The proximal objective of the project is to examine what role, if any, protein synthesis and CREB-mediated transcription play in the long-term stabilization of spatial representations in the hippocampus. These place representations are believed to be used by animals to solve spatial learning problems. Likewise, the long-term (but not short-term) stability of memory depends on protein synthesis and CREB-mediated transcription. First, the effect of cerebral protein synthesis inhibition on the stability of hippocampal place representations will be examined in mice according to a conventional technique. Second, two novel techniques for inducing CREB disruption have been developed and are both expected to produce deficits in long-term, but not short-term stability of the hippocampal spatial map.
The specific aims of the proposal are to examine the effects on hippocampal place cell firing field stability of [1] protein synthesis inhibiton in wildtype mice, [2] inhibition of the cAMP/PKA pathway, via dopamine D1/D5 receptor blockade, in heterozygous CREBalphadelta+/- mice, and [3] the induction of a CREB repressor in transgenic mice. The ultimate objective is to test the hypothesis that spatial representations maintained by place cells mediate long-term spatial memory. This research will improve our understanding of the cellular mechanisms of hippocampus-dependent memory.
| Anagnostaras, Stephan G; Murphy, Geoffrey G; Hamilton, Susan E et al. (2003) Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice. Nat Neurosci 6:51-8 |
| Anagnostaras, Stephan G; Gale, Greg D; Fanselow, Michael S (2002) The hippocampus and Pavlovian fear conditioning: reply to Bast et al. Hippocampus 12:561-5 |
| Anagnostaras, S G; Josselyn, S A; Frankland, P W et al. (2000) Computer-assisted behavioral assessment of Pavlovian fear conditioning in mice. Learn Mem 7:58-72 |
