Key Aspects of Neurovascular Control Mediated by Specific Populations of Inhibitory Cortical Interneurons.

J Berwick,C Howarth,E Glendenning,O Shabir,P Redgrave,P Sharp,C Christmas,L Boorman,L Lee,E Bracci

doi:10.1093/cercor/bhz251

J Berwick, C Howarth + Show 8 more

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https://doi.org/10.1093/cercor/bhz251

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Abstract

Inhibitory interneurons can evoke vasodilation and vasoconstriction, making them potential cellular drivers of neurovascular coupling. However, the specific regulatory roles played by particular interneuron subpopulations remain unclear. Our purpose was therefore to adopt a cell-specific optogenetic approach to investigate how somatostatin (SST) and neuronal nitric oxide synthase (nNOS)-expressing interneurons might influence the neurovascular relationship. In mice, specific activation of SST- or nNOS-interneurons was sufficient to evoke hemodynamic changes. In the case of nNOS-interneurons, robust hemodynamic changes occurred with minimal changes in neural activity, suggesting that the ability of blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) to reliably reflect changes in neuronal activity may be dependent on type of neuron recruited. Conversely, activation of SST-interneurons produced robust changes in evoked neural activity with shallow cortical excitation and pronounced deep layer cortical inhibition. Prolonged activation of SST-interneurons often resulted in an increase in blood volume in the centrally activated area with an accompanying decrease in blood volume in the surrounding brain regions, analogous to the negative BOLD signal. These results demonstrate the role of specific populations of cortical interneurons in the active control of neurovascular function.

Highlights

Neurovascular coupling (NVC) is the mechanism through which local cerebral blood flow (CBF) changes are tightly coupled to increases in neural activity (Roy and Sherrington 1890)
Expression of ChR2 was evidenced by the presence of enhanced yellow fluorescent protein (EYFP), the reporter for ChR2 expression, and co-localization was seen with either SST (Fig. 1A) or neuronal nitric oxide synthase (nNOS) (Fig. 1B), as appropriate
We demonstrated that photoactivation of either SST- or nNOS-expressing interneurons was sufficient to evoke a robust localized hemodynamic response

Summary

Introduction

Neurovascular coupling (NVC) is the mechanism through which local cerebral blood flow (CBF) changes are tightly coupled to increases in neural activity (Roy and Sherrington 1890). After activating SST interneurons negative hemodynamic responses were observed in the cortical areas surrounding the local area of optogenetic stimulation This observation is similar to reported negative BOLD fMRI responses, which have been linked to inhibitory neuron activity (Shmuel et al 2002, 2006; Stefanovic et al 2004; Boorman et al 2010, 2015). These observations suggest that specific subpopulations of cortical GABAergic interneurons have specific roles in NVC. That the ability of BOLD signals to act as a surrogate measure of local neural activation may in part be dependent upon which subpopulation of neurons are being activated

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