A Guide to Delineate the Logic of Neurovascular Signaling in the Brain

Department of Physics, University of California San Diego La Jolla, CA, USA.
Frontiers in Neuroenergetics 04/2011; 3:1. DOI: 10.3389/fnene.2011.00001
Source: PubMed

ABSTRACT The neurovascular system may be viewed as a distributed nervous system within the brain. It transforms local neuronal activity into a change in the tone of smooth muscle that lines the walls of arterioles and microvessels. We review the current state of neurovascular coupling, with an emphasis on signaling molecules that convey information from neurons to neighboring vessels. At the level of neocortex, this coupling is mediated by: (i) a likely direct interaction with inhibitory neurons, (ii) indirect interaction, via astrocytes, with excitatory neurons, and (iii) fiber tracts from subcortical layers. Substantial evidence shows that control involves competition between signals that promote vasoconstriction versus vasodilation. Consistent with this picture is evidence that, under certain circumstances, increased neuronal activity can lead to vasoconstriction rather than vasodilation. This confounds naïve interpretations of functional brain images. We discuss experimental approaches to detect signaling molecules in vivo with the goal of formulating an empirical basis for the observed logic of neurovascular control.

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Available from: Philbert S Tsai, Sep 26, 2015
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    • "At the interface of the vascular and neural compartments is the blood-brain barrier (BBB) that limits the access of molecules and peripheral cells to the brain. In the healthy brain, neuronal and glial activity will influence vascular function by neurovascular coupling to regulate their energetic demands by maintaining tissue oxygenation and nutrient influx [2]. In the case that this energetic demand is not met, a rapid physiological response to hypoxia (i.e. "
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    ABSTRACT: Brain and vascular cells form a functionally integrated signalling network that is known as the neurovascular unit (NVU). The signalling (autocrine, paracrine and juxtacrine) between different elements of this unit, especially in humans, is difficult to disentangle in vivo. Developing representative in vitro models is therefore essential to better understand the cellular interactions that govern the neurovascular environment. We here describe a novel approach to assay these cellular interactions by combining a human adult cerebral microvascular endothelial cell line (hCMEC/D3) with a fetal ganglionic eminence-derived neural stem cell (hNSC) line. These cell lines provide abundant homogeneous populations of cells to produce a consistently reproducible in vitro model of endothelial morphogenesis and the ensuing NVU. Vasculature-like structures (VLS) interspersed with patches of differentiating neural cells only occurred when hNSCs were seeded onto a differentiated endothelium. These VLS emerged within 3 days of coculture and by day 6 were stabilizing. After 7 days of coculture, neuronal differentiation of hNSCs was increased 3-fold, but had no significant effect on astrocyte or oligodendrocyte differentiation. ZO1, a marker of adherens and tight junctions, was highly expressed in both undifferentiated and differentiated endothelial cells, but the adherens junction markers CD31 and VE-cadherin were significantly reduced in coculture by approximately 20%. A basement membrane, consisting of laminin, vitronectin, and collagen I and IV, separated the VLS from neural patches. This simple assay can assist in elucidating the cellular and molecular signaling involved in the formation of VLS, as well as the enhancement of neuronal differentiation through endothelial signaling.
    PLoS ONE 09/2014; 9(9):e106346. DOI:10.1371/journal.pone.0106346 · 3.23 Impact Factor
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    • "Given that SOM+ neurons are a major neuronal target of CR+ bipolar interneurons (see chapter 6.1.1), it is likely that CR+/VIP+ bipolar interneurons and CR+/SOM+ interneurons (Figure 6), via vascular and/or synaptic interactions, play opposite roles in the control of regional cerebral blood flow (Kleinfeld et al., 2011). "
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    ABSTRACT: Cortical calretinin (CR)-expressing interneurons represent a heterogeneous subpopulation of about 10-30% of GABAergic interneurons, which altogether total ca. 12-20% of all cortical neurons. In the rodent neocortex, CR cells display different somatodendritic morphologies ranging from bipolar to multipolar but the bipolar cells and their variations dominate. They are also diverse at the molecular level as they were shown to express numerous neuropeptides in different combinations including vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), neurokinin B (NKB) corticotrophin releasing factor (CRF), enkephalin (Enk) but also neuropeptide Y (NPY) and somatostatin (SOM) to a lesser extent. CR-expressing interneurons exhibit different firing behaviors such as adapting, bursting or irregular. They mainly originate from the caudal ganglionic eminence (CGE) but a subpopulation also derives from the dorsal part of the medial ganglionic eminence (MGE). Cortical GABAergic CR-expressing interneurons can be divided in two main populations: VIP-bipolar interneurons deriving from the CGE and SOM-Martinotti-like interneurons originating in the dorsal MGE. Although bipolar cells account for the majority of CR-expressing interneurons, the roles they play in cortical neuronal circuits and in the more general metabolic physiology of the brain remained elusive and enigmatic. The aim of this review is, firstly, to provide a comprehensive view of the morphological, molecular and electrophysiological features defining this cell type. We will, secondly, also summarize what is known about their place in the cortical circuit, their modulation by subcortical afferents and the functional roles they might play in neuronal processing and energy metabolism.
    Frontiers in Neuroanatomy 06/2014; 8:52. DOI:10.3389/fnana.2014.00052 · 3.54 Impact Factor
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    • "This suggests the ability of specific subsets of cortical GABA interneurons to translate neuronal signals into vascular responses. Moreover, it has been proposed that local activation of neurons and astrocytes leads to a change in tone of smooth muscles in surrounding arterioles thus precisely modulating the blood flow in a particular capillary bed (Kleinfeld et al., 2011). To test the last hypothesis, Urban et al. (2012) used the optogenetic tools for activating specific local neuronal networks and monitoring whether this causes changes in a diameter of blood vessels in the mouse brain slices. "
    Frontiers in Pharmacology 05/2014; 5:107. DOI:10.3389/fphar.2014.00107 · 3.80 Impact Factor
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