scholarly journals Astrocytic modulation of information processing by layer 5 pyramidal neurons of the mouse visual cortex

2020 ◽  
Author(s):  
Dimitri Ryczko ◽  
Maroua Hanini-Daoud ◽  
Steven Condamine ◽  
Benjamin J. B. Bréant ◽  
Maxime Fougère ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Cortical Neurons ◽  
Calcium Binding ◽  
Pyramidal Neurons ◽  
Binding Protein ◽  
Contextual Information ◽  
Dendritic Tree ◽  
Cortical Layer ◽  
List Type ◽  
Ionic Environment

AbstractThe most complex cerebral functions are performed by the cortex which most important output is carried out by its layer 5 pyramidal neurons. Their firing reflects integration of sensory and contextual information that they receive. There is evidence that astrocytes influence cortical neurons firing through the release of gliotransmitters such as ATP, glutamate or GABA. These effects were described at the network and at the synaptic levels, but it is still unclear how astrocytes influence neurons input-output transfer function at the cellular level. Here, we used optogenetic tools coupled with electrophysiological, imaging and anatomical approaches to test whether and how astrocytic activation affected processing and integration of distal inputs to layer 5 pyramidal neurons (L5PN). We show that optogenetic activation of astrocytes near L5PN cell body prolonged firing induced by distal inputs to L5PN and potentiated their ability to trigger spikes. The observed astrocytic effects on L5PN firing involved glutamatergic transmission to some extent but relied on release of S100β, an astrocytic Ca2+-binding protein that decreases extracellular Ca2+ once released. This astrocyte-evoked decrease of extracellular Ca2+ elicited firing mediated by activation of Nav1.6 channels. Our findings suggest that astrocytes contribute to the cortical fundamental computational operations by controlling the extracellular ionic environment.Key Points SummaryIntegration of inputs along the dendritic tree of layer 5 pyramidal neurons is an essential operation as these cells represent the most important output carrier of the cerebral cortex. However, the contribution of astrocytes, a type of glial cell to these operations is poorly documented.Here we found that optogenetic activation of astrocytes in the vicinity of layer 5 in the mouse primary visual cortex induce spiking in local pyramidal neurons through Nav1.6 ion channels and prolongs the responses elicited in these neurons by stimulation of their distal inputs in cortical layer 1.This effect partially involved glutamatergic signalling but relied mostly on the astrocytic calcium-binding protein S100β, which regulates the concentration of calcium in the extracellular space around neurons.These findings show that astrocytes contribute to the fundamental computational operations of the cortex by acting on the ionic environment of neurons.

scholarly journals Classical-contextual interactions in V1 may rely on dendritic computations

2018 ◽  
Author(s):  
Lei Jin ◽  
Bardia F. Behabadi ◽  
Monica P. Jadi ◽  
Chaithanya A. Ramachandra ◽  
Bartlett W. Mel
Keyword(s):  
Visual Cortex ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Contextual Information ◽  
Flexible Substrate ◽  
Receptive Fields ◽  
Boundary Detection ◽  
Synaptic Interactions ◽  
Horizontal Connections ◽  
Local Circuits

AbstractA signature feature of the neocortex is the dense network of horizontal connections (HCs) through which pyramidal neurons (PNs) exchange “contextual” information. In primary visual cortex (V1), HCs are thought to facilitate boundary detection, a crucial operation for object recognition, but how HCs modulate PN responses to boundary cues within their classical receptive fields (CRF) remains unknown. We began by “asking” natural images, through a structured data collection and ground truth labeling process, what function a V1 cell should use to compute boundary probability from aligned edge cues within and outside its CRF. The “answer” was an asymmetric 2-D sigmoidal function, whose nonlinear form provides the first normative account for the “multiplicative” center-flanker interactions previously reported in V1 neurons (Kapadia et al. 1995, 2000; Polat et al. 1998). Using a detailed compartmental model, we then show that this boundary-detecting classical-contextual interaction function can be computed with near perfect accuracy by NMDAR-dependent spatial synaptic interactions within PN dendrites – the site where classical and contextual inputs first converge in the cortex. In additional simulations, we show that local interneuron circuitry activated by HCs can powerfully leverage the nonlinear spatial computing capabilities of PN dendrites, providing the cortex with a highly flexible substrate for integration of classical and contextual information.Significance StatementIn addition to the driver inputs that establish their classical receptive fields, cortical pyramidal neurons (PN) receive a much larger number of “contextual” inputs from other PNs through a dense plexus of horizontal connections (HCs). However by what mechanisms, and for what behavioral purposes, HC’s modulate PN responses remains unclear. We pursued these questions in the context of object boundary detection in visual cortex, by combining an analysis of natural boundary statistics with detailed modeling PNs and local circuits. We found that nonlinear synaptic interactions in PN dendrites are ideally suited to solve the boundary detection problem. We propose that PN dendrites provide the core computing substrate through which cortical neurons modulate each other’s responses depending on context.

scholarly journals Analyzing Branch‐specific Dendritic Spikes Using an Ultrafast Laser Scalpel

2020 ◽  
Vol 8 ◽  
Author(s):  
Michael L. Castañares ◽  
Hans-A. Bachor ◽  
Vincent R. Daria
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Dendritic Tree ◽  
Cortical Layer ◽  
Ultrafast Laser ◽  
Laser Scalpel ◽  
Dendritic Spikes ◽  
Dendritic Spike ◽  
Neuronal Computation

Dendritic spikes facilitate neuronal computation and they have been reported to occur in various regions of the dendritic tree of cortical neurons. Spikes that occur only on a select few branches are particularly difficult to analyze especially in complex and intertwined dendritic arborizations where highly localized application of pharmacological blocking agents is not feasible. Here, we present a technique based on highly targeted dendrotomy to tease out and study dendritic spikes that occur in oblique branches of cortical layer five pyramidal neurons. We first analyze the effect of cutting dendrites in silico and then confirmed in vitro using an ultrafast laser scalpel. A dendritic spike evoked in an oblique branch manifests at the soma as an increase in the afterdepolarization (ADP). The spikes are branch-specific since not all but only a few oblique dendrites are observed to evoke spikes. Both our model and experiments show that cutting certain oblique branches, where dendritic spikes are evoked, curtailed the increase in the ADP. On the other hand, cutting neighboring oblique branches that do not evoke spikes maintained the ADP. Our results show that highly targeted dendrotomy can facilitate causal analysis of how branch-specific dendritic spikes influence neuronal output.

Developmental Expression of Calcium-Binding Protein-Containing Neurons in Neocortical Transplants

1998 ◽  
Vol 7 (2) ◽  
pp. 121-129 ◽  
Author(s):  
Jeffrey M. Rosenstein ◽  
Newton S. More ◽  
Nina Mani ◽  
Janette M. Krum
Keyword(s):  
Oxidative Stress ◽  
Cortical Neurons ◽  
Calcium Binding ◽  
Binding Protein ◽  
Substantial Reduction ◽  
Qualitative Change ◽  
Afferent Input ◽  
Calcium Binding Protein ◽  
Developmental Expression ◽  
Parvalbumin Neurons

The present study examined the development of calcium binding protein-containing neurons in a timed series of fetal neocortical transplants. The immunoexpression of parvalbumin and calbindin, which are subpopulations of GABAergic neurons, have been widely studied in normal development and in disease and injury states. Because of their purported resistance to oxidative injury by their ability to buffer Ca++ influx, these neurons have been particularly studied following ischemia. Because it is likely that oxidative stress is associated with the grafting procedure, we sought to determine if these neurons displayed enhanced survival characteristics. Normally, parvalbumin and calbindin represent about 5-10% of cortical neurons. Within 2-4 wk after grafting the expression of both proteins increased markedly in that a relatively larger number of neurons (27% for parvalbumin) were immunopositive. This increase was transitory, however, and by 4 mo and beyond, confocal microscopic data showed a reduction of over 50% of parvalbumin (+) neurons and processes. Calbindin (+) processes showed a qualitative change in that they were smaller with less terminal branching. Electron microscopy confirmed a substantial reduction in parvalbumin synaptic contacts. Interestingly, in older grafts, remaining parvalbumin neurons were those that were strongly NSE (+) suggesting a link between normal metabolism and Ca++ buffering in grafted neurons. It is possible that in early grafts certain neuronal populations transiently upregulated calcium binding proteins as a defensive mechanism against Ca++ influx associated with oxidative stress. Over time, however, following physiological normalization within grafts, the calcium binding protein (+) neurons are diminished, possibly due to lack of appropriate afferent input to the interneuronal pool.

Immunoreactivity of calcium binding protein secretagogin in the human hippocampus is restricted to pyramidal neurons

2007 ◽  
Vol 42 (3) ◽  
pp. 215-222 ◽  
Author(s):  
J ATTEMS ◽  
M QUASS ◽  
W GARTNER ◽  
A NABOKIKH ◽  
L WAGNER ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Pyramidal Neurons ◽  
Binding Protein ◽  
Calcium Binding Protein ◽  
Human Hippocampus

scholarly journals Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits

2019 ◽  
Author(s):  
Daniele Linaro ◽  
Ben Vermaercke ◽  
Ryohei Iwata ◽  
Arjun Ramaswamy ◽  
Brittany A. Davis ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Human Brain ◽  
Cortical Neurons ◽  
Single Cells ◽  
Functional Integration ◽  
List Type ◽  
Visual Responses ◽  
Mouse Cortex ◽  
Human Neurons ◽  
Species Specific

SummaryHow neural circuits develop in the human brain has remained almost impossible to study at the neuronal level. Here we investigate human cortical neuron development, plasticity and function, using a mouse/human chimera model in which xenotransplanted human cortical pyramidal neurons integrate as single cells into the mouse cortex. Combined neuronal tracing, electrophysiology, andin vivostructural and functional imaging revealed that the human neurons develop morphologically and functionally following a prolonged developmental timeline, revealing the cell-intrinsic retention of juvenile properties of cortical neurons as an important mechanism underlying human brain neoteny. Following maturation, human neurons transplanted in the visual cortex display tuned responses to visual stimuli that are similar to those of mouse neurons, indicating capacity for physiological synaptic integration of human neurons in mouse cortical circuits. These findings provide new insights into human neuronal development, and open novel experimental avenues for the study of human neuronal function and diseases.Highlights:Coordinated morphological and functional maturation of ESC-derived human cortical neurons transplanted in the mouse cortex.Transplanted neurons display prolonged juvenile features indicative of intrinsic species-specific neoteny.Transplanted neurons develop elaborate dendritic arbors, stable spine patterns and long-term synaptic plasticity.In the visual cortex transplanted neurons display tuned visual responses that resemble those of the host cortical neurons.

scholarly journals Spontaneous retinal waves generate long-range horizontal connectivity in visual cortex

2020 ◽  
Author(s):  
Jinwoo Kim ◽  
Min Song ◽  
Se-Bum Paik
Keyword(s):  
Visual Cortex ◽  
Long Range ◽  
Primary Visual Cortex ◽  
Cortical Neurons ◽  
Activity Patterns ◽  
Developmental Model ◽  
List Type ◽  
Retinal Waves ◽  
Horizontal Connections ◽  
Eye Opening

AbstractIn the primary visual cortex (V1) of higher mammals, long-range horizontal connections (LHCs) are observed to develop, linking iso-orientation domains of cortical tuning. It is unknown how this feature-specific wiring of circuitry develops before eye opening. Here, we show that LHCs in V1 may originate from spatio-temporally structured feedforward activities generated from spontaneous retinal waves. Using model simulations based on the anatomy and observed activity patterns of the retina, we show that waves propagating in retinal mosaics can initialize the wiring of LHCs by co-activating neurons of similar tuning, whereas equivalent random activities cannot induce such organizations. Simulations showed that emerged LHCs can produce the patterned activities observed in V1, matching topography of the underlying orientation map. We also confirmed that the model can also reproduce orientation-specific microcircuits in salt-and-pepper organizations in rodents. Our results imply that early peripheral activities contribute significantly to cortical development of functional circuits.HighlightsDevelopmental model of long-range horizontal connections (LHCs) in V1 is simulatedSpontaneous retinal waves generate feature-specific wiring of LHCs in visual cortexEmerged LHCs induce orientation-matching patterns of spontaneous cortical activityRetinal waves induce orientation-specific microcircuits of visual cortex in rodentsSignificance statementLong-range horizontal connections (LHCs) in the primary visual cortex (V1) are observed to emerge before the onset of visual experience, selectively connecting iso-domains of orientation maps. However, it is unknown how such tuning-specific wirings develop before eye-opening. Here, we show that LHCs in V1 originate from the tuning-specific activation of cortical neurons by spontaneous retinal waves during early developmental stages. Our simulations of a visual cortex model show that feedforward activities from the retina initialize the spatial organization of activity patterns in V1, which induces visual feature-specific wirings of V1 neurons. Our model also explains the origin of cortical microcircuits observed in rodents, suggesting that the proposed developmental mechanism is applicable universally to circuits of various mammalian species.

Abstract 341: Both Beta-1 and Beta-2 Adrenergic Receptors (ARs) are Required for Pressure Overload Cardiac Hypertrophy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Mingming Zhao ◽  
Roger Wagner ◽  
Giovanni Fajardo ◽  
Takashi Urashima ◽  
Sara Farahani ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Kinase Inhibitor ◽  
Binding Protein ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Heart Weight ◽  
Lv Function ◽  
List Type ◽  
Hypertrophic Response ◽  
Calgranulin B

In isolated myocytes, hypertrophy induced by norepinephrine is mediated via β-ARs, however, in vivo, mice with deletions of both major cardiac β-ARs still develop hypertrophy with pressure overload. The mechanism by which the heart adapts to pressure overload, producing either adaptive or maladaptive remodeling is still not completely understood. To study the role of β-ARs in pressure overload hypertrophy, we performed transverse aortic constriction (TAC) in congenic mice with targeted deletions of β1, β2 and both β1 and β2-ARs and in sham controls. After 3 wks, β1−/− mice showed a 21% increase in heart weight to body weight ratio (HW/BW) vs. sham, similar to WT (HW/BW 5.02 ± 0.72 for β1−/− vs. 5.20 ± 0.92 for WT). β2−/− mice showed an exaggerated (49%) hypertrophic response (HW/BW 5.81 ± 0.53, p < 0.001 vs. WT). Only when both β-ARs were ablated was hypertrophy fully attenuated: in β1β2−/− mice HW/BW increased only 8% (HW/BW 4.30 ± 0.31, p < 0.01 vs. WT). Echocardiography showed that peak band gradient was not different between groups (WT 45.3 ± 4.1, β1−/− 47.2 ± 10.2, β2−/− 49.0 ± 9.7, β1β2−/− 53.2 ± 11.3 mmHg) and all groups maintained normal LV function. Morphometric analysis confirmed the absence of hypertrophy in the β1β2−/−: mean cross-sectional area for WT was 254.7 ± 34.9 vs. β1β2−/− 115.8 ± 16.7μm 2 , which was not different from sham. Gene microarray analysis detected a set of genes which were differentially expressed in β1β2−/− vs. WT, β1−/−, or β2−/−: S100 calcium binding protein A9/calgranulin B (S100a9, 4.5-fold up); Cyclin-dependent kinase inhibitor 1A/P21 (Cdkn1a, 3.8-fold up); Metallothioneins Mt1 (3-fold up) and Mt2 (2.7-fold up); FK506 binding protein 5, a glucocorticoid receptor-regulating co-chaperone and calcineurin inhibitor (3.2-fold up). In contrast, TGFβ2 was upregulated in WT, β1−/− and β2−/− but not in β1β2−/−. Differentially regulated genes were validated by SYBR QRT-PCR on the same RNA samples. Thus, β2-AR signaling may serve to limit the hypertrophic response to pressure afterload. However, both β-ARs are required for the development of a normal hypertrophic response. Ablation of both β-AR subtypes alters expression of several genes, some of which may be critical to the hypertrophic program.

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