Amygdala upregulation of NCAM polysialylation induced by auditory fear conditioning is not required for memory formation, but plays a role in fear extinction.
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.
Markram
Kamila
K
Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Switzerland.
Lopez Fernandez
Miguel Angel
MA
Abrous
Djoher Nora
DN
Sandi
Carmen
C
D000161:Acoustic Stimulation; D000679:Amygdala / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001362:Avoidance Learning / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012794:Sialic Acids / Q000378:metabolism*; D018709:Statistics, Nonparametric
D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule