Cell type specificity of neurovascular coupling in cerebral cortex

Abstract

Identification of the cellular players and molecular messengers that communicate neuronal activity to the vasculature driving cerebral hemodynamics is important for (1) the basic understanding of cerebrovascular regulation and (2) interpretation of functional Magnetic Resonance Imaging (fMRI) signals. Using a combination of optogenetic stimulation and 2-photon imaging in mice, we demonstrate that selective activation of cortical excitation and inhibition elicits distinct vascular responses and identify the vasoconstrictive mechanism as Neuropeptide Y (NPY) acting on Y1 receptors. The latter implies that task-related negative Blood Oxygenation Level Dependent (BOLD) fMRI signals in the cerebral cortex under normal physiological conditions may be mainly driven by the NPY-positive inhibitory neurons. Further, the NPY-Y1 pathway may offer a potential therapeutic target in cerebrovascular disease.DOI: http://dx.doi.org/10.7554/eLife.14315.001

Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons

“…6C) (P < 0.005 for both models, double-sided Student's t test; n = 6). These temporal features agree well with stimulus-evoked HRFs measured in awake and urethane-anesthetized rats (31), including the observation of stronger poststimulus undershoots in the awake state (38). Differences cannot be accounted for by the minimal (<0.1-s) difference between the temporal properties of these two GCaMP types, as demonstrated in Fig.…”

“…Interneurons, for example, have been implicated to play a role in neurovascular coupling (38,50), although there has also been significant debate regarding the BOLD response that should result from interneuron activation (51)(52)(53)(54). Our results demonstrate that the activity of excitatory neurons is correlated to resting-state hemodynamics.…”

“…Similarly, synchronous activation of astrocytes, pericytes, or interneurons in the context of neurovascular coupling could contribute to the properties of the HRF, with the delayed undershoot observed in our awake, deconvolved HRFs (Fig. 6A) being particularly interesting in the context of interneuron involvement (38). Thus, although our studies here focused on correlations between excitatory neural activity and resting-state hemodynamics, further work is needed to chart the cellular pathways and dependencies of both neuromodulation, and neurovascular coupling in the resting state.…”

The roadmap for estimation of cell-type-specific neuronal activity from non-invasive measurements

“…Twophoton measurements at different depths revealed that the earliest dilation onset occurs in deep cortical layers, below layer IV (in the mouse, dilation in layer V starts approx. 500 ms prior to that in layer I) [63]. The dilation latency gradually increases with decreasing cortical depth ( figure 2f,g) [59][60][61]63] and, in the upper layers, also with increasing branching order such that diving trunks precede their side branches (figure 2h) [59].…”

Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states

“…However, much work is needed to clarify the role of neuronal metabolic substrates [74,145], and identify the receptor subtypes and cellular localization through which vasoactive messengers act on the vascular unit. Additionally, changes in microdomains of the microcirculation should be better explored, as both constriction and dilation are likely to occur to generate the final integrated haemodynamic response [174,175]. In view of recent findings [130][131][132]176], the exact role of astrocytes and pericytes, and the extent and timescale of their contribution in the haemodynamic responses need clarification.…”