TY - JOUR
T1 - Inherent Motor Impulsivity Associates with Specific Gene Targets in the Rat Medial Prefrontal Cortex
AU - Sholler, Dennis J.
AU - Merritt, Christina R.
AU - Davis-Reyes, Brionna D.
AU - Golovko, George
AU - Anastasio, Noelle C.
AU - Cunningham, Kathryn A.
N1 - Funding Information:
We thank Victoria D. Brehm, Susan J. Stafford, Sonja J. Stutz, Robert G. Fox, Andrea L. Dimet, Konrad Pazdrak, Erica D. Holliday, and Kelly T. Dineley for their technical assistance and helpful discussions during the present study. This work was supported by NIDA grants T32 DA007287 (DJS, BDDR) P50 DA033935 (KAC, NCA), and the Center for Addiction Research at the University of Texas Medical Branch. The RNA-sequencing data associated with this study are available on Gene Expression Omnibus (GEO) using the accession number GSE141073; a complete quality control report is available upon request to the corresponding author. The authors have no conflicts of interest to declare. DJS, CRM, and BDDR conducted experiments. DJS, CRM, BDDR, and GG performed data analysis. DJS drafted the manuscript. KAC and NCA conceptualized the projected, supervised the experimental design/interpretation/analyses, and wrote/edited the manuscript.
Funding Information:
We thank Victoria D. Brehm, Susan J. Stafford, Sonja J. Stutz, Robert G. Fox, Andrea L. Dimet, Konrad Pazdrak, Erica D. Holliday, and Kelly T. Dineley for their technical assistance and helpful discussions during the present study. This work was supported by NIDA grants T32 DA007287 (DJS, BDDR) P50 DA033935 (KAC, NCA), and the Center for Addiction Research at the University of Texas Medical Branch . The RNA-sequencing data associated with this study are available on Gene Expression Omnibus (GEO) using the accession number GSE141073; a complete quality control report is available upon request to the corresponding author.
Publisher Copyright:
© 2020 IBRO
PY - 2020/5/21
Y1 - 2020/5/21
N2 - High impulsivity characterizes a myriad of neuropsychiatric diseases, and identifying targets for neuropharmacological intervention to reduce impulsivity could reveal transdiagnostic treatment strategies. Motor impulsivity (impulsive action) reflects in part the failure of “top-down” executive control by the medial prefrontal cortex (mPFC). The present study profiled the complete set of mRNA molecules expressed from genes (transcriptome) in the mPFC of male, outbred rats stably expressing high (HI) or low (LI) motor impulsivity based upon premature responses in the 1-choice serial reaction time (1-CSRT) task. RNA-sequencing identified expression of 18 genes that was higher in the mPFC of HI vs. LI rats. Functional gene enrichment revealed that biological processes related to calcium homeostasis and G protein-coupled receptor (GPCR) signaling pathways, particularly glutamatergic, were overrepresented in the mPFC of HI vs. LI rats. Transcription factor enrichment identified mothers against decapentaplegic homolog 4 (SMAD4) and RE1 silencing transcription factor (REST) as overrepresented in the mPFC of HI rats relative to LI rats, while in silico analysis predicted a conserved SMAD binding site within the voltage-gated calcium channel subunit alpha1 E (CACNA1E) promoter region. qRT-PCR analyses confirmed that mRNA expression of CACNA1E, as well as expression of leucyl and cystinyl aminopeptidase (LNPEP), were higher in the mPFC of HI vs. LI rats. These outcomes establish a transcriptomic landscape in the mPFC that is related to individual differences in motor impulsivity and propose novel gene targets for future impulsivity research.
AB - High impulsivity characterizes a myriad of neuropsychiatric diseases, and identifying targets for neuropharmacological intervention to reduce impulsivity could reveal transdiagnostic treatment strategies. Motor impulsivity (impulsive action) reflects in part the failure of “top-down” executive control by the medial prefrontal cortex (mPFC). The present study profiled the complete set of mRNA molecules expressed from genes (transcriptome) in the mPFC of male, outbred rats stably expressing high (HI) or low (LI) motor impulsivity based upon premature responses in the 1-choice serial reaction time (1-CSRT) task. RNA-sequencing identified expression of 18 genes that was higher in the mPFC of HI vs. LI rats. Functional gene enrichment revealed that biological processes related to calcium homeostasis and G protein-coupled receptor (GPCR) signaling pathways, particularly glutamatergic, were overrepresented in the mPFC of HI vs. LI rats. Transcription factor enrichment identified mothers against decapentaplegic homolog 4 (SMAD4) and RE1 silencing transcription factor (REST) as overrepresented in the mPFC of HI rats relative to LI rats, while in silico analysis predicted a conserved SMAD binding site within the voltage-gated calcium channel subunit alpha1 E (CACNA1E) promoter region. qRT-PCR analyses confirmed that mRNA expression of CACNA1E, as well as expression of leucyl and cystinyl aminopeptidase (LNPEP), were higher in the mPFC of HI vs. LI rats. These outcomes establish a transcriptomic landscape in the mPFC that is related to individual differences in motor impulsivity and propose novel gene targets for future impulsivity research.
KW - RNA-sequencing
KW - choice serial reaction time
KW - medial prefrontal cortex
KW - motor impulsivity
KW - transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85083357522&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083357522&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2020.03.045
DO - 10.1016/j.neuroscience.2020.03.045
M3 - Article
C2 - 32240784
AN - SCOPUS:85083357522
SN - 0306-4522
VL - 435
SP - 161
EP - 173
JO - Neuroscience
JF - Neuroscience
ER -