Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Sensory experience restricts cortical plasticity by inducing IGF-1 in VIP neurons

ABSTRACT: RNA-seq libraries purified from the visual cortices of neurons expressing Emx-, GAD2-, PV-, SST-, or VIP-Cre using the Ribotag allele. Seq libraries are provided from mice raised in standard housing, or housed in the dark for two weeks (dark-housed), or dark-housed and then exposed to light for 1, 3, or 7.5 hours. These seq libraries represent the genetic response of distinct types of cortical interneurons to altered sensory experience. To explore how sensory experience affects gene expression, we examined this process in the visual cortex of adult mice that were housed in standard conditions, in complete darkness (i.e. dark-housed), or dark-housed and then exposed to light for increasing amounts of time. We generated mice that were heterozygous for alleles of either Emx-,Gad2-,Sst-,Vip- or Pv-Cre, and were also heterozygous for the Rpl22-HA (RiboTag) allele, which expresses an HA-tagged ribosomal protein specifically in Cre-expressing neurons. We performed RNA-Seq on RNA isolated from the dark-housed/light-exposed RiboTag-mice; Experiments were done in 3 biological replicates and the visual cortices of 3 mice were pooled per sample at each time-point and for each Cre line.

ORGANISM(S): Mus musculus

SUBMITTER: Ivo Spiegel

PROVIDER: E-GEOD-77243 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons.

Mardinly A R AR Spiegel I I Patrizi A A Centofante E E Bazinet J E JE Tzeng C P CP Mandel-Brehm C C Harmin D A DA Adesnik H H Fagiolini M M Greenberg M E ME

Nature 20160309 7594

Inhibitory neurons regulate the adaptation of neural circuits to sensory experience, but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibito ...[more]

PMID: 26958833

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Project description:Major depressive disorder (MDD) is a severe psychiatric disorder, characterized by deficits in GABAergic and glutamatergic signaling in cortical brain regions. Unpredictable chronic mild stress (UCMS), a murine stress model, induces behavioural and neurobiological changes reminiscent of MDD. Despite increasing knowledge of the cellular complexity of the cortical microcircuitry, our understanding of how distinct cell-types are impacted by UCMS is extremely limited. We thus endeavoured to determine the effect of UCMS on Pyramidal (PYR) cells and three classes of interneurons: Somatostatin (SST), Parvalbumin (PV), and Vasoactive intestinal peptide-expressing (VIP) cells in the medial prefrontal cortex. C57Bl/6 mice, exposed to UCMS or control housing for five weeks, were assessed with a battery of anxiety- and depressive-like behavioural tests. Laser-capture microdissection was used to isolate samples of microcircuit cell-types, which underwent RNA-sequencing. UCMS-exposed mice showed significantly elevated emotionality, and isolate cell-types showed robust specificity. Cell-types exhibited unique transcriptomic profiles after UCMS. Briefly, PYR-cells showed decreased signaling and post-synaptic receptor expression, SST-cells showed increased activation of the unfolded protein response, PV-cells showed increased axonal microtubule expression, and VIP-cells showed increased apoptotic signaling and altered cytoskeletal gene expression. Co-expression analyses revealed that these changes were largely correlated across cell-types and that UCMS increased transcriptome-wide co-expression between PYR and both PV and SST cells. Overall, these findings suggest decreased PYR, SST, and VIP-cell function, elevated PV-cell function, and identify the dysregulation of PYR-cells as a central locus of UCMS-induced transcriptomic change. Further studies interrogating potential antidepressant-like activity of compounds reversing these cell-specific changes are warranted.

Dataset Information

Sensory experience restricts cortical plasticity by inducing IGF-1 in VIP neurons

Publications

Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons.

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