Whole Brain Gene Expression Correlates for HARGREAVES_MEANBOTH measured in BXD RI Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The HARGREAVES_MEANBOTH measures Thermal Nociception Hargreaves' Test under the domain Pain. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
QTL for METH responses for climbing on Chr4 at Mltr3 (34.50 Mbp , Build 37)
Description:
METH responses for climbing spans 9.50 - 59.50 Mbp (NCBI Build 37) on Chr4. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for METH responses for body temperature on Chr4 at D4Nds8 (40.90 Mbp , Build 37)
Description:
METH responses for body temperature spans 15.90 - 65.90 Mbp (NCBI Build 37) on Chr4. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for METH responses for chewing on Chr4 at Lyb4 (46.47 Mbp , Build 37)
Description:
METH responses for chewing spans 21.47 - 71.47 Mbp (NCBI Build 37) on Chr4. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Average rotarod training latency Chr# 4 rs13477617(26886337) with right flanking marker rs3660863(7127435) and left marker rs3684104 (38269953). This was mapped in 300 + (b6x129)F2 mice.
Genes identified as expressed lower (down) in the AJ strain than in the NOD strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the NZO strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the NOD strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the NOD strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the NZO strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the NOD strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the S129 strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the NOD strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the S129 strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the NOD strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Microglia depletion and alcohol gene expression logFC
Description:
Alcohol abuse induces changes in microglia morphology and immune function, but whether microglia initiate or simply amplify the harmful effects of alcohol exposure is still a matter of debate. Here, we determine microglia function in acute and voluntary drinking behaviors using a colony-stimulating factor 1 receptor inhibitor (PLX5622). We show that microglia depletion does not alter the sedative or hypnotic effects of acute intoxication. Microglia depletion also does not change the escalation or maintenance of chronic voluntary alcohol consumption. Transcriptomic analysis revealed that although many immune genes have been implicated in alcohol abuse, down regulation of microglia genes does not necessitate changes in alcohol intake. Instead, microglia depletion and chronic alcohol result in compensatory upregulation of alcohol-responsive, reactive astrocyte genes, indicating astrocytes may play a role in regulation of these alcohol behaviors. Taken together, our behavioral and transcriptional data indicate that microglia are not theprimary effector cell responsible for regulation of acute and voluntary alcohol behaviors. Because microglia depletion did not regulate acute or voluntary alcohol behaviors, we hypothesized that these doses were insufficient to activate microglia and recruit them to an effector phenotype. Therefore, we used a model of repeated immune activation using polyinosinic:polycytidylic acid
Microglia depletion and alcohol gene expression p-value
Description:
Alcohol abuse induces changes in microglia morphology and immune function, but whether microglia initiate or simply amplify the harmful effects of alcohol exposure is still a matter of debate. Here, we determine microglia function in acute and voluntary drinking behaviors using a colony-stimulating factor 1 receptor inhibitor (PLX5622). We show that microglia depletion does not alter the sedative or hypnotic effects of acute intoxication. Microglia depletion also does not change the escalation or maintenance of chronic voluntary alcohol consumption. Transcriptomic analysis revealed that although many immune genes have been implicated in alcohol abuse, down regulation of microglia genes does not necessitate changes in alcohol intake. Instead, microglia depletion and chronic alcohol result in compensatory upregulation of alcohol-responsive, reactive astrocyte genes, indicating astrocytes may play a role in regulation of these alcohol behaviors. Taken together, our behavioral and transcriptional data indicate that microglia are not theprimary effector cell responsible for regulation of acute and voluntary alcohol behaviors. Because microglia depletion did not regulate acute or voluntary alcohol behaviors, we hypothesized that these doses were insufficient to activate microglia and recruit them to an effector phenotype. Therefore, we used a model of repeated immune activation using polyinosinic:polycytidylic acid
We investigated the role of microglia in a mouse model of alcohol dependence using a colony stimulating factor 1 receptor inhibitor (PLX5622) to deplete microglia and a chronic intermittent ethanol vapor two-bottle choice drinking procedure. Additionally, we examined anxiety-like behavior during withdrawal. We then analyzed synaptic neuroadaptations in the central nucleus of the amygdala (CeA) and gene expression changes in the medial prefrontal cortex (mPFC) and CeA from the same animals used for behavioral studies.
Alcohol dependence in the medial prefrontal cortex q-value
Description:
We investigated the role of microglia in a mouse model of alcohol dependence using a colony stimulating factor 1 receptor inhibitor (PLX5622) to deplete microglia and a chronic intermittent ethanol vapor two-bottle choice drinking procedure. Additionally, we examined anxiety-like behavior during withdrawal. We then analyzed synaptic neuroadaptations in the central nucleus of the amygdala (CeA) and gene expression changes in the medial prefrontal cortex (mPFC) and CeA from the same animals used for behavioral studies.
Alcohol interaction of dependence and MG depletion the medial prefrontal cortex q-value
Description:
We investigated the role of microglia in a mouse model of alcohol dependence using a colony stimulating factor 1 receptor inhibitor (PLX5622) to deplete microglia and a chronic intermittent ethanol vapor two-bottle choice drinking procedure. Additionally, we examined anxiety-like behavior during withdrawal. We then analyzed synaptic neuroadaptations in the central nucleus of the amygdala (CeA) and gene expression changes in the medial prefrontal cortex (mPFC) and CeA from the same animals used for behavioral studies.
Authors develop a brain reward circuit-wide atlas of opioid-induced transcriptional regulation by combining RNA sequencing (RNA-seq) and heroin self-administration in male mice modeling multiple OUD-relevant conditions: acute heroin exposure, chronic heroin intake, context-induced drug-seeking following abstinence, and relapse. Bioinformatics analysis of this rich dataset identified numerous patterns of transcriptional regulation, with both region-specific and pan-circuit biological domains affected by heroin. Integration of RNA-seq data. This design enabled investigation of the transcriptomic landscape in multiple conditions that model distinct aspects of the OUD syndrome: first-ever heroin exposure (SH), ongoing/early withdrawal from heroin intake (H24), context-induced heroin-seeking following protracted abstinence (HS), and a combination of drug-induced and context-induced heroin-seeking representative of a relapse-like episode (HH). with OUD-relevant behavioral outcomes uncovered region-specific molecular changes and biological processes that predispose to OUD vulnerability.
Authors:
Caleb J Browne, Rita Futamura, Angélica Minier-Toribio, Emily M Hicks, Aarthi Ramakrishnan, Freddyson J Martínez-Rivera, Molly Estill, Arthur Godino, Eric M Parise, Angélica Torres-Berrío, Ashley M Cunningham, Peter J Hamilton, Deena M Walker, Laura M Huckins, Yasmin L Hurd, Li Shen, Eric J Nestler
Authors develop a brain reward circuit-wide atlas of opioid-induced transcriptional regulation by combining RNA sequencing (RNA-seq) and heroin self-administration in male mice modeling multiple OUD-relevant conditions: acute heroin exposure, chronic heroin intake, context-induced drug-seeking following abstinence, and relapse. Bioinformatics analysis of this rich dataset identified numerous patterns of transcriptional regulation, with both region-specific and pan-circuit biological domains affected by heroin. Integration of RNA-seq data. This design enabled investigation of the transcriptomic landscape in multiple conditions that model distinct aspects of the OUD syndrome: first-ever heroin exposure (SH), ongoing/early withdrawal from heroin intake (H24), context-induced heroin-seeking following protracted abstinence (HS), and a combination of drug-induced and context-induced heroin-seeking representative of a relapse-like episode (HH). with OUD-relevant behavioral outcomes uncovered region-specific molecular changes and biological processes that predispose to OUD vulnerability.
Authors:
Caleb J Browne, Rita Futamura, Angélica Minier-Toribio, Emily M Hicks, Aarthi Ramakrishnan, Freddyson J Martínez-Rivera, Molly Estill, Arthur Godino, Eric M Parise, Angélica Torres-Berrío, Ashley M Cunningham, Peter J Hamilton, Deena M Walker, Laura M Huckins, Yasmin L Hurd, Li Shen, Eric J Nestler
Differential gene expression in nucleus accumbens somatostatin interneurons_cocaine_mice_pvalue
Description:
To characterize transcriptional alterations that cocaine induces in these cells, we perform cell type-specific RNA-sequencing on FACS-isolated nuclei of somatostatin interneurons and identified 1100 DETs enriched for processes related to neural plasticity. To profile the entire (non poly-A selected) transcriptome of NAc somatostatin interneurons, we generated a transgenic reporter line (SST-TLG498 mice) to label the nuclei of these cells with a modified form of EGFP that is retained in the nuclear membrane (EGFP-F)22, enabling their isolation from NAc dissections using FACS. We succeeded in FACS-isolating nuclei suitable for RNA-sequencing from individual SST-TLG498 mice. We proceeded with differential expression analysis of the RNA-sequencing data to identify differentially expressed transcripts (DETs) in NAc somatostatin interneurons in response to repeated cocaine exposure: 778 transcripts were upregulated by cocaine and 322 were downregulated.
Authors:
Efrain A Ribeiro, Marine Salery, Joseph R Scarpa, Erin S Calipari, Peter J Hamilton, Stacy M Ku, Hope Kronman, Immanuel Purushothaman, Barbara Juarez, Mitra Heshmati, Marie Doyle, Casey Lardner, Dominicka Burek, Ana Strat, Stephen Pirpinias, Ezekiell Mouzon, Ming-Hu Han, Rachael L Neve, Rosemary C Bagot, Andrew Kasarskis, Ja Wook Koo, Eric J Nestler
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