Parvalbumin interneuron activity drives fast inhibition-induced vasoconstriction followed by slow substance P-mediated vasodilation

Abstract

The role of parvalbumin (PV) interneurons in vascular control is poorly understood. Here, we investigated the hemodynamic responses elicited by optogenetic stimulation of PV interneurons using electrophysiology, functional magnetic resonance imaging (fMRI), wide-field optical imaging (OIS), and pharmacological applications. As a control, forepaw stimulation was used. Stimulation of PV interneurons in the somatosensory cortex evoked a biphasic fMRI response in the photostimulation site and negative fMRI signals in projection regions. Activation of PV neurons engaged two separable neurovascular mechanisms in the stimulation site. First, an early vasoconstrictive response caused by the PV-driven inhibition is sensitive to the brain state affected by anesthesia or wakefulness. Second, a later ultraslow vasodilation lasting a minute is closely dependent on the sum of interneuron multiunit activities, but is not due to increased metabolism, neural or vascular rebound, or increased glial activity. The ultraslow response is mediated by neuropeptide substance P (SP) released from PV neurons under anesthesia, but disappears during wakefulness, suggesting that SP signaling is important for vascular regulation during sleep. Our findings provide a comprehensive perspective about the role of PV neurons in controlling the vascular response.

Resting state brain networks arise from electrophysiology-invisible signals

“…Chemogenetic or pharmacological stimulation of nNOS neurons causes vasodilation without detectable changes in LFP (Echagarruga et al, 2020). In addition, stimulation of PV neurons leads to release of substance P, which can activate a subset of nNOS neurons and result in vasodilation without electrophysiological changes (Endo et al, 2016;Vo et al, 2023). These studies collectively suggest some electrophysiology-invisible activities can signi cantly drive the rsfMRI signal.…”

“…Brain activities include components that can be measured by electrophysiology and components that are electrophysiology invisible. Electrophysiology-invisible brain activities, such as activities of nNOS neurons and/or parvalbumin (PV) interneurons (Vo et al, 2023), are actively involved in NVC, and play a dominant role in the rsfMRI signal, whereas neural activity measured by electrophysiology has minimal effects on the rsfMRI signal. At the resting state, these two components are not necessarily synchronized, leading to low temporal correlations between electrophysiology and rsfMRI signals.…”

Long-range inhibitory neurons mediate cortical neurovascular coupling

“… 19 Several studies now show that activation of nNOS neurons is strongly correlated with vascular responses and that pharmacological interventions targeting substance P receptors result in changes in blood flow. 11 , 20 – 23 Altogether, these features make Tacr1 neurons ideally poised to modulate blood flow. 24 However, the extent to which Tacr1 neurons contribute to NVC, compared to other Nos1 neurons, is unknown.…”