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A rational account of memory predicts left prefrontal activation during controlled retrieval.

ABSTRACT: What is the role of the left prefrontal cortex in the controlled retrieval of learned information? We present a theory of declarative retrieval that posits that the amount of control exerted by this region during retrieval is inversely proportional to 1) the frequency and recency of previous experiences with the retrieved memory and 2) the associative strength between the current context and the retrieved memory. This theory is rational in the sense that it claims that declarative retrieval is highly sensitive to the statistical regularities in the environment. We demonstrate how our theory produces precise predictions of response time and neural activity during recall and test these predictions in an experiment that manipulates the frequency of previous experiences and the associative strength to the retrieval cues. Our findings suggest that the control process performed by the left prefrontal cortex directly reflects the demands of the environment on memory.

SUBMITTER: Danker JF

PROVIDER: S-EPMC2733322 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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A rational account of memory predicts left prefrontal activation during controlled retrieval.

Danker Jared F JF Gunn Pat P Anderson John R JR

Cerebral cortex (New York, N.Y. : 1991) 20080304 11

What is the role of the left prefrontal cortex in the controlled retrieval of learned information? We present a theory of declarative retrieval that posits that the amount of control exerted by this region during retrieval is inversely proportional to 1) the frequency and recency of previous experiences with the retrieved memory and 2) the associative strength between the current context and the retrieved memory. This theory is rational in the sense that it claims that declarative retrieval is h ...[more]

PMID: 18321871

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Project description:Presentation of drug-associated cues provokes craving and drug seeking, and elimination of these associative memories would facilitate recovery from addiction. Emotionally salient memories are maintained during retrieval, as particular pharmacologic or optogenetic perturbations of memory circuits during retrieval, but not after, can induce long-lasting memory impairments. For example, in rats, inhibition of noradrenergic beta-receptors, which control intrinsic neuronal excitability, in the prelimbic medial prefrontal cortex (PL-mPFC) can cause long-term memory impairments that prevent subsequent cocaine-induced reinstatement. The physiologic mechanisms that allow noradrenergic signaling to maintain drug-associated memories during retrieval, however, are unclear. Here we combine patch-clamp electrophysiology ex vivo and behavioral neuropharmacology in vivo to evaluate the mechanisms that maintain drug-associated memory during retrieval in rats. Consistent with previous studies, we find that cocaine experience increases the intrinsic excitability of pyramidal neurons in PL-mPFC. In addition, we now find that this intrinsic plasticity positively predicts the retrieval of a cocaine-induced conditioned place preference (CPP) memory, suggesting that such plasticity may contribute to drug-associated memory retrieval. In further support of this, we find that pharmacological blockade of a cAMP-dependent signaling cascade, which allows noradrenergic signaling to elevate neuronal excitability, is required for memory maintenance during retrieval. Thus, inhibition of PL-mPFC neuronal excitability during memory retrieval not only leads to long-term deficits in the memory, but this memory deficit provides protection against subsequent cocaine-induced reinstatement. These data reveal that PL-mPFC intrinsic neuronal excitability maintains a cocaine-associated memory during retrieval and suggest a unique mechanism whereby drug-associated memories could be targeted for elimination.

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A rational account of memory predicts left prefrontal activation during controlled retrieval.

Publications

A rational account of memory predicts left prefrontal activation during controlled retrieval.

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