go/no-go, olfactory-cued discrimination task. The observed transient reduction in cholinergic tone was mirrored by a suppression in basal forebrain GABAergic neuronal activity. Together, these findings suggest that cholinergic tone in the basal forebrain changes rapidly to reflect rewardseeking behavior and positive reinforcement to impact basal forebrain circuit activity.

2021 ◽  
Vol 15 ◽  
Author(s):  
Elizabeth Hanson ◽  
Katie L. Brandel-Ankrapp ◽  
Benjamin R. Arenkiel

Sensory perception underlies how we internalize and interact with the external world. In order to adapt to changing circumstances and interpret signals in a variety of contexts, sensation needs to be reliable, but perception of sensory input needs to be flexible. An important mediator of this flexibility is top-down regulation from the cholinergic basal forebrain. Basal forebrain projection neurons serve as pacemakers and gatekeepers for downstream neural networks, modulating circuit activity across diverse neuronal populations. This top-down control is necessary for sensory cue detection, learning, and memory, and is disproportionately disrupted in neurodegenerative diseases associated with cognitive decline. Intriguingly, cholinergic signaling acts locally within the basal forebrain to sculpt the activity of basal forebrain output neurons. To determine how local cholinergic signaling impacts basal forebrain output pathways that participate in top-down regulation, we sought to define the dynamics of cholinergic signaling within the basal forebrain during motivated behavior and learning. Toward this, we utilized fiber photometry and the genetically encoded acetylcholine indicator GAChR2.0 to define temporal patterns of cholinergic signaling in the basal forebrain during olfactory-guided, motivated behaviors and learning. We show that cholinergic signaling reliably increased during reward seeking behaviors, but was strongly suppressed by reward delivery in a go/no-go olfactory-cued discrimination task. The observed transient reduction in cholinergic tone was mirrored by a suppression in basal forebrain GABAergic neuronal activity. Together, these findings suggest that cholinergic tone in the basal forebrain changes rapidly to reflect reward-seeking behavior and positive reinforcement and may impact downstream circuitry that modulates olfaction.


2021 ◽  
Author(s):  
Prithviraj Rajebhosale ◽  
Mala R Ananth ◽  
Richard B Crouse ◽  
Li Jiang ◽  
Gretchen López- Hernández ◽  
...  

Although the engagement of cholinergic signaling in threat memory is well established (Knox, 2016a), our finding that specific cholinergic neurons are requisite partners in a threat memory engram is likely to surprise many. Neurons of the basal forebrain nucleus basalis and substantia innonimata (NBM/SIp) comprise the major source of cholinergic input to the basolateral amygdala (BLA), whose activation are required for both the acquisition and retrieval of cued threat memory and innate threat response behavior. The retrieval of threat memory by the presentation of the conditioning tone alone elicits acetylcholine (ACh) release in the BLA and the BLA-projecting cholinergic neurons manifest immediate early gene responses and display increased intrinsic excitability for 2-5 hours following the cue-elicited memory response to the conditioned stimulus. Silencing cue-associated engram-enrolled cholinergic neurons prevents the expression of the defensive response and the subset of cholinergic neurons activated by cue is distinct from those engaged by innate threat. Taken together we find that distinct populations of cholinergic neurons are recruited to signal distinct aversive stimuli via the BLA, demonstrating exquisite, functionally refined organization of specific types of memory within the cholinergic basal forebrain.


Author(s):  
Peter Gombkoto ◽  
Matthew Gielow ◽  
Peter Varsanyi ◽  
Candice Chavez ◽  
Laszlo Zaborszky

AbstractBasal forebrain (BF) cholinergic neurons provide the cerebral cortex with acetylcholine. Despite the long-established involvement of these cells in sensory processing, attention, and memory, the mechanisms by which cholinergic signaling regulates cognitive processes remain elusive. In this study, we recorded spiking and local field potential data simultaneously from several locations in the BF, and sites in the orbitofrontal and visual cortex in transgenic ChAT-Cre rats performing a visual discrimination task. We observed distinct differences in the fine spatial distributions of gamma coherence values between specific basalo-cortical and cortico-cortical sites that shifted across task phases. Additionally, cholinergic firing induced spatial changes in cortical gamma power, and optogenetic activation of BF increased coherence between specific cortico-cortical sites, suggesting that the cholinergic system contributes to selective modulation of cortico-cortical circuits. Furthermore, the results suggest that cells in specific BF locations are dynamically recruited across behavioral epochs to coordinate interregional cortical processes underlying cognition.


Sign in / Sign up

Export Citation Format

Share Document