Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Hippocampus Hypothesized to Mediate Pattern Separation of Mnemonic Representations


Science 10 July 2009:  Vol. 325. no. 5937, pp. 210 - 213

A Functional Role for Adult Hippocampal Neurogenesis in Spatial Pattern Separation

C. D. Clelland,1,2 M. Choi,2 C. Romberg,3 G. D. Clemenson, Jr.,1 A. Fragniere,2 P. Tyers,2 S. Jessberger,4 L. M. Saksida,3,5 R. A. Barker,2,6 F. H. Gage,1 T. J. Bussey3,5

1 Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
2 Centre for Brain Repair, University of Cambridge, Cambridge CB2 2PY, UK.
3 Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, UK.
4 Institute of Cell Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
5 Medical Research Council and Wellcome Trust Behavioral and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK.
6 Department of Neurology, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK.


The dentate gyrus (DG) of the mammalian hippocampus is hypothesized to mediate pattern separation—the formation of distinct and orthogonal representations of mnemonic information—and also undergoes neurogenesis throughout life. How neurogenesis contributes to hippocampal function is largely unknown. Using adult mice in which hippocampal neurogenesis was ablated, we found specific impairments in spatial discrimination with two behavioral assays: (i) a spatial navigation radial arm maze task and (ii) a spatial, but non-navigable, task in the mouse touch screen. Mice with ablated neurogenesis were impaired when stimuli were presented with little spatial separation, but not when stimuli were more widely separated in space. Thus, newborn neurons may be necessary for normal pattern separation function in the DG of adult mice.

The dentate gyrus is thought to contribute to spatial or episodic memory by functioning as a pattern separator. Pattern separation is the formation of distinct representations of similar inputs. At the cellular level, pattern separation is achieved through the dispersion of cortical inputs from the entorhinal cortex onto a greater number of dentate granule cells (DGCs) with small place fields. By virtue of low firing rates and sparse connectivity between DGCs and CA3 pyramidal cells, DGCs are particularly adapted to maintain and transmit orthogonalized information. This ability to pattern separate, or to differentially encode small or weak changes derived from increasingly similar or interfering inputs, is particularly important for the accuracy of memory encoding. Similarly, at the behavioral level, the ability to form and use memories derived from very similar stimuli that are closely presented in space and/or time depends on the ability to pattern separate incoming, and often complex, information. Lesions of the complete DG circuitry result in impaired pattern separation–dependent memory.

The DG is also one of two sites where neurogenesis is ongoing throughout life. Adult-born neurons integrate into DG circuitry and are thought to play a role in learning and memory.

This study provides experimental evidence of a role for newborn neurons in the adult DG in spatial discrimination, consistent with a role in spatial pattern separation. We used two independent strategies to ablate neurogenesis, and the observed deficits were similar in two very distinct testing contexts.

The DG has been shown to be important for pattern separation, and our results show that adult neurogenesis appears to be important for the ability of the DG to perform that function optimally.

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