Src inhibition reduces NR2B surface expression and suppresses memory and synaptic plasticity in the amygdala
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1
Hospital for Sick Children, Cell Biology, Canada
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2
University of Toronto, Institute of Medical Science, Molecular and Medical Genetics, Canada
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 intra-cellularly. 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 non-associative 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, pre-incubation 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.
Conference:
B.R.A.I.N. platform in Physiology poster day 2009, Toronto, ON, Canada, 16 Dec - 16 Dec, 2009.
Presentation Type:
Poster Presentation
Topic:
Poster presentations
Citation:
Sinai
L,
Duffy
S and
Roder
JC
(2010). Src inhibition reduces NR2B surface expression and suppresses memory and synaptic plasticity in the amygdala.
Front. Neurosci.
Conference Abstract:
B.R.A.I.N. platform in Physiology poster day 2009.
doi: 10.3389/conf.neuro.03.2009.17.062
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Received:
05 Jan 2010;
Published Online:
05 Jan 2010.
*
Correspondence:
Laleh Sinai, Hospital for Sick Children, Cell Biology, Toronto, Canada, sinai.laleh@gmail.com