Striatum Gene Expression Correlates for AMDIST165 measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The AMDIST165 measures Morphine distance (cm) travelled minutes 150-165 under the domain Morphine. 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
Striatum Gene Expression Correlates for MORPH_NX measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The MORPH_NX measures Change in distance travelled last 15 min morphine-15 min naloxone under the domain Morphine. 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
Striatum Gene Expression Correlates for HAND_6HOURS measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The HAND_6HOURS measures Handling induced convulsions 6 hrs after ethanol under the domain Ethanol HIC. 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 morphine antinociception on Chr10 at D10Mit51 (19.52 Mbp , Build 37)
Description:
morphine antinociception spans 0.00 - 44.52 Mbp (NCBI Build 37) on Chr10. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Bergeson SE, Helms ML, O\'Toole LA, Jarvis MW, Hain HS, Mogil JS, Belknap JK
QTL for morphine preference on Chr10 at D10MIT282 (24.33 Mbp , Build 37)
Description:
morphine preference spans 0.00 - 49.33 Mbp (NCBI Build 37) on Chr10. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Berrettini WH, Ferraro TN, Alexander RC, Buchberg AM, Vogel WH
Transcriptomic analysis of gene expression in the nucleus accumbens somatostatin interneurons of male 8�12-week-old Sst-Cre mice or Sst-Cre x TLG498 (SST-TLG498) mice following repeated cocaine intake. Expression was measured via RNA-seq. Values presented are p-values. Data taken from Supplementary Data 1. Data can be accessed at GEO with accession number: GSE116484.A7
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
The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains.
Authors:
Samuel J Harp, Mariangela Martini, Will Rosenow, Larry D Mesner, Hugh Johnson, Charles R Farber, Emilie F Rissman
The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains.
Authors:
Samuel J Harp, Mariangela Martini, Will Rosenow, Larry D Mesner, Hugh Johnson, Charles R Farber, Emilie F Rissman
The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains.
Authors:
Samuel J Harp, Mariangela Martini, Will Rosenow, Larry D Mesner, Hugh Johnson, Charles R Farber, Emilie F Rissman
Analysis using RNA-seq of FACS-purified oligodendrocytes revealed a large cohort of morphine-regulated genes. In addition, to investigate cell-type-specific opioid responses, we performed single-cell RNA sequencing (scRNA-seq) of the nucleus accumbens of mice following acute morphine treatment. Differential expression analysis uncovered unique morphine-dependent transcriptional responses by oligodendrocytes and astrocytes.
Authors:
Denis Avey, Sumithra Sankararaman, Aldrin K Y Yim, Ruteja Barve, Jeffrey Milbrandt, Robi D Mitra
Differential gene expression in nucleus accumbens somatostatin interneurons_cocaine_mice_logFC
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
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
Small intestine transcriptome changes in morphine treated mice. Eight-week-old, pathogen free, C57BL/6 male mice were used for this study (morphine n = 5, control n = 5). The animals were anesthetized using isoflurane (Pivetal®) and a 25mg slow-release morphine pellet or placebo pellet was implanted subcutaneously. Treatment lasted 16 hours. mRNA was purified from total RNA from using poly T-magnetic beads and strand specific library was constructed by using NEBNext Ultra RNA library prep kit. After quality control, the libraries were sequenced paired end by using Illumina sequencers (Illumina HiSeq 4000) for a read length of 150 base pairs. Clean reads were mapped to the mouse transcriptome using “STAR” software. The subsequent differential gene expression analysis was performed using DESeq2 R package (log2 (Fold change) > 1, P adj<0.05).
DEG male mouse forebrain PND14 morphine vs saline_pvalue
Description:
To examine forebrain transcriptomic changes that might elucidate mechanisms of withdrawal, delayed development, and any long-term behavior changes, we generated transcriptomic signatures following our “3-trimester” exposure model (3-Tri). In addition, we also examined transcriptomes from animals that received opioids only during the gestational period (PND1) or only during the last trimester from PND 1–14 (PND 14). We sought to determine whether transcriptomic signatures vary based on the window of exposure, perhaps contributing to the discrepancies in the literature regarding acute and long-term outcomes. Brains were dissected from PND 1 pups 6 h after discovery. Brains were dissected from post-natal exposure only (PND 14) or 3-trimester exposure (3-tri) 6 h after the last morphine or saline injection. The number of animals per group was similar (N = 5–7 animals, male and female C57Bl/6NTac mice), and the quality controls, library construction and sequence parameters were also identical across all groups. Libraries were sequenced on a NovaSeq 6000 at a depth of 30 million total reads/sample using paired-end sequencing of 150 base pairs (PE150), to a depth of 30 million total reads/sample. Reads were then mapped to the mouse reference genome (Mus Musculus, GRCm38/mm10) using HISAT2 (version 2.2.1), and duplicated fragments were removed using Picard MarkDuplicates. Differential expression analysis between two conditions (e.g., Morphine and Saline) was performed in R (version 4.1.1) with DESeq2 (v1.32.0) package. Genes were assigned by the authors as differentially expressed if the (adjusted) (nominal) p-value < 0.05. All genes/scores are presented here.
Authors:
Amelia D Dunn, Shivon A Robinson, Chiso Nwokafor, Molly Estill, Julia Ferrante, Li Shen, Crystal O Lemchi, Jordi Creus-Muncunill, Angie Ramirez, Juliet Mengaziol, Julia K Brynildsen, Mark Leggas, Jamie Horn, Michelle E Ehrlich, Julie A Blendy
DEG male mouse forebrain PND1 morphine vs saline_pvalue
Description:
To examine forebrain transcriptomic changes that might elucidate mechanisms of withdrawal, delayed development, and any long-term behavior changes, we generated transcriptomic signatures following our “3-trimester” exposure model (3-Tri). In addition, we also examined transcriptomes from animals that received opioids only during the gestational period (PND1) or only during the last trimester from PND 1–14 (PND 14). We sought to determine whether transcriptomic signatures vary based on the window of exposure, perhaps contributing to the discrepancies in the literature regarding acute and long-term outcomes. Brains were dissected from PND 1 pups 6 h after discovery. Brains were dissected from post-natal exposure only (PND 14) or 3-trimester exposure (3-tri) 6 h after the last morphine or saline injection. The number of animals per group was similar (N = 5–7 animals, male and female C57Bl/6NTac mice), and the quality controls, library construction and sequence parameters were also identical across all groups. Libraries were sequenced on a NovaSeq 6000 at a depth of 30 million total reads/sample using paired-end sequencing of 150 base pairs (PE150), to a depth of 30 million total reads/sample. Reads were then mapped to the mouse reference genome (Mus Musculus, GRCm38/mm10) using HISAT2 (version 2.2.1), and duplicated fragments were removed using Picard MarkDuplicates. Differential expression analysis between two conditions (e.g., Morphine and Saline) was performed in R (version 4.1.1) with DESeq2 (v1.32.0) package. Genes were assigned by the authors as differentially expressed if the (adjusted) (nominal) p-value < 0.05. All genes/scores are presented here.
Authors:
Amelia D Dunn, Shivon A Robinson, Chiso Nwokafor, Molly Estill, Julia Ferrante, Li Shen, Crystal O Lemchi, Jordi Creus-Muncunill, Angie Ramirez, Juliet Mengaziol, Julia K Brynildsen, Mark Leggas, Jamie Horn, Michelle E Ehrlich, Julie A Blendy
DEG mouse BLA 24hr withdrawal cocaine vs saline SA_pvalue
Description:
To determine how a history of cocaine self-administration (SA) influences circuit-wide transcriptomes, RNA-seq was performed on PFC, dorsal striatum (DStr), NAc, basolateral amygdala (BLA), ventral hippocampus (vHIP), and VTA, obtained from the following six groups of male C57BL/6J mice (Figure 1A): saline SA + 24 hr withdrawal (WD) (S24, n=5–8); cocaine SA + 24 hr WD (C24, n=5–8); saline SA + 30 d WD + saline re-exposure (SS, n=5–8); saline SA + 30 d WD + cocaine exposure (SC, n=5–8); cocaine SA + 30 d WD + saline exposure (CS, n=3–7); and cocaine SA + 30 d WD + cocaine re-exposure (CC, n=5–7). Genes presensted here are from the cocaine or saline SA + 24hr withdrawal paradigm for each brain region.
Authors:
Deena M Walker, Hannah M Cates, Yong-Hwee E Loh, Immanuel Purushothaman, Aarthi Ramakrishnan, Kelly M Cahill, Casey K Lardner, Arthur Godino, Hope G Kronman, Jacqui Rabkin, Zachary S Lorsch, Philipp Mews, Marie A Doyle, Jian Feng, Benoit Labonté, Ja Wook Koo, Rosemary C Bagot, Ryan W Logan, Marianne L Seney, Erin S Calipari, Li Shen, Eric J Nestler
To determine how a history of cocaine self-administration (SA) influences circuit-wide transcriptomes, RNA-seq was performed on PFC, dorsal striatum (DStr), NAc, basolateral amygdala (BLA), ventral hippocampus (vHIP), and VTA, obtained from the following six groups of male C57BL/6J mice (Figure 1A): saline SA + 24 hr withdrawal (WD) (S24, n=5–8); cocaine SA + 24 hr WD (C24, n=5–8); saline SA + 30 d WD + saline re-exposure (SS, n=5–8); saline SA + 30 d WD + cocaine exposure (SC, n=5–8); cocaine SA + 30 d WD + saline exposure (CS, n=3–7); and cocaine SA + 30 d WD + cocaine re-exposure (CC, n=5–7). Genes presensted here are from the cocaine SA + 30 day withdrawal followed by saline exposure (CS) paradigm versus saline SA + 30 day withdrawal followed by saline re-exposure (SS), for each brain region.
Authors:
Deena M Walker, Hannah M Cates, Yong-Hwee E Loh, Immanuel Purushothaman, Aarthi Ramakrishnan, Kelly M Cahill, Casey K Lardner, Arthur Godino, Hope G Kronman, Jacqui Rabkin, Zachary S Lorsch, Philipp Mews, Marie A Doyle, Jian Feng, Benoit Labonté, Ja Wook Koo, Rosemary C Bagot, Ryan W Logan, Marianne L Seney, Erin S Calipari, Li Shen, Eric J Nestler
Gene expression mouse PFC pattern B CS vs S24_pvalue
Description:
RNA-seq was performed on PFC, dorsal striatum (DStr), NAc, basolateral amygdala (BLA), ventral hippocampus (vHIP), and VTA, obtained from the following six groups of male C57BL/6J mice (Figure 1A): saline SA + 24 hr withdrawal (WD) (S24, n=5–8); cocaine SA + 24 hr WD (C24, n=5–8); saline SA + 30 d WD + saline re-exposure (SS, n=5–8); saline SA + 30 d WD + cocaine exposure (SC, n=5–8); cocaine SA + 30 d WD + saline exposure (CS, n=3–7); and cocaine SA + 30 d WD + cocaine re-exposure (CC, n=5–7). To focus on genes that were uniquely altered following context/drug re-exposure after WD, we compared all groups to the same baseline (S24). We focused on three patterns associated with drug use: first-ever exposure to cocaine (SC; Pattern A; Figure 2B), re-exposure to cocaine-paired context (CS, Pattern B, Figure 2C), and re-exposure to cocaine-paired context + cocaine (CC, Pattern C, Figure 2D). Each Pattern includes genes that were both differentially expressed from S24 (p<0.05; fold change>15%) and distinct from all other groups. The pattern B genes were significantly differentially expressed (see above) between the cocaine SA with saline exposure after 30 days and baseline (i.e. CS vs S4). Differential expression of the pattern B genes are presented for each group (C24 vs S24, SS vs S4, SC vs S4, CS vs S4, and CC vs S4).
Authors:
Deena M Walker, Hannah M Cates, Yong-Hwee E Loh, Immanuel Purushothaman, Aarthi Ramakrishnan, Kelly M Cahill, Casey K Lardner, Arthur Godino, Hope G Kronman, Jacqui Rabkin, Zachary S Lorsch, Philipp Mews, Marie A Doyle, Jian Feng, Benoit Labonté, Ja Wook Koo, Rosemary C Bagot, Ryan W Logan, Marianne L Seney, Erin S Calipari, Li Shen, Eric J Nestler
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