Correlations of Neuronal and Microvascular Densities in Murine Cortex Revealed by Direct Counting and Colocalization of Nuclei and Vessels

Tsai, Philbert S.; Kaufhold, J.; Blinder, Pablo; Friedman, Beth; Drew, Patrick J.; Karten, Harvey J.; Lyden, Patrick D.; Kleinfeld, David

doi:10.1523/jneurosci.3287-09.2009

Cited by 520 publications

(617 citation statements)

References 87 publications

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“…Some morphological mathematical opening/ closure procedures were then used to finalize this step, so as to remove black islands inside white vessels (Risser et al, 2007). The vessel's density, volume, and length, which is obtained after this procedure, has been recently found consistent with other reported measures in primate and rodents (Risser et al, 2009;Tsai et al, 2009). …”

Section: Image Acquisition and Segmentationmentioning

confidence: 71%

Cerebral Blood Flow Modeling in Primate Cortex

Guibert

Fonta

Plouraboué

2010

J Cereb Blood Flow Metab

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We report new results on blood flow modeling over large volumes of cortical gray matter of primate brain. We propose a network method for computing the blood flow, which handles realistic boundary conditions, complex vessel shapes, and complex nonlinear blood rheology. From a detailed comparison of the available models for the blood flow rheology and the phase separation effect, we are able to derive important new results on the impact of network structure on blood pressure, hematocrit, and flow distributions. Our findings show that the network geometry (vessel shapes and diameters), the boundary conditions associated with the arterial inputs and venous outputs, and the effective viscosity of the blood are essential components in the flow distribution. In contrast, we show that the phase separation effect has a minor function in the global microvascular hemodynamic behavior. The behavior of the pressure, hematocrit, and blood flow distributions within the network are described through the depth of the primate cerebral cortex and are discussed.

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Section: Image Acquisition and Segmentationmentioning

confidence: 71%

Cerebral Blood Flow Modeling in Primate Cortex

Guibert

Fonta

Plouraboué

2010

J Cereb Blood Flow Metab

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“…Previous studies, however, used Nissl staining and GABA IHC of very thin slices and random statistical sampling of only a few somata (disector method), which may have hampered these analyses, as indicated by their disagreeing results (13,16). In the present study, using IHC of consecutive thick sections in combination with confocal microscopy, mosaic scanning, visualization software, and computer-aided data analysis, the actual counting of tens of thousands of neurons and differentiation of columns from the surrounding cortex were feasible (21,30). The data presented here are from adolescent rats.…”

Section: Molecular Markers Of Ins In a Corticalmentioning

confidence: 82%

Inhibitory interneurons in a cortical column form hot zones of inhibition in layers 2 and 5A

Meyer

Schwarz

Wimmer

et al. 2011

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

218

170

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Although physiological data on microcircuits involving a few inhibitory neurons in the mammalian cerebral cortex are available, data on the quantitative relation between inhibition and excitation in cortical circuits involving thousands of neurons are largely missing. Because the distribution of neurons is very inhomogeneous in the cerebral cortex, it is critical to map all neurons in a given volume rather than to rely on sparse sampling methods. Here, we report the comprehensive mapping of interneurons (INs) in cortical columns of rat somatosensory cortex, immunolabeled for neuron-specific nuclear protein and glutamate decarboxylase. We found that a column contains ∼2,200 INs (11.5% of ∼19,000 neurons), almost a factor of 2 less than previously estimated. The density of GABAergic neurons was inhomogeneous between layers, with peaks in the upper third of L2/3 and in L5A. IN density therefore defines a distinct layer 2 in the sensory neocortex. In addition, immunohistochemical markers of IN subtypes were layer-specific. The "hot zones" of inhibition in L2 and L5A match the reported low stimulus-evoked spiking rates of excitatory neurons in these layers, suggesting that these inhibitory hot zones substantially suppress activity in the neocortex.F or a quantitative understanding of the interaction between excitatory and inhibitory synaptic transmission in the neocortex, it is crucial to obtain data on the absolute numbers and the relative distribution of excitatory and inhibitory (mostly GABAergic) neurons [interneurons (INs)] in a cortical column. Only on the basis of such prevalence numbers is it possible to interpret data on single-cell physiology (1-8) and synaptic connections of pairs of neurons (9-12) at the circuit level. The distribution of cortical neurons and INs has therefore been the objective of several studies over the past decades (13-15). Statistical sampling methods were used because mapping tens of thousands of neurons was not feasible. Although the nominal error bounds of such methods are in the range of 10-20%, the reported absolute numbers differed strongly among studies, especially for sparse neuron populations, such as INs and their subtypes. The ratio of INs reported for the somatosensory cortex varied between 15% and 25%, thus by almost a factor of 2 (13,16,17). Data on possible differences in IN density between layers in a cortical column were contradictory (13,15,16,18,19).To resolve these substantial discrepancies, we undertook the complete mapping of INs in entire cortical columns using the cytoarchitectonic barrels in L4 as a reference frame for the thalamocortical innervation volume (20) in postnatal day (P) 25-36 rat vibrissal cortex. Our data show that the overall prevalence of inhibitory neurons was previously overestimated by almost a factor of 2. We find a unique substructure of the distribution of INs in a cortical column that can explain the layer-specific differences in the excitability in neocortex. The distribution of INs defines layer 2 as a distinct neocortical layer.

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“…We generated angiograms of the MCA by transcardial perfusion of mice and rats with a gel perfusate cross-linked with fluorescein, as described (46). The perfused brain was removed from the skull under extreme care to avoid disruption of the pial network, and the two cortices were dissected along the ventricles and flattened between two coverslips separated by a spacer, 3.6 mm for rats and 1.8 mm for mice (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Animals were allowed to recover and were killed for histological analysis 6 to 8 d after the occlusion. We stained with antibodies for NeuN, as described (46), and outlined the regions of tissue with labeled neurons (45) and calculated their 3D area from successive sections (Fig. 5 E and F).…”

Section: Methodsmentioning

confidence: 99%

Topological basis for the robust distribution of blood to rodent neocortex

Blinder¹,

Shih²,

Rafie³

et al. 2010

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

168

224

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The maintenance of robust blood flow to the brain is crucial to the health of brain tissue. We examined the pial network of the middle cerebral artery, which distributes blood from the cerebral arteries to the penetrating arterioles that source neocortical microvasculature, to characterize how vascular topology may support such robustness. For both mice and rats, two features dominate the topology. First, interconnected loops span the entire territory sourced by the middle cerebral artery. Although the loops comprise <10% of all branches, they maintain the overall connectivity of the network after multiple breaks. Second, >80% of offshoots from the loops are stubs that end in a single penetrating arteriole, as opposed to trees with multiple penetrating arterioles. We hypothesize that the loops and stubs protect blood flow to the parenchyma from an occlusion in a surface vessel. To test this, we assayed the viability of tissue that was sourced by an individual penetrating arteriole following occlusion of a proximal branch in the surface loop. We observed that neurons remained healthy, even when occlusion led to a reduction in the local blood flow. In contrast, direct blockage of a single penetrating arteriole invariably led to neuronal death and formation of a cyst. Our results show that the surface vasculature functions as a grid for the robust allocation of blood in the event of vascular dysfunction. The combined results of the present and prior studies imply that the pial network reallocates blood in response to changing metabolic needs.anastomoses | imaging | networks | stroke | vasculature

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Correlations of Neuronal and Microvascular Densities in Murine Cortex Revealed by Direct Counting and Colocalization of Nuclei and Vessels

Cited by 520 publications

References 87 publications

Cerebral Blood Flow Modeling in Primate Cortex

Cerebral Blood Flow Modeling in Primate Cortex

Inhibitory interneurons in a cortical column form hot zones of inhibition in layers 2 and 5A

Topological basis for the robust distribution of blood to rodent neocortex

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