Chronic optical access through a polished and reinforced thinned skull

Drew, Patrick J.; Shih, Andy Y.; Driscoll, Jonathan D.; Knutsen, Per Magne; Blinder, Pablo; Davalos, Dimitrios; Akassoglou, Katerina; Tsai, Philbert S.; Kleinfeld, David

doi:10.1038/nmeth.1530

Cited by 388 publications

(436 citation statements)

References 29 publications

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“…Consistent with this idea, we have demonstrated the persistence of cortical motif structure derived from both infraslow and slow spontaneous activity in both anaesthetized and quiet awake states 27 . The advent of increasingly sensitive genetically encoded voltage indicators (GEVI) 55,56 may permit future studies whereby longduration awake state recordings may more readily be facilitated in combination with less invasive chronic imaging window preparations 57,58 . In addition, this strategy is advantaged by cell type-specific expression of the genetically encoded voltage indicators and the potential to minimize contaminating nonneuronal signals through a noise gain equalization of Förster resonance energy transfer signals 55 .…”

Section: Discussionmentioning

confidence: 99%

Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

et al. 2015

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Neuroimaging of spontaneous, resting-state infraslow (o0.1 Hz) brain activity has been used to reveal the regional functional organization of the brain and may lead to the identification of novel biomarkers of neurological disease. However, these imaging studies generally rely on indirect measures of neuronal activity and the nature of the neuronal activity correlate remains unclear. Here we show, using wide-field, voltage-sensitive dye imaging, the mesoscale spatiotemporal structure and pharmacological dependence of spontaneous, infraslow cortical activity in anaesthetized and awake mice. Spontaneous infraslow activity is regionally distinct, correlates with electroencephalography and local field potential recordings, and shows bilateral symmetry between cortical hemispheres. Infraslow activity is attenuated and its functional structure abolished after treatment with voltage-gated sodium channel and glutamate receptor antagonists. Correlation analysis reveals patterns of infraslow regional connectivity that are analogous to cortical motifs observed from higher-frequency spontaneous activity and reflect the underlying framework of intracortical axonal projections.

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Section: Discussionmentioning

confidence: 99%

Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

et al. 2015

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“…Especially along the z axis, the effect of the point spread function (PSF) introduces dispersion of the signal (24). The size of the axial distribution width of our system along the x, y, and z axes was estimated by scanning of fluorescent micro beads (24,25) and was found to be 1.46 μm along the z axis, and 0.20 and 0.29 μm along the x and y axes, respectively (Fig. 5E).…”

Section: Significancementioning

confidence: 93%

“…The center of the centroid and the difference between actual and perceived diameter were used to calculate sigma, as described (24,25) (Fig. 5E).…”

Section: Methodsmentioning

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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“…Bilateral common carotid artery stenosis was induced in mice using 0.18 mm inner diameter steel coils (total length: 2.5 mm, Sawane Spring, Hamamatsu, Shizuoka Prefect, Japan). 6 Twenty-four hours before BCAS, bilateral, thinned-skull, glass coverslip-reinforced cranial windows 17 were created, overlying the middle and anterior cerebral artery watershed territory. Animals were allowed to recover overnight.…”

Section: Animal Preparationmentioning

confidence: 99%

Micro-Heterogeneity of Flow in a Mouse Model of Chronic Cerebral Hypoperfusion Revealed by Longitudinal Doppler Optical Coherence Tomography and Angiography

Srinivasan

Radhakrishnan

et al. 2015

J Cereb Blood Flow Metab

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Although microvascular dysfunction accompanies cognitive decline in aging, vascular dementia, and Alzheimer's disease, tools to study microvasculature longitudinally in vivo are lacking. Here, we use Doppler optical coherence tomography (OCT) and angiography for noninvasive, longitudinal imaging of mice with chronic cerebral hypoperfusion for up to 1 month. In particular, we optimized the OCT angiography method to selectively image red blood cell (RBC)-perfused capillaries, leading to a novel way of assessing capillary supply heterogeneity in vivo. After bilateral common carotid artery stenosis (BCAS), cortical blood flow measured by Doppler OCT dropped to half of baseline throughout the imaged tissue acutely. Microscopic imaging of the capillary bed with OCT angiography further revealed local heterogeneities in cortical flow supply during hypoperfusion. The number of RBC-perfused capillaries decreased, leading to increased oxygen diffusion distances in the days immediately after BCAS. Linear regression showed that RBC-perfused capillary density declined by 0.3% for a drop in flow of 1 mL/100 g per minute, and decreases in RBC-perfused capillary density as high as 25% were observed. Taken together, these results demonstrate the existence of local supply heterogeneity at the capillary level even at nonischemic global flow levels, and demonstrate a novel imaging method to assess this heterogeneity. Keywords: angiography; capillary recruitment; Doppler optical coherence tomography; hypoperfusion; vascular dementia INTRODUCTION Chronic cerebral hypoperfusion induced by small-artery occlusion or critical arterial stenosis is a pathophysiologic hallmark of vascular dementia. Histologically characterized by white matter changes and multifocal infarctions, chronic cerebral hypoperfusion is associated with cognitive decline. 1-3 Rodent models of chronic cerebral hypoperfusion that use common carotid artery stenosis or occlusion mimic many aspects of vascular cognitive impairment in patients, including decreased cerebral blood flow, inflammation and blood-brain barrier abnormalities, brain atrophy, white matter degeneration, decreased metabolism, as well as impaired working memory. 4 Bilateral common carotid artery occlusion has been widely used in the rat to model chronic cerebral hypoperfusion. 5 Recently, mouse bilateral common carotid artery stenosis (BCAS) models have emerged. 6 In these models, although the degree of hypoperfusion is correlated with the extent of ischemic lesions and neurologic impairment, 7 the magnitude of flow reductions after BCAS were moderate at best (~30 to 40%), 8 at least relative to classic ischemic thresholds of 80 to 85%, 9-11 and lasted only a few days before collateral development and recovery of flow. The lack of classic ischemia raises questions about the precise mechanism of tissue loss and cognitive impairment. Previous studies have used laser Doppler Journal of Cerebral Blood

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Chronic optical access through a polished and reinforced thinned skull

Cited by 388 publications

References 29 publications

Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

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

Micro-Heterogeneity of Flow in a Mouse Model of Chronic Cerebral Hypoperfusion Revealed by Longitudinal Doppler Optical Coherence Tomography and Angiography

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Chronic optical access through a polished and reinforced thinned skull

Cited by 388 publications

References 29 publications

Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

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

Micro-Heterogeneity of Flow in a Mouse Model of Chronic Cerebral Hypoperfusion Revealed by Longitudinal Doppler Optical Coherence Tomography and Angiography

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