Heller, Elizabeth AZhang, WenzhuSelimi, FekrijeEarnheart, John CŚlimak, Marta ASantos-Torres, JulioIbañez-Tallon, InesAoki, ChiyeChait, Brian THeintz, Nathaniel2023-05-232023-05-232012-01-012018-01-22https://repository.upenn.edu/handle/20.500.14332/42608Classical electron microscopic studies of the mammalian brain revealed two major classes of synapses, distinguished by the presence of a large postsynaptic density (PSD) exclusively at type 1, excitatory synapses. Biochemical studies of the PSD have established the paradigm of the synapse as a complex signal-processing machine that controls synaptic plasticity. We report here the restuls of a proteomic analysis of type 2, inhibitory synaptic complexes isolated by affinity purification from the cerebral cortex. We show that these synaptic complexes contain a variety of neurotransmitter receptors, neural cell-scaffolding and adhesion molecules, but that they are entirely lacking in cell signaling proteins. This fundamental distinction between the functions of type 1 and type 2 synapses in the nervous system has far reaching implications for models of synaptic plasticity, rapid adaptations in neural circuits, and homeostatic mechanisms controlling the balance of excitation and inhibition in the mature brain.© 2012 Heller et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Biochemistry, Biophysics, and Structural BiologyNeurologyNeuroscience and NeurobiologyPharmacy and Pharmaceutical SciencesTranslational Medical ResearchReport