Divergent cellular pathways of hippocampal memory consolidation and reconsolidation
Version of Record online: 29 NOV 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 23, Issue 3, pages 233–244, March 2013
How to Cite
Lee, J. L.C. and Hynds, R. E. (2013), Divergent cellular pathways of hippocampal memory consolidation and reconsolidation. Hippocampus, 23: 233–244. doi: 10.1002/hipo.22083
- Issue online: 27 FEB 2013
- Version of Record online: 29 NOV 2012
- Manuscript Accepted: 27 OCT 2012
- UK Medical Research Council. Grant Number: GG0700991
- Welcome Trust Vacation Scholarship (to R.H.)
- NMDA receptor;
- contextual fear conditioning;
The reconsolidation of memories after their retrieval involves cellular mechanisms that recapitulate much of the initial consolidation process. However, we have previously demonstrated that there are independent cellular mechanisms of consolidation and reconsolidation in the dorsal hippocampus for contextual fear memories. Expression of BDNF was required for consolidation, while Zif268 expression was necessary for reconsolidation. Given the dichotomy between the obvious mechanistic similarity and notable dissociations between consolidation and reconsolidation, we sought to determine whether the separation at the level of gene expression reflected either parallel and independent upstream signaling pathways, or common upstream mechanisms that diverge by the level of transcriptional activation. Here we show that while consolidation and reconsolidation are commonly dependent upon NMDA receptor activation in the dorsal hippocampus there is a double dissociation between the effects of the MEK inhibitor U0126 and the IKK inhibitor sulfasalazine. Moreover, rescue experiments and western blot analyses show that there are functional NMDA receptor–ERK1–BDNF and NMDA receptor–IKKα–Zif268 pathways for consolidation and reconsolidation, respectively. Therefore, there are divergent pathways of hippocampal memory consolidation and reconsolidation, involving commonality at the cell surface, but separable downstream kinase cascades and transcriptional regulation. © 2012 Wiley Periodicals, Inc.