PMID- 26774487
OWN - NLM
STAT- MEDLINE
DCOM- 20161020
LR  - 20220316
IS  - 2211-1247 (Electronic)
VI  - 14
IP  - 3
DP  - 2016 Jan 26
TI  - An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development.
PG  - 471-478
LID - S2211-1247(15)01502-8 [pii]
LID - 10.1016/j.celrep.2015.12.061 [doi]
AB  - In the mammalian brain, GABAergic synaptic transmission provides inhibitory 
      balance to glutamatergic excitatory drive and controls neuronal output. The 
      molecular mechanisms underlying the development of GABAergic synapses remain 
      largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors 
      (NMDARs) in individual immature neurons are the upstream signaling 
      molecules essential for GABAergic synapse development, which requires signaling 
      via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. 
      Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission 
      is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA 
      receptors is increased, suggesting a compensatory mechanism for the lack of 
      synaptic inhibition. These results demonstrate a crucial role for NMDARs in 
      specifying the development of inhibitory synapses, and suggest an important 
      mechanism for controlling the establishment of the balance between synaptic 
      excitation and inhibition in the developing brain.
CI  - Copyright (c) 2016 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Gu, Xinglong
AU  - Gu X
AD  - Synapse and Neural Circuit Research Unit, National Institute of Neurological 
      Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 3C1000, 
      Bethesda, MD 20892, USA.
FAU - Zhou, Liang
AU  - Zhou L
AD  - Synapse and Neural Circuit Research Unit, National Institute of Neurological 
      Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 3C1000, 
      Bethesda, MD 20892, USA.
FAU - Lu, Wei
AU  - Lu W
AD  - Synapse and Neural Circuit Research Unit, National Institute of Neurological 
      Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 3C1000, 
      Bethesda, MD 20892, USA. Electronic address: luw4@mail.nih.gov.
LA  - eng
GR  - Z99 NS999999/Intramural NIH HHS/United States
GR  - ZIA NS003136-01/Intramural NIH HHS/United States
GR  - ZIA NS003136-02/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20160107
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Receptors, GABA-A)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Brain/growth & development/metabolism/pathology
MH  - Calcium/chemistry/metabolism
MH  - Cells, Cultured
MH  - Embryo, Mammalian/cytology/metabolism
MH  - Genes, Reporter
MH  - HEK293 Cells
MH  - Hippocampus/cytology/metabolism/pathology
MH  - Humans
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Transgenic
MH  - Microscopy, Fluorescence
MH  - Patch-Clamp Techniques
MH  - Receptors, GABA-A/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/chemistry/*metabolism
MH  - Synapses/*metabolism
MH  - Synaptic Transmission
PMC - PMC4765167
MID - NIHMS756089
EDAT- 2016/01/18 06:00
MHDA- 2016/10/21 06:00
PMCR- 2016/02/24
CRDT- 2016/01/18 06:00
PHST- 2015/05/15 00:00 [received]
PHST- 2015/11/09 00:00 [revised]
PHST- 2015/12/10 00:00 [accepted]
PHST- 2016/01/18 06:00 [entrez]
PHST- 2016/01/18 06:00 [pubmed]
PHST- 2016/10/21 06:00 [medline]
PHST- 2016/02/24 00:00 [pmc-release]
AID - S2211-1247(15)01502-8 [pii]
AID - 10.1016/j.celrep.2015.12.061 [doi]
PST - ppublish
SO  - Cell Rep. 2016 Jan 26;14(3):471-478. doi: 10.1016/j.celrep.2015.12.061. Epub 2016 
      Jan 7.