scholarly journals Selective optogenetic stimulation of cholinergic axons in neocortex

2012 ◽  
Vol 107 (7) ◽  
pp. 2008-2019 ◽  
Author(s):  
Abigail Kalmbach ◽  
Tristan Hedrick ◽  
Jack Waters
Keyword(s):  
Cellular Network ◽  
Viral Vector ◽  
Field Potential ◽  
Cholinergic Neurons ◽  
Nucleus Basalis ◽  
Novel Technique ◽  
Optogenetic Stimulation ◽  
Cholinergic Signaling ◽  
Behavioral Physiology ◽  
Stimulation Of

Acetylcholine profoundly affects neocortical function, being involved in arousal, attention, learning, memory, sensory and motor function, and plasticity. The majority of cholinergic afferents to neocortex are from neurons in nucleus basalis. Nucleus basalis also contains projecting neurons that release other transmitters, including GABA and possibly glutamate. Hence, electrical stimulation of nucleus basalis evokes the release of a mixture of neurotransmitters in neocortex, and this lack of selectivity has impeded research on cholinergic signaling in neocortex. We describe a method for the selective stimulation of cholinergic axons in neocortex. We used the Cre-lox system and a viral vector to express the light-activated protein channelrhodopsin-2 in cholinergic neurons in nucleus basalis and their axons in neocortex. Labeled neurons depolarized on illumination with blue light but were otherwise unchanged. In anesthetized mice, illumination of neocortex desynchronized the local field potential, indicating that light evoked release of ACh. This novel technique will enable many new studies of the cellular, network, and behavioral physiology of ACh in neocortex.

scholarly journals Cholinergic upregulation by optogenetic stimulation of nucleus basalis after photothrombotic stroke in forelimb somatosensory cortex improves endpoint and motor but not sensory control of skilled reaching in mice

2020 ◽  
Author(s):  
Behroo Mirza Agha ◽  
Roya Akbary ◽  
Arashk Ghasroddashti ◽  
Mojtaba Nazari-Ahangarkolaee ◽  
Ian Q. Whishaw ◽  
...  
Keyword(s):  
Somatosensory Cortex ◽  
Sensorimotor Integration ◽  
Motor Behavior ◽  
Field Potential ◽  
Cholinergic Neurons ◽  
Nucleus Basalis ◽  
Optogenetic Stimulation ◽  
Photothrombotic Stroke ◽  
Skilled Reaching ◽  
Stimulation Of

AbstractA network of cholinergic neurons in the basal forebrain innerve the forebrain and are proposed to contribute to a variety of functions including attention, and cortical plasticity. This study examined the contribution of the nucleus basalis cholinergic projection to the sensorimotor cortex on recovery on a skilled reach-to-eat task following photothrombotic stroke in the forelimb region of the somatosensory cortex. Mice were trained to perform a single-pellet skilled reaching task and their pre and poststroke performance, from Day 4 to Day 28 poststroke, was assessed frame-by-frame by video analysis with end point, movement and sensorimotor integration measures. Somatosensory forelimb lesions produced impairments in endpoint and movement component measures of reaching and increased the incidence of fictive eating, a sensory impairment in mistaking a missed reach for a successful reach. Upregulated acetylcholine (ACh) release, as measured by local field potential recording, elicited via optogenetic stimulation of the nucleus basalis improved recovery of reaching and improved movement scores but did not affect a sensorimotor integration impairment poststroke. The results show that the mouse cortical forelimb somatosensory region contributes to forelimb motor behavior and suggest that ACh upregulation could serve as an adjunct to behavioral therapy for the acute treatment of stroke.

scholarly journals Cholinergic upregulation by optogenetic stimulation of nucleus basalis after photothrombotic stroke in forelimb somatosensory cortex improves endpoint and motor but not sensory control of skilled reaching in mice

2020 ◽  
pp. 0271678X2096893
Author(s):  
Behroo Mirza Agha ◽  
Roya Akbary ◽  
Arashk Ghasroddashti ◽  
Mojtaba Nazari-Ahangarkolaee ◽  
Ian Q Whishaw ◽  
...  
Keyword(s):  
Somatosensory Cortex ◽  
Sensorimotor Integration ◽  
Motor Behavior ◽  
Field Potential ◽  
Cholinergic Neurons ◽  
Nucleus Basalis ◽  
Optogenetic Stimulation ◽  
Photothrombotic Stroke ◽  
Skilled Reaching ◽  
Stimulation Of

A network of cholinergic neurons in the basal forebrain innerve the forebrain and are proposed to contribute to a variety of functions including cortical plasticity, attention, and sensorimotor behavior. This study examined the contribution of the nucleus basalis cholinergic projection to the sensorimotor cortex on recovery on a skilled reach-to-eat task following photothrombotic stroke in the forelimb region of the somatosensory cortex. Mice were trained to perform a single pellet skilled reaching task and their pre and poststroke performance, from Day 4 to Day 28 poststroke, was assessed frame-by-frame by video analysis with endpoint, movement and sensorimotor integration measures. Somatosensory forelimb lesions produced impairments in endpoint and movement component measures of reaching and increased the incidence of fictive eating, a sensory impairment in mistaking a missed reach for a successful reach. Upregulated acetylcholine (ACh) release, as measured by local field potential recording, elicited via optogenetic stimulation of the nucleus basalis improved recovery of reaching and improved movement scores but did not affect sensorimotor integration impairment poststroke. The results show that the mouse cortical forelimb somatosensory region contributes to forelimb motor behavior and suggest that ACh upregulation could serve as an adjunct to behavioral therapy for acute treatment of stroke.

scholarly journals Cholinergic suppression of hippocampal sharp-wave ripples impairs working memory

2021 ◽  
Vol 118 (15) ◽  
pp. e2016432118
Author(s):  
Yiyao Zhang ◽  
Liang Cao ◽  
Viktor Varga ◽  
Miao Jing ◽  
Mursel Karadas ◽  
...  
Keyword(s):  
Memory Performance ◽  
Cholinergic Neurons ◽  
Receptor Activation ◽  
Optogenetic Stimulation ◽  
Sharp Wave ◽  
Cholinergic Signaling ◽  
Gamma Power ◽  
Hippocampal Theta ◽  
G Protein Coupled ◽  
Stimulation Of

Learning and memory are assumed to be supported by mechanisms that involve cholinergic transmission and hippocampal theta. Using G protein–coupled receptor-activation–based acetylcholine sensor (GRABACh3.0) with a fiber-photometric fluorescence readout in mice, we found that cholinergic signaling in the hippocampus increased in parallel with theta/gamma power during walking and REM sleep, while ACh3.0 signal reached a minimum during hippocampal sharp-wave ripples (SPW-R). Unexpectedly, memory performance was impaired in a hippocampus-dependent spontaneous alternation task by selective optogenetic stimulation of medial septal cholinergic neurons when the stimulation was applied in the delay area but not in the central (choice) arm of the maze. Parallel with the decreased performance, optogenetic stimulation decreased the incidence of SPW-Rs. These findings suggest that septo–hippocampal interactions play a task-phase–dependent dual role in the maintenance of memory performance, including not only theta mechanisms but also SPW-Rs.

scholarly journals Contribution of the basal forebrain to corticocortical network interactions

2021 ◽  
Author(s):  
Peter Gombkoto ◽  
Matthew Gielow ◽  
Peter Varsanyi ◽  
Candice Chavez ◽  
Laszlo Zaborszky
Keyword(s):  
Sensory Processing ◽  
Basal Forebrain ◽  
Field Potential ◽  
Cholinergic Neurons ◽  
Attention And Memory ◽  
Cortical Circuits ◽  
Cholinergic Signaling ◽  
Spatial Changes ◽  
Gamma Power ◽  
Gamma Coherence

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.

scholarly journals Basal forebrain cholinergic neurons are part of the threat memory engram

2021 ◽  
Author(s):  
Prithviraj Rajebhosale ◽  
Mala R Ananth ◽  
Richard B Crouse ◽  
Li Jiang ◽  
Gretchen López- Hernández ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Basolateral Amygdala ◽  
Cholinergic Neurons ◽  
Nucleus Basalis ◽  
Early Gene ◽  
Intrinsic Excitability ◽  
Cholinergic Basal Forebrain ◽  
Basal Forebrain Cholinergic Neurons ◽  
Cholinergic Signaling ◽  
Memory Engram

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.

074 Basal Forebrain GABAergic Neurons Promote Arousal by Disinhibiting the Orexin Neurons via Local GABAergic Interneurons

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A31-A31
Author(s):  
Michela Cristofolini ◽  
Roberto De Luca ◽  
Anne Venner ◽  
Loris Ferrari ◽  
Kevin Grace ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Viral Vector ◽  
Brain Slices ◽  
Nrem Sleep ◽  
Gabaergic Neurons ◽  
Gabaergic Interneurons ◽  
Optogenetic Stimulation ◽  
Stimulation Of

Abstract Introduction Optogenetic and chemogenetic studies have shown that activation of basal forebrain (BF) GABAergic neurons rapidly wakes up mice from non-REM (NREM) sleep. These wake-promoting responses have been attributed to BF GABAergic neurons projecting to the cerebral cortex and more specifically to the inhibition of cortical fast-spiking interneurons. Tracing studies have however found that BF GABAergic neurons also densely innervate the lateral hypothalamus (LH) perifornical area, although the role of this pathway in behavioral state control remains mostly unexplored. Methods We conducted in vivo and in vitro optogenetic studies. We selectively expressed channelrhodopsin-2 (ChR2) in BF GABAergic neurons by injecting a cre-dependent viral vector encoding for ChR2 into the BF of VGAT-cre mice. We photostimulated the BF GABAergic input to the LH with optical fibers placed into the LH of EEG instrumented mice. For in vitro recordings we expressed ChR2 in BF GABAergic neurons and we fluorescently labeled orexin or LH GABAergic neurons. We recorded in brain slices from identified orexin neurons or GABA neurons while photostimulating the BF GABAergic input. Results Optogenetic stimulation of the BF GABAergic fibers in the LH produced rapid arousals from NREM sleep. The same stimulation however did not wake up the mice if they were in REM sleep. We conducted additional studies in brain slices to identify the postsynaptic neurons in the LH targeted by the BF GABAergic input. We found that while optogenetic stimulation of the BF GABAergic input did not produce opto-evoked synaptic responses in the orexin neurons, it produced short-latency opto-evoked inhibitory postsynaptic currents (IPSCs) in LH GABAergic neurons. These opto-evoked IPSCs were GABAA receptor-mediated and were maintained in tetrodotoxin (TTX) indicating monosynaptic connectivity. We have previously found that orexin neurons are inhibited by local LH GABAergic neurons. Our hypothesis is that these local GABAergic interneurons are the target of the BF GABAergic arousal input. Conclusion BF GABAergic neurons drive arousal through projections to the LH. We propose that this arousal response is due to the inhibition of local GABAergic interneurons which in turn disinhibit the LH wake-promoting neurons including the orexin neurons. Support (if any) NS091126 and HL149630

scholarly journals Impaired spatial learning and suppression of sharp wave ripples by cholinergic activation at the goal location

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Przemyslaw Jarzebowski ◽  
Clara S Tang ◽  
Ole Paulsen ◽  
Y Audrey Hay
Keyword(s):  
Cholinergic Neurons ◽  
Memory Formation ◽  
Long Term Memory ◽  
Term Memory ◽  
Goal Location ◽  
Optogenetic Stimulation ◽  
Sharp Wave ◽  
Network States ◽  
Stimulation Of

The hippocampus plays a central role in long-term memory formation, and different hippocampal network states are thought to have different functions in this process. These network states are controlled by neuromodulatory inputs, including the cholinergic input from the medial septum. Here, we used optogenetic stimulation of septal cholinergic neurons to understand how cholinergic activity affects different stages of spatial memory formation in a reward-based navigation task in mice. We found that optogenetic stimulation of septal cholinergic neurons (1) impaired memory formation when activated at goal location but not during navigation; (2) reduced sharp wave-ripple (SWR) incidence at goal location; and (3) reduced SWR incidence and enhanced theta-gamma oscillations during sleep. These results underscore the importance of appropriate timing of cholinergic input in long-term memory formation, which might help explain the limited success of cholinesterase inhibitor drugs in treating memory impairment in Alzheimer's disease.

scholarly journals Impaired spatial learning and suppression of sharp wave ripples by cholinergic activation at the goal location

2020 ◽  
Author(s):  
Przemyslaw Jarzebowski ◽  
Clara S Tang ◽  
Ole Paulsen ◽  
Y. Audrey Hay
Keyword(s):  
Cholinergic Neurons ◽  
Memory Formation ◽  
Long Term Memory ◽  
Term Memory ◽  
Goal Location ◽  
Optogenetic Stimulation ◽  
Sharp Wave ◽  
Network States ◽  
Stimulation Of

The hippocampus plays a central role in long-term memory formation, and different hippocampal network states are thought to have different functions in this process. These network states are controlled by neuromodulatory inputs, including the cholinergic input from the medial septum. Here, we used optogenetic stimulation of septal cholinergic neurons to understand how cholinergic activity affects different stages of spatial memory formation in a reward-based navigation task in mice. We found that optogenetic stimulation of septal cholinergic neurons (1) impaired memory formation when activated at goal location but not during navigation; (2) reduced sharp wave-ripple (SWR) incidence at goal location; and (3) reduced SWR incidence and enhanced theta-gamma oscillations during sleep. These results underscore the importance of appropriate timing of cholinergic input in long-term memory formation, which might help explain the limited success of cholinesterase inhibitor drugs in treating memory impairment in Alzheimer's disease.

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