Novelty exposure overcomes foot shock-induced spatial-memory impairment by processes of synaptic-tagging in rats

Novelty processing can transform short-term into long-termmemory. We propose that this memory-reinforcing effect of novelty could be explained by mechanisms outlined in the "synaptic tagging hypothesis."Initial short-term memory is sustained by a transient plasticity change at activated synapses and sets synaptic tags. These tags are later able to capture and process the plasticity-related proteins (PRPs), which are required to transform a short-term synaptic change into a long-termone. Novelty is involved in inducing the synthesis of PRPs [Moncada D, et al. (2011) Proc Natl Acad Sci USA 108:12937-12936], which are then captured by the tagged synapses, consolidatingmemory. In contrast to novelty, stress can impair learning, memory, and synaptic plasticity. Here, we address questions as towhether novelty-induced PRPs are able to prevent the loss ofmemory caused by stress and if the latter would not interact with the tag-setting process. We usedwater-maze (WM) training as a spatial learning paradigmto test our hypothesis. Stress was induced by a strong foot shock (FS; 5 x 1 mA, 2 s) applied 5 min after WM training. Our data show that FS reduced long-term but not short-term memory in the WM paradigm. This negative effect onmemory consolidationwas time- and training-dependent. Interestingly, novelty exposure prevented the stress-induced memory loss of the spatial task and increased BDNF and Arc expression. This rescuing effectwas blocked by anisomycin, suggesting that WM-tagged synapses were not reset by FS and were thus able to capture the novelty-induced PRPs, re-establishing FS-impaired long-term memory.