Open AccessCortical nNOS/NK1 Receptor Neurons are Regulated by Cholinergic Projections From the Basal Forebrain
Author(s) -
Rhîannan H. Williams,
Jacqueline Vazquez-DeRose,
Alexia M. Thomas,
Juliette Piquet,
Bruno Cauli,
Thomas S. Kilduff
Publication year - 2017
Publication title -
cerebral cortex
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.694
H-Index - 250
eISSN - 1460-2199
pISSN - 1047-3211
DOI - 10.1093/cercor/bhx102
Subject(s) - basal forebrain , cholinergic neuron , neuroscience , cholinergic , wakefulness , glutamatergic , biology , chemistry , receptor , glutamate receptor , biochemistry , electroencephalography
Cholinergic (ACh) basal forebrain (BF) neurons are active during wakefulness and rapid eye movement (REM) sleep and are involved in sleep homeostasis. We have previously shown in adult animals that cortical neurons that express neuronal nitric oxide synthase (nNOS) and the receptor for Substance P (NK1R) are activated during non-REM (NREM) sleep in proportion to homeostatic sleep drive. Here, we show that BF neurons modulate cortical nNOS/NK1R cells. In vitro optogenetic stimulation of BF terminals both activated and inhibited nNOS/NK1R neurons. Pharmacological studies revealed cholinergic responses mediated by postsynaptic activation of muscarinic receptors (mAChRs; M3R > M2/4R > M1R) and that presynaptic M3R and M2R activation reduced glutamatergic input onto nNOS/NK1R neurons whereas nicotinic receptor (nAChR)-mediated responses of nNOS/NK1R neurons were mixed. Cholinergic responses of nNOS/NK1R neurons were largely unaffected by prolonged wakefulness. ACh release, including from BF cells, appears to largely excite cortical nNOS/NK1R cells while reducing glutamatergic inputs onto these neurons. We propose that cholinergic signaling onto cortical nNOS/NK1R neurons may contribute to the regulation of cortical activity across arousal states, but that this response is likely independent of the role of these neurons in sleep homeostasis.