Abstract
The retrosplenial cortex (RSC) plays a critical role in episodic memory, but the molecular mechanisms governing plasticity in this structure are poorly understood. Diverse studies have demonstrated a role for RSC in acquisition, early consolidation and retrieval similar to the hippocampus (HC), as well as in systems consolidation similar to the anterior cingulate cortex. Here, we asked whether established molecular and structural substrates of memory consolidation in the HC also engage in RSC shortly after learning. We show striking parallels in training induced gene-activation in HC and RSC following contextual conditioning, which is blocked by systemic administration of an NMDA receptor antagonist. Long-term memory is enhanced by retrosplenial and hippocampal knockdown (KD) of the cAMP specific phosphodiesterase Pde4d. However, while training per se induces lasting spine changes in HC, this does not occur in RSC. Instead, increases in the number of mature dendritic spines are found in the RSC only if cAMP signaling is augmented by Pde4d KD, and spine changes are at least partially independent of training. This research highlights parallels and differences in spine plasticity mechanisms between HC and RSC, and provides evidence for a functional dissociation of the two.
Highlights
Since the first description of amnesia in a patient with retrosplenial lesion by Valenstein and colleagues almost 30 years ago[1], much of the insight on the role of the retrosplenial cortex (RSC) in memory comes from studies examining its activation, or the effect of its inactivation in animal models[2]
We characterized the time-course of immediate early gene (IEG) expression in RSC after learning, and asked how the response relates to the hippocampus
We have shown that (i) contextual learning induces a strikingly similar pattern of gene-expression in HC and RSC, which is NMDA receptor dependent; (ii) augmentation of cyclic adenosine monophosphate (cAMP) signaling by Pde4D KD enhances memory whether targeted to HC or RSC; (iii) spine-changes coincide with memory enhancement in HC and RSC; but (iv) training-induced spine changes only occur in HC
Summary
Since the first description of amnesia in a patient with retrosplenial lesion by Valenstein and colleagues almost 30 years ago[1], much of the insight on the role of the retrosplenial cortex (RSC) in memory comes from studies examining its activation, or the effect of its inactivation in animal models[2]. These studies have revealed that RSC is activated by contextual fear conditioning (cFC)[3]; and training in spatial learning tasks such as the Morris Water Maze[4,5], and that its inactivation or lesion impairs performance[6,7,8,9,10,11], These and other studies demonstrate the necessity of the RSC for contextual and spatial tasks in rodents, findings consistent with clinical observations[1,2]. While Pde4D knockdown in RSC enhances memory, there are no training- but only Pde4D KD-dependent spine changes
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