Neuroligin-1 is required for normal expression of LTP and associative fear memory in the amygdala of adult animals

doi:10.1073/pnas.0803448105

Neuroligin-1 is required for normal expression of LTP and associative fear memory in the amygdala of adult animals

*Department of Life Science, Pohang University of Science and Technology, Pohang, Gyungbuk 790-784, Korea;
^‡Department of Psychology, Korea University, Seoul 136-701, Korea;
^§Center for Neural Science, Korea Institute of Science and Technology, Seoul 136-791, Korea;
^¶Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799, Korea; and
^‖Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York, NY 10032

Contributed by Eric R. Kandel, April 10, 2008
↵ ^†J.K. and S.-Y.J. contributed equally to this work. (received for review February 21, 2008)

Abstract

Neuroligin-1 is a potent trigger for the de novo formation of synaptic connections, and it has recently been suggested that it is required for the maturation of functionally competent excitatory synapses. Despite evidence for the role of neuroligin-1 in specifying excitatory synapses, the underlying molecular mechanisms and physiological consequences that neuroligin-1 may have at mature synapses of normal adult animals remain unknown. By silencing endogenous neuroligin-1 acutely in the amygdala of live behaving animals, we have found that neuroligin-1 is required for the storage of associative fear memory. Subsequent cellular physiological studies showed that suppression of neuroligin-1 reduces NMDA receptor-mediated currents and prevents the expression of long-term potentiation without affecting basal synaptic connectivity at the thalamo-amygdala pathway. These results indicate that persistent expression of neuroligin-1 is required for the maintenance of NMDAR-mediated synaptic transmission, which enables normal development of synaptic plasticity and long-term memory in the amygdala of adult animals.

Footnotes

**To whom correspondence may be addressed. E-mail: erk5{at}columbia.edu or joungkim{at}postech.ac.kr
Author contributions: J.K., E.R.K., and J.-H.K. designed research; J.K., S.-Y.J., Y.K.L., J.-S.C., and C.J.L. performed research; S.P., J.-S.C., H.-S.K., and P.S. contributed new reagents/analytic tools; J.K., S.-Y.J., Y.-B.C., C.H.B., and J.-H.K. analyzed data; and J.K., S.-Y.J., C.J.L., Y.-B.C., C.H.B., E.R.K., and J.-H.K. wrote the paper.
Conflict of interest statement: E.R.K. is one of four founders of Memory Pharmaceuticals and is Chairman of its Scientific Advisory Board. Memory Pharmaceuticals is concerned with developing drugs for age-related memory loss. Some of these drugs are also potentially useful in depression and schizophrenia. E.R.K.'s laboratory is not involved in developing these drugs. E.R.K. is also a consultant for BrainCells, Inc., which works on neurogenesis, an area in which he is not directly involved.
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