Abstract
Consolidation of remote memory enhances immediate early genes induction (IEGs), augments the expression of the pre-synaptic growth associated protein-43 (GAP-43), and increases the density and size of dendritic spines in anterior cingulate (aCC) and infra-limbic (ILC) cortices. Remote memory extinction, however, does not uniformly alter consolidation-induced structural changes. In the aCC, the density, but not the size, of spines is reset to pseudo-conditioning levels while novel thin spines are formed in the ILC. Whether IEGs and GAP-43 also undergo region-specific changes upon remote memory extinction is undetermined. Here we confirm in the same batch of mice that c-Fos induction and GAP-43 expression are increased in both the aCC and the ILC 36 days after contextual fear conditioning. We then show that, in both regions, remote memory extinction is associated with decrease of c-Fos induction but no change in GAP-43 expression thus revealing similar, although protein-specific, pre-synaptic adaptations in aCC and ILC neurons. These observations, in addition to our previous report of region-specific post-synaptic structural changes, disclose a complex pattern of extinction-driven neocortical alterations suitable to support erasure or reinstatement of fear according to the environment demand.
Highlights
Consolidation of remotely acquired memories require protein synthesis and structural re-arrangements in the neocortex, Mapping expression of activity-regulated immediate early genes (IEGs) or plasticity/cytoscheletal proteins several weeks after training revealed a parallel increase in c-Fos, and Zif induction (Frankland et al, 2004; Frankland and Bontempi, 2005) and in the pre-synaptic growth associated protein-43 (GAP-43) expression (Maviel et al, 2004) in anterior cingulate and/or infra-limbic (ILC) cortices
In both regions, remote memory extinction is associated with decrease of c-Fos induction but no change in GAP-43 expression revealing similar, protein-specific, pre-synaptic adaptations in aCC and ILC neurons
BEHAVIOR Behavioral experiments were run using the same contextual fear conditioning, remote extinction and remote memory test paradigms we set up for previous experiments aimed at analyzing changes in the density and size of dendritic spines were analyzed (Vetere et al, 2011b)
Summary
Consolidation of remotely acquired memories require protein synthesis and structural re-arrangements in the neocortex, Mapping expression of activity-regulated immediate early genes (IEGs) or plasticity/cytoscheletal proteins several weeks after training revealed a parallel increase in c-Fos, and Zif induction (Frankland et al, 2004; Frankland and Bontempi, 2005) and in the pre-synaptic growth associated protein-43 (GAP-43) expression (Maviel et al, 2004) in anterior cingulate (aCC) and/or infra-limbic (ILC) cortices. ACC and ILC neurons show a similar increase in spine density and size upon remote consolidation, these neurons undergo opposed remodeling upon remote extinction (Vetere et al, 2011b). We present data demonstrating that, differently from the dendritic spines which undergo region-specific changes, remote extinction decreases c-Fos induction and leaves unchanged GAP-43 expression in aCC and ILC neurons upon the remote memory test. Our findings reveal that remote memory extinction promotes a complex pattern of neocortical adaptations which might support erasure or reinstatement of fear according to the environment demand
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