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Cortical nNOS/NK1 Receptor Neurons are Regulated by Cholinergic Projections From the Basal Forebrain
Rhîannan H Williams1, Jacqueline Vazquez-DeRose1, Alexia M Thomas1
1Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA 94025, USA.
Cerebral Cortex (New York, N.Y. : 1991)
|May 5, 2017
Summary
Cholinergic basal forebrain neurons influence cortical nNOS/NK1R cells via acetylcholine. This modulation impacts neuronal activity across sleep-wake states, independent of sleep homeostasis.
Area of Science:
- Neuroscience
- Sleep Science
- Cellular Signaling
Background:
- Cholinergic basal forebrain (BF) neurons are active during wakefulness and REM sleep, influencing sleep homeostasis.
- Cortical neurons expressing neuronal nitric oxide synthase (nNOS) and NK1R are activated during NREM sleep proportional to sleep drive.
Purpose of the Study:
- To investigate the modulatory role of BF neurons on cortical nNOS/NK1R cells.
- To elucidate the specific cholinergic receptor subtypes involved in this modulation.
Main Methods:
- In vitro optogenetic stimulation of BF terminals.
- Pharmacological studies using muscarinic and nicotinic receptor agonists/antagonists.
- Electrophysiological recordings of nNOS/NK1R neurons.
Main Results:
- Optogenetic stimulation of BF terminals elicited both excitatory and inhibitory responses in nNOS/NK1R neurons.
- Cholinergic modulation involved postsynaptic muscarinic receptors (M3R > M2/4R > M1R).
- Presynaptic M3R and M2R activation reduced glutamatergic input, while nAChR responses were mixed.
Conclusions:
- Acetylcholine from BF neurons excites cortical nNOS/NK1R cells and reduces glutamatergic input.
- Cholinergic signaling onto these neurons may regulate cortical activity across arousal states.
- This cholinergic response appears independent of sleep homeostasis mechanisms.
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