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- Bauer, Ulrich Stefan, et al.
(författare)
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Validation of Functional Connectivity of Engineered Neuromuscular Junction With Recombinant Monosynaptic Pseudotyped ΔG-Rabies Virus Tracing
- 2022
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media S.A.. - 1662-5145. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Current preclinical models of neurodegenerative disease, such as amyotrophic lateral sclerosis (ALS), can significantly benefit from in vitro neuroengineering approaches that enable the selective study and manipulation of neurons, networks, and functional units of interest. Custom-designed compartmentalized microfluidic culture systems enable the co-culture of different relevant cell types in interconnected but fluidically isolated microenvironments. Such systems can thus be applied for ALS disease modeling, as they enable the recapitulation and study of neuromuscular junctions (NMJ) through co-culturing of motor neurons and muscle cells in separate, but interconnected compartments. These in vitro systems are particularly relevant for investigations of mechanistic aspects of the ALS pathological cascade in engineered NMJ, as progressive loss of NMJ functionality may constitute one of the hallmarks of disease related pathology at early onset, in line with the dying back hypothesis. In such models, ability to test whether motor neuron degeneration in ALS starts at the nerve terminal or at the NMJ and retrogradely progresses to the motor neuron cell body largely relies on robust methods for verification of engineered NMJ functionality. In this study, we demonstrate the functionality of engineered NMJs within a microfluidic chip with a differentially perturbable microenvironment using a designer pseudotyped ΔG-rabies virus for retrograde monosynaptic tracing.
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3. |
- de Haan, Roel, et al.
(författare)
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Octopaminergic modulation of contrast sensitivity
- 2012
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media SA. - 1662-5145. ; 6:Article 55
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Tidskriftsartikel (refereegranskat)abstract
- Sensory systems adapt to prolonged stimulation by decreasing their response to continuous stimuli. Whereas visual motion adaptation has traditionally been studied in immobilized animals, recent work indicates that the animal's behavioral state influences the response properties of higher-order motion vision-sensitive neurons. During insect flight octopamine is released, and pharmacological octopaminergic activation can induce a fictive locomotor state. In the insect optic ganglia, lobula plate tangential cells (LPTCs) spatially pool input from local elementary motion detectors (EMDs) that correlate luminosity changes from two spatially discrete inputs after delaying the signal from one. The LPTC velocity optimum thereby depends on the spatial separation of the inputs and on the EMD's delay properties. Recently it was shown that behavioral activity increases the LPTC velocity optimum, with modeling suggesting this to originate in the EMD's temporal delay filters. However, behavior induces an additional post-EMD effect: the LPTC membrane conductance increases in flying flies. To physiologically investigate the degree to which activity causes presynaptic and postsynaptic effects, we conducted intracellular recordings of Eristalis horizontal system (HS) neurons. We constructed contrast response functions before and after adaptation at different temporal frequencies, with and without the octopamine receptor agonist chlordimeform (CDM). We extracted three motion adaptation components, where two are likely to be generated presynaptically of the LPTCs, and one within them. We found that CDM affected the early, EMD-associated contrast gain reduction, temporal frequency dependently. However, a CDM-induced change of the HS membrane conductance disappeared during and after visual stimulation. This suggests that physical activity mainly affects motion adaptation presynaptically of LPTCs, whereas post-EMD effects have a minimal effect.
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- Fiskum, Vegard, et al.
(författare)
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Silencing of Activity During Hypoxia Improves Functional Outcomes in Motor Neuron Networks in vitro
- 2021
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media S.A.. - 1662-5145. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- The effects of hypoxia, or reduced oxygen supply, to brain tissue can be disastrous, leading to extensive loss of function. Deoxygenated tissue becomes unable to maintain healthy metabolism, which leads to increased production of reactive oxygen species (ROS) and loss of calcium homoeostasis, with damaging downstream effects. Neurons are a highly energy demanding cell type, and as such they are highly sensitive to reductions in oxygenation and some types of neurons such as motor neurons are even more susceptible to hypoxic damage. In addition to the immediate deleterious effects hypoxia can have on neurons, there can be delayed effects which lead to increased risk of developing neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), even if no immediate consequences are apparent. Furthermore, impairment of the function of various hypoxia-responsive factors has been shown to increase the risk of developing several neurodegenerative disorders. Longitudinal assessment of electrophysiological network activity is underutilised in assessing the effects of hypoxia on neurons and how their activity and communication change over time following a hypoxic challenge. This study utilised multielectrode arrays and motor neuron networks to study the response to hypoxia and the subsequent development of the neuronal activity over time, as well as the effect of silencing network activity during the hypoxic challenge. We found that motor neuron networks exposed to hypoxic challenge exhibited a delayed fluctuation in multiple network activity parameters compared to normoxic networks. Silencing of activity during the hypoxic challenge leads to maintained bursting activity, suggesting that functional outcomes are better maintained in these networks and that there are activity-dependent mechanisms involved in the network damage following hypoxia.
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- Kalpouzos, Grégoria, et al.
(författare)
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Impact of negative emotion on the neural correlates of long-term recognition in younger and older adults
- 2012
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media SA. - 1662-5145. ; 6:74, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- Some studies have suggested that the memory advantage for negative emotional information over neutral information (“negativity effect”) is reduced in aging. Besides the fact that most findings are based on immediate retrieval, the neural underpinnings of long-term emotional memory in aging have so far not been investigated. To address these issues, we assessed recognition of neutral and negative scenes after 1- and 3-week retention intervals in younger and older adults using functional magnetic resonance imaging. We further used an event-related design in order to disentangle successful, false, and true recognition. This study revealed four key findings: (1) increased retention interval induced an increased rate of false recognitions for negative scenes, canceling out the negativity effect (present for hit rates only) on discrimination in both younger and older adults; (2) in younger, but not older, adults, reduced activity of the medial temporal lobe was observed over time for neutral scenes, but not for negative scenes, where stable or increased activity was seen; (3) engagement of amygdala (AMG) was observed in older adults after a 3-week delay during successful recognition of negative scenes (hits vs. misses) in comparison with neutral scenes, which may indicate engagement of automatic processes, but engagement of ventrolateral prefrontal cortex was unrelated to AMG activity and performance; and (4) after 3 weeks, but not after 1 week, true recognition of negative scenes was characterized by more activity in left hippocampus and lateral occipito-temporal regions (hits vs. false alarms). As these regions are known to be related to consolidation mechanisms, the observed pattern may indicate the presence of delayed consolidation of true memories. Nonetheless, older adults’ low performance in discrimination of negative scenes could reflect the fact that overall, after long delays of retention, they rely more on general information rather than on perceptual detail in making recognition judgments.
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- Pruszynski, J. Andrew
(författare)
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Primary motor cortex and fast feedback responses to mechanical perturbations : a primer on what we know now and some suggestions on what we should find out next
- 2014
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media S.A.. - 1662-5145. ; 8
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Forskningsöversikt (refereegranskat)abstract
- Many researchers have drawn a clear distinction between fast feedback responses to mechanical perturbations (e.g., stretch responses) and voluntary control processes. But this simple distinction is difficult to reconcile with growing evidence that long-latency stretch responses share most of the defining capabilities of voluntary control. My general view-and I believe a growing consensus-is that the functional similarities between long-latency stretch responses and voluntary control processes can be readily understood based on their shared neural circuitry, especially a transcortical pathway through primary motor cortex. Here I provide a very brief and selective account of the human and monkey studies linking a transcortical pathway through primary motor cortex to the generation and functional sophistication of the long-latency stretch response. I then lay out some of the notable issues that are ready to be answered.
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- Ren, Liqun, et al.
(författare)
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Heterogenic Distribution of Aromatic L-Amino Acid Decarboxylase Neurons in the Rat Spinal Cord
- 2017
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media SA. - 1662-5145. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Aromatic L-amino acid decarboxylase (AADC) is an essential enzyme in the synthesis of serotonin, dopamine, and certain trace amines and is present in a variety of organs including the brain and spinal cord. It is previously reported that in mammalian spinal cord AADC cells (called D-cells) were largely confined to a region around the central canal and that they do not produce monoamines. To date, there has not been a detailed description of their distribution and morphology in mammals. In the present study this issue is systematically investigated using immunohistochemistry. We have found that AADC cells in the rat spinal cord are both more numerous and more widely distributed than previously reported. In the gray matter, AADC neurons immunolabeled for NeuN were not only found in the region around the central canal but also in the dorsal horn, intermediate zone, and ventral horn. In the white matter a large number of glial cells were AADC-immunopositive in different spinal segments and the vast majority of these cells expressed oligodendrocyte and radial glial phenotypes. Additionally, a small number of AADC neurons labeled for NeuN were found in the white matter along the ventral median fissure. The shapes and sizes of AADC neurons varied according to their location. For example, throughout cervical and lumbar segments AADC neurons in the intermediate zone and ventral horn tended to be rather large and weakly immunolabeled, whereas those in comparable regions of sacrocaudal segments were smaller and more densely immunolabeled. The diverse morphological characteristics of the AADC cells suggests that they could be further divided into several subtypes. These results indicate that AADC cells are heterogeneously distributed in the rat spinal cord and they may exert different functions in different physiological and pathological situations.
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- Sciutti, Alessandra, et al.
(författare)
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Editorial : Affective shared perception
- 2022
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media S.A.. - 1662-5145. ; 16
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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11. |
- Stapel, Janny C., et al.
(författare)
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Panoramic Uncertainty in Vertical Perception
- 2021
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media S.A.. - 1662-5145. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Judgments of the orientation of a visual line with respect to earth vertical are affected by panoramic visual cues. This is illustrated by the rod-and-frame effect (RFE), the finding that the perceived orientation of a luminous rod is biased by the orientation of a surrounding squared frame. In this study, we tested how the uncertainty of frame orientation affects the RFE by asking upright or tilted participants to psychometrically judge the orientation of a briefly flashed rod contained within either a circular frame, a squared frame, or either of two intermediate frame forms, called squircles, presented in various orientations. Results showed a cyclical modulation of frame-induced bias across the range of the square and squircular frame orientations. The magnitude of this bias increased with increasing squaredness of the frame, as if the more unequivocal the orientation cues of the frame, the larger the reliance on them for rod orientation judgments. These findings are explained with a Bayesian optimal integration model in which participants flexibly weigh visual panoramic cues, depending on their orientation reliability, and non-visual cues in the perception of vertical.
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- von Hofsten, Claes, et al.
(författare)
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Perception-action in children with ASD
- 2012
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media SA. - 1662-5145. ; :NOV
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Forskningsöversikt (refereegranskat)abstract
- How do disturbances to perception and action relate to the deficiencies expressed by children with autism? The ability to predict what is going to happen next is crucial for the construction of all actions and children develop these predictive abilities early in development. Children with autism, however, are deficient in the ability to foresee future events and to plan movements and movement sequences. They are also deficient in the understanding of other people's actions. This includes communicative actions as they are ultimately based on movements. Today there are two promising neurobiological interpretation of ASD. First, there is strong evidence that the Mirror Neuron System (MNS) is impaired. As stated by this hypothesis, action production and action understanding are intimately related. Both these functions rely on predictive models of the sensory consequences of actions and depend on connectivity between the parietal and pre-motor areas. Secondly, action prediction is accomplished through a system that includes a loop from the posterior parietal cortex through the cerebellum and back to the premotor and motor areas of the brain. Impairment of this loop is probably also part of the explanation of the prediction problems in children with ASD. Both the cortico-cerebellar loop and the MNS rely on distant neural connections. There are multiple evidence that such connections are weak in children with autism.
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- Yilmaz, Ayse, et al.
(författare)
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The balbyter ant Camponotus fulvopilosus combines several navigational strategies to support homing when foraging in the close vicinity of its nest
- 2022
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media SA. - 1662-5145. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Many insects rely on path integration to define direct routes back to their nests. When shuttling hundreds of meters back and forth between a profitable foraging site and a nest, navigational errors accumulate unavoidably in this compass- and odometer-based system. In familiar terrain, terrestrial landmarks can be used to compensate for these errors and safely guide the insect back to its nest with pin-point precision. In this study, we investigated the homing strategies employed by Camponotus fulvopilosus ants when repeatedly foraging no more than 1.25 m away from their nest. Our results reveal that the return journeys of the ants, even when setting out from a feeder from which the ants could easily get home using landmark information alone, are initially guided by path integration. After a short run in the direction given by the home vector, the ants then switched strategies and started to steer according to the landmarks surrounding their nest. We conclude that even when foraging in the close vicinity of its nest, an ant still benefits from its path-integrated vector to direct the start of its return journey.
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