PMID- 22700469
OWN - NLM
STAT- MEDLINE
DCOM- 20121022
LR  - 20211203
IS  - 1549-5485 (Electronic)
IS  - 1072-0502 (Linking)
VI  - 19
IP  - 7
DP  - 2012 Jun 14
TI  - Molecular and behavioral changes associated with adult hippocampus-specific 
      SynGAP1 knockout.
PG  - 268-81
LID - 10.1101/lm.026351.112 [doi]
AB  - The synaptic Ras/Rap-GTPase-activating protein (SynGAP1) plays a unique role in 
      regulating specific downstream intracellular events in response to 
      N-methyl-D-aspartate receptor (NMDAR) activation. Constitutive heterozygous loss 
      of SynGAP1 disrupts NMDAR-mediated physiological and behavioral processes, but 
      the disruptions might be of developmental origin. Therefore, the precise role of 
      SynGAP1 in the adult brain, including its relative functional significance within 
      specific brain regions, remains unexplored. The present study constitutes the 
      first attempt in achieving adult hippocampal-specific SynGAP1 knockout using the 
      Cre/loxP approach. Here, we report that this manipulation led to a significant 
      numerical increase in both small and large GluA1 and NR1 immunoreactive clusters, 
      many of which were non-opposed to presynaptic terminals. In parallel, the 
      observed marked decline in the amplitude of spontaneous excitatory currents 
      (sEPSCs) and inter-event intervals supported the impression that SynGAP1 loss 
      might facilitate the accumulation of extrasynaptic glutamatergic receptors. In 
      addition, SynGAP1-mediated signaling appears to be critical for the proper 
      integration and survival of newborn neurons. The manipulation impaired reversal 
      learning in the probe test of the water maze and induced a delay-dependent 
      impairment in spatial recognition memory. It did not significantly affect anxiety 
      or reference memory acquisition but induced a substantial elevation in 
      spontaneous locomotor activity in the open field test. Thus, the present study 
      demonstrates the functional significance of SynGAP1 signaling in the adult brain 
      by capturing several changes that are dependent on NMDAR and hippocampal 
      integrity.
FAU - Muhia, Mary
AU  - Muhia M
AD  - Laboratory of Behavioral Neurobiology, Swiss Federal Institute of Technology, 
      CH-8063 Schwerzenbach, Switzerland.
FAU - Willadt, Silvia
AU  - Willadt S
FAU - Yee, Benjamin K
AU  - Yee BK
FAU - Feldon, Joram
AU  - Feldon J
FAU - Paterna, Jean-Charles
AU  - Paterna JC
FAU - Schwendener, Severin
AU  - Schwendener S
FAU - Vogt, Kaspar
AU  - Vogt K
FAU - Kennedy, Mary B
AU  - Kennedy MB
FAU - Knuesel, Irene
AU  - Knuesel I
LA  - eng
GR  - R01 NS028710/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120614
PL  - United States
TA  - Learn Mem
JT  - Learning & memory (Cold Spring Harbor, N.Y.)
JID - 9435678
RN  - 0 (Doublecortin Domain Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (NR1 NMDA receptor)
RN  - 0 (Neuropeptides)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Syngap1 protein, mouse)
RN  - 0 (enhanced green fluorescent protein)
RN  - 0 (ras GTPase-Activating Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.7.- (Cre recombinase)
RN  - EC 2.7.7.- (Integrases)
RN  - TFZ3H25BS1 (glutamate receptor ionotropic, AMPA 1)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Avoidance Learning/physiology
MH  - Doublecortin Domain Proteins
MH  - Gene Expression Regulation/genetics
MH  - Genetic Vectors/genetics
MH  - Green Fluorescent Proteins/genetics
MH  - Hippocampus/*cytology/metabolism
MH  - Integrases/genetics/metabolism
MH  - Learning Disabilities/*genetics
MH  - Maze Learning/physiology
MH  - Membrane Potentials/genetics
MH  - Memory Disorders/genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Microtubule-Associated Proteins/metabolism
MH  - Motor Activity/genetics
MH  - Neurons/cytology/drug effects/*physiology
MH  - Neuropeptides/metabolism
MH  - Patch-Clamp Techniques
MH  - Reaction Time/genetics
MH  - Receptors, AMPA/genetics/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/genetics/metabolism
MH  - Spatial Behavior/physiology
MH  - Synaptic Transmission/drug effects/*genetics
MH  - Transduction, Genetic
MH  - ras GTPase-Activating Proteins/*deficiency/metabolism
EDAT- 2012/06/16 06:00
MHDA- 2012/10/23 06:00
CRDT- 2012/06/16 06:00
PHST- 2012/06/16 06:00 [entrez]
PHST- 2012/06/16 06:00 [pubmed]
PHST- 2012/10/23 06:00 [medline]
AID - 19/7/268 [pii]
AID - 10.1101/lm.026351.112 [doi]
PST - epublish
SO  - Learn Mem. 2012 Jun 14;19(7):268-81. doi: 10.1101/lm.026351.112.