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 “neurovascular coupling” (NVC). It is unknown whether this relationship remains reliable under altered brain states associated to acetylcholine (ACh) levels, such as attention and arousal, and in pathological conditions like 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 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 co-expressing 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 rostro-caudal 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 significantly disturbed 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.
Conflict of Interest: None declared.
Funding: Supported by grants from the Canadian Institute of Health Research (CIHR, MOP-84209 and MOP-142417, EH; MOP-102599, AS), the Heart & Stroke Foundation of Canada (EH), the Human Frontier Science Program (RGY0080/2008, AS), a Jeanne Timmins Costello Postdoctoral Fellowship (CL), and a Jeanne Timmins Costello studentship (CHS).