<i>in vivo</i> 3D Morphology of Astrocyte—Vasculature Interactions in the Somatosensory Cortex: Implications for Neurovascular Coupling

McCaslin, Addason F.H.; Chen, Brenda R.; Radosevich, Andrew J.; Cauli, Bruno; Hillman, Elizabeth M. C.

doi:10.1038/jcbfm.2010.204

Cited by 146 publications

(164 citation statements)

References 39 publications

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“…We attribute the drop in neuron and astrocyte densities measured by TPM beyond 250 µm to vessel shadowing and the limited penetration depth of TPM. The TPM astrocyte densities agree with previously reported values [18] up to 250 µm depth. Cell densities were not compared for depths of less than 60 µm because of surface artifacts.…”

Section: Resultssupporting

confidence: 82%

Volumetric imaging and quantification of cytoarchitecture and myeloarchitecture with intrinsic scattering contrast

Leahy

Radhakrishnan

Srinivasan

2013

Biomed. Opt. Express

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Abstract:We present volumetric imaging and computational techniques to quantify neuronal and myelin architecture with intrinsic scattering contrast. Using spectral / Fourier domain Optical Coherence Microscopy (OCM) and software focus-tracking we validate imaging of neuronal cytoarchitecture and demonstrate quantification in the rodent cortex in vivo. Additionally, by ex vivo imaging in conjunction with optical clearing techniques, we demonstrate that intrinsic scattering contrast is preserved in the brain, even after sacrifice and fixation. We volumetrically image cytoarchitecture and myeloarchitecture ex vivo across the entire depth of the rodent cortex. Cellular-level imaging up to the working distance of our objective (~3 mm) is demonstrated ex vivo. Architectonic features show the expected laminar characteristics; moreover, changes in contrast after the application of acetic acid suggest that entire neuronal cell bodies are responsible for the "negative contrast" present in the images. Clearing and imaging techniques that preserve tissue architectural integrity have the potential to enable noninvasive studies of the brain during development, disease, and remodeling, even in samples where exogenous labeling is impractical.

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Section: Resultssupporting

confidence: 82%

Volumetric imaging and quantification of cytoarchitecture and myeloarchitecture with intrinsic scattering contrast

Leahy

Radhakrishnan

Srinivasan

2013

Biomed. Opt. Express

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“…The evoked signals had the same appearance, with fast onset and short duration in all three ROI types. The fast Ca 2+ response in the end-feet was of particular interest because dynamic changes in this subcellular element have been claimed to be a major factor in the control of CBF (6). This idea was supported by the occurrence of vasodilatation following fast Ca 2+ responses in the adjacent end-feet ( Fig.…”

Section: Significancesupporting

confidence: 57%

“…and associated astrocytes, which causes fluctuations in cerebral blood flow (CBF) (1)(2)(3)(4)(5). Astrocytes are ideally situated for controlling activity-dependent increases in CBF because they closely associate with synapses and contact blood vessels with their end-feet (1,6). Whether or not astrocytic Ca 2+ responses develop often or rapidly enough to account for vascular signals in vivo is still controversial (7)(8)(9)(10).…”

mentioning

confidence: 99%

Rapid stimulus-evoked astrocyte Ca ²⁺ elevations and hemodynamic responses in mouse somatosensory cortex in vivo

Lind

Brazhe

Jessen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

165

197

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Increased neuron and astrocyte activity triggers increased brain blood flow, but controversy exists over whether stimulationinduced changes in astrocyte activity are rapid and widespread enough to contribute to brain blood flow control. Here, we provide evidence for stimulus-evoked Ca 2+ elevations with rapid onset and short duration in a large proportion of cortical astrocytes in the adult mouse somatosensory cortex. Our improved detection of the fast Ca 2+ signals is due to a signal-enhancing analysis of the Ca 2+ activity. The rapid stimulation-evoked Ca 2+ increases identified in astrocyte somas, processes, and end-feet preceded local vasodilatation. Fast Ca 2+ responses in both neurons and astrocytes correlated with synaptic activity, but only the astrocytic responses correlated with the hemodynamic shifts. These data establish that a large proportion of cortical astrocytes have brief Ca 2+ responses with a rapid onset in vivo, fast enough to initiate hemodynamic responses or influence synaptic activity. and associated astrocytes, which causes fluctuations in cerebral blood flow (CBF) (1-5). Astrocytes are ideally situated for controlling activity-dependent increases in CBF because they closely associate with synapses and contact blood vessels with their end-feet (1, 6). Whether or not astrocytic Ca 2+ responses develop often or rapidly enough to account for vascular signals in vivo is still controversial (7-10). Ca 2+ responses are of interest because intracellular Ca 2+ is a key messenger in astrocytic communication and because enzymes that synthesize the vasoactive substances responsible for neurovascular coupling are Ca 2+ -dependent (1, 4). Neuronal activity releases glutamate at synapses and activates metabotropic glutamate receptors on astrocytes, and this activation can be monitored by imaging cytosolic Ca 2+ changes (11). Astrocytic Ca 2+ responses are often reported to evolve on a slow (seconds) time scale, which is too slow to account for activity-dependent increases in CBF (8,10,12,13). Furthermore, uncaging of Ca 2+ in astrocytes triggers vascular responses in brain slices through specific Ca 2+ -dependent pathways with a protracted time course (14, 15). More recently, stimulation of single presynaptic neurons in hippocampal slices was shown to evoke fast, brief, local Ca 2+ elevations in astrocytic processes that were essential for local synaptic functioning in the adult brain (16,17). This work prompted us to reexamine the characteristics of fast, brief astrocytic Ca 2+ signals in vivo with special regard to neurovascular coupling, i.e., the association between local increases in neural activity and the concomitant rise in local blood flow, which constitutes the physiological basis for functional neuroimaging.Here, we describe how a previously undescribed method of analysis enabled us to provide evidence for fast Ca 2+ responses in a main fraction of astrocytes in mouse whisker barrel cortical layers II/III in response to somatosensory stimulation. The astrocytic Ca 2+ responses were brief en...

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“…Astrocytes contact many synapses and astrocyte endfeet surround Ͼ99% of cerebral vascular surface (Mathiisen et al, 2010;McCaslin et al, 2011). It is hypothesized that neurotransmitter spillover from synapses stimulates astrocytic Gq-GPCRs, resulting in IP 3 R-dependent Ca 2ϩ release from endoplastic reticulum stores (Duffy and MacVicar, 1995;Porter and McCarthy, 1996;Araque et al, 2002;Newman, 2005) and Ca 2ϩ -dependent release of vasoactive molecules onto arteriole smooth muscle (Zonta et al, 2003;Mulligan and MacVicar, 2004;, thereby modulating blood flow.…”

Section: Discussionmentioning

confidence: 99%

Astrocytic Gq-GPCR-Linked IP₃R-Dependent Ca²⁺Signaling Does Not Mediate Neurovascular Coupling in Mouse Visual CortexIn Vivo

Bonder¹,

2014

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Local blood flow is modulated in response to changing patterns of neuronal activity (Roy and Sherrington, 1890), a process termed neurovascular coupling. It has been proposed that the central cellular pathway driving this process is astrocytic Gq-GPCR-linked IP 3 Rdependent Ca 2ϩ signaling, though in vivo tests of this hypothesis are largely lacking. We examined the impact of astrocytic Gq-GPCR and IP 3 R-dependent Ca 2ϩ signaling on cortical blood flow in awake, lightly sedated, responsive mice using multiphoton laser-scanning microscopy and novel genetic tools that enable the selective manipulation of astrocytic signaling pathways in vivo.

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in vivo 3D Morphology of Astrocyte—Vasculature Interactions in the Somatosensory Cortex: Implications for Neurovascular Coupling

Abstract: Supplementary Figure S1. Volume renderings of the two-photon image stack shown in Figure 1D-G, and in the supplemental movie. The image to the left shows only astrocytes. The center image shows only blood vessels, and the image to the right shows the merge of the two.

Cited by 146 publications

References 39 publications

Volumetric imaging and quantification of cytoarchitecture and myeloarchitecture with intrinsic scattering contrast

Volumetric imaging and quantification of cytoarchitecture and myeloarchitecture with intrinsic scattering contrast

Rapid stimulus-evoked astrocyte Ca ²⁺ elevations and hemodynamic responses in mouse somatosensory cortex in vivo

Astrocytic Gq-GPCR-Linked IP₃R-Dependent Ca²⁺Signaling Does Not Mediate Neurovascular Coupling in Mouse Visual CortexIn Vivo

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in vivo 3D Morphology of Astrocyte—Vasculature Interactions in the Somatosensory Cortex: Implications for Neurovascular Coupling

Abstract: Supplementary Figure S1. Volume renderings of the two-photon image stack shown in Figure 1D-G, and in the supplemental movie. The image to the left shows only astrocytes. The center image shows only blood vessels, and the image to the right shows the merge of the two.

Cited by 146 publications

References 39 publications

Volumetric imaging and quantification of cytoarchitecture and myeloarchitecture with intrinsic scattering contrast

Volumetric imaging and quantification of cytoarchitecture and myeloarchitecture with intrinsic scattering contrast

Rapid stimulus-evoked astrocyte Ca 2+ elevations and hemodynamic responses in mouse somatosensory cortex in vivo

Astrocytic Gq-GPCR-Linked IP3R-Dependent Ca2+Signaling Does Not Mediate Neurovascular Coupling in Mouse Visual CortexIn Vivo

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Resources

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Rapid stimulus-evoked astrocyte Ca ²⁺ elevations and hemodynamic responses in mouse somatosensory cortex in vivo

Astrocytic Gq-GPCR-Linked IP₃R-Dependent Ca²⁺Signaling Does Not Mediate Neurovascular Coupling in Mouse Visual CortexIn Vivo