Cholinergic basal forebrain nucleus of Meynert regulates chronic pain-like behavior via modulation of the prelimbic cortex

Manfred J. Oswald, Yechao Han, Han Li, Samuel Marashli, Deniz Nouri Oglo, Bhavya Ojha, Paul V. Naser, Zheng Gan and Rohini Kuner ()
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Manfred J. Oswald: Heidelberg University
Yechao Han: Heidelberg University
Han Li: Heidelberg University
Samuel Marashli: Heidelberg University
Deniz Nouri Oglo: Heidelberg University
Bhavya Ojha: Heidelberg University
Paul V. Naser: Heidelberg University
Zheng Gan: Heidelberg University
Rohini Kuner: Heidelberg University

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract The basal nucleus of Meynert (NBM) subserves critically important functions in attention, arousal and cognition via its profound modulation of neocortical activity and is emerging as a key target in Alzheimer’s and Parkinson’s dementias. Despite the crucial role of neocortical domains in pain perception, however, the NBM has not been studied in models of chronic pain. Here, using in vivo tetrode recordings in behaving mice, we report that beta and gamma oscillatory activity is evoked in the NBM by noxious stimuli and is facilitated at peak inflammatory pain-like behavior. Optogenetic and chemogenetic cell-specific, reversible manipulations of NBM cholinergic-GABAergic neurons reveal their role in endogenous control of nociceptive hypersensitivity, which are manifest via projections to the prelimbic cortex, resulting in layer 5-mediated antinociception. Our data unravel the importance of the NBM in top-down control of neocortical processing of pain-like behavior.

Date: 2022
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DOI: 10.1038/s41467-022-32558-9

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