Basal forebrain circuit for sleep-wake control

Xu, Min; Chung, Shinjae; Zhang, Siyu; Zhong, Peng; Ma, Chenyan; Chang, W.S.C.; Weissbourd, Brandon; Sakai, Noriaki; Luo, Liqun; Nishino, Seiji; Dan, Yang

doi:10.1038/nn.4143

Cited by 441 publications

(579 citation statements)

References 57 publications

Supporting

Mentioning

537

Contrasting

Unclassified

Order By: Relevance

“…Local BF afferents may also contain GABA and/or glutamate. Local inputs to cholinergic outputs both drive and inhibit ChAT cells, depending on afferent cell identity (Xu et al, 2015). Recent awake behaving physiological data indicate heterogeneous response patterns among BF units becoming activated and inhibited to different phases of a directed attention task (Tingley et al, 2014), patterns which may be carried by local subgroups of BF input impinging on different cholinergic output targets.…”

Section: Resultsmentioning

confidence: 99%

The Input-Output Relationship of the Cholinergic Basal Forebrain

2017

View full text Add to dashboard Cite

Summary Basal forebrain cholinergic neurons influence cortical state, plasticity, learning and attention. They collectively innervate the entire cerebral cortex, differentially controlling acetylcholine efflux across different cortical areas and timescales. Such control might be achieved by differential inputs driving separable cholinergic outputs, although no input-output relationship on a brain-wide level has ever been demonstrated. Here we identify input neurons to cholinergic cells projecting to specific cortical regions by infecting cholinergic axon terminals with a monosynaptically-restricted viral tracer. This approach revealed several circuit motifs, such as central amygdala neurons synapsing onto basolateral amygdala-projecting cholinergic neurons or strong somatosensory cortical input to motor cortex-projecting cholinergic neurons. The presence of input cells in the parasympathetic midbrain nuclei contacting frontally projecting cholinergic neurons suggest that the network regulating the inner eye muscles are additionally regulating cortical state via acetylcholine efflux. This dataset enables future circuit-level experiments to identify drivers of known cholinergic cortical functions.

show abstract

Section: Resultsmentioning

confidence: 99%

The Input-Output Relationship of the Cholinergic Basal Forebrain

2017

View full text Add to dashboard Cite

show abstract

“…In vitro studies have shown that both these BF populations exhibit maximum firing rates above 50 Hz and thus could participate in rhythmic firing at the gamma frequencies reported in the present study. Interestingly, the glutamatergic projection has been shown to be inhibited by cholinergic activation (60,61), which would provide a mechanism by which the DMN is suppressed during externally directed attentional processing. However, the glutamatergic BF population does not support a pronounced projection to the DMN or even to cortex more generally.…”

Section: Discussionmentioning

confidence: 99%

Basal forebrain contributes to default mode network regulation

Nair

Klaassen

Arató³

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The default mode network (DMN) is a collection of cortical brain regions that is active during states of rest or quiet wakefulness in humans and other mammalian species. A pertinent characteristic of the DMN is a suppression of local field potential gamma activity during cognitive task performance as well as during engagement with external sensory stimuli. Conversely, gamma activity is elevated in the DMN during rest. Here, we document that the rat basal forebrain (BF) exhibits the same pattern of responses, namely pronounced gamma oscillations during quiet wakefulness in the home cage and suppression of this activity during active exploration of an unfamiliar environment. We show that gamma oscillations are localized to the BF and that gamma-band activity in the BF has a directional influence on a hub of the rat DMN, the anterior cingulate cortex, during DMNdominated brain states. The BF is well known as an ascending, activating, neuromodulatory system involved in wake-sleep regulation, memory formation, and regulation of sensory information processing. Our findings suggest a hitherto undocumented role of the BF as a subcortical node of the DMN, which we speculate may be important for switching between internally and externally directed brain states. We discuss potential BF projection circuits that could underlie its role in DMN regulation and highlight that certain BF nuclei may provide potential target regions for up-or down-regulation of DMN activity that might prove useful for treatment of DMN dysfunction in conditions such as epilepsy or major depressive disorder.gamma suppression | anterior cingulate cortex | granger causality A highly consistent finding across a wide range of functional imaging studies in humans is that a network of brain regions, referred to as the "default mode network" (DMN), increases its activity during passive mental states compared with the performance of cognitive tasks. This was initially shown in a metaanalysis of several PET studies (1), in which a distribution of brain regions broadly including the medial prefrontal, retrosplenial, and anterior cingulate cortex (ACC), as well as lateral parietal and temporal cortices, was shown to be activated when subjects were in a state of quiet restfulness. The DMN areas are thought to form a cohesive set of intrinsically coupled brain regions, such that fMRI activations in its component regions exhibit similar time courses, allowing them to be identified reliably using seed-region analysis (2-4). Activity in the DMN exhibits anticorrelation with a complementary, largely nonoverlapping, set of fronto-parietal brain areas known as the "dorsal attention network" (DAN) (5). It should be noted, however, that particular brain structures may harbor functionally heterogeneous elements and thus may contribute to multiple functions, as was shown for the ACC (6). During wakefulness, the human brain thus alternates between DAN-and DMN-dominated activation states, corresponding to effortful cognitive task performance on the one hand and quiet restful...

show abstract

“…These cholinergic neurons are known to project widely and diffusely, innervating neurons throughout the CNS. They also exhibit extensive local collaterals terminating on GABAergic neurons within the BF, thus controlling sleep and wakefulness [42,43]. We identified the fundamental role of the septo-hippocampal cholinergic system in the development of the behavioral deficits in Chat-Mecp2 −/y mice.…”

Section: Chat-mecp2mentioning

confidence: 97%

Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus

et al. 2016

View full text Add to dashboard Cite

Mutations in the X-linked MECP2 gene cause Rett syndrome (RTT), an autism spectrum disorder characterized by impaired social interactions, motor abnormalities, cognitive defects and a high risk of epilepsy. Here, we showed that conditional deletion of Mecp2 in cholinergic neurons caused part of RTT-like phenotypes, which could be rescued by re-expressing Mecp2 in the basal forebrain (BF) cholinergic neurons rather than in the caudate putamen of conditional knockout (Chat-Mecp2 −/y ) mice. We found that choline acetyltransferase expression was decreased in the BF and that α7 nicotine acetylcholine receptor signaling was strongly impaired in the hippocampus of Chat-Mecp2 −/y mice, which is sufficient to produce neuronal hyperexcitation and increase seizure susceptibility. Application of PNU282987 or nicotine in the hippocampus rescued these phenotypes in Chat-Mecp2 −/y mice. Taken together, our findings suggest that MeCP2 is critical for normal function of cholinergic neurons and dysfunction of cholinergic neurons can contribute to numerous neuropsychiatric phenotypes.

show abstract

Basal forebrain circuit for sleep-wake control

Cited by 441 publications

References 57 publications

The Input-Output Relationship of the Cholinergic Basal Forebrain

The Input-Output Relationship of the Cholinergic Basal Forebrain

Basal forebrain contributes to default mode network regulation

Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus

Contact Info

Product

Resources

About