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 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 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.

scholarly journals Age-Dependent Changes in Synaptic NMDA Receptor Composition in Adult Human Cortical Neurons

2020 ◽  
Vol 30 (7) ◽  
pp. 4246-4256 ◽  
Author(s):  
Chrysia M Pegasiou ◽  
Ardalan Zolnourian ◽  
Diego Gomez-Nicola ◽  
Katrin Deinhardt ◽  
James A R Nicoll ◽  
...  
Keyword(s):  
Human Brain ◽  
Cortical Neurons ◽  
Critical Role ◽  
Memory Storage ◽  
Neurosurgical Procedures ◽  
Adult Human ◽  
Age Related ◽  
Human Neurons ◽  
Age Dependent ◽  
Cortical Synapses

Abstract The molecular processes underlying the aging-related decline in cognitive performance and memory observed in humans are poorly understood. Studies in rodents have shown a decrease in N-methyl-D-aspartate receptors (NMDARs) that contain the GluN2B subunit in aging synapses, and this decrease is correlated with impaired memory functions. However, the age-dependent contribution of GluN2B-containing receptors to synaptic transmission in human cortical synapses has not been previously studied. We investigated the synaptic contribution of GluN2A and GluN2B-containing NMDARs in adult human neurons using fresh nonpathological temporal cortical tissue resected during neurosurgical procedures. The tissue we obtained fulfilled quality criteria by the absence of inflammation markers and proteomic degradation. We show an age-dependent decline in the NMDA/AMPA receptor ratio in adult human temporal cortical synapses. We demonstrate that GluN2B-containing NMDA receptors contribute to synaptic responses in the adult human brain with a reduced contribution in older individuals. With previous evidence demonstrating the critical role of synaptic GluN2B in regulating synaptic strength and memory storage in mice, this progressive reduction of GluN2B in the human brain during aging may underlie a molecular mechanism in the age-related decline in cognitive abilities and memory observed in humans.

scholarly journals Xenotransplanted Human Cortical Neurons Reveal Species-Specific Development and Functional Integration into Mouse Visual Circuits

Neuron ◽  
2019 ◽  
Vol 104 (5) ◽  
pp. 972-986.e6 ◽  
Author(s):  
Daniele Linaro ◽  
Ben Vermaercke ◽  
Ryohei Iwata ◽  
Arjun Ramaswamy ◽  
Baptiste Libé-Philippot ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Functional Integration ◽  
Species Specific

scholarly journals Age dependent changes in synaptic NMDA receptor composition in adult human cortical neurons

2020 ◽  
Author(s):  
C.M. Pegasiou ◽  
A. Zolnourian ◽  
D. Gomez-Nicola ◽  
K. Deinhardt ◽  
J.A.R. Nicoll ◽  
...  
Keyword(s):  
Human Brain ◽  
Cortical Neurons ◽  
Critical Role ◽  
Memory Storage ◽  
Neurosurgical Procedures ◽  
Adult Human ◽  
Age Related ◽  
Human Neurons ◽  
Age Dependent ◽  
Cortical Synapses

AbstractThe molecular processes underlying the ageing-related decline in cognitive performance and memory observed in humans are poorly understood. Studies in rodents have shown a decrease in N-methyl-D-aspartate receptors (NMDARs) that contain the GluN2B subunit in ageing synapses, and this decrease is correlated with impaired memory functions. However, the age-dependent contribution of GluN2B containing receptors to synaptic transmission in human cortical synapses has not been previously studied. We investigated the synaptic contribution of GluN2A and GluN2B containing NMDARs in adult human neurons using fresh non-pathological temporal cortical tissue resected during neurosurgical procedures. The tissue we obtained fulfilled quality criteria by the absence of inflammation markers and proteomic degradation. We show an age-dependent decline in the NMDA/AMPA receptor ratio in adult human temporal cortical synapses. We demonstrate that GluN2B containing NMDA receptors contribute to synaptic responses in the adult human brain with a reduced contribution in older individuals. With previous evidence demonstrating the critical role of synaptic GluN2B in regulating synaptic strength and memory storage in mice, this progressive reduction of GluN2B in the human brain during ageing may underlie a molecular mechanism in the age-related decline in cognitive abilities and memory observed in humans.

scholarly journals Species-specific mitochondria dynamics and metabolism regulate the timing of neuronal development.

2021 ◽  
Author(s):  
Ryohei Iwata ◽  
Pierre Casimir ◽  
Emir Erkol ◽  
Leila Boubakar ◽  
Melanie Planque ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Neuronal Development ◽  
Brain Evolution ◽  
Complex Cells ◽  
Human Neurons ◽  
Mitochondria Dynamics ◽  
Species Specific ◽  
Human And Mouse ◽  
Human Specific ◽  
Stimulation Of

The evolution of species involves changes in the timeline of key developmental programs. Among these, neuronal development is considerably prolonged in the human cerebral cortex compared with other mammals, leading to brain neoteny. Here we explore whether mitochondria influence the species-specific properties of cortical neuron maturation. By comparing human and mouse cortical neuronal maturation at high temporal and cell resolution, we found a slower pattern of mitochondria development in human cortical neurons compared with the mouse, together with lower mitochondria metabolic activity, particularly oxidative phosphorylation. Stimulation of mitochondria metabolism in human neurons resulted in accelerated maturation, leading to excitable and complex cells weeks ahead of time. Our data identify mitochondria as important regulators of the pace of neuronal development underlying human-specific features of brain evolution.

scholarly journals Categorically distinct types of receptive fields in early visual cortex

2016 ◽  
Vol 115 (5) ◽  
pp. 2556-2576 ◽  
Author(s):  
Vargha Talebi ◽  
Curtis L. Baker
Keyword(s):  
Visual Cortex ◽  
System Identification ◽  
Cortical Neurons ◽  
Temporal Dynamics ◽  
High Reliability ◽  
Receptive Fields ◽  
Direction Selectivity ◽  
Natural Image ◽  
Visual Responses ◽  
Neurophysiological Studies

In the visual cortex, distinct types of neurons have been identified based on cellular morphology, response to injected current, or expression of specific markers, but neurophysiological studies have revealed visual receptive field (RF) properties that appear to be on a continuum, with only two generally recognized classes: simple and complex. Most previous studies have characterized visual responses of neurons using stereotyped stimuli such as bars, gratings, or white noise and simple system identification approaches (e.g., reverse correlation). Here we estimate visual RF models of cortical neurons using visually rich natural image stimuli and regularized regression system identification methods and characterize their spatial tuning, temporal dynamics, spatiotemporal behavior, and spiking properties. We quantitatively demonstrate the existence of three functionally distinct categories of simple cells, distinguished by their degree of orientation selectivity (isotropic or oriented) and the nature of their output nonlinearity (expansive or compressive). In addition, these three types have differing average values of several other properties. Cells with nonoriented RFs tend to have smaller RFs, shorter response durations, no direction selectivity, and high reliability. Orientation-selective neurons with an expansive output nonlinearity have Gabor-like RFs, lower spontaneous activity and responsivity, and spiking responses with higher sparseness. Oriented RFs with a compressive nonlinearity are spatially nondescript and tend to show longer response latency. Our findings indicate multiple physiologically defined types of RFs beyond the simple/complex dichotomy, suggesting that cortical neurons may have more specialized functional roles rather than lying on a multidimensional continuum.

scholarly journals Astrocytes in the mouse visual cortex reliably respond to visual stimulation

2018 ◽  
Author(s):  
Keita Sonoda ◽  
Teppei Matsui ◽  
Haruhiko Bito ◽  
Kenichi Ohki
Keyword(s):  
Visual Cortex ◽  
Primary Visual Cortex ◽  
Common Mechanism ◽  
List Type ◽  
Visual Responses ◽  
Two Photon ◽  
Dual Color ◽  
Cross Correlation Analysis ◽  
Mouse Visual Cortex

AbstractAstrocytes are known to contact with a great number of synapses and may integrate sensory inputs. In the ferret primary visual cortex, astrocytes respond to a visual stimulus with a delay of several seconds with respect to the surrounding neurons. However, in the mouse visual cortex, it remains unclear whether astrocytes respond to visual stimulations. In this study, using dual-color simultaneous in vivo two-photon Ca2+ imaging of neurons and astrocytes in the awake mouse visual cortex, we examined the visual responsiveness of astrocytes and their precise response timing relative to the surrounding neurons. Neurons reliably responded to visual stimulations, whereas astrocytes often showed neuromodulator-mediated global activities, which largely masked small periodic activities. Administration of the selective α1-adrenergic receptor antagonist prazosin substantially reduced such global astrocytic activities without affecting the neuronal visual responses. In the presence of prazosin, astrocytes showed weak but consistent visual responses mostly at their somata. Cross-correlation analysis estimated that the astrocytic visual responses were delayed by approximately 5 s relative to the surrounding neuronal responses. In conclusion, our research demonstrated that astrocytes in the primary visual cortex of awake mice responded to visual stimuli with a delay of several seconds relative to the surrounding neurons, which may indicate the existence of a common mechanism of neuron–astrocyte communication across species.HighlightsWe performed dual-color in vivo two-photon Ca2+ imaging of neurons and astrocytes.α1-adrenoblocker prazosin substantially reduced global astrocytic activities.Astrocytes showed weak but reliable visual responses in the awake mouse visual cortex.Astrocytic visual responses were delayed by 5 s relative to the neuronal ones.

Effects of cholinergic depletion on neuron activities in the cat visual cortex

1987 ◽  
Vol 58 (4) ◽  
pp. 781-794 ◽  
Author(s):  
H. Sato ◽  
Y. Hata ◽  
K. Hagihara ◽  
T. Tsumoto
Keyword(s):  
Visual Cortex ◽  
Cortical Neurons ◽  
Response Magnitude ◽  
Nucleus Basalis ◽  
Visual Responses ◽  
Cortical Cells ◽  
Contralateral Cortex ◽  
Almost All ◽  
Mean Current ◽  
Cholinergic Projection

1. Unilateral lesions of the nucleus basalis magnocellularis (nBM), a source of cholinergic projection to the cerebral cortex, were produced by injection of kainic acid in the cat. The lesions caused a significant reduction in density of choline acetyltransferase-immunoreactive terminals in the visual cortex ipsilateral to the lesions. 2. In the primary visual cortex ipsilateral to the lesions [acetylcholine (ACh)-depleted cortex], about half of the cells had weak or undetectable visual responses, whereas in the contralateral visual cortex almost all the cells had normal responsivity. The response selectivity, such as orientation and direction selectivities, of cortical cells was not affected by the depletion of ACh. 3. The microionophoretic application of ACh to cells under observation facilitated visual responses in 83% of the cells recorded from the ACh-depleted cortex, whereas it suppressed the responses in only 9%. The application of a muscarinic antagonist, atropine, to cells in the ACh-depleted cortex was ineffective, suggesting no residual ACh activity. 4. The mean current required to induce facilitation in the cortex ipsilateral to the lesion was significantly smaller than that required in the contralateral cortex and the visual cortex of the normal cat, suggesting a supersensitivity of receptors mediating the effect or a reduction in catabolism of exogenous ACh in the ACh-depleted cortex. 5. More than half of the cells that had been unresponsive to visual stimuli became clearly responsive during the ACh application. The response magnitude of cortical cells, as a whole, increased to the same degree as that observed during the ACh application in the normal cat. 6. In addition to the decrease in the average response magnitude, there was a remarkable variability in responses of cells to motion of the slit from sweep to sweep in the ACh-depleted cortex. The application of ACh to cortical cells decreased the variability of responses and consequently made the responses much more consistent. 7. These results suggest that without ACh supplied from the nBM, most of the cortical neurons could not respond briskly and consistently to excitatory inputs and that exogenously applied ACh could reverse such an impairment of cortical neurons through intact or even supersensitive postsynaptic receptors.

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