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.

Download full-text


Available from: Philbert S Tsai, Aug 19, 2015
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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 · 4.18 Impact Factor
  • Source
    • "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
  • Source
    • "The increases in blood flow induced by activation depend on the concerted action of neurons, astrocytes, and vascular cells through a wide variety of molecular signals including ions, arachidonic acid metabolites, nitric oxide (NO), adenosine, neurotransmitters, and neuropeptides (Drake and Iadecola, 2007). The hemodynamic changes underlying the increases in blood flow are mediated by vasoactive agents with opposing vascular actions (vasodilatation or vasoconstriction), generated by synaptic activity, astrocytes, interneurons, and afferent projections from the basal forebrain and brainstem (Cauli and Hamel, 2010; Drake and Iadecola, 2007; Kleinfeld et al., 2011). These highly coordinated signals converge on specific sites of the cerebrovascular network to shape the hemodynamic response to neural activation with a remarkable degree of spatial and temporal precision (Iadecola, 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer's disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that inextricably links the well-being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer's disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia.
    Neuron 11/2013; 80(4):844-866. DOI:10.1016/j.neuron.2013.10.008 · 15.98 Impact Factor
Show more