Amygdala upregulation of NCAM polysialylation induced by auditory fear conditioning is not required for memory formation, but plays a role in fear extinction.

Full Abstract

There is much interest to understand the mechanisms leading to the establishment, maintenance, and extinction of fear memories. The amygdala has been critically involved in the processing of fear memories and a number of molecular changes have been implicated in this brain region in relation to fear learning. Although neural cell adhesion molecules (NCAMs) have been hypothesized to play a role, information available about their contribution to fear memories is scarce. We investigate here whether polysialylated NCAM (PSA-NCAM) contributes to auditory fear conditioning in the amygdala. First, PSA-NCAM expression was evaluated in different amygdala nuclei after auditory fear conditioning at two different shock intensities. Results showed that PSA-NCAM expression was increased 24 h post-training only in animals subjected to the highest shock intensity (1mA). Second, PSA-NCAM was cleaved in the basolateral amygdaloid complex through micro-infusions of the enzyme endoneuraminidase N, and the consequences of such treatment were investigated on the acquisition, consolidation, remote memory expression, and extinction of conditioned fear memories. Intra-amygdaloid cleavage of PSA-NCAM did not affect acquisition, consolidation or expression of remote fear memories. However, intra-amygdaloid PSA-NCAM cleavage enhanced fear extinction processes. These results suggest that upregulation of PSA-NCAM is a correlate of fear conditioning that is not necessary for the establishment of fear memory in the amygdala, but participates in mechanisms precluding fear extinction. These findings point out PSA-NCAM as a potential target for the treatment of psychopathologies that involve impairment in fear extinction.

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Author information

Author/s: Markram, Kamila (K); Lopez Fernandez, Miguel Angel (MA); Abrous, Djoher Nora (DN); Sandi, Carmen (C);

Affiliation: Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Switzerland.

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: Neurobiology of learning and memory (Neurobiol Learn Mem), published in United States. (Language: eng)

Reference: 2007-May; vol 87 (issue 4) : pp 573-82

Dates: Created 2007/04/02; Completed 2007/07/16; Revised 2007/10/17;

PMID: 17223582, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Acoustic Stimulation
Amygdala - metabolism
Analysis of Variance
Animals
Association Learning - physiology
Avoidance Learning - physiology
Conditioning, Classical - physiology
Extinction, Psychological - physiology

Fear - physiology
Male
Memory - physiology
Neural Cell Adhesion Molecule L1 - metabolism
Rats
Rats, Wistar
Sialic Acids - metabolism
Statistics, Nonparametric

Associated Chemicals: Neural Cell Adhesion Molecule L1 (0) ; Sialic Acids (0) ; polysialyl neural cell adhesion molecule (0)

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