| Title: |
SRC Inhibition Reduces NR2B Surface Expression and Synaptic Plasticity in the Amygdala |
| Language: |
English |
| Authors: |
Sinai, Laleh; Duffy, Steven; Roder, John C. |
| Source: |
Learning & Memory. Aug 2010 17(8):364-371. |
| Availability: |
Cold Spring Harbor Laboratory Press. 500 Sunnyside Boulevard, Woodbury, NY 11797-2924. Tel: 800-843-4388; Tel: 516-367-8800; Fax: 516-422-4097; e-mail: cshpres@cshl.edu; Web site: http://www.learnmem.org/ |
| Peer Reviewed: |
Y |
| Physical Description: |
PDF |
| Page Count: |
8 |
| Publication Date: |
2010 |
| Document Type: |
Journal Articles; Reports - Evaluative |
| Descriptors: |
Brain Hemisphere Functions; Biochemistry; Auditory Stimuli; Role; Animals; Fear; Conditioning; Task Analysis; Cues; Metacognition; Drug Use; Learning Processes |
| DOI: |
10.1101/lm.1765710 |
| ISSN: |
1072-0502 |
| Abstract: |
The Src protein tyrosine kinase plays a central role in the regulation of N-methyl-d-aspartate receptor (NMDAR) activity by regulating NMDAR subunit 2B (NR2B) surface expression. In the amygdala, NMDA-dependent synaptic plasticity resulting from convergent somatosensory and auditory inputs contributes to emotional memory; however, the role of Src tyrosine kinase has not been investigated. We have synthesized a Src-derived peptide, Tat-Src (40-58), that crosses the blood-brain barrier following injection and accumulates intracellularly. Tat-Src (40-58) blocks the interaction of Src with NMDA receptors. Following injection, mice demonstrate impaired amygdala-dependent cued fear conditioning, as well as impairments in an amygdala-dependent nonassociative social recognition task. The Src inhibitor decreased NR2B phosphorylation in amygdala tissue and reduced NR2B surface expression in cultured amygdala neurons with a concomitant reduction in NMDA multimer-containing dendritic puncta. In addition, preincubation of this inhibitory peptide blocked amygdalar long-term potentiation in the lateral to basolateral pathway in vitro. These results indicate that Src is a key regulator of NMDAR trafficking in the amygdala. Furthermore, Src-dependent phosphorylation of NR2B supports amygdala plasticity and amygdalar-dependent learning. |
| Abstractor: |
As Provided |
| Entry Date: |
2010 |
| Accession Number: |
EJ892608 |
| Database: |
ERIC |