The contribution of hippocampal circuits to high-capacity episodic memory is often attributed to the large number of orthogonal activity patterns that may be stored in these networks. Evidence for high-capacity storage in the hippocampus is missing, however. When animals are tested in pairs of environments, different combinations of place cells are recruited, consistent with the notion of independent representations. However, the extent to which representations remain independent across larger numbers of environments has not been determined. To investigate whether spatial firing patterns recur when animals are exposed to multiple environments, we tested rats in 11 recording boxes, each in a different room, allowing for 55 comparisons of place maps in each animal. In each environment, activity was recorded from neuronal ensembles in hippocampal area CA3, with an average of 30 active cells per animal. Representations were highly correlated between repeated tests in the same room but remained orthogonal across all combinations of different rooms, with minimal overlap in the active cell samples from each environment. A low proportion of cells had activity in many rooms but the firing locations of these cells were completely uncorrelated. Taken together, the results suggest that the number of independent spatial representations stored in hippocampal area CA3 is large, with minimal recurrence of spatial firing patterns across environments.

Kavli Institute for Systems Neuroscience and Centre for Neural Computation Norwegian University of Science and Technology 7491 Trondheim Norway;

Kavli Institute for Systems Neuroscience and Centre for Neural Computation Norwegian University of Science and Technology 7491 Trondheim Norway; Biomedical Centre and Department of Pathophysiology Faculty of Medicine in Pilsen Charles University Prague 306 05 Pilsen Czech Republic; and

Kavli Institute for Systems Neuroscience and Centre for Neural Computation Norwegian University of Science and Technology 7491 Trondheim Norway; Cognitive Neuroscience SISSA 34136 Trieste Italy

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Marr D. Simple memory: A theory for archicortex. Philos Trans R Soc Lond B Biol Sci. 1971;262(841):23–81. PubMed

McNaughton BL, Morris RG. Hippocampal synaptic enhancement and information storage within a distributed memory system. Trends Neurosci. 1987;10:408–415.

Treves A, Rolls ET. Computational analysis of the role of the hippocampus in memory. Hippocampus. 1994;4(3):374–391. PubMed

Leutgeb JK, Leutgeb S, Moser MB, Moser EI. Pattern separation in the dentate gyrus and CA3 of the hippocampus. Science. 2007;315(5814):961–966. PubMed

Treves A, Rolls ET. Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network. Hippocampus. 1992;2(2):189–199. PubMed

Leutgeb S, Leutgeb JK, Treves A, Moser MB, Moser EI. Distinct ensemble codes in hippocampal areas CA3 and CA1. Science. 2004;305(5688):1295–1298. PubMed

O’Keefe J, Dostrovsky J. The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res. 1971;34(1):171–175. PubMed

O'Keefe J, Nadel L. The Hippocampus As a Cognitive Map. Oxford Univ Press; Oxford: 1978.

Wilson MA, McNaughton BL. Dynamics of the hippocampal ensemble code for space. Science. 1993;261(5124):1055–1058. PubMed

Muller RU, Kubie JL. The effects of changes in the environment on the spatial firing of hippocampal complex-spike cells. J Neurosci. 1987;7(7):1951–1968. PubMed PMC

Bostock E, Muller RU, Kubie JL. Experience-dependent modifications of hippocampal place cell firing. Hippocampus. 1991;1(2):193–205. PubMed

Markus EJ, et al. Interactions between location and task affect the spatial and directional firing of hippocampal neurons. J Neurosci. 1995;15(11):7079–7094. PubMed PMC

Colgin LL, Moser EI, Moser MB. Understanding memory through hippocampal remapping. Trends Neurosci. 2008;31(9):469–477. PubMed

Battaglia FP, Treves A. Stable and rapid recurrent processing in realistic autoassociative memories. Neural Comput. 1998;10(2):431–450. PubMed

Deguchi Y, Donato F, Galimberti I, Cabuy E, Caroni P. Temporally matched subpopulations of selectively interconnected principal neurons in the hippocampus. Nat Neurosci. 2011;14(4):495–504. PubMed

Xu HT, et al. Distinct lineage-dependent structural and functional organization of the hippocampus. Cell. 2014;157(7):1552–1564. PubMed PMC

Dragoi G, Tonegawa S. Preplay of future place cell sequences by hippocampal cellular assemblies. Nature. 2011;469(7330):397–401. PubMed PMC

McNaughton BL, et al. Deciphering the hippocampal polyglot: The hippocampus as a path integration system. J Exp Biol. 1996;199(Pt 1):173–185. PubMed

Samsonovich A, McNaughton BL. Path integration and cognitive mapping in a continuous attractor neural network model. J Neurosci. 1997;17(15):5900–5920. PubMed PMC

Buzsáki G, Mizuseki K. The log-dynamic brain: How skewed distributions affect network operations. Nat Rev Neurosci. 2014;15(4):264–278. PubMed PMC

Rich PD, Liaw HP, Lee AK. Place cells. Large environments reveal the statistical structure governing hippocampal representations. Science. 2014;345(6198):814–817. PubMed

Jezek K, Henriksen EJ, Treves A, Moser EI, Moser MB. Theta-paced flickering between place-cell maps in the hippocampus. Nature. 2011;478(7368):246–249. PubMed

Wilson MA, McNaughton BL. Reactivation of hippocampal ensemble memories during sleep. Science. 1994;265(5172):676–679. PubMed

Claiborne BJ, Amaral DG, Cowan WM. A light and electron microscopic analysis of the mossy fibers of the rat dentate gyrus. J Comp Neurol. 1986;246(4):435–458. PubMed

Leutgeb JK, et al. Progressive transformation of hippocampal neuronal representations in “morphed” environments. Neuron. 2005;48(2):345–358. PubMed

Hayman RM, Chakraborty S, Anderson MI, Jeffery KJ. Context-specific acquisition of location discrimination by hippocampal place cells. Eur J Neurosci. 2003;18(10):2825–2834. PubMed

Wood ER, Dudchenko PA, Eichenbaum H. The global record of memory in hippocampal neuronal activity. Nature. 1999;397(6720):613–616. PubMed

Singer AC, Karlsson MP, Nathe AR, Carr MF, Frank LM. Experience-dependent development of coordinated hippocampal spatial activity representing the similarity of related locations. J Neurosci. 2010;30(35):11586–11604. PubMed PMC

McKenzie S, et al. Hippocampal representation of related and opposing memories develop within distinct, hierarchically organized neural schemas. Neuron. 2014;83(1):202–215. PubMed PMC

McKenzie S, Robinson NT, Herrera L, Churchill JC, Eichenbaum H. Learning causes reorganization of neuronal firing patterns to represent related experiences within a hippocampal schema. J Neurosci. 2013;33(25):10243–10256. PubMed PMC

Skaggs WE, McNaughton BL, Wilson MA, Barnes CA. Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences. Hippocampus. 1996;6(2):149–172. PubMed

Henriksen EJ, et al. Spatial representation along the proximodistal axis of CA1. Neuron. 2010;68(1):127–137. PubMed PMC

Muller RU, Kubie JL. The firing of hippocampal place cells predicts the future position of freely moving rats. J Neurosci. 1989;9(12):4101–4110. PubMed PMC

O’Keefe J, Burgess N. Geometric determinants of the place fields of hippocampal neurons. Nature. 1996;381(6581):425–428. PubMed

Wilks SS. Weighting systems for linear functions of correlated variables when there is no dependent variable. Psychometrica. 1938;(3):23–40.

Retrieval of spatial representation on network level in hippocampal CA3 accompanied by overexpression and mixture of stored network patterns