Journal
CURRENT BIOLOGY
Volume 28, Issue 18, Pages 2900-+Publisher
CELL PRESS
DOI: 10.1016/j.cub.2018.07.037
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Funding
- Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN 249880-11, SMFSU 373515-09, RGPIN-249880-06]
- Canadian Institutes of Health Research (CIHR) [MOP-74672, MOP-93540, MOP-123430]
- Royal Society [RG130216]
- NSERC Canada Graduate Scholarships - Master's (CGS-M) research fellowship
- NSERC Canada Graduate Scholarships - Doctoral (CGS-D) research fellowship
- BBSRC [BB/P025315/1, BB/M025128/1] Funding Source: UKRI
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The neurobiology of memory formation has been studied primarily in experimentally naive animals, but the majority of learning unfolds on a background of prior experience. Considerable evidence now indicates that the brain processes initial and subsequent learning differently. In rodents, a first instance of contextual fear conditioning requires NMDA receptor (NMDAR) activation in the dorsal hippocampus, but subsequent conditioning to another context does not. This shift may result from a change in molecular plasticity mechanisms or in the information required to learn the second task. To clarify how related events are encoded, it is critical to identify which aspect of a first task engages NMDAR-independent learning and the brain regions that maintain this state. Here, we show in rats that the requirement for NMDARs in hippocampus depends neither on prior exposure to context nor footshock alone but rather on the procedural similarity between two conditioning tasks. Importantly, NMDAR-independent learning requires the memory of the first task to remain hippocampus dependent. Furthermore, disrupting memory maintenance in the anterior cingulate cortex after the first task also reinstates NMDAR dependency. These results reveal cortico-hippocampal interactions supporting experience-dependent learning.
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