title: Photoreceptor ablation initiates the immediate loss of glutamate receptors in postsynaptic bipolar cells in retina.
abstract: Structural changes underlying neurodegenerative diseases include dismantling of synapses, degradation of circuitry, and even massive rewiring. Our limited understanding of synapse dismantling stems from the inability to control the timing and extent of cell death. In this study, selective ablation of cone photoreceptors in live mouse retina and tracking of postsynaptic partners at the cone-to-ON cone bipolar cell synapse reveals that early reaction to cone loss involves rapid and local changes in postsynaptic glutamate receptor distribution. Glutamate receptors disappear with a time constant of 2 h. Furthermore, binding of glutamate receptors by agonists and antagonists is insufficient to rescue glutamate receptor loss, suggesting that receptor allocation depends on the physical presence of cones. These findings demonstrate that the initial step in synapse disassembly involves postsynaptic receptor loss rather than dendritic retraction, providing insight into the early stages of neurodegenerative disease.
authors: Department of Ophthalmology, University of California, San Francisco, San Francisco, California 94143 dunnf@vision.ucsf.edu.
authors: Felice A
authors: FA
authors: Dunn
mesh_terms: D000818:Animals; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051245:Retinal Bipolar Cells / Q000378:metabolism* / Q000648:ultrastructure; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6
keywords: glutamate receptor; neurodegenerative disease; retina; synapse; synapse disassembly; vision