System Consolidation of Spatial Memories in Mice: Effects of Enriched Environment

Abstract

Environmental enrichment (EE) is known to enhance learning and memory. Declarative memories are thought to undergo a first rapid and local consolidation process, followed by a prolonged process of system consolidation, which consist in a time-dependent gradual reorganization of brain regions supporting remote memory storage and crucial for the formation of enduring memories. At present, it is not known whether EE can affect the process of declarative memory system consolidation. We characterized the time course of hippocampal and cortical activation following recall of progressively more remote spatial memories. Wild-type mice either exposed to EE for 40 days or left in standard environment were subjected to spatial learning in the Morris water maze and to the probe test 1, 10, 20, 30, and 50 days after learning. Following the probe test, regional expression of the inducible immediate early gene c-Fos was mapped by immunohistochemistry, as an indicator of neuronal activity. We found that activation of the medial prefrontal cortex (mPFC), suggested to have a privileged role in processing remote spatial memories, was evident at shorter time intervals after learning in EE mice; in addition, EE induced the progressive activation of a distributed cortical network not activated in non-EE mice. This suggests that EE not only accelerates the process of mPFC recruitment but also recruits additional cortical areas into the network supporting remote spatial memories.

Environmental enrichment and mouse models: Current perspectives

“…The authors suggest that enrichment causes a significant increase in hippocampal Ng levels. More recent research has demonstrated that an enriched environment may result in enhancing memory by accelerating the activity of the medial prefrontal cortex, which has a role in processing spatial memories, and results in the recruitment of additional cortical areas into the network sustaining spatial memories …”

Anterior thalamic nuclei lesions and recovery of function: Relevance to cognitive thalamus

“…The benefits of enrichment are thought to arise from a combination of increased exercise, socialisation, and novelty, producing stronger effects than each of these components administered individually (Cracchiolo et al, 2007;Einon et al, 1980;Olson et al, 2006;Sozda et al, 2010;Will et al, 1986;Wood et al, 2001). These effects are likely to be mediated by increased activation of multiple brain networks, including changes to their recruitment during behavioural tasks, together with neurobiological effects that range from the size and morphology of brain regions to the survival and complexity of neurons, adult neurogenesis, enhanced cell excitability and synaptic plasticity, and a wide array of neuroprotective molecular responses that reflect multiple genetic processes, including neuroinflammation and levels of trophic factors (Alwis and Rajan, 2014; Bonaccorsi et al, 2013;Briones et al, 2013;Eckert and Abraham, 2013;Hirase and Q5 Shinohara, 2014;Leger et al, 2012;Rampon, 2000;Will et al, 2004).…”

A Synaptic and Systems Level Investigation of Memory Processes Using a Novel Multiple Memory Behavioural Procedure

“…Discrepancies in c-Fos labeling in the hippocampus may result from different behavioural tasks used in assessment. Bonaccorsi et al (2013), Wartman and Holahan (2013), and Lopez et al (2012), used the water maze task as a behavioural measure and found increased activation of the hippocampus at remote compared to recent time points, consistent with the present set of results. Schlesiger et al (2013) used a modified radial arm maze task that incorporated different start locations and retention testing in a single trial in an effort to incorporate aspects of a standard water maze procedure.…”

“…Stereological analyses revealed remotely tested groups had significantly higher numbers of c-Fos positive cells than recently tested groups. This finding contradicts some earlier reports that revealed lower hippocampal activation at remote time points (Frankland et al, 2004;Maviel et al, 2004) but is similar to other reported data (Bonaccorsi et al, 2013;Lopez et al, 2012;Schlesiger et al, 2013;Wartman and Holahan, 2013). As the WM task is a hippocampal-dependent task, it comes as no surprise the hippocampus was activated during the probe test (Broadbent et al, 2006;Clark et al, 2005a,b;D'Hooge and De Deyn, 2001;Holahan and Routtenberg, 2011;Morris et al, 1986Morris et al, , 1982Ramos, 2009;Remondes and Schuman, 2004;Sutherland et al, 2001Sutherland et al, , 1983Teixeira et al, 2006;Wiltgen et al, 2010).…”

“…A large body of research from primates and rodents exists supporting a timelimited role of the hippocampus in memory storage (Anagnostaras et al, 1999;Cho et al, 1993;Cho and Kesner, 1996;Clark et al, 2002;Debiec et al, 2002;Gaskin et al, 2009;Glenn et al, 2003;Izquierdo et al, 1997;Kim et al, 1995;Kim and Fanselow, 1992;Kubie et al, 1999;Laurent-Demir and Jaffard, 1997;Maren et al, 1997;Maviel et al, 2004;Quillfeldt et al, 1996;Quinn et al, 2008;Ramos, 1998Ramos, , 2009Remondes and Schuman, 2004;Ross and Eichenbaum, 2006;Shimizu et al, 2000;Squire et al, 2004;Takehara et al, 2003Takehara et al, , 2002Tse et al, 2007;Vnek and Rothblat, 1993;Ward et al, 1999;Winocur, 1990;Winocur et al, 2001;Zola-Morgan and Squire, 1990). Mounting evidence suggests the ACC becomes a critical node in memory storage at remote time points after encoding (Bonaccorsi et al, 2013;Bontempi et al, 1999;Ding et al, 2008;Frankland et al, 2004;Gafford et al, 2013;Lopez et al, 2012;Maviel et al, 2004;Restivo et al, 2009;Teixeira et al, 2006;…”