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.

The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease

“…Zhang et al, 1995). Although its lesion does not alter the changes in CBF induced by neural activity (Ibayashi et al, 1991), this pathway may contribute to maintain resting CBF and modulate the increases in CBF produced by somatosensory activation (Iadecola et al, 1983; Lecrux and Hamel, 2016; Lecrux et al, 2017). On the other hand, cortical norepinephrine levels, which depend in large part on the noradrenergic innervation from the locus coeruleus, have been shown to increase the vasoconstrictor tone in cerebral cortex and help focus oxygen delivery to the activated areas (Bekar et al, 2012).…”

Neurovascular coupling during deep brain stimulation

“…The integrated evoked potential represents low frequency electrophysiological activity while multi-unit power represents high frequency activity. Other studies under various experimental conditions (such as, auditory stimulation in epilepsy patients [36], resting state condition [37], whisker stimulation under altered cholinergic tone [38]) found hemodynamic response to be correlated with the power of the local field potential in the gamma band [28,36e40]. Despite these many studies, only a few have measured NVC with direct brain stimulation using electrical [34,35,41] or optogenetic [42,43]…”

Target-specific co-transmission of acetylcholine and GABA from a subset of cortical VIP+ interneurons

“…The net effect of activating cholinergic fibers in cortex is the desynchronization of neuronal firing (Pinto et al, 2013), and ACh can gate the induction of synaptic plasticity (Morishita et al, 2010;Rasmusson, 2000), enabling learning. In addition, ACh dilates cortical blood vessels (Lecrux et al, 2017;Yamada et al, 2001) allowing for greater delivery of oxygen and nutrients to support increased metabolic demand. In summary, ACh is a vital signaling molecule that coordinates cortical activation and plasticity.…”