Search results for " POS"
showing 10 items of 3656 documents
Fast Regulation of GABAAR Diffusion Dynamics by Nogo-A Signaling.
2019
Summary: Precisely controlling the excitatory and inhibitory balance is crucial for the stability and information-processing ability of neuronal networks. However, the molecular mechanisms maintaining this balance during ongoing sensory experiences are largely unclear. We show that Nogo-A signaling reciprocally regulates excitatory and inhibitory transmission. Loss of function for Nogo-A signaling through S1PR2 rapidly increases GABAAR diffusion, thereby decreasing their number at synaptic sites and the amplitude of GABAergic mIPSCs at CA3 hippocampal neurons. This increase in GABAAR diffusion rate is correlated with an increase in Ca2+ influx and requires the calcineurin-mediated dephospho…
Shank3 Mice Carrying the Human Q321R Mutation Display Enhanced Self-Grooming, Abnormal Electroencephalogram Patterns, and Suppressed Neuronal Excitab…
2019
Shank3, a postsynaptic scaffolding protein involved in regulating excitatory synapse assembly and function, has been implicated in several brain disorders, including autism spectrum disorders (ASD), Phelan-McDermid syndrome, schizophrenia, intellectual disability, and mania. Here we generated and characterized a Shank3 knock-in mouse line carrying the Q321R mutation (Shank3Q321R mice) identified in a human individual with ASD that affects the ankyrin repeat region (ARR) domain of the Shank3 protein. Homozygous Shank3Q321R/Q321R mice show a selective decrease in the level of Shank3a, an ARR-containing protein variant, but not other variants. CA1 pyramidal neurons in the Shank3Q321R/Q321R hip…
Histones, Their Variants and Post-translational Modifications in Zebrafish Development.
2020
Complex multi-cellular organisms are shaped starting from a single-celled zygote, owing to elaborate developmental programs. These programs involve several layers of regulation to orchestrate the establishment of progressively diverging cell type-specific gene expression patterns. In this scenario, epigenetic modifications of chromatin are central in influencing spatiotemporal patterns of gene transcription. In fact, it is generally recognized that epigenetic changes of chromatin states impact on the accessibility of genomic DNA to regulatory proteins. Several lines of evidence highlighted that zebrafish is an excellent vertebrate model for research purposes in the field of developmental ep…
Phenotypic characterization of MCP-1 expressing neurons in the rat cerebral cortex.
2020
Chemokines are small, secreted molecules that mediate inflammatory reactions. Neurons and astrocytes constitutively express chemokines implicated in the process of neuroinflammation associated with neurodegenerative diseases. The monocyte chemoattractant protein-1 (MCP-1) has been widely related to this process. However, the constitutive expression of this molecule by neurons has not been elucidated so far. In this study, we set out to characterize the neurochemical phenotype of MCP-1-expressing neurons in the rat neocortex to infer its role in basal conditions. We observed the presence of two populations of neurons expressing MCP-1: One population of cells with weak expression of MCP-1 cor…
Characterization and Stage-Dependent Lineage Analysis of Intermediate Progenitors of Cortical GABAergic Interneurons
2021
Intermediate progenitors of both excitatory and inhibitory neurons, which can replenish neurons in the adult brain, were recently identified. However, the generation of intermediate progenitors of GABAergic inhibitory neurons (IPGNs) has not been studied in detail. Here, we characterized the spatiotemporal distribution of IPGNs in mouse cerebral cortex. IPGNs generated neurons during both embryonic and postnatal stages, but the embryonic IPGNs were more proliferative. Our lineage tracing analyses showed that the embryonically proliferating IPGNs tended to localize to the superficial layers rather than the deep cortical layers at 3 weeks after birth. We also found that embryonic IPGNs derive…
Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation.
2016
Neutrophil granulocytes, also called polymorphonuclear leukocytes (PMNs), extrude molecular lattices of decondensed chromatin studded with histones, granule enzymes, and antimicrobial peptides that are referred to as neutrophil extracellular traps (NETs). NETs capture and contain bacteria, viruses, and other pathogens. Nevertheless, experimental evidence indicates that NETs also cause inflammatory vascular and tissue damage, suggesting that identifying pathways that inhibit NET formation may have therapeutic implications. Here, we determined that neonatal NET-inhibitory factor (nNIF) is an inhibitor of NET formation in umbilical cord blood. In human neonatal and adult neutrophils, nNIF inhi…
Cannabinoid Control of Learning and Memory through HCN Channels
2016
The mechanisms underlying the effects of cannabinoids on cognitive processes are not understood. Here we show that cannabinoid type-1 receptors (CB1Rs) control hippocampal synaptic plasticity and spatial memory through the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that underlie the h-current (Ih), a key regulator of dendritic excitability. The CB1R-HCN pathway, involving c-Jun-N-terminal kinases (JNKs), nitric oxide synthase, and intracellular cGMP, exerts a tonic enhancement of Ih selectively in pyramidal cells located in the superficial portion of the CA1 pyramidal cell layer, whereas it is absent from deep-layer cells. Activation of the CB1R-HCN pathway impairs d…
Activation of Corticothalamic Layer 6 Cells Decreases Angular Tuning in Mouse Barrel Cortex.
2019
In the mouse whisker system, the contribution of L6 corticothalamic cells (L6 CT) to cortical and thalamic processing of the whisker deflection direction was investigated. A genetically defined population of L6 CT cells project to infragranular GABAergic interneurons that hyperpolarize neurons in somatosensory barrel cortex (BC). Optogenetic activation of these neurons switched BC to an adapted mode in which excitatory cells lost their angular tuning. In contrast, however, this was not the case with a general activation of inhibitory interneurons via optogenetic activation of Gad2-expressing cells. The decrease in angular tuning, when L6 CT cells were activated, was due to changes in cortic…
Reduced interneuronal dendritic arborization in CA1 but not in CA3 region of mice subjected to chronic mild stress
2016
Abstract Introduction Chronic stress induces dendritic atrophy and decreases spine density in excitatory hippocampal neurons, although there is also ample evidence indicating that the GABAergic system is altered in the hippocampus after this aversive experience. Chronic stress causes dendritic remodeling both in excitatory neurons and interneurons in the medial prefrontal cortex and the amygdala. Methods In order to know whether it also has an impact on the structure and neurotransmission of hippocampal interneurons, we have analyzed the dendritic arborization, spine density, and the expression of markers of inhibitory synapses and plasticity in the hippocampus of mice submitted to 21 days …
Immature excitatory neurons develop during adolescence in the human amygdala.
2019
The human amygdala grows during childhood, and its abnormal development is linked to mood disorders. The primate amygdala contains a large population of immature neurons in the paralaminar nuclei (PL), suggesting protracted development and possibly neurogenesis. Here we studied human PL development from embryonic stages to adulthood. The PL develops next to the caudal ganglionic eminence, which generates inhibitory interneurons, yet most PL neurons express excitatory markers. In children, most PL cells are immature (DCX+PSA-NCAM+), and during adolescence many transition into mature (TBR1+VGLUT2+) neurons. Immature PL neurons persist into old age, yet local progenitor proliferation sharply d…