Leblancguerrero8593

Huntington disease (HD) is a devastating neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Disrupted cortico-striatal transmission is an early event that contributes to neuronal spine and synapse dysfunction primarily in striatal medium spiny neurons, the most vulnerable cell type in the disease, but also in neurons of other brain regions including the cortex. Although striatal and cortical neurons eventually degenerate, these synaptic and circuit changes may underlie some of the earliest motor, cognitive, and psychiatric symptoms. Moreover, synaptic dysfunction and spine loss are hypothesized to be therapeutically reversible before neuronal death occurs, and restoration of normal synaptic function may delay neurodegeneration. One of the earliest synaptic alterations to occur in HD mouse models is enhanced striatal extrasynaptic NMDA receptor expression and activity. This activity is mediated primarily through GluN2B subunit-containing receptors and is associated with increasget for synaptic protection in HD and warranting further development of DAPK1-targeted therapies for neurodegeneration.Microglia-the brain's primary immune cells-exert a tightly regulated cascade of pro- and anti-inflammatory effects upon brain pathology, either promoting regeneration or neurodegeneration. Therefore, harnessing microglia emerges as a potential therapeutic concept in neurological research. Recent studies suggest that-besides being affected by chemokines and cytokines-various cell entities in the brain relevantly respond to the mechanical properties of their microenvironment. For example, we lately reported considerable effects of elasticity on neural stem cells, regarding quiescence and differentiation potential. However, the effects of elasticity on microglia remain to be explored.Under the hypothesis that the elasticity of the microenvironment affects key characteristics and functions of microglia, we established an in vitro model of primary rat microglia grown in a polydimethylsiloxane (PDMS) elastomer-based cell culture system. This way, we simulated the brain's physiological elasticity range and compared els. The results highlight the significance of the omnipresent but mostly overlooked mechanobiological effects exerted on microglia and contribute to a better understanding of the complex spatial and temporal interactions between microglia, neural stem cells, and glia, in health and disease.Recent evidence highlighted the importance of white matter tracts in typical and atypical behaviors. White matter dynamically changes in response to learning, stress, and social experiences. Several lines of evidence have reported white matter dysfunction in psychiatric conditions, including depression, stress- and anxiety-related disorders. The mechanistic underpinnings of these associations, however, remain poorly understood. Here, we outline an integrative perspective positing a link between aberrant myelin plasticity and anxiety. Drawing on extant literature and emerging new findings, we suggest that in anxiety, unique changes may occur in response to threat and to safety learning and the ability to discriminate between both types of stimuli. We propose that altered myelin plasticity in the neural circuits underlying these two forms of learning relates to the emergence of anxiety-related disorders, by compromising mechanisms of neural network synchronization. The clinical and translational implications of this model for anxiety-related disorders are discussed.Fast learning designates the behavioral and neuronal mechanisms underlying the acquisition of a long-term memory trace after a unique and brief experience. As such it is opposed to incremental, slower reinforcement or procedural learning requiring repetitive training. This learning process, found in most animal species, exists in a large spectrum of natural behaviors, such as one-shot associative, spatial, or perceptual learning, and is a core principle of human episodic memory. We review here the neuronal and synaptic long-term changes associated with fast learning in mammals and discuss some hypotheses related to their underlying mechanisms. We first describe the variety of behavioral paradigms used to test fast learning memories those preferentially involve a single and brief (from few hundred milliseconds to few minutes) exposures to salient stimuli, sufficient to trigger a long-lasting memory trace and new adaptive responses. We then focus on neuronal activity patterns observed during fast learning and the emergence of long-term selective responses, before documenting the physiological correlates of fast learning. In the search for the engrams of fast learning, a growing body of evidence highlights long-term changes in gene expression, structural, intrinsic, and synaptic plasticities. Finally, we discuss the potential role of the sparse and bursting nature of neuronal activity observed during the fast learning, especially in the induction plasticity mechanisms leading to the rapid establishment of long-term synaptic modifications. We conclude with more theoretical perspectives on network dynamics that could enable fast learning, with an overview of some theoretical approaches in cognitive neuroscience and artificial intelligence.Acute alcohol exposure impairs hippocampus-dependent spatial memory. However, there is little evidence for the effects of ethanol on the spike patterns of hippocampal cell populations. Here, we examined how the spatial firing patterns of place cells, neurons that encode specific locations, were altered in rats that were intraperitoneally injected with 1.5 g/kg ethanol. Ethanol administration partly reduced or abolished place-selective spiking of a subset of place cells during running periods in a spatial task, whereas a subset of place fields newly emerged, suggesting a partial reorganization of hippocampal spatial maps by ethanol. On the other hand, ethanol administration did not significantly alter the frequency of hippocampal sharp-wave ripple (SWRs) and synchronous spike patterns during resting periods, suggesting that offline memory consolidation and retrieval mechanisms underpinned by hippocampal neuronal synchronization are not strongly affected by ethanol. These results indicate that acute ethanol intake mainly affects the encoding of external information but has little impact on internal memory processing.It is necessary to understand the morphology of the vagus nerve (VN) to design and deliver effective and selective vagus nerve stimulation (VNS) because nerve morphology influences fiber responses to electrical stimulation. Specifically, nerve diameter (and thus, electrode-fiber distance), fascicle diameter, fascicular organization, and perineurium thickness all significantly affect the responses of nerve fibers to electrical signals delivered through a cuff electrode. We quantified the morphology of cervical and subdiaphragmatic VNs in humans, pigs, and rats effective nerve diameter, number of fascicles, effective fascicle diameters, proportions of endoneurial, perineurial, and epineurial tissues, and perineurium thickness. The human and pig VNs were comparable sizes (∼2 mm cervically; ∼1.6 mm subdiaphragmatically), while the rat nerves were ten times smaller. The pig nerves had ten times more fascicles-and the fascicles were smaller-than in human nerves (47 vs. 7 fascicles cervically; 38 vs. 5 fascicles subdiaphragmatically). Comparing the cervical to the subdiaphragmatic VNs, the nerves and fascicles were larger at the cervical level for all species and there were more fascicles for pigs. Human morphology generally exhibited greater variability across samples than pigs and rats. A prior study of human somatic nerves indicated that the ratio of perineurium thickness to fascicle diameter was approximately constant across fascicle diameters. However, our data found thicker human and pig VN perineurium than those prior data the VNs had thicker perineurium for larger fascicles and thicker perineurium normalized by fascicle diameter for smaller fascicles. Understanding these differences in VN morphology between preclinical models and the clinical target, as well as the variability across individuals of a species, is essential for designing suitable cuff electrodes and stimulation parameters and for informing translation of preclinical results to clinical application to advance the therapeutic efficacy of VNS.The global mean signal of resting-state fMRI (rs-fMRI) shows a characteristic spatiotemporal pattern that is closely related to the pattern of vascular perfusion. Although being increasingly adopted in the mapping of the flow of neural activity, the mechanism that gives rise to the BOLD signal time lag remains controversial. In the present study, we compared the time lag of the global mean signal with those of the local network components obtained by applying temporal independent component analysis to the resting-state fMRI data, as well as by using simultaneous wide-field visual stimulation, and demonstrated that the time lag patterns are highly similar across all types of data. These results suggest that the time lag of the rs-fMRI signal reflects the local variance of the hemodynamic responses rather than the arrival or transit time of the stimulus, whether the trigger is neuronal or non-neuronal in origin as long as it is mediated by local hemodynamic responses. Examinations of the internal carotid artery signal further confirmed that the arterial signal is tightly inversely coupled with the global mean signal in accordance with previous studies, presumably reflecting the blood flow or blood pressure changes that are occurring almost simultaneously in the internal carotid artery and the cerebral pial/capillary arteries, within the low-frequency component in human rs-fMRI.

The purpose of the present study was to investigate Mandarin tone production performance of prelingually deafened children with cochlear implants (CIs) using modified acoustic analyses and to evaluate the relationship between demographic factors of those CI children and their tone production ability.

Two hundred seventy-eight prelingually deafened children with CIs and 173 age-matched normal-hearing (NH) children participated in the study. Thirty-six monosyllabic Mandarin Chinese words were recorded from each subject. The fundamental frequencies (F0) were extracted from the tone tokens. Two acoustic measures (i.e., differentiability and hit rate) were computed based on the F0 onset and offset values (i.e., the tone ellipses of the two-dimensional [2D] method) or the F0 onset, midpoint, and offset values (i.e., the tone ellipsoids of the 3D method). The correlations between the acoustic measures as well as between the methods were performed. The relationship between demographic factors and acoustic measureI users.Early brain insult, interfering with its maturation, may result in psychotic-like disturbances in adult life. Redox dysfunctions and neuroinflammation contribute to long-term psychiatric consequences due to neurodevelopmental abnormalities. Here, we investigated the effects of early pharmacological modulation of the redox and inflammatory states, through celastrol, and indomethacin administration, on reactive oxygen species (ROS) amount, levels of malondialdehyde (MDA) and antioxidant enzymes (superoxide dismutase 1, SOD1, glutathione, GSH, and catalase, CAT), as well as of pro-inflammatory cytokines (tumor necrosis factor-alpha, TNF-α, interleukin-6, IL-6, and interleukin-1 beta, IL-1β), in the prefrontal cortex of adult mice exposed to a neurotoxic insult, i.e. ketamine administration, in postnatal life. Early celastrol or indomethacin prevented ketamine-induced elevations in cortical ROS production. Deferiprone ic50 MDA levels in ketamine-treated mice, also administered with celastrol, were comparable with the control ones.