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

Entorhinal Cortex for Temporal Association Memory


Science 9 December 2011:  Vol. 334 no. 6061 pp. 1415-1420

Entorhinal Cortex Layer III Input to the Hippocampus Is Crucial for Temporal Association Memory

Junghyup Suh1, Alexander J. Rivest1, Toshiaki Nakashiba1, Takashi Tominaga2, Susumu Tonegawa1

1The Picower Institute for Learning and Memory, RIKEN–MIT Center for Neural Circuit Genetics, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

2Department of Neurophysiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Kagawa, Japan.


Associating temporally discontinuous elements is crucial for the formation of episodic and working memories that depend on the hippocampal-entorhinal network. However, the neural circuits subserving these associations have remained unknown. The layer III inputs of the entorhinal cortex to the hippocampus may contribute to this process. To test this hypothesis, we generated a transgenic mouse in which these inputs are specifically inhibited. The mutant mice displayed significant impairments in spatial working-memory tasks and in the encoding phase of trace fear-conditioning. These results indicate a critical role of the entorhinal cortex layer III inputs to the hippocampus in temporal association memory.

A critical feature of episodic memory shared by some forms of working memory is the ability to associate temporally discontinuous elements, called temporal association memory. However, the neural circuits within the entorhinal cortex (EC)–hippocampus (HP) network subserving this type of association have remained unknown. The EC provides inputs to the HP via two major projections: the trisynaptic pathway (TSP) originating from EC layer II and the monosynaptic pathway (MSP) originating from EC layer III (ECIII). Studies on genetically engineered mice and lesioned rats have demonstrated crucial roles of the TSP in several features of episodic-memory processing, such as pattern completion and separation. In contrast, the MSP contributions to episodic-memory processing remain poorly known. We tested the hypothesis that the MSP is necessary for temporal association memory.

Apart from specific mechanisms, our overall results demonstrate a crucial role of the EC layer III input to the HP in hippocampal-dependent temporal association memory.

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