title: Impact of Altered Cholinergic Tones on the Neurovascular Coupling Response to Whisker Stimulation.
abstract: Brain imaging techniques that use vascular signals to map changes in neuronal activity rely on the coupling between electrophysiology and hemodynamics, a phenomenon referred to as "neurovascular coupling" (NVC). It is unknown whether this relationship remains reliable under altered brain states associated with acetylcholine (ACh) levels, such as attention and arousal and in pathological conditions such as Alzheimer's disease. We therefore assessed the effects of varying ACh tone on whisker-evoked NVC responses in rat barrel cortex, measured by cerebral blood flow (CBF) and neurophysiological recordings (local field potentials, LFPs). We found that acutely enhanced ACh tone significantly potentiated whisker-evoked CBF responses through muscarinic ACh receptors and concurrently facilitated neuronal responses, as illustrated by increases in the amplitude and power in high frequencies of the evoked LFPs. However, the cellular identity of the activated neuronal network within the responsive barrel was unchanged, as characterized by c-Fos upregulation in pyramidal cells and GABA interneurons coexpressing vasoactive intestinal polypeptide. In contrast, chronic ACh deprivation hindered whisker-evoked CBF responses and the amplitude and power in most frequency bands of the evoked LFPs and reduced the rostrocaudal extent and area of the activated barrel without altering its identity. Correlations between LFP power and CBF, used to estimate NVC, were enhanced under high ACh tone and disturbed significantly by ACh depletion. We conclude that ACh is not only a facilitator but also a prerequisite for the full expression of sensory-evoked NVC responses, indicating that ACh may alter the fidelity of hemodynamic signals in assessing changes in evoked neuronal activity.SIGNIFICANCE STATEMENTNeurovascular coupling, defined as the tight relationship between activated neurons and hemodynamic responses, is a fundamental brain function that underlies hemodynamic-based functional brain imaging techniques. However, the impact of altered brain states on this relationship is largely unknown. We therefore investigated how acetylcholine (ACh), known to drive brain states of attention and arousal and to be deficient in pathologies such as Alzheimer's disease, would alter neurovascular coupling responses to sensory stimulation. Whereas acutely increased ACh enhanced neuronal responses and the resulting hemodynamic signals, chronic loss of cholinergic input resulted in dramatic impairments in both types of sensory-evoked signals. We conclude that ACh is not only a potent modulator but also a requirement for the full expression of sensory-evoked neurovascular coupling responses.
authors.affiliation: Laboratory of Cerebrovascular Research and clotilde.lecrux@mcgill.ca.|Laboratory of Brain Imaging Signals, Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada H3A 2B4.
authors.forename: Clotilde
authors.identifier: 0000-0003-3521-5266
authors.initials: C
authors.lastname: Lecrux
authors.affiliation: Laboratory of Cerebrovascular Research and.
authors.forename: Claire H
authors.initials: CH
authors.lastname: Sandoe
authors.affiliation: Laboratory of Brain Imaging Signals, Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada H3A 2B4.
authors.forename: Sujaya
authors.initials: S
authors.lastname: Neupane
authors.affiliation: Laboratory of Brain Imaging Signals, Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada H3A 2B4.
authors.forename: Pascal
authors.initials: P
authors.lastname: Kropf
authors.affiliation: Laboratory of Cerebrovascular Research and.
authors.forename: Xavier
authors.identifier: 0000-0001-5923-6673
authors.initials: X
authors.lastname: Toussay
authors.affiliation: Laboratory of Cerebrovascular Research and.
authors.forename: Xin-Kang
authors.initials: XK
authors.lastname: Tong
authors.affiliation: Laboratory of Cerebrovascular Research and.
authors.forename: María
authors.initials: M
authors.lastname: Lacalle-Aurioles
authors.affiliation: Laboratory of Brain Imaging Signals, Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada H3A 2B4.
authors.forename: Amir
authors.initials: A
authors.lastname: Shmuel
authors.affiliation: Laboratory of Cerebrovascular Research and.
authors.forename: Edith
authors.identifier: 0000-0001-5223-7315
authors.initials: E
authors.lastname: Hamel
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D000069336:Neurovascular Coupling / Q000187:drug effects / Q000502:physiology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D014738:Vibrissae / Q000187:drug effects / Q000502:physiology*
chemical_list: D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D000109:Acetylcholine
keywords: acetylcholine; hemodynamics; interneurons; neurovascular coupling; pyramidal cells