Brain Structure and Function

, Volume 223, Issue 6, pp 2785–2808 | Cite as

Pattern separation in the hippocampus: distinct circuits under different conditions

  • Randa Kassab
  • Frédéric Alexandre
Original Article


Pattern separation is a fundamental hippocampal process thought to be critical for distinguishing similar episodic memories, and has long been recognized as a natural function of the dentate gyrus (DG), supporting autoassociative learning in CA3. Understanding how neural circuits within the DG-CA3 network mediate this process has received much interest, yet the exact mechanisms behind remain elusive. Here, we argue for the case that sparse coding is necessary but not sufficient to ensure efficient separation and, alternatively, propose a possible interaction of distinct circuits which, nevertheless, act in synergy to produce a unitary function of pattern separation. The proposed circuits involve different functional granule-cell populations, a primary population mediates sparsification and provides recurrent excitation to the other populations which are related to additional pattern separation mechanisms with higher degrees of robustness against interference in CA3. A variety of top-down and bottom-up factors, such as motivation, emotion, and pattern similarity, control the selection of circuitry depending on circumstances. According to this framework, a computational model is implemented and tested against model variants in a series of numerical simulations and biological experiments. The results demonstrate that the model combines fast learning, robust pattern separation and high storage capacity. It also accounts for the controversy around the involvement of the DG during memory recall, explains other puzzling findings, and makes predictions that can inform future investigations.


Computational model Dentate gyrus Episodic memory Hippocampus Pattern separation 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Authors and Affiliations

  1. 1.INRIABordeaux Sud-OuestTalenceFrance
  2. 2.Institut des Maladies NeurodégénérativesUniversity of Bordeaux, CNRS UMR 5293-Case 28, Centre Broca Nouvelle-AquitaineBordeauxFrance
  3. 3.LaBRI, UMR 5800, CNRS, Bordeaux INPUniversity of BordeauxTalenceFrance

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