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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.(More)
To explore the role of protein kinase A (PKA) in the late phase of long-term potentiation (L-LTP) and memory, we generated transgenic mice that express R(AB), an inhibitory form of the regulatory subunit of PKA, only in the hippocampus and other forebrain regions by using the promoter from the gene encoding Ca2+/ calmodulin protein kinase IIalpha. In these(More)
Brain-derived neurotrophic factor (BDNF) is expressed at high levels in hippocampal neurons, and its expression is modulated by neural activity. Knockout mice can be used to study the roles of molecules like BDNF in synaptic plasticity with more molecular specificity than is possible using pharmacological approaches. Because in conventional knockouts the(More)
Hippocampal long-term potentiation (LTP) is thought to serve as an elementary mechanism for the establishment of certain forms of explicit memory in the mammalian brain. As is the case with behavioral memory, LTP in the CA1 region has stages: a short-term early potentiation lasting 1 to 3 hours, which is independent of protein synthesis, precedes a later,(More)
Effective mental functioning requires that cognition be protected from emotional conflict due to interference by task-irrelevant emotionally salient stimuli. The neural mechanisms by which the brain detects and resolves emotional conflict are still largely unknown, however. Drawing on the classic Stroop conflict task, we developed a protocol that allowed us(More)
may lead to severe developmental defects or premature death (for a review, see Joyner, 1994), which can pre-of the experimental results often runs into two types of *Howard Hughes Medical Institute difficulties. First, global gene knockout makes it difficult Center for Learning and Memory to attribute abnormal phenotypes to a particular type of Center for(More)
We studied a mouse model of the haploinsufficiency form of Rubinstein-Taybi syndrome (RTS), an inheritable disorder caused by mutations in the gene encoding the CREB binding protein (CBP) and characterized by mental retardation and skeletal abnormalities. In these mice, chromatin acetylation, some forms of long-term memory, and the late phase of hippocampal(More)
Although hippocampal neurogenesis has been described in many adult mammals, the functional impact of this process on physiology and behavior remains unclear. In the present study, we used two independent methods to ablate hippocampal neurogenesis and found that each procedure caused a limited behavioral deficit and a loss of synaptic plasticity within the(More)
Both long-term and short-term sensitization of the gill and siphon withdrawal reflex in Aplysia involve facilitation of the monosynaptic connections between the sensory and motor neurons. To analyze the relationship between these two forms of synaptic facilitation at the cellular and molecular level, this monosynaptic sensorimotor component of the(More)