Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Parallel social information processing circuits are differentially impacted in autism

ABSTRACT: Parallel processing circuits are thought to dramatically expand the network capabilities of the nervous system. Magnocellular and parvocellular oxytocin neurons have been proposed to subserve two parallel streams of social information processing, which allow a single molecule to encode a diverse array of ethologically distinct behaviors, although to date direct evidence to support this hypothesis is lacking. Here we provide the first comprehensive characterization of magnocellular and parvocellular oxytocin neurons, validated across anatomical, projection target, electrophysiological, and transcriptional criteria. We next used novel multiple feature selection tools in Fmr1 KO mice to provide direct evidence that normal functioning of the parvocellular but not magnocellular oxytocin pathway is required for autism-relevant social reward behavior. Finally, we demonstrate that autism risk genes are uniquely enriched in parvocellular oxytocin neurons. Taken together these results provide the first evidence that oxytocin pathway specific pathogenic mechanisms account for social impairments across a broad range of autism etiologies.

ORGANISM(S): Mus musculus

PROVIDER: GSE147092 | GEO | 2020/03/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Rescue of oxytocin response and social behavior in a rodent model of autism

Project description:One of the most fundamental challenges in developing treatments for autism-spectrum disorders is the heterogeneity of the condition. More than one hundred genetic mutations confer high risk for autism, with each individual mutation accounting for only a small fraction of autism cases. Subsets of risk genes can be grouped into functionally-related pathways, most prominently synaptic proteins, translational regulation, and chromatin modifications. To possibly circumvent this genetic complexity, recent therapeutic strategies have focused on the neuropeptides oxytocin and vasopressin which regulate aspects of social behavior in mammals. However, whether genetic risk factors might predispose to autism due to modification of oxytocinergic signaling remains largely unknown. Here, we report that an autism-associated mutation in the synaptic adhesion molecule neuroligin-3 (Nlgn3) results in impaired oxytocin signaling in dopaminergic neurons and in altered social novelty responses in mice. Surprisingly, loss of Nlgn3 is accompanied by a disruption of translation homeostasis in the ventral tegmental area. Treatment of Nlgn3KO mice with a novel, highly specific, brain-penetrant inhibitor of MAP-kinase interacting kinases resets mRNA translation and restores oxytocin and social novelty responses. Thus, this work identifies an unexpected convergence between the genetic autism risk factor Nlgn3, translational regulation, and oxytocinergic signaling. Focus on such common core plasticity elements might provide a pragmatic approach to reduce the heterogeneity of autism phenotypes. Ultimately, this would allow for mechanism-based stratification of patient populations to increase the success of therapeutic interventions.

2020-04-27 | PXD018808 | Pride

Selective Vulnerability of Parvocellular Oxytocin Neuron in Social Dysfunction

Project description:Despite the rapid progress in dissecting neural circuits for social behaviors, it remains unknown whether specific neural cell types are selectively vulnerable in social dysfunction cases often associated with neurodevelopmental disorders. Here, employing a single-cell transcriptome analysis in mice, we show that an embryonic disturbance known to induce social dysfunction preferentially impairs gene expressions crucial for neural functions in parvocellular oxytocin (OT) neurons—a subtype linked to social rewards—while neighboring cell types experience a lesser impact. Chemogenetic stimulation of OT neurons at the neonatal stage ameliorated social deficits, concomitant with a cell-type-specific sustained recovery of the pivotal gene expressions. Our data illuminates the transcriptomic selective vulnerability within the hypothalamic social behavioral center, offering a potential therapeutic target through specific neonatal neurostimulation.

2023-12-05 | GSE245555 | GEO

Single-cell transcriptome analysis of secretagogin mRNA expressing cells from the mouse hypothalamic paraventricular nucleus

Project description:The molecular mechanism regulating phasic corticotropin-releasing hormone (CRH) release from parvocellular neurons (PVN) remains poorly understood. Here, we find a cohort of parvocellular cells interspersed with magnocellular PVN neurons expressing secretagogin. Single-cell transcriptome analysis combined with protein interactome profiling identifies secretagogin neurons as a distinct CRH-releasing neuron population reliant on secretagogin’s Ca2+ sensor properties and protein interactions with the vesicular traffic and exocytosis release machineries to liberate this key hypothalamic releasing hormone.

2014-11-20 | GSE63093 | GEO

Single-cell transcriptome analysis of secretagogin mRNA expressing cells from the mouse hypothalamic paraventricular nucleus

Project description:The molecular mechanism regulating phasic corticotropin-releasing hormone (CRH) release from parvocellular neurons (PVN) remains poorly understood. Here, we find a cohort of parvocellular cells interspersed with magnocellular PVN neurons expressing secretagogin. Single-cell transcriptome analysis combined with protein interactome profiling identifies secretagogin neurons as a distinct CRH-releasing neuron population reliant on secretagoginM-bM-^@M-^Ys Ca2+ sensor properties and protein interactions with the vesicular traffic and exocytosis release machineries to liberate this key hypothalamic releasing hormone. single cells from the PVN region juvenile (21-28 days) mice were dissected and subject to whole transcriptome analysis

2014-11-20 | E-GEOD-63093 | biostudies-arrayexpress

Parallel social information processing circuits are differentially impacted in autism

Project description:Parallel social information processing circuits are differentially impacted in autism

| PRJNA613044 | ENA

Functional Involvement of Septal miR-132 in Extinction and Oxytocin-mediated Reversal of Social Fear

Project description:Social interactions are critical components for the survival of mammalian biology and evolution. Dysregulation of social behavior often leads to psychopathologies such as social anxiety disorder, which is characterized by an intense fear and avoidance of social situations. Using the social fear conditioning (SFC) paradigm, we analyzed expression levels of miR-132-3p and miR-124-3p within the septum, a brain region essential for social behavior and fear, after acquisition and extinction of social fear. Functional in vivo approaches using pharmacology, functional inhibition of miR-132-3p, viral miR-132 overexpression and shRNA-mediated knockdown of miR-132-3p within oxytocin receptor positive neurons confirmed septal miR-132-3p to be involved in social fear extinction and the oxytocin-mediated reversal of social fear. Moreover, Argonaute-RNA-co-immunoprecipitation-microarray analysis and further target mRNA quantification, depicted growth differentiation factor-5 (GDF-5) to be involved in miR-132-3p-mediated regulation of social fear extinction. Local application of GDF-5 resulted in impaired social fear extinction, an effect which seems to be mediated by miR-132-3p. In summary, we show that septal miR-132-3p is functionally involved in social fear extinction learning and oxytocin-mediated reversal of social fear.

2023-11-08 | GSE211449 | GEO

Gene expression data from the hippocampus of rats with prenatal valproic acid exposure

Project description:In this study, we explored molecular alterations in the hippocampus of prenatal valproic acid (VPA)-exposed rats as a model of autism spectrum disorders (ASD). In addition, we assessed effects of chronic administration of intranasal oxytocin, a promising peptide for ASD treatment. Comparative analyses revealed that prenatal VPA exposure altered gene expression, a part of which is involved in key features including memory, developmental process, and epilepsy. Oxytocin partly improved these gene expression, which were predicted to interact with those involved in social behaviors and hippocampal-dependent memory. The present study documented molecular profiling in the hippocampus related to ASD and improvement by chronic treatment of oxytocin.

2022-02-12 | GSE196500 | GEO

Excessive β-catenin in excitatory neurons results in reduced social and increased repetitive behaviors and altered expression of multiple genes linked to human autism

Project description:Multiple human autism risk genes are predicted to converge on the β‐catenin (β‐cat)/Wnt pathway. However, direct tests to link β‐cat up‐ or down‐regulation with autism are largely lacking, and the associated pathophysiological changes are poorly defined. Here we identify excessive β‐cat as a risk factor that causes expression changes in several genes relevant to human autism. Our studies utilize mouse lines with β‐cat dysregulation in forebrain excitatory neurons, identified as cell types with convergent expression of autism‐linked genes in both human and mouse brains. We show that mice expressing excessive β‐cat display behavioral and molecular changes, including decreased social interest, increased repetitive behaviors, reduced parvalbumin and altered expression levels of additional genes identified as potential risk factors for human autism. These behavioral and molecular phenotypes are averted by reducing β‐cat in neurons predisposed by gene mutations to express elevated β‐cat. Using next-generation sequencing of the prefrontal cortex, we identify dysregulated genes that are shared between mouse lines with excessive β‐cat and autism‐like behaviors, but not mouse lines with reduced β‐cat and normal social behavior. Our findings provide critical new insights into β‐cat, Wnt pathway dysregulation in the brain causing behavioral phenotypes relevant to the disease and the molecular etiology which includes several human autism risk genes.

2020-03-17 | GSE147034 | GEO

Single-cell and single-nucleus RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates, and humans

Project description:Abundant evidence supports the presence of at least three distinct types of thalamocortical (TC) neurons in the primate dorsal lateral geniculate nucleus (dLGN) of the thalamus, the brain region that conveys visual information from the retina to the primary visual cortex (V1). Different types of TC neurons in mice, humans, and macaques have distinct morphologies, distinct connectivity patterns, and convey different aspects of visual information to the cortex. To investigate the molecular underpinnings of these cell types, and how these relate to differences in dLGN between human, macaque, and mice, we profiled gene expression in single nuclei and cells using RNA-sequencing. These efforts identified four distinct types of TC neurons in the primate dLGN: magnocellular (M) neurons, parvocellular (P) neurons, and two types of koniocellular (K) neurons. Despite extensively documented morphological and physiological differences between M and P neurons, we identified few genes with significant differential expression between transcriptomic cell types corresponding to these two neuronal populations. Likewise, the dominant feature of TC neurons of the adult mouse dLGN is high transcriptomic similarity, with an axis of heterogeneity that aligns with core vs. shell portions of mouse dLGN. Together, these data show that transcriptomic differences between principal cell types in the mature mammalian dLGN are subtle relative to the observed differences in morphology and cortical projection targets. Finally, alignment of transcriptome profiles across species highlights expanded diversity of GABAergic neurons in primate versus mouse dLGN and homologous types of TC neurons in primates that are distinct from TC neurons in mouse.

2021-09-08 | GSE182211 | GEO

Maternal oxytocin treatment at birth increases epigenetic age in male offspring [array]

Project description:Rates of oxytocin use to induce or augment labor are increasing in the United States with little understanding of the impact on offspring development. Using a prairie vole animal model, we have shown that oxytocin administered to mothers can reach offspring brains with long lasting impacts on the development of social behaviors. Here, we examine the epigenetic and transcriptomic consequences of oxytocin exposure during birth in juvenile male offspring. First, we show that male offspring exposed to oxytocin at birth have increased epigenetic age compared to the saline exposed group. We also find 900 differentially methylated CpG sites (annotated to 589 genes), with 2 CpG sites (2 genes) remaining significant after correction for multiple comparisons. Differentially methylated CpG sites are involved in regulation of gene expression and neurodevelopment. Using RNA-sequencing we find 217 nominally differentially expressed genes (p<0.05) in nucleus accumbens, a brain region involved in reward circuitry and social behavior, including 6 genes that remain significantly differentially expressed after corrections for multiple comparisons. Finally, we show that maternal oxytocin administration leads to widespread alternative splicing in the nucleus accumbens. These results indicate that oxytocin exposure during birth has long lasting epigenetic consequences in the brain and warrant further investigation of how oxytocin administration impacts development and behavior throughout the lifespan.

2024-04-03 | GSE240833 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data