PMID- 30618752
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 9
DP  - 2018
TI  - Ethanol Modulates Glutamatergic Transmission and NMDAR-Mediated Synaptic 
      Plasticity in the Agranular Insular Cortex.
PG  - 1458
LID - 10.3389/fphar.2018.01458 [doi]
LID - 1458
AB  - The agranular insular cortex (AIC) has recently been investigated by the alcohol 
      field because of its connectivity to and modulatory control over limbic and 
      brainstem regions implicated in alcohol use disorder (AUD), and because it has 
      shown involvement in animal models of alcohol drinking. Despite evidence of AIC 
      involvement in AUD, there has not yet been an examination of whether ethanol 
      modulates glutamatergic and gamma-amino-butyric acid (GABA)ergic synaptic 
      transmission and plasticity in the AIC. Characterizing how the synaptic 
      transmission and plasticity states of AIC cortical processing neurons are 
      modulated by acute ethanol will likely reveal the molecular targets by which 
      chronic ethanol alters AIC function as alcohol drinking transitions from 
      controlled to problematic. Therefore, we collected brain slices from 
      ethanol-naive adult male mice, obtained whole-cell recording configuration in 
      layer 2/3 AIC pyramidal neurons, and bath-applied ethanol at pharmacologically 
      relevant concentrations during electrophysiological assays of glutamatergic and 
      GABAergic synaptic transmission and plasticity. We found that ethanol inhibited 
      electrically evoked N-methyl-D-aspartate receptor (NMDAR)-mediated excitatory 
      post-synaptic currents (EPSCs) in a concentration-related fashion, and had little 
      effect on evoked alpha-amino-3-hydrox-5-methylisoxazole-4-propionic acid-type 
      receptor (AMPAR)-mediated EPSCs. Ethanol had no effect on spontaneous excitatory 
      post-synaptic currents (sEPSCs) or inhibitory GABA(A)R-mediated post-synaptic 
      currents (sIPSCs). We found that synaptic conditioning (low-frequency stimulation 
      for 15 min at 1 Hz) induced a form of long-term depression (LTD) of evoked 
      AMPAR-mediated EPSCs. The ability to induce LTD was inhibited by a non-selective 
      NMDAR antagonist (DL-2-amino-5-phosphonovaleric acid), and also by acute, 
      intoxicating concentrations of ethanol. Taken together these data suggest that 
      the glutamate, but not GABA system in the AIC is uniquely sensitive to ethanol, 
      and that in particular NMDAR-mediated processes in the AIC may be disrupted by 
      pharmacologically relevant concentrations of ethanol.
FAU - Shillinglaw, Joel E
AU  - Shillinglaw JE
AD  - Division of Pharmacology and Toxicology, College of Pharmacy, The University of 
      Texas at Austin, Austin, TX, United States.
FAU - Morrisett, Richard A
AU  - Morrisett RA
AD  - Division of Pharmacology and Toxicology, College of Pharmacy, The University of 
      Texas at Austin, Austin, TX, United States.
FAU - Mangieri, Regina A
AU  - Mangieri RA
AD  - Division of Pharmacology and Toxicology, College of Pharmacy, The University of 
      Texas at Austin, Austin, TX, United States.
LA  - eng
GR  - R01 AA015167/AA/NIAAA NIH HHS/United States
GR  - U24 AA016651/AA/NIAAA NIH HHS/United States
PT  - Journal Article
DEP - 20181218
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6305468
OTO - NOTNLM
OT  - electrophysiology
OT  - ethanol
OT  - glutamate
OT  - insular cortex
OT  - mouse
OT  - synaptic plasticity
EDAT- 2019/01/09 06:00
MHDA- 2019/01/09 06:01
PMCR- 2018/12/18
CRDT- 2019/01/09 06:00
PHST- 2018/09/05 00:00 [received]
PHST- 2018/11/29 00:00 [accepted]
PHST- 2019/01/09 06:00 [entrez]
PHST- 2019/01/09 06:00 [pubmed]
PHST- 2019/01/09 06:01 [medline]
PHST- 2018/12/18 00:00 [pmc-release]
AID - 10.3389/fphar.2018.01458 [doi]
PST - epublish
SO  - Front Pharmacol. 2018 Dec 18;9:1458. doi: 10.3389/fphar.2018.01458. eCollection 
      2018.