SRC Inhibition Reduces NR2B Surface Expression and Synaptic Plasticity in the Amygdala
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| Title: | SRC Inhibition Reduces NR2B Surface Expression and Synaptic Plasticity in the Amygdala |
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| 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: | |
| 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 |
| 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. |
|---|---|
| ISSN: | 1072-0502 |
| DOI: | 10.1101/lm.1765710 |
