scholarly journals Dynamic connectivity maps of pericytes and endothelial cells mediate neurovascular coupling in health and disease

2019 ◽  
Author(s):  
Tamas Kovacs-Oller ◽  
Elena Ivanova ◽  
Paola Bianchimano ◽  
Botir T. Sagdullaev

SummaryFunctional hyperemia, or matching blood flow to activity, is spatially accurate to direct the oxygen and nutrients to regionally firing neurons. The underlying signaling mechanisms of neurovascular coupling remain unclear, but are critical for brain function and establish the diagnostic power of BOLD-fMRI. Here, we described a mosaic of pericytes, the vasomotor capillary cells in the living retina. We then tested if this symmetric net of pericytes and surrounding neuroglia predicted a connectivity map in response to sensory stimuli. Surprisingly, we found that these connections were not only discriminatory across cell types, but also highly asymmetric spatially. First, pericytes connected predominantly to other neighboring pericytes and endothelial cells, and less to arteriolar smooth muscle cells, and not to surrounding neurons or glia. Second, focal, but not global stimulation evoked a directional vasomotor response by strengthening connections along the feeding vascular branch. This activity required local NO signaling and occurred by means of direct coupling via gap-junctions. By contrast, bath application of NO or diabetes, a common microvascular pathology, not only weakened the vascular signaling but also abolished its directionality. We conclude that the discriminatory nature of neurovascular interactions may thus establish spatial accuracy of blood delivery with the precision of the neuronal receptive field size, and is disrupted early in microvascular disease.HighlightsWithin a structurally symmetric mosaic, pericytes form discriminatory connectionsPericyte connectome tunes with a precision matching a neuronal receptive fieldFocal but not global input evokes a vasomotor response by strengthening the gap-junction mediated signaling towards a feeding vascular branchDisrupted functional connectivity map triggers loss of the functional hyperemia in diabetic neuropathy




1993 ◽  
Vol 90 (23) ◽  
pp. 11142-11146 ◽  
Author(s):  
S Bisti ◽  
C Trimarchi

Prenatal unilateral enucleation in mammals causes an extensive anatomical reorganization of visual pathways. The remaining eye innervates the entire extent of visual subcortical and cortical areas. Electrophysiological recordings have shown that the retino-geniculate connections are retinotopically organized and geniculate neurones have normal receptive field properties. In area 17 all neurons respond to stimulation of the remaining eye and retinotopy, orientation columns, and direction selectivity are maintained. The only detectable change is a reduction in receptive field size. Are these changes reflected in the visual behavior? We studied visual performance in cats unilaterally enucleated 3 weeks before birth (gestational age at enucleation, 39-42 days). We tested behaviorally the development of visual acuity and, in the adult, the extension of the visual field and the contrast sensitivity. We found no difference between prenatal monocularly enucleated cats and controls in their ability to orient to targets in different positions of the visual field or in their visual acuity (at any age). The major difference between enucleated and control animals was in contrast sensitivity:prenatal enucleated cats present a loss in sensitivity for gratings of low spatial frequency (below 0.5 cycle per degree) as well as a slight increase in sensitivity at middle frequencies. We conclude that prenatal unilateral enucleation causes a selective change in the spatial performance of the remaining eye. We suggest that this change is the result of a reduction in the number of neurones with large receptive fields, possibly due to a severe impairment of the Y system.



2005 ◽  
Vol 93 (6) ◽  
pp. 3537-3547 ◽  
Author(s):  
Chong Weng ◽  
Chun-I Yeh ◽  
Carl R. Stoelzel ◽  
Jose-Manuel Alonso

Each point in visual space is encoded at the level of the thalamus by a group of neighboring cells with overlapping receptive fields. Here we show that the receptive fields of these cells differ in size and response latency but not at random. We have found that in the cat lateral geniculate nucleus (LGN) the receptive field size and response latency of neighboring neurons are significantly correlated: the larger the receptive field, the faster the response to visual stimuli. This correlation is widespread in LGN. It is found in groups of cells belonging to the same type (e.g., Y cells), and of different types (i.e., X and Y), within a specific layer or across different layers. These results indicate that the inputs from the multiple geniculate afferents that converge onto a cortical cell (approximately 30) are likely to arrive in a sequence determined by the receptive field size of the geniculate afferents. Recent studies have shown that the peak of the spatial frequency tuning of a cortical cell shifts toward higher frequencies as the response progresses in time. Our results are consistent with the idea that these shifts in spatial frequency tuning arise from differences in the response time course of the thalamic inputs.



1996 ◽  
Vol 75 (6) ◽  
pp. 2441-2450 ◽  
Author(s):  
D. D. Rasmusson

1. Single neurons in the ventroposterior lateral thalamic nucleus were studied in 10 anesthetized raccoons, 4 of which had undergone amputation of the fourth digit 4-5 mo before recording. Neurons with receptive fields on the glabrous skin of a forepaw digit were examined in response to electrical stimulation of the “on-focus” digit that contained the neuron's receptive field and stimulation of an adjacent, “off-focus” digit. 2. In normal raccoons all neurons responded to on-focus stimulation with an excitation at a short latency (mean 13 ms), whereas only 63% of the neurons responded to off-focus digit stimulation. The off-focus responses had a longer latency (mean 27.2 ms) and a higher threshold than the on-focus responses (800 and 452 microA, respectively). Only 3 of 32 neurons tested with off-focus stimulation had both a latency and a threshold within the range of on-focus values. Inhibition following the excitation was seen in the majority of neurons with both types of stimulation. 3. In the raccoons with digit removal, the region of the thalamus that had lost its major peripheral input (the “deafferented” region) was distinguished from the normal third and fifth digit regions on the basis of the sequence of neuronal receptive fields within a penetration and receptive field size as described previously. 4. Almost all of the neurons in the deafferented region (91%) were excited by stimulation of one or both adjacent digits. The average latency for these responses was shorter (15.3 ms) and the threshold was lower than was the case with off-focus stimulation in control animals. These values were not significantly different from the responses to on-focus stimulation in the animals with digit amputation. 5. These results confirm that reorganization of sensory pathways can be observed at the thalamic level. In addition to the changes in the somatotopic map that have been shown previously with the use of mechanical stimuli, the present paper demonstrates an improvement in several quantitative measures of single-unit responses. Many of these changes suggest that this reorganization could be explained by an increased effectiveness of preexisting, weak connections from the off-focus digits; however, the increase in the proportion of neurons responding to stimulation of adjacent digits may indicate that sprouting of new connections also occurs.



1994 ◽  
Vol 11 (4) ◽  
pp. 703-720 ◽  
Author(s):  
Ming Sun ◽  
A. B. Bonds

AbstractThe two-dimensional organization of receptive fields (RFs) of 44 cells in the cat visual cortex and four cells from the cat LGN was measured by stimulation with either dots or bars of light. The light bars were presented in different positions and orientations centered on the RFs. The RFs found were arbitrarily divided into four general types: Punctate, resembling DOG filters (11%); those resembling Gabor filters (9%); elongate (36%); and multipeaked-type (44%). Elongate RFs, usually found in simple cells, could show more than one excitatory band or bifurcation of excitatory regions. Although regions inhibitory to a given stimulus transition (e.g. ON) often coincided with regions excitatory to the opposite transition (e.g. OFF), this was by no means the rule. Measurements were highly repeatable and stable over periods of at least 1 h. A comparison between measurements made with dots and with bars showed reasonable matches in about 40% of the cases. In general, bar-based measurements revealed larger RFs with more structure, especially with respect to inhibitory regions. Inactivation of lower cortical layers (V-VI) by local GABA injection was found to reduce sharpness of detail and to increase both receptive-field size and noise in upper layer cells, suggesting vertically organized RF mechanisms. Across the population, some cells bore close resemblance to theoretically proposed filters, while others had a complexity that was clearly not generalizable, to the extent that they seemed more suited to detection of specific structures. We would speculate that the broadly varying forms of cat cortical receptive fields result from developmental processes akin to those that form ocular-dominance columns, but on a smaller scale.



1990 ◽  
Vol 2 (1) ◽  
pp. 71-84 ◽  
Author(s):  
Kamil A. Grajski ◽  
Michael M. Merzenich

The inverse magnification rule in cortical somatotopy is the experimentally derived inverse relationship between cortical magnification (area of somatotopic map representing a unit area of skin surface) and receptive field size (area of restricted skin surface driving a cortical neuron). We show by computer simulation of a simple, multilayer model that Hebb-type synaptic modification subject to competitive constraints is sufficient to account for the inverse magnification rule.



2021 ◽  
Author(s):  
Maria Sancho ◽  
Nicholas R. Klug ◽  
Amreen Mughal ◽  
Thomas J. Heppner ◽  
David Hill-Eubanks ◽  
...  

SUMMARYThe dense network of capillaries composed of capillary endothelial cells (cECs) and pericytes lies in close proximity to all neurons, ideally positioning it to sense neuro/glial-derived compounds that regulate regional and global cerebral perfusion. The membrane potential (VM) of vascular cells serves as the essential output in this scenario, linking brain activity to vascular function. The ATP-sensitive K+ channel (KATP) is a key regulator of vascular VM in other beds, but whether brain capillaries possess functional KATP channels remains unknown. Here, we demonstrate that brain capillary ECs and pericytes express KATP channels that robustly control VM. We further show that the endogenous mediator adenosine acts through A2A receptors and the Gs/cAMP/PKA pathway to activate capillary KATP channels. Moreover, KATP channel stimulation in vivo causes vasodilation and increases cerebral blood flow (CBF). These findings establish the presence of KATP channels in cECs and pericytes and suggest their significant influence on CBF.HIGHLIGHTSCapillary network cellular components—endothelial cells and pericytes—possess functional KATP channels.Activation of KATP channels causes profound hyperpolarization of capillary cell membranes.Capillary KATP channels are activated by exogenous adenosine via A2A receptors and cAMP-dependent protein kinase.KATP channel activation by adenosine or synthetic openers increases cerebral blood flow.



1987 ◽  
Vol 510 (1 Olfaction and) ◽  
pp. 504-505
Author(s):  
CHARLOTTE M. MISTRETTA ◽  
TAKATOSHI NAGAI ◽  
ROBERT M. BRADLEY


2008 ◽  
Vol 25 (4) ◽  
pp. 419-427 ◽  
Author(s):  
Kazunori Yamamoto ◽  
Hiroshi Jouhou ◽  
Masanori Iwasaki ◽  
Akimichi Kaneko ◽  
Masahiro Yamada


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