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A Balance between Excitatory and Inhibitory Synapses Is Controlled by PSD-95 and Neuroligin

Factors that control differentiation of presynaptic and postsynaptic elements into excitatory or inhibitory synapses are poorly defined. Here we show that the postsynaptic density (PSD) proteins PSD-95 and neuroligin-1 (NLG) are critical for dictating the ratio of excitatory-to-inhibitory synaptic c...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2004-09, Vol.101 (38), p.13915-13920
Main Authors: Prange, Oliver, Wong, Tak Pan, Gerrow, Kimberly, Wang, Yu Tian, El-Husseini, Alaa, Nicoll, Roger A.
Format: Article
Language:English
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Summary:Factors that control differentiation of presynaptic and postsynaptic elements into excitatory or inhibitory synapses are poorly defined. Here we show that the postsynaptic density (PSD) proteins PSD-95 and neuroligin-1 (NLG) are critical for dictating the ratio of excitatory-to-inhibitory synaptic contacts. Exogenous NLG increased both excitatory and inhibitory presynaptic contacts and the frequency of miniature excitatory and inhibitory synaptic currents. In contrast, PSD-95 overexpression enhanced excitatory synapse size and miniature frequency, but reduced the number of inhibitory synaptic contacts. Introduction of PSD-95 with NLG augmented synaptic clustering of NLG and abolished NLG effects on inhibitory synapses. Interfering with endogenous PSD-95 expression alone was sufficient to reduce the ratio of excitatory-to-inhibitory synapses. These findings elucidate a mechanism by which the amounts of specific elements critical for synapse formation control the ratio of excitatory-to-inhibitory synaptic input.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0405939101