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

Memory Encoding in Neocortex


Science 12 August 2011: Vol. 333 no. 6044 pp. 891-895
Schema-Dependent Gene Activation and Memory Encoding in Neocortex

Dorothy Tse, Tomonori Takeuchi1, Masaki Kakeyama, Yasushi Kajii, Hiroyuki Okuno, Chiharu Tohyama, Haruhiko Bito, Richard G. M. Morris

1Centre for Cognitive and Neural Systems, University of Edinburgh, Edinburgh EH8 9JZ, UK.

2Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

3Pharmacology Research Laboratories I, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.

4Department of Neurochemistry, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.


When new learning occurs against the background of established prior knowledge, relevant new information can be assimilated into a schema and thereby expand the knowledge base. An animal model of this important component of memory consolidation reveals that systems memory consolidation can be very fast. In experiments with rats, we found that the hippocampal-dependent learning of new paired associates is associated with a striking up-regulation of immediate early genes in the prelimbic region of the medial prefrontal cortex, and that pharmacological interventions targeted at that area can prevent both new learning and the recall of remotely and even recently consolidated information. These findings challenge the concept of distinct fast (hippocampal) and slow (cortical) learning systems, and shed new light on the neural mechanisms of memory assimilation into schemas.

Memory consolidation consists of two processes. Cellular consolidation is mediated by synaptic and signal transduction mechanisms that store newly encoded memory traces on-line. Systems consolidation involves a time-limited interaction between the medial temporal lobe and the neocortical areas that eventually store long-term memory traces. Studies monitoring cerebral glucose use, immediate early gene (IEG) activation, and dendritic spine formation indicate that rapid on-line encoding of episodic-like memory in the hippocampus can be followed by temporally graded neural changes in the medial prefrontal (mPFC), orbitofrontal (Orb), and retrosplenial (RSC) cortices.

This apparent sequence of events does not preclude the possibility of simultaneous encoding or “tagging” in the hippocampus and cortex. Indeed, when systems consolidation occurs in the presence of relevant prior knowledge, the “assimilation” of new paired-associate (PA) memories into existing activated cortical schemas proceeds very rapidly, reflecting an influence of prior knowledge on the rate of consolidation. The associative encoding of such PAs requires the hippocampus, accompanied by novelty-triggered cellular consolidation, but may also involve simultaneous cortical encoding. However, if parallel cortical encoding into a schema occurs, it may be driven solely in a bottom-up manner by the hippocampus or may also reflect the influence of activated prior knowledge already stored in cortex.

Connections from the hippocampus to mPFC display long-term potentiation, and mPFC interacts with the hippocampus in the acquisition of object-place associations. Coherence in the theta-frequency band between mPFC and the hippocampus is observed during working-memory tasks, which our PA task also entails as the animals move about the arena to find locations in space that have been recalled by the flavor cue. Intrinsic dynamical oscillations may also be important for integration of cortical circuit performance, for episodic-like memory, and during the learning of schemas or their later reactivation. Thus, the opportunity to learn about the neural basis of cortical schemas of knowledge is opening up and, as it does so, the use of experienced animals possessing activated cortical networks of prior knowledge points to new ways of thinking about systems consolidation and reconsolidation.

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