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Basal forebrain control of wakefulness and cortical rhythms.
Nat Commun 2015; 6:8744NC

Abstract

Wakefulness, along with fast cortical rhythms and associated cognition, depend on the basal forebrain (BF). BF cholinergic cell loss in dementia and the sedative effect of anti-cholinergic drugs have long implicated these neurons as important for cognition and wakefulness. The BF also contains intermingled inhibitory GABAergic and excitatory glutamatergic cell groups whose exact neurobiological roles are unclear. Here we show that genetically targeted chemogenetic activation of BF cholinergic or glutamatergic neurons in behaving mice produced significant effects on state consolidation and/or the electroencephalogram but had no effect on total wake. Similar activation of BF GABAergic neurons produced sustained wakefulness and high-frequency cortical rhythms, whereas chemogenetic inhibition increased sleep. Our findings reveal a major contribution of BF GABAergic neurons to wakefulness and the fast cortical rhythms associated with cognition. These findings may be clinically applicable to manipulations aimed at increasing forebrain activation in dementia and the minimally conscious state.

Authors+Show Affiliations

Division of Sleep Medicine, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.Division of Sleep Medicine, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. Comprehensive Epilepsy Clinic, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.Division of Sleep Medicine, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.Division of Sleep Medicine, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York 14214, USA.Division of Sleep Medicine, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.Division of Sleep Medicine, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26524973

Citation

Anaclet, Christelle, et al. "Basal Forebrain Control of Wakefulness and Cortical Rhythms." Nature Communications, vol. 6, 2015, p. 8744.
Anaclet C, Pedersen NP, Ferrari LL, et al. Basal forebrain control of wakefulness and cortical rhythms. Nat Commun. 2015;6:8744.
Anaclet, C., Pedersen, N. P., Ferrari, L. L., Venner, A., Bass, C. E., Arrigoni, E., & Fuller, P. M. (2015). Basal forebrain control of wakefulness and cortical rhythms. Nature Communications, 6, p. 8744. doi:10.1038/ncomms9744.
Anaclet C, et al. Basal Forebrain Control of Wakefulness and Cortical Rhythms. Nat Commun. 2015 Nov 3;6:8744. PubMed PMID: 26524973.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Basal forebrain control of wakefulness and cortical rhythms. AU - Anaclet,Christelle, AU - Pedersen,Nigel P, AU - Ferrari,Loris L, AU - Venner,Anne, AU - Bass,Caroline E, AU - Arrigoni,Elda, AU - Fuller,Patrick M, Y1 - 2015/11/03/ PY - 2015/03/04/received PY - 2015/09/25/accepted PY - 2015/11/4/entrez PY - 2015/11/4/pubmed PY - 2016/5/11/medline SP - 8744 EP - 8744 JF - Nature communications JO - Nat Commun VL - 6 N2 - Wakefulness, along with fast cortical rhythms and associated cognition, depend on the basal forebrain (BF). BF cholinergic cell loss in dementia and the sedative effect of anti-cholinergic drugs have long implicated these neurons as important for cognition and wakefulness. The BF also contains intermingled inhibitory GABAergic and excitatory glutamatergic cell groups whose exact neurobiological roles are unclear. Here we show that genetically targeted chemogenetic activation of BF cholinergic or glutamatergic neurons in behaving mice produced significant effects on state consolidation and/or the electroencephalogram but had no effect on total wake. Similar activation of BF GABAergic neurons produced sustained wakefulness and high-frequency cortical rhythms, whereas chemogenetic inhibition increased sleep. Our findings reveal a major contribution of BF GABAergic neurons to wakefulness and the fast cortical rhythms associated with cognition. These findings may be clinically applicable to manipulations aimed at increasing forebrain activation in dementia and the minimally conscious state. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/26524973/Basal_forebrain_control_of_wakefulness_and_cortical_rhythms_ L2 - http://dx.doi.org/10.1038/ncomms9744 DB - PRIME DP - Unbound Medicine ER -