RT Journal Article SR Electronic T1 Lipid Rafts in the Maintenance of Synapses, Dendritic Spines, and Surface AMPA Receptor Stability JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 3262 OP 3271 DO 10.1523/JNEUROSCI.23-08-03262.2003 VO 23 IS 8 A1 Heike Hering A1 Chih-Chun Lin A1 Morgan Sheng YR 2003 UL http://www.jneurosci.org/content/23/8/3262.abstract AB Cholesterol/sphingolipid microdomains (lipid rafts) in the membrane are involved in protein trafficking, formation of signaling complexes, and regulation of actin cytoskeleton. Here, we show that lipid rafts exist abundantly in dendrites of cultured hippocampal neurons, in which they are associated with several postsynaptic proteins including surface AMPA receptors. Depletion of cholesterol/sphingolipid leads to instability of surface AMPA receptors and gradual loss of synapses (both inhibitory and excitatory) and dendritic spines. The remaining synapses and spines in raft-depleted neurons become greatly enlarged. The importance of lipid rafts for normal synapse density and morphology could explain why cholesterol promotes synapse maturation in retinal ganglion cells (Mauch et al., 2001) and offers a potential link between disordered cholesterol metabolism and the synapse loss seen in neurodegenerative disease.