Sang-Yong Jung
a, Juhyun Kim
a, Oh Bin Kwon
a, Jung Hoon Jung
a, Kyongman An
a, A Young Jeong
a, C. Justin Lee
b, Yun-Beom Choi
c, Craig H. Bailey
c, Eric R. Kandel
c, and Joung-Hun Kim
a,1
aDepartment of Life Science, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 790-784, Korea;
bCenter for Neural Science, Korea Institute of Science and Technology (KIST), Seoul 136-791, Korea; and
cDepartment of Neuroscience, College of Physicians and Surgeons, Columbia University, New York, NY 10032
Contributed by Eric Richard Kandel, January 28, 2010 (sent for review October 29, 2009)
Abstract
Despite considerable evidence for a critical role of neuroligin-1 in the specification of excitatory synapses, the cellular mechanisms and physiological roles of neuroligin-1 in mature neural circuits are poorly understood. In mutant mice deficient in neuroligin-1, or adult rats in which neuroligin-1 was depleted, we have found that neuroligin-1 stabilizes the NMDA receptors residing in the postsynaptic membrane of amygdala principal neurons, which allows for a normal range of NMDA receptor-mediated synaptic transmission. We observed marked decreases in NMDA receptor-mediated synaptic currents at afferent inputs to the amygdala of neuroligin-1 knockout mice. However, the knockout mice exhibited a significant impairment in spike-timing-dependent long-term potentiation (STD-LTP) at the thalamic but not the cortical inputs to the amygdala. Subsequent electrophysiological analyses indicated that STD-LTP in the cortical pathway is largely independent of activation of postsynaptic NMDA receptors. These findings suggest that neuroligin-1 can modulate, in a pathway-specific manner, synaptic plasticity in the amygdala circuits of adult animals, likely by regulating the abundance of postsynaptic NMDA receptors.
STD-LTP, thalamic pathway, cortical pathway, autism
Footnotes
1To whom correspondence should be addressed.
Author contributions: S-Y.J., J.K., and J-H.K. designed research; S-Y.J., J.K., O.B.K., J.H.J., and C.J.L.
performed research; K.A., A.Y.J., and E.R.K. contributed new reagents/analytic tools; S-Y.J., O.B.K., Y-B.C., C.H.B., and J-H.K. analyzed data; and J.K., O.B.K., Y-B.C., C.H.B., E.R.K., and J-H.K. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at
www.pnas.org/cgi/content/full/1001084107/DCSupplemental.