BigNeuron: a resource to benchmark and predict performance of algorithms for automated tracing of neurons in light microscopy datasets.

BigNeuron is an open community bench-testing platform with the goal of setting open standards for accurate and fast automatic neuron tracing. We gathered a diverse set of image volumes across several species that is representative of the data obtained in many neuroscience laboratories interested in neuron tracing. Here, we report generated gold standard manual annotations for a subset of the available imaging datasets and quantified tracing quality for 35 automatic tracing algorithms.

Impact of α-Synuclein Fibrillar Strains and β-Amyloid Assemblies on Mouse Cortical Neurons Endo-Lysosomal Logistics.

Endosomal transport and positioning cooperate in the establishment of neuronal compartment architecture, dynamics, and function, contributing to neuronal intracellular logistics. Furthermore, dysfunction of endo-lysosomal has been identified as a common mechanism in neurodegenerative diseases. Here, we analyzed endo-lysosomal transport when α-synuclein (α-syn) fibrillar polymorphs, β-amyloid (Aβ) fibrils, and oligomers were externally applied on primary cultures of mouse cortical neurons.

Looking beyond the usual suspects: sulfide stress in schizophrenia pathophysiology.

Schizophrenia is a complex, multifactorial disease that displays heterogeneous behavioral and cognitive syndrome (Lieberman & First, 2018). The origin of schizophrenia appears to lie in genetic and/or environmental disruption of brain development (Owen et al, 2016). In spite of current treatment that largely consists in antipsychotic drugs combined with psychological therapies, social support, and rehabilitation, developing more effective therapeutic interventions is an essential issue.

HENA, heterogeneous network-based data set for Alzheimer's disease.

Alzheimer's disease and other types of dementia are the top cause for disabilities in later life and various types of experiments have been performed to understand the underlying mechanisms of the disease with the aim of coming up with potential drug targets. These experiments have been carried out by scientists working in different domains such as proteomics, molecular biology, clinical diagnostics and genomics. The results of such experiments are stored in the databases designed for collecting data of similar types.

Increased expression of BDNF mRNA in the frontal cortex of autistic patients.

Autistic spectrum disorders (ASDs) are neurodevelopmental disorders for which genetic components have been well defined. However, specific gene deregulations related to synapse function in the autistic brain have not been as extensively described. Based on a candidate genes approach, we present in this study the expression data of 4 transcripts of interest (BDNF, CAMK2a, NR-CAM and RIMS1) located at the synapse in two regions of interest in the context of the ASDs; the lobule VI of cerebellum and the Brodmann area 46.

Somatostatin-IRES-Cre Mice: Between Knockout and Wild-Type?

The neuropeptide somatostatin (SOM) is widely expressed in rodent brain and somatostatin-IRES-Cre (SOM-cre) mouse strains are increasingly used to unravel the physiology of SOM-containing neurons. However, while knock-in targeting strategy greatly improves Cre-Lox system accuracy, recent reports have shown that genomic insertion of Cre construct can markedly affect physiological function. We show that Cre transgene insertion into the 3'UTR of the somatostatin gene leads to the selective and massive depletion of endogenous SOM in all tested brain regions.

Netrin G1: its downregulation in the nucleus accumbens of cocaine-conditioned mice and genetic association in human cocaine dependence.

Netrin G1 is a presynaptic ligand involved in axonal projection. Although molecular mechanisms underlying cocaine addiction are still poorly understood, Netrin G1 might have a role as a regulator of anxiety, fear and spatial memory, behavioural traits impaired in the context of cocaine exposure. In this study, the Netrin G1 (Ntng1) expression was investigated in the nucleus accumbens of mice primarily conditioned to cocaine using a place preference paradigm.

Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors.

Brain diseases such as autism and Alzheimer's disease (each inflicting >1% of the world population) involve a large network of genes displaying subtle changes in their expression. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients, suggesting the relevance of measuring this key biological process. However, current techniques are not sensitive enough to detect minor abnormalities.

Single KTP nanocrystals as second-harmonic generation biolabels in cortical neurons.

We report an efficient colloidal synthesis of KTiOPO4 (KTP) nanocrystals with excellent crystallinity and the direct observation of optical second-harmonic generation (SHG) from discrete KTP nanocrystals in neurons cultured from mammalian brain cortex. Direct internalization and monitoring of these nanoparticles was successfully achieved without limitations from cytotoxicity, bleaching and blinking emission.

Genetics of dopamine receptors and drug addiction.

Dopamine plays a key role in reward behavior, yet the association of drug dependence as a chronic, relapsing disorder with the genes encoding the various dopaminergic receptor subtypes remains difficult to delineate. In the context of subsequent genome-wide association (GWAS) research and post-GWAS investigations, we summarize the novel data that link genes encoding molecules involved in the dopaminergic system (dopamine receptors, transporter and enzymes in charge of its metabolism) to drug addiction. Recent reports indicate that the heritability of drug addiction should be high enough to allow a significant role for a specific set of genes, and the available genetic studies, which might not be already conclusive because of the heterogeneity of designs, methods and recruited samples, should support the idea of a significant role of at least one gene related to dopaminergic system.

Convergent evidence identifying MAP/microtubule affinity-regulating kinase 1 (MARK1) as a susceptibility gene for autism.

Autism spectrum disorders (ASDs) are common, heritable, but genetically heterogeneous neurodevelopmental conditions. We recently defined a susceptibility locus for ASDs on chromosome 1q41-q42. High-resolution single-nucleotide polymorphisms (126 SNPs) genotyping across the chromosome 1q41-q42 region, followed by a MARK1 (microtubule affinity-regulating kinase 1)-tagged-SNP association study in 276 families with autism from the Autism Genetic Research Exchange, showed that several SNPs within the MARK1 gene were significantly associated with ASDs by transmission disequilibrium tests.

Nrxn3 upregulation in the globus pallidus of mice developing cocaine addiction.

Dysfunctions affecting the connections of basal ganglia lead to major neurological and psychiatric disorders. We investigated levels of mRNA for three neurexins (Nrxn) and three neuroligins (Nlgn) in the globus pallidus, subthalamic nucleus, and substantia nigra, in control conditions and after short-term exposure to cocaine. The expression of Nrxn2beta and Nlgn3 in the substantia nigra and Nlgn1 in the subthalamic nucleus depended on genetic background.

The fragile X mental retardation protein is a molecular adaptor between the neurospecific KIF3C kinesin and dendritic RNA granules.

Fragile X mental retardation 1 protein (FMRP) is an RNA-binding protein whose absence results in the fragile X syndrome, the most common inherited form of mental retardation. FMRP contains multiple domains with apparently differential affinity to mRNA and interacts also with protein partners present in ribonucleoprotein complexes called RNA granules. In neurons, these particles travel along dendrites and axons to translocate mRNAs to specific destinations in spines and growth cones, where local synthesis of neuro-specific proteins is taking place.