PMID- 8939850
OWN - NLM
STAT- MEDLINE
DCOM- 19970103
LR  - 20220510
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 274
IP  - 5293
DP  - 1996 Dec 6
TI  - Control of memory formation through regulated expression of a CaMKII transgene.
PG  - 1678-83
AB  - One of the major limitations in the use of genetically modified mice for studying 
      cognitive functions is the lack of regional and temporal control of gene 
      function. To overcome these limitations, a forebrain-specific promoter was 
      combined with the tetracycline transactivator system to achieve both regional and 
      temporal control of transgene expression. Expression of an activated 
      calcium-independent form of calcium-calmodulin-dependent kinase II (CaMKII) 
      resulted in a loss of hippocampal long-term potentiation in response to 10-hertz 
      stimulation and a deficit in spatial memory, a form of explicit memory. 
      Suppression of transgene expression reversed both the physiological and the 
      memory deficit. When the transgene was expressed at high levels in the lateral 
      amygdala and the striatum but not other forebrain structures, there was a deficit 
      in fear conditioning, an implicit memory task, that also was reversible. Thus, 
      the CaMKII signaling pathway is critical for both explicit and implicit memory 
      storage, in a manner that is independent of its potential role in development.
FAU - Mayford, M
AU  - Mayford M
AD  - Center for Neurobiology and Behavior, College of Physicians and Surgeons of 
      Columbia University, and Howard Hughes Medical Institute, 722 West 168 Street, 
      New York, NY 10032, USA.
FAU - Bach, M E
AU  - Bach ME
FAU - Huang, Y Y
AU  - Huang YY
FAU - Wang, L
AU  - Wang L
FAU - Hawkins, R D
AU  - Hawkins RD
FAU - Kandel, E R
AU  - Kandel ER
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - N12000U13O (Doxycycline)
SB  - IM
MH  - Amygdala/physiology
MH  - Animals
MH  - Brain/*physiology
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2
MH  - Calcium-Calmodulin-Dependent Protein Kinases/genetics/*metabolism
MH  - Conditioning, Psychological
MH  - Corpus Striatum/physiology
MH  - Doxycycline/pharmacology
MH  - Fear
MH  - *Gene Expression Regulation, Enzymologic
MH  - Genes, Reporter
MH  - Hippocampus/physiology
MH  - Long-Term Potentiation
MH  - Maze Learning
MH  - Memory/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neuronal Plasticity
MH  - Promoter Regions, Genetic
MH  - Prosencephalon/physiology
MH  - Signal Transduction
MH  - Transgenes
EDAT- 1996/12/06 00:00
MHDA- 2000/03/23 09:00
CRDT- 1996/12/06 00:00
PHST- 1996/12/06 00:00 [pubmed]
PHST- 2000/03/23 09:00 [medline]
PHST- 1996/12/06 00:00 [entrez]
AID - 10.1126/science.274.5293.1678 [doi]
PST - ppublish
SO  - Science. 1996 Dec 6;274(5293):1678-83. doi: 10.1126/science.274.5293.1678.