Neuroscience
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Philippe Ascher spent his last two decades as an emeritus Professor, working in the heart of Paris. Together with his wife Jacsue they were hosted in Alain Marty's laboratory and enjoyed the happiest retirement. ⋯ This period led us from NMDA receptors to the corelease of acetylcholine and glutamate by spinal motoneurons to Renshaw cells and then to the stoichiometric variants of nicotinic acetylcholine receptors. Here I present a brief history of our collaboration during this period.
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This study aimed to evaluate the potential benefits of acetyl-L-carnitine (ALCAR) in the context of valproate-induced autism. After prenatal exposure to valproate (VPA; 600 mg/kg, i.p.) on embryonic day 12.5, followed by ALCAR treatment (300 mg/kg on postnatal days 21-49, p.o.), assessment of oxidative stress, mitochondrial membrane potential (MMP), mitochondrial biogenesis, parvalbumin interneurons, and hippocampal volume was conducted. These assessments were carried out subsequent to the evaluation of autism-like behaviors. ⋯ In contrast, administrating ALCAR attenuated behavioral deficits, reduced oxidative stress, improved parvalbumin-positive neuronal population, and properly modified MMP and mitochondrial biogenesis. Collectively, our results indicate that oral administration of ALCAR ameliorates autism-like behaviors, partly through its targeting oxidative stress and mitochondrial biogenesis. This suggests that ALCAR may have potential benefits ASD managing.
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Sensorimotor adaptation alters mappings between motor commands and their predicted outcomes. Such remapping has been extensively studied in the visual domain, but the degree to which it occurs in modalities other than vision remains less well understood. Here, we manipulated the modality of reach target presentation to compare sensorimotor adaptation in response to perturbations of visual and auditory feedback location. ⋯ Presentation durations for target stimuli (500 ms) and (non-veridical) endpoint feedback of reach direction (100 ms) were matched for visual and auditory modalities. For all three groups, when endpoint feedback was perturbed, adaptation was evident: reach-directions increased significantly in the direction opposite the clamped feedback, and a significant aftereffect persisted after participants were instructed that the perturbation had been removed. This study provides new evidence that implicit sensorimotor adaptation occurs in response to perturbed auditory feedback of reach direction, suggesting that an implicit neural process to recalibrate sensory to motor maps in response to sensory prediction errors may be ubiquitous across sensory modalities.
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Primary angle-closure glaucoma (PACG) is a severe and irreversible blinding eye disease characterized by progressive retinal ganglion cell death. However, prior research has predominantly focused on static brain activity changes, neglecting the exploration of how PACG impacts the dynamic characteristics of functional brain networks. This study enrolled forty-four patients diagnosed with PACG and forty-four age, gender, and education level-matched healthy controls (HCs). ⋯ Subsequently, a support vector machine (SVM) model leveraging functional connectivity (FC) and FNC was applied to differentiate PACG patients from HCs. Our study underscores the presence of modified functional connectivity within large-scale brain networks and abnormalities in dynamic temporal metrics among PACG patients. By elucidating the impact of changes in large-scale brain networks on disease evolution, researchers may enhance the development of targeted therapies and interventions to preserve vision and cognitive function in PACG.
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Maintenance of proper electrophysiological and connectivity profiles in the adult brain may be a perturbation point in neurodevelopmental disorders (NDDs). How these profiles are maintained within mature circuits is unclear. We recently demonstrated that postnatal ablation of the Aristaless (Arx) homeobox gene in parvalbumin interneurons (PVIs) alone led to dysregulation of their transcriptome and alterations in their functional as well as network properties in the hippocampal cornu Ammoni first region (CA1). ⋯ Current clamp recordings showed increase excitability in several sub- and threshold membrane properties that correlated with an increase in voltage-gated Na+ current. Our data suggest that, in addition to cell-autonomous disruption in PVIs, loss of Arx postnatal transcriptional activity in PVIs led to complex dysfunctions in PCs in CA1 microcircuits. These non-cell autonomous effects are likely the product of breakdown in feedback and/or feedforward processes and should be considered as fundamental contributors to the circuit mechanisms of NDDs such as Arx-linked early-onset epileptic encephalopathies.