Neuron migration is a hallmark of nervous system development that allows the gathering of neurons from different origins for the assembling of functional neuronal circuits. Cortical inhibitory interneurons arise in the ventral telencephalon and migrate tangentially forming three transient migratory streams in the cortex before reaching their final laminar destination. Although migration defects lead to the disruption of inhibitory circuits and are linked to aspects of psychiatric disorders such as autism and schizophrenia, the molecular mechanisms controlling cortical interneuron development and final layer positioning are incompletely understood. Here we show that mouse embryos with a double deletion of FLRT2 and FLRT3 genes encoding cell adhesion molecules, exhibit an abnormal distribution of interneurons within the streams during development, which in turn, affect the layering of somatostatin+ interneurons postnatally. Mechanistically, FLRT2 and FLRT3 proteins act in a non cell-autonomous manner, possib...

Current theories of visual consciousness disagree about whether it emerges during early stages of processing in sensory brain regions or later when a widespread fronto-parietal network becomes involved. Moreover, disentangling conscious perception from task-related post-perceptual processes (e.g., report) and integrating results across different neuroscientific methods remain ongoing challenges. The present study addressed these problems using simultaneous EEG-fMRI and a specific inattentional-blindness paradigm with three physically identical phases in female and male human participants. In phase 1, participants performed a distractor task during which line drawings of faces and control stimuli were presented centrally. While some participants spontaneously noticed the faces in phase 1, others remained inattentionally blind. In phase 2, all participants were made aware of the task-irrelevant faces, but continued the distractor task. In phase 3, the faces became task-relevant. Bayesian analysis of brain re...

Human language learning differs significantly across individuals in the process and ultimate attainment. Although decades of research exploring the neural substrates of language learning have identified distinct and overlapping neural networks subserving learning of different components, the neural mechanisms that drive the large inter-individual differences are still far from being understood. Here we examine to what extent the neural dynamics of multiple brain networks in men and women across sessions of training contribute to explaining individual differences in learning multiple linguistic components (i.e., vocabulary, morphology, and phrase and sentence structures) of an artificial language in a seven-day training and imaging paradigm with functional Magnetic Resonance Imaging. With machine-learning and predictive modeling, neural activation patterns across training sessions were highly predictive of individual learning success profiles derived from the four components. We identified four neural learn...

The mu opioid receptor regulates reward derived from both drug use and natural experiences, including social interaction, through actions in the nucleus accumbens. Here, we studied nucleus accumbens microcircuitry and social behavior in male and female mice with heterozygous genetic knockout of the mu opioid receptor (Oprm1+/-). This genetic condition models the partial reduction of mu opioid receptor signaling reported in several neuropsychiatric disorders. We first analyzed inhibitory synapses in the nucleus accumbens, using methods that differentiate between medium spiny neurons (MSNs) expressing the D1 or D2 dopamine receptor. Inhibitory synaptic transmission was increased in D2-MSNs of male mutants, but not female mutants, while the expression of gephyrin mRNA and density of inhibitory synaptic puncta at the cell body of D2-MSNs was increased in mutants of both sexes. Some of these changes were more robust in Oprm1+/- mutants than Oprm1-/- mutants, demonstrating that partial reductions of mu opioid si...

Neurons in the prefrontal cortex (PFC) are typically activated by different cognitive tasks, and also by different stimuli and abstract variables within these tasks. A single neuron’s selectivity for a given stimulus dimension often changes depending on its context, a phenomenon known as nonlinear mixed selectivity (NMS). It has previously been hypothesized that NMS emerges as a result of training to perform tasks in different contexts. We tested this hypothesis directly by examining the neuronal responses of different PFC areas before and after male monkeys were trained to perform different working memory tasks involving visual stimulus locations and/or shapes. We found that training induces a modest increase in the proportion of PFC neurons with NMS exclusively for spatial working memory, but not for shape working memory tasks, with area 9/46 undergoing the most significant increase in NMS cell proportion. We also found that increased working memory task complexity, in the form of simultaneously storing ...

Both nucleus reuniens and the anterior thalamic nuclei are densely interconnected with medial cortical and hippocampal areas, connections that reflect their respective contributions to learning and memory. To better appreciate their comparative roles, pairs of different retrograde tracers were placed in these two thalamic sites in adult rats. Both thalamic sites receive modest cortical inputs from layer V that contrasted with much denser projections from layer VI. Despite frequent overlap in layer VI, ventral prefrontal and anterior cingulate inputs to nucleus reuniens were concentrated in the deepest sublayer (VIb). Meanwhile, inputs to the anterior thalamic nuclei originated more evenly from both sublayers VIa and VIb, with the result that they were often located more superficially than the projections to nucleus reuniens. Again, while the many hippocampal (subiculum) neurons projecting to nucleus reuniens and the anterior thalamic nuclei were partially intermingled within the deep cellular parts of the ...

Background: In auditory behavioral and EEG experiments, the variability of stimulation solutions, for both software and hardware, adds unnecessary technical constraints. Currently, there is no easy to use, inexpensive and shareable solution that could improve collaborations and data comparisons across different sites and contexts. Method: This paper outlines a system composed by a Raspberry Pi coupled with Python programming and associated with a HifiBerry sound card. We compare its sound performances with those of a wide variety of material and configurations. This solution achieves the high timing accuracy and sound quality important in auditory cognition experiments, while being simple to use and open source. Results: The present system shows high performances and results along with excellent feedback from users. It is inexpensive, easy to build, share and improve-upon. Working with such low cost, powerful and collaborative hardware and software tools allow people to create their own specific, adapted...

Astrocytes provide neurons with diffusible factors that promote synapse formation and maturation. In particular, glypican-4/GPC4 released from astrocytes promotes the maturation of excitatory synapses. Unlike other secreted factors, GPC4 contains the C-terminal GPI-anchorage signal. However, the mechanism by which membrane-tethered GPC4 is released from astrocytes is unknown. Using mouse primary astrocyte cultures and a quantitative luciferase-based release assay, we show that GPC4 is expressed on the astrocyte surface via a GPI-anchorage. Soluble GPC4 is robustly released from the astrocytes largely by proteolytic shedding and, to a lesser extent, by GPI-anchor cleavage, but not by vesicular release. Pharmacological, overexpression, and loss of function screens showed that ADAM9 in part mediates the release of GPC4 from astrocytes. The released GPC4 contains the heparan sulfate side chain, suggesting that these release mechanisms provide the active form that promotes synapse maturation and function. Overa...

Here we report the independent discovery and validation of Stearoyl-CoA desaturase (SCD) as a modulator of alpha-synuclein (αSyn) induced pathology and toxicity in cell-based Parkinson’s Disease models (PD). We identified SCD as top altered gene from transcriptional profiling in primary neurons exogenously expressing αSyn with the amplified familial PD mutation 3K. Thus, we sought to further explore SCD as a therapeutic target in neurodegeneration. We report that SCD inhibitors are toxic to early human and rat neuron cultures while displaying minimal toxicity to late cultures. The fatty acid product of SCD, oleic acid, fully rescues this toxicity in early cultures, suggesting on-target toxicity. Furthermore, SCD inhibition rescues αSyn 3K induced toxicity in late primary neurons. We also confirm that SCD inhibitors reduce formation of αSyn accumulations while oleic acid increases these accumulations in an αSyn 3K neuroblastoma model. However, we identify a caveat with this model where αSyn 3K levels can be...