PMID- 32240784
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20210514
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 435
DP  - 2020 May 21
TI  - Inherent Motor Impulsivity Associates with Specific Gene Targets in the Rat 
      Medial Prefrontal Cortex.
PG  - 161-173
LID - S0306-4522(20)30204-9 [pii]
LID - 10.1016/j.neuroscience.2020.03.045 [doi]
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.
CI  - Copyright (c) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Sholler, Dennis J
AU  - Sholler DJ
AD  - Center for Addiction Research, University of Texas Medical Branch, 301 University 
      Boulevard, Galveston, TX 77555, USA; Department of Pharmacology and Toxicology, 
      University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 
      77555, USA.
FAU - Merritt, Christina R
AU  - Merritt CR
AD  - Center for Addiction Research, University of Texas Medical Branch, 301 University 
      Boulevard, Galveston, TX 77555, USA; Department of Pharmacology and Toxicology, 
      University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 
      77555, USA.
FAU - Davis-Reyes, Brionna D
AU  - Davis-Reyes BD
AD  - Center for Addiction Research, University of Texas Medical Branch, 301 University 
      Boulevard, Galveston, TX 77555, USA.
FAU - Golovko, George
AU  - Golovko G
AD  - Department of Pharmacology and Toxicology, University of Texas Medical Branch, 
      301 University Boulevard, Galveston, TX 77555, USA.
FAU - Anastasio, Noelle C
AU  - Anastasio NC
AD  - Center for Addiction Research, University of Texas Medical Branch, 301 University 
      Boulevard, Galveston, TX 77555, USA; Department of Pharmacology and Toxicology, 
      University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 
      77555, USA.
FAU - Cunningham, Kathryn A
AU  - Cunningham KA
AD  - Center for Addiction Research, University of Texas Medical Branch, 301 University 
      Boulevard, Galveston, TX 77555, USA; Department of Pharmacology and Toxicology, 
      University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 
      77555, USA. Electronic address: kcunning@utmb.edu.
LA  - eng
GR  - T32 DA007287/DA/NIDA NIH HHS/United States
GR  - P50 DA033935/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200330
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
SB  - IM
MH  - Animals
MH  - *Choice Behavior
MH  - Executive Function
MH  - *Impulsive Behavior
MH  - Male
MH  - Prefrontal Cortex
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - RNA-sequencing
OT  - choice serial reaction time
OT  - medial prefrontal cortex
OT  - motor impulsivity
OT  - transcriptomics
EDAT- 2020/04/03 06:00
MHDA- 2021/05/15 06:00
CRDT- 2020/04/03 06:00
PHST- 2020/01/23 00:00 [received]
PHST- 2020/03/22 00:00 [revised]
PHST- 2020/03/26 00:00 [accepted]
PHST- 2020/04/03 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/04/03 06:00 [entrez]
AID - S0306-4522(20)30204-9 [pii]
AID - 10.1016/j.neuroscience.2020.03.045 [doi]
PST - ppublish
SO  - Neuroscience. 2020 May 21;435:161-173. doi: 10.1016/j.neuroscience.2020.03.045. 
      Epub 2020 Mar 30.