SRC Inhibition Reduces NR2B Surface Expression and Synaptic Plasticity in the Amygdala

Autor/inn/en	Sinai, Laleh; Duffy, Steven; Roder, John C.
Titel	SRC Inhibition Reduces NR2B Surface Expression and Synaptic Plasticity in the Amygdala
Quelle	In: Learning & Memory, 17 (2010) 8, S.364-371 (8 Seiten) PDF als Volltext Verfügbarkeit
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	1072-0502
DOI	10.1101/lm.1765710
Schlagwörter	Brain Hemisphere Functions; Biochemistry; Auditory Stimuli; Role; Animals; Fear; Conditioning; Task Analysis; Cues; Metacognition; Drug Use; Learning Processes + Suchen Sie Ihr Suchwort? Biochemie; Auditive Stimulation; Rollen; Animal; Tier; Tiere; Furcht; Aufgabenanalyse; Stichwort; Meta cognitive ability; Meta-cognition; Metakognitive Fähigkeit; Metakognition; Drug consumption; Substance abuse; Drogenkonsum; Learning process; Lernprozess
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. (As Provided).
Anmerkungen	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/
Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2017/4/10