Spatial Memory Engram in the Mouse Retrosplenial Cortex

Abstract

Memory relies on lasting adaptations of neuronal properties elicited by stimulus-driven plastic changes [1Hebb D.O. The Organization of Behavior. John Wiley & Sons, Inc, New York1949Google Scholar]. The strengthening (and weakening) of synapses results in the establishment of functional ensembles. It is presumed that such ensembles (or engrams) are activated during memory acquisition and re-activated upon memory retrieval. The retrosplenial cortex (RSC) has emerged as a key brain area supporting memory [2Vann S.D. Aggleton J.P. Maguire E.A. What does the retrosplenial cortex do?.Nat. Rev. Neurosci. 2009; 10: 792-802Crossref PubMed Scopus (899) Google Scholar], including episodic and topographical memory in humans [3Maguire E.A. The retrosplenial contribution to human navigation: a review of lesion and neuroimaging findings.Scand. J. Psychol. 2001; 42: 225-238Crossref PubMed Scopus (459) Google Scholar, 4Auger S.D. Maguire E.A. Assessing the mechanism of response in the retrosplenial cortex of good and poor navigators.Cortex. 2013; 49: 2904-2913Crossref PubMed Scopus (64) Google Scholar, 5Bird C.M. Keidel J.L. Ing L.P. Horner A.J. Burgess N. Consolidation of Complex Events via Reinstatement in Posterior Cingulate Cortex.J. Neurosci. 2015; 35: 14426-14434Crossref PubMed Scopus (81) Google Scholar], as well as spatial memory in rodents [6Czajkowski R. Jayaprakash B. Wiltgen B. Rogerson T. Guzman-Karlsson M.C. Barth A.L. Trachtenberg J.T. Silva A.J. Encoding and storage of spatial information in the retrosplenial cortex.Proc. Natl. Acad. Sci. USA. 2014; 111: 8661-8666Crossref PubMed Scopus (141) Google Scholar, 7Cooper B.G. Manka T.F. Mizumori S.J.Y. Finding your way in the dark: the retrosplenial cortex contributes to spatial memory and navigation without visual cues.Behav. Neurosci. 2001; 115: 1012-1028Crossref PubMed Scopus (100) Google Scholar]. Dysgranular RSC is densely connected with dorsal stream visual areas [8Wang Q. Sporns O. Burkhalter A. Network analysis of corticocortical connections reveals ventral and dorsal processing streams in mouse visual cortex.J. Neurosci. 2012; 32: 4386-4399Crossref PubMed Scopus (234) Google Scholar] and contains place-like and head-direction cells, making it a prime candidate for integrating navigational information [9Miller A.M.P. Vedder L.C. Law L.M. Smith D.M. Cues, context, and long-term memory: the role of the retrosplenial cortex in spatial cognition.Front. Hum. Neurosci. 2014; 8: 586Crossref PubMed Scopus (105) Google Scholar]. While previous reports [6Czajkowski R. Jayaprakash B. Wiltgen B. Rogerson T. Guzman-Karlsson M.C. Barth A.L. Trachtenberg J.T. Silva A.J. Encoding and storage of spatial information in the retrosplenial cortex.Proc. Natl. Acad. Sci. USA. 2014; 111: 8661-8666Crossref PubMed Scopus (141) Google Scholar, 10Xie H. Liu Y. Zhu Y. Ding X. Yang Y. Guan J.S. In vivo imaging of immediate early gene expression reveals layer-specific memory traces in the mammalian brain.Proc. Natl. Acad. Sci. USA. 2014; 111: 2788-2793Crossref PubMed Scopus (53) Google Scholar] describe the recruitment of RSC ensembles during navigational tasks, such ensembles have never been tracked long enough to provide evidence of stable engrams and have not been related to the retention of long-term memory. Here, we used in vivo 2-photon imaging to analyze patterns of activity of over 6,000 neurons within dysgranular RSC. Eight mice were trained on a spatial memory task. Learning was accompanied by the gradual emergence of a context-specific pattern of neuronal activity over a 3-week period, which was re-instated upon retrieval more than 3 weeks later. The stability of this memory engram was predictive of the degree of forgetting; more stable engrams were associated with better performance. This provides direct evidence for the interdependence of spatial memory consolidation and RSC engram formation. Our results demonstrate the participation of RSC in spatial memory storage at the level of neuronal ensembles.