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 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.
Prange
Oliver
O
Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Wong
Tak Pan
TP
Gerrow
Kimberly
K
Wang
Yu Tian
YT
El-Husseini
Alaa
A
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008853:Microscopy; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D016133:Polymerase Chain Reaction; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D014162:Transfection
D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C093438:neuroligin 1; C033652:postsynaptic density proteins; D051528:Guanylate Kinases