bioRxiv Subject Collection: Neuroscience
The following are the titles of recent articles syndicated from bioRxiv Subject Collection: Neuroscience
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Thursday, April 25th, 2024 makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
12:34 pm
Uncovering Effects of Schizophrenia upon a Maximally Significant, Minimally Complex Subset of Default Mode Network Connectivity Features
A common analysis approach for resting state functional magnetic resonance imaging (rs-fMRI) dynamic functional network connectivity (dFNC) data involves clustering windowed correlation time-series and assigning time windows to clusters (i.e., states) that can be quantified to summarize aspects of the dFNC dynamics. However, those methods can be dominated by a select few features and obscure key dynamics related to less dominant features. This study presents an iterative feature learning approach to identify a maximally significant and minimally complex subset of dFNC features within the default mode network (DMN) in schizophrenia (SZ). Utilizing dFNC data from individuals with SZ and healthy controls (HC), our approach uncovers a subset of features that has a greater number of dFNC states with disorder-related dynamics than is found when all features are present in the clustering. We find that anterior cingulate cortex/posterior cingulate cortex (ACC/PCC) interactions are consistently related to SZ across the most significant iterations of the feature learning analysis and that individuals with SZ tend to spend more time in states with greater intra-ACC anticorrelation and almost no time in a state of high intra-ACC correlation that HCs periodically enter. Our findings highlight the need for nuanced analyses to reveal disorder-related dynamics and advance our understanding of neuropsychiatric disorders. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
10:31 am
Models optimized for real-world tasks reveal the necessity of precise temporal coding in hearing
Neurons encode information in the timing of their spikes in addition to their firing rates. Spike timing is particularly precise in the auditory nerve, where action potentials phase lock to sound with sub- millisecond precision, but its behavioral relevance is uncertain. To investigate the role of this temporal coding, we optimized machine learning models to perform real-world hearing tasks with simulated cochlear input. We asked how precise auditory nerve spike timing needed to be to reproduce human behavior. Models with high-fidelity phase locking exhibited more human-like sound localization and speech perception than models without, consistent with an essential role in human hearing. Degrading phase locking produced task-dependent effects, revealing how the use of fine-grained temporal information reflects both ecological task demands and neural implementation constraints. The results link neural coding to perception and clarify conditions in which prostheses that fail to restore high-fidelity temporal coding could in principle restore near-normal hearing. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
10:31 am
The hippocampus pre-orders movements for skilled action sequences
Plasticity in the subcortical motor basal ganglia-thalamo-cerebellar network plays a key role in the acquisition and control of long-term memory for new procedural skills, from the formation of population trajectories controlling trained motor skills in the striatum to the adaptation of sensorimotor maps in the cerebellum. However, recent findings demonstrate the involvement of a wider cortical and subcortical brain network in the consolidation and control of well-trained actions, including an area traditionally associated with declarative memory - the hippocampus. Here, we probe which role these subcortical areas play in skilled motor sequence control, from sequence feature selection during planning to their integration during sequence execution. An fMRI dataset collected after participants learnt to produce four finger sequences entirely from memory with high accuracy over several days was examined for both changes in BOLD activity and their informational content in subcortical regions of interest. Although there was a widespread activity increase in effector-related striatal, thalamic and cerebellar regions, the associated activity did not contain information on the motor sequence identity. In contrast, hippocampal activity increased during planning and predicted the order of the upcoming sequence of movements. Our findings show that the hippocampus pre-orders movements for skilled action sequences, thus contributing to the higher-order control of skilled movements. These findings challenge the traditional taxonomy of episodic and procedural memory and carries implications for the rehabilitation of individuals with neurodegenerative disorders. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
10:31 am
Hierarchical cortical entrainment orchestrates the multisensory processing of biological motion
When observing others' behaviors, we continuously integrate their movements with the corresponding sounds to achieve efficient perception and develop adaptive responses. However, how human brains integrate these complex audiovisual cues based on their natural temporal correspondence remains unknown. Using electroencephalogram, we demonstrated that cortical oscillations entrained to hierarchical rhythmic structures in audiovisually congruent human walking movements and footstep sounds. Remarkably, the entrainment effects at different time scales exhibit distinct modes of multisensory integration, i.e., an additive integration effect at a basic-level integration window (step-cycle) and a super-additive multisensory enhancement at a higher-order temporal integration window (gait-cycle). Moreover, only the cortical tracking of higher-order rhythmic structures is specialized for the multisensory integration of human motion signals and correlates with individuals' autistic traits, suggesting its functional relevance to biological motion perception and social cognition. These findings unveil the multifaceted roles of entrained cortical activity in the multisensory perception of human motion, shedding light on how hierarchical cortical entrainment orchestrates the processing of complex, rhythmic stimuli in natural contexts. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
10:31 am
A theory of temporal self-supervised learning in neocortical layers
The neocortex constructs an internal representation of the world, but the underlying circuitry and computational principles remain unclear. Inspired by self-supervised learning algorithms, we introduce a computational model wherein layer 2/3 (L2/3) learns to predict incoming sensory stimuli by comparing previous sensory inputs, relayed via layer 4, with current thalamic inputs arriving at layer 5 (L5). We demonstrate that our model accurately predicts sensory information in a contextual temporal task, and that its predictions are robust to noisy or partial sensory input. Additionally, our model generates layer-specific sparsity and latent representations, consistent with experimental observations. Next, using a sensorimotor task, we show that the model's L2/3 and L5 prediction errors mirror mismatch responses observed in awake, behaving mice. Finally, through manipulations, we offer testable predictions to unveil the computational roles of various cortical features. In summary, our findings suggest that the multi-layered neocortex empowers the brain with self-supervised learning capabilities. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
7:50 am
Non-resolving neuroinflammation regulates axon regeneration in chronic spinal cord injury
Chronic spinal cord injury (SCI) lesions retain increased densities of microglia and macrophages. In acute SCI, macrophages induce growth cone collapse, facilitate axon retraction away from lesion boundaries, as well as play a key role in orchestrating the growth-inhibitory glial scar. Little is known about the role of sustained inflammation in chronic SCI, or whether chronic inflammation affects repair and regeneration. We performed transcriptional analysis using the Nanostring Neuropathology panel to characterize the resolution of inflammation into chronic SCI, to characterize the chronic SCI microenvironment, as well as to identify spinal cord responses to macrophage depletion and repopulation using the CSF1R inhibitor, PLX-5622. We determined the ability for macrophage depletion and repopulation to augment axon growth into chronic lesions both with and without regenerative stimulation using neuronal-specific PTEN knockout (PTEN-KO). PTEN-KO was delivered with spinal injections of retrogradely transported adeno associated viruses (AAVrgs). Both transcriptional analyses and immunohistochemistry revealed the ability for PLX-5622 to significantly deplete inflammation around and within chronic SCI lesions, with a return to pre-depleted inflammatory densities after treatment removal. Neuronal-specific transcripts were significantly elevated in mice after inflammatory repopulation, but no significant effects were observed with macrophage depletion alone. Axon densities significantly increased within the lesion after PLX-5622 treatment with a more consistent effect observed in mice with inflammatory repopulation. PTEN-KO did not further increase axon densities within the lesion beyond effects induced by PLX-5622. We identified that PLX-5622 increased axon densities within the lesion that are histologically identified as 5-HT+ and CGRP+, both of which are not robustly transduced by AAVrgs. Our work identified that increased macrophage/microglia densities in the chronic SCI environment may be actively retained by homeostatic mechanisms likely affiliated with a sustained elevated expression of CSF1 and other chemokines. Finally, we identify a novel role of sustained inflammation as a prospective barrier to axon regeneration in chronic SCI. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
5:04 am
Non-apoptotic role of EGL-1 in exopher production and neuronal health in Caenorhabditis elegans
While traditionally studied for their pro-apoptotic functions, recent research suggests BH3-only proteins also have non-apoptotic roles. Here, we find that EGL-1, the BH3-only protein in Caenorhabditis elegans, promotes the cell-autonomous production of exophers in adult neurons. Exophers are large, micron-scale vesicles that are ejected from the cell and contain cellular components such as mitochondria. EGL-1 facilitates exopher production potentially through regulation of mitochondrial dynamics. Moreover, an endogenous, low level of EGL-1 expression appears to benefit dendritic health. Our findings provide insights into the mechanistic role of BH3-only protein in mitochondrial dynamics, downstream exopher production, and ultimately neuronal health. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
3:31 am
A recurrent neural circuit in Drosophila deblurs visual inputs
A critical goal of vision is to detect changes in light intensity, even when these changes are blurred by the spatial resolution of the eye and the motion of the animal. Here we describe a recurrent neural circuit in Drosophila that compensates for blur and thereby selectively enhances the perceived contrast of moving edges. Using in vivo, two-photon voltage imaging, we measured the temporal response properties of L1 and L2, two cell types that receive direct synaptic input from photoreceptors. These neurons have biphasic responses to brief flashes of light, a hallmark of cells that encode changes in stimulus intensity. However, the second phase was often much larger than the first, creating an unusual temporal filter. Genetic dissection revealed that recurrent neural circuitry strongly shapes the second phase of the response, informing the structure of a dynamical model. By applying this model to moving natural images, we demonstrate that rather than veridically representing stimulus changes, this temporal processing strategy systematically enhances them, amplifying and sharpening responses. Comparing the measured responses of L2 to model predictions across both artificial and natural stimuli revealed that L2 tunes its properties as the model predicts in order to deblur images. Since this strategy is tunable to behavioral context, generalizable to any time-varying sensory input, and implementable with a common circuit motif, we propose that it could be broadly used to selectively enhance sharp and salient changes. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
3:31 am
Deviation from typical brain activity during naturalistic stimulation predicts personality traits
The relationship between personality and brain activity has been an increasingly popular topic of neuroscientific research. However, the limitations of both personality measures and neuroimaging, as well as methodological issues, continue to pose challenges to its understanding. The naturalistic viewing condition has been shown to enhance individual differences and might, therefore, be of benefit to the endeavor. Here, we thus examine this relationship using naturalistic fMRI of 82 healthy subjects. We implemented a simple dimensionality reduction method to characterize brain activity by its 'typicality', assessed a range of personality traits using widely-used personality inventories, and tested the relationship between the two. We found that there is, indeed, a relationship between personality traits and the typicality of brain activity, most consistently manifested by lower typicality in subjects with higher Neuroticism/Harm Avoidance. Our results highlight the usefulness of naturalistic viewing data for exploring the relationship between individual differences in personality and brain activity. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
2:18 am
Novel inhibitors of acute, axonal DLK palmitoylation are neuroprotective and avoid the deleterious side effects of cell-wide DLK inhibition
Dual leucine-zipper kinase (DLK) drives acute and chronic forms of neurodegeneration, suggesting that inhibiting DLK signaling could ameliorate diverse neuropathological conditions. However, direct inhibition of the kinase domain of DLK in human patients and conditional knockout of DLK in mice both cause unintended side effects, including elevated plasma neurofilament levels, indicative of neuronal cytoskeletal disruption. Indeed, we found that a DLK kinase domain inhibitor acutely disrupted the axonal cytoskeleton and caused vesicle aggregation in cultured dorsal root ganglion (DRG) neurons, further cautioning against this therapeutic strategy. In seeking a more precise intervention, we found that retrograde (axon-to-soma) pro-degenerative signaling requires acute, axonal palmitoylation of DLK and hypothesized that modulating this post-translational modification might be more specifically neuroprotective than cell-wide DLK inhibition. To address this possibility, we screened >28,000 compounds using a high-content imaging assay that quantitatively evaluates the palmitoylation-dependent subcellular localization of DLK. Of the 33 hits that significantly altered DLK localization in non-neuronal cells, several reduced DLK retrograde signaling and protected cultured DRG neurons from DLK-dependent neurodegeneration. Mechanistically, the two most neuroprotective compounds selectively prevent stimulus-dependent palmitoylation of axonal pools of DLK, a process crucial for the recruitment of DLK to axonal vesicles. In contrast, these compounds minimally impact DLK localization and signaling in healthy neurons and avoid the cytoskeletal disruption associated with direct DLK inhibition. Importantly, our hit compounds also reduce pro-degenerative retrograde signaling in vivo, suggesting that modulating the palmitoylation-dependent localization of DLK could be a novel neuroprotective strategy.
Wednesday, April 24th, 2024 makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
10:03 pm
Epg5 links proteotoxic stress due to defective autophagic clearance and epileptogenesis in Drosophila and Vici Syndrome patients
Epilepsy is a common neurological condition that arises from dysfunctional neuronal circuit control due to either acquired or innate disorders. Autophagy is an essential neuronal housekeeping mechanism, which causes severe proteotoxic stress when impaired. Autophagy impairment has been associated to epileptogenesis through a variety of molecular mechanisms. Vici Syndrome (VS) is the paradigmatic congenital autophagy disorder in humans due to recessive variants in the ectopic P-granules autophagy tethering factor 5 (EPG5) gene that is crucial for autophagosome-lysosome fusion and ultimately for effective autophagic clearance. VS is characterized by a wide range of neurodevelopmental, neurodegenerative, and neurological features, including epilepsy. Here, we used Drosophila melanogaster to study the importance of epg5 in development, ageing, and seizures. Our data indicate that proteotoxic stress due to impaired autophagic clearance and seizure-like behaviors correlate and are commonly regulated, suggesting that seizures occur as a direct consequence of proteotoxic stress and age-dependent neurodegenerative progression in epg5 Drosophila mutants, in the absence of evident neurodevelopmental abnormalities. We provide complementary evidence from EPG5-mutated patients demonstrating an epilepsy phenotype consistent with Drosophila predictions and propose autophagy stimulating diets as a feasible approach to control EPG5-related pharmacoresistant seizures. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
10:03 pm
Anatomical circuits for flexible spatial mapping by single neurons in posterior parietal cortex
Primate lateral intraparietal area (LIP) is critical for cognitive processing. Its contribution to categorization and decision-making has been causally linked to neurons' spatial sensorimotor selectivity. We reveal the intrinsic anatomical circuits and neuronal responses within LIP that provide the substrate for this flexible generation of motor responses to sensory targets. Retrograde tracers delineate a loop between two distinct operational compartments, with a sensory-like, point-to-point projection from ventral to dorsal LIP and an asymmetric, more widespread projection in reverse. Neurophysiological recordings demonstrate that especially more ventral LIP neurons exhibit motor response fields that are spatially distinct from its sensory receptive field. The different associations of response and receptive fields in single neurons tile visual space. These anatomical circuits and neuronal responses provide the basis for the flexible allocation of attention and motor responses to salient or instructive visual input across the visual field. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
5:32 pm
Characterising time-on-task effects on oscillatory and aperiodic EEG components and their co-variation with visual task performance.
Fluctuations in oscillatory brain activity have been shown to co-occur with variations in task performance. More recently, part of these fluctuations has been attributed to long-term (>1hr) monotonous trends in the power and frequency of alpha oscillations (8-13 Hz). Here we tested whether these time-on-task changes in EEG activity are limited to activity in the alpha band and whether they are linked to task performance. Thirty-six participants performed 900 trials of a two-alternative forced choice visual discrimination task with confidence ratings. Pre- and post-stimulus spectral power (1-40Hz) and aperiodic (i.e., non-oscillatory) components were compared across blocks of the experimental session and tested for relationships with behavioural performance. We found that time-on-task effects on oscillatory EEG activity were primarily localised within the alpha band, with alpha power increasing and peak alpha frequency decreasing over time, even when controlling for aperiodic contributions. Aperiodic, broadband activity on the other hand did not show time-on-task effects in our data set. Importantly, time-on-task effects in alpha frequency and power explained variability in single-trial reaction times. Moreover, controlling for time-on-task effectively removed the relationships between alpha activity and reaction times. However, time-on-task effects did not affect other EEG signatures of behavioural performance, including post-stimulus predictors of single-trial decision confidence. Therefore, our results dissociate alpha-band brain-behaviour relationships that can be explained away by time-on-task from those that remain after accounting for it - thereby further specifying the potential functional roles of alpha in human visual perception.
Tuesday, April 23rd, 2024 makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
8:17 pm
Spinal cord injury: What are the lesion effects on transplanted cells in an autograft model?
Spinal cord injury (SCI) is a serious pathology of the central nervous system that result in loss of motor, sensory and autonomic functions below the level of the lesion and for which, unfortunately, there is currently no cure. In addition to the loss of function, SCI induces a systemic inflammation that is not confined to the spinal cord and whose effects are increasingly well characterized. In particular, SCI causes cerebral inflammation, which is responsible for the impairment of hippocampal and bulbar neurogenesis. Many therapies have been tested as potential treatments for SCI. In animal models, cell therapies have shown interesting effects such as medullary scar reduction, anti-inflammatory properties, axonal regrowth or neuronal survival, allowing better functional recovery. However, in human studies, their therapeutic capacities are less significant. Beyond obvious differences in pathophysiology and cell culture procedures, a key paradigm of cell transplantation differs between humans and animals. In animal models, transplanted cells are systematically taken from healthy animals, whereas in humans the immune incompatibility leads to the realization of autologous transplantation. Therefore, we were interested in the lesion effects on the neuro-repairing potential of olfactory ensheathing cells (OECs) harvested from olfactory bulbs. Using functional sensory-motor studies, histological and gene expression analyses, we were able to demonstrate for the first time that the lesion negatively affects the therapeutic properties of cells used to treat SCI. These innovative results shed new light on the future use of cell transplantation in autologous transplantation after SCI. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
8:17 pm
Probing sensitivity to statistical structure in rapid sound sequences using deviant detection tasks
Statistical structures and our ability to exploit them are a ubiquitous component of daily life. Yet, we still do not fully understand how we track these sophisticated statistics and the role they play in sensory processing. Predictive coding frameworks hypothesise that for stimuli that can be accurately anticipated based on prior experience, we rely more strongly on our internal model of the sensory world and are more "surprised" when that expectation is unmet. The current study used this phenomenon to probe listeners' sensitivity to probabilistic structures generated using rapid 50 milli-second tone-pip sequences that precluded conscious prediction of upcoming stimuli. Over three experiments we measured listeners' sensitivity and response time to deviants of a frequency outside the expected range. Predictable sequences were generated using either a triplet-based or community structure and deviance detection contrasted against the same set of tones but in a random, unpredictable order. All experiments found structured sequences enhanced deviant detection relative to random sequences. Additionally, Experiment 2 used three different instantiations of the community structure to demonstrate that the level of uncertainty in the structured sequences modulated deviant saliency. Finally, Experiment 3 placed the deviant within an established community or immediately after a transition between communities, where the perceptual boundary should generate momentary uncertainty. However, this manipulation did not impact performance. Together these results demonstrate that probabilistic contexts generated from statistical structures modulate the processing of an ongoing auditory signal, leading to an improved ability to detect unexpected deviant stimuli, consistent with the predictive coding framework. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
8:17 pm
SqueakOut: Autoencoder-based segmentation of mouse ultrasonic vocalizations
Mice emit ultrasonic vocalizations (USVs) that are important for social communication. Despite great advancements in tools to detect USVs from audio files in recent years, highly accurate segmentation of USVs from spectrograms (i.e., removing noise) remains a significant challenge. Here, we present a new dataset of 12,954 annotated spectrograms explicitly labeled for mouse USV segmentation. Leveraging this dataset, we developed SqueakOut, a lightweight (4.6M parameters) fully convolutional autoencoder that achieves high accuracy in supervised segmentation of USVs from spectrograms, with a Dice score of 90.22. SqueakOut combines a MobileNetV2 backbone with skip connections and transposed convolutions to precisely segment USVs. Using stochastic data augmentation techniques and a hybrid loss function, SqueakOut learns robust segmentation across varying recording conditions. We evaluate SqueakOut's performance, demonstrating substantial improvements over existing methods like VocalMat (63.82 Dice score). The accurate USV segmentations enabled by SqueakOut will facilitate novel methods for vocalization classification and more accurate analysis of mouse communication. To promote further research, we release the annotated 12,954 spectrogram USV segmentation dataset and the SqueakOut implementation publicly. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
8:17 pm
Activity-driven trafficking of endogenous synaptic proteins through proximity labeling
To enable transmission of information in the brain, synaptic vesicles fuse to presynaptic membranes, liberating their content and exposing transiently a myriad of vesicular transmembrane proteins. However, versatile methods for quantifying the synaptic translocation of endogenous proteins during neuronal activity remain unavailable, as the fast dynamics of synaptic vesicle cycling difficult specific isolation trafficking proteins during such a transient surface exposure. Here we developed a novel approach using synaptic cleft proximity labeling to capture and quantify activity-driven trafficking of endogenous synaptic proteins at the synapse. We show that accelerating cleft biotinylation times to match the fast dynamics of vesicle exocytosis allows capturing endogenous proteins transiently exposed at the synaptic surface during neural activity, enabling for the first time the study of the translocation of nearly every endogenous synaptic protein. As proof-of-concept, we further applied this technology to obtain direct evidence of the surface translocation of non-canonical trafficking proteins, such as ATG9A and NPTX1, which had been proposed to traffic during activity but for which direct proof had not yet been shown. The technological advancement presented here will facilitate future studies dissecting the molecular identity of proteins exocytosed at the synapse during activity, helping to define the molecular machinery that sustains neurotransmission in the mammalian brain. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
8:17 pm
Sequential and dynamic coding of water-sucrose categorization in rat gustatory cortices
The gustatory system underlies our conscious perception of sweetness and allows us to distinguish a sweet solution from plain water. However, the neural mechanisms in gustatory cortices that enable rats to differentiate sweetness from water remain elusive. In this study, we designed a novel sucrose categorization task in which rats classified water from a gradient of sucrose solutions. We found that in the anterior Insular Cortex (aIC) and the Orbitofrontal Cortex (OFC), neural activity prioritized encoding the categorization of water versus sucrose rather than the specific concentrations within the sucrose solutions. aIC neurons more rapidly encoded sucrose/water distinction, followed by the OFC. In contrast, the OFC encoded choice information slightly earlier than aIC, but both gustatory cortices maintained a comparable encoding of the rat's choices in parallel. The encoding of sensory and categorical decisions was dynamic and sequentially encoded, with neurons carrying significant information in moving bumps at different time bins across the trial. Our results demonstrate that sucrose categorization relies on dynamic encoding sequences in the neuronal activity of aIC and the OFC rather than static, long-lasting (sustained) neural representations. Single-cell, population decoding, and principal component analyses confirmed our results. This aligns with the concept of a dynamic code, where the brain updates its representation of sucrose categorization as new information becomes available. Additionally, aIC and the OFC rapidly encoded reward outcomes. Our data supports the view that gustatory cortices use sequential and dynamic coding to compute sensorimotor transformations from taste detection to encoding categorical taste decisions and reward outcomes. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
6:21 pm
JNK and PI3K signaling pathways mediate synapse formation and network spontaneous activities in primary neurons
Background: Cellular signals orchestrating synapse formation and neuronal network function remain poorly understood. To explore the critical signaling pathways in neurons and their influence on network development, pharmacological assays were employed to inhibit multiple signaling pathways in cultured neurons. Methods: Immunofluorescence and western blotting are applied to identify the expression of synapse-related proteins within neurons. micro-electrode arrays (MEAs) are employed to study the developmental characteristics of neuronal networks. RNA sequencing is utilized to determine the gene expression profiles pertaining to multiple signaling pathways. Results: Canonical c-jun N-terminal kinases (JNK) pathway is necessary for pre- and post-synaptic specializations, while phosphatidylinositide3-kinases (PI3K) is a key to postsynaptic specialization and affects the puncta sizes of presynaptic marker. Unexpectedly, pharmacological inhibition of JNK pathway significantly suppressed the mean firing rate (MFR), network burst frequency (NBF) and regularity of network firing after 4 weeks, but did not alter the synchrony of the network. During network development, PI3K pathway regulates the longer burst duration and lower network synchrony. Gene sets associated with neurodevelopmental processes and myelination was disturbed during restraining these signal pathways. Furthermore, inhibition of the PI3K signaling pathway obviously transformed voltage-gated ion channel activity, synaptic transmission and synaptic plasticity of neurons. Conclusion: This study reveals that JNK and PI3K signaling pathways play different roles during synapse formation, and these signaling pathways have a lasting impact on the development of neuronal networks. Thus, this study provides further insights into the intracellular signaling pathways associated with synapse formation in the development of neuronal networks. makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.
6:21 pm
Changes in intra- and interlimb reflexes from forelimb cutaneous afferents after staggered thoracic lateral hemisections during locomotion in cats
In quadrupeds, such as cats, cutaneous afferents from the forepaw dorsum signal external perturbations and send signals to spinal circuits to coordinate the activity in muscles of all four limbs. How these cutaneous reflex pathways from forelimb afferents are reorganized after an incomplete spinal cord injury is not clear. Using a staggered thoracic lateral hemisections paradigm, we investigated changes in intralimb and interlimb reflex pathways by electrically stimulating the left and right superficial radial nerves in seven adult cats and recording reflex responses in five forelimb and ten hindlimb muscles. After the first (right T5-T6) and second (left T10-T11) hemisections, forelimb-hindlimb coordination was altered and weakened. After the second hemisection, cats required balance assistance to perform quadrupedal locomotion. Short-, mid- and long-latency homonymous and crossed reflex responses in forelimb muscles and their phase modulation remained largely unaffected after staggered hemisections. The occurrence of homolateral and diagonal mid- and long-latency responses in hindlimb muscles evoked with left and right superficial radial nerve stimulation was significantly reduced at the first time point after the first hemisection, but partially recovered at the second time point with left superficial radial nerve stimulation. These responses were lost or reduced after the second hemisection. When present, all reflex responses, including homolateral and diagonal, maintained their phase-dependent modulation. Therefore, our results show a considerable loss in cutaneous reflex transmission from cervical to lumbar levels after incomplete spinal cord injury, albeit with preservation of phase modulation, likely affecting functional responses to external perturbations.
[ << Previous 20 ] makes no claim to the content supplied through this journal account. Articles are retrieved via a public feed supplied by the site for this purpose.