Optogenetic assessment of VIP, PV, SOM and NOS inhibitory neuron activity and cerebral blood flow regulation in mouse somato-sensory cortex

Abstract

The impact of different neuronal populations on local cerebral blood flow (CBF) regulation is not well known and insight into these relationships could enhance the interpretation of brain function and dysfunction from brain imaging data. We investigated the role of sub-types of inhibitory neuron activity on the regulation of CBF using optogenetics, laser Doppler flowmetry and different transgenic mouse models (parvalbumin (PV), vasoactive intestinal peptide (VIP), somatostatin (SOM) and nitric oxide synthase (NOS)). Whisker stimulation was used to verify that typical CBF responses were obtained in all mice. Photo-stimulation of SOM-cre and NOS-cre mice produced significant increases in CBF that were similar to whisker responses. In NOS-cre mice, CBF responses scaled with the photo-stimulus pulse duration and frequency. In SOM-cre mice, CBF increases were followed by decreases. In VIP-cre mice, photo-stimulation did not consistently produce significant changes in CBF, while slower increases in CBF that peaked 14–18 s after stimulation onset were observed in PV-cre mice. Control experiments performed in non-expressing regions showed no changes in CBF. These findings suggest that dysfunction in NOS or SOM neurons can have a significant impact on vascular responses that are detected by brain imaging methods like functional magnetic resonance imaging (fMRI).

Sleep deprivation triggers somatostatin neurons in prefrontal cortex to initiate nesting and sleep via the preoptic and lateral hypothalamus

“…As to be expected, the SOM cells within the PFC are involved in many functions; for example, some PFC SOM cells contribute to reading emotions (affective state discrimination) 52 , others encode fear memories 53 ; and locally opto-activating neocortical NOS1 and SOM cells increases cerebral blood flow 54,55 . The c-fosdependent activity-tagging technique allows the SOM/GABA cells that become activated by sleep deprivation to be highlighted from the other functions that these cells carry out.…”

nNOS-expressing interneurons control basal and behaviorally evoked arterial dilation in somatosensory cortex of mice

“…Previous work has implicated neuronally-generated nitric oxide (NO) (Hosford and Gourine, 2018), generated by interneurons (Krawchuk et al, 2019;Lee et al, 2020) in the dilation of cerebral arteries.…”

“…Optogenetic stimulation of interneurons drives a larger vasodilation than optogenetic stimulation of pyramidal neurons (Vazquez et al, 2014;Anenberg et al, 2015;Uhlirova et al, 2016b;Vazquez et al, 3 2018; Krawchuk et al, 2019), suggesting a subset of neurons exerts a disproportionate control over vasodilation. Optogenetic stimulation of neuronal nitric oxide (nNOS, also known as NOS1) expressing interneuron neurons, but not in VIP or parvalbumin interneurons, produces increase in blood flow and vasodilation (Krawchuk et al, 2019;Lee et al, 2020), and this vasodilation is not accompanied by a detectable increase in neural activity (Lee et al, 2020), suggesting that nNOS neurons can influence local hemodynamics without detectably altering the activity of the rest of the network.…”

Updating the picture of layer 2/3 VIP-expressing interneuron function in the mouse cerebral cortex

“…Some of the VIP interneurons produce perivascular neuronal endings (Martin et al, 1992;Chédotal et al, 1994). The most recent in vivo finding, however, indicates that different gamma aminobutyric acid (GABA)-ergic interneurons can contribute to neurovascular coupling in the cerebral cortex (Krawchuk et al, 2019). The power supply-function of VIP neurons is controlled with great spatial resolution by the restricted horizontal spread of their dendritic and axonal arbor (Magistretti, 1986;Karnani et al, 2016;Prönneke et al, 2015Prönneke et al, , 2019.…”