title: A presynaptic role for FMRP during protein synthesis-dependent long-term plasticity in Aplysia.
abstract: Loss of the Fragile X mental retardation protein (FMRP) is associated with presumed postsynaptic deficits in mouse models of Fragile X syndrome. However, the possible presynaptic roles of FMRP in learning-related plasticity have received little attention. As a result, the mechanisms whereby FMRP influences synaptic function remain poorly understood. To investigate the cellular locus of the effects of FMRP on synaptic plasticity, we cloned the Aplysia homolog of FMRP and find it to be highly expressed in neurons. By selectively down-regulating FMRP in individual Aplysia neurons at the sensory-to-motor neuron synapse reconstituted in co-cultures, we demonstrate that FMRP functions both pre- and postsynaptically to constrain the expression of long-term synaptic depression induced by repeated pulses of FMRF-amide. In contrast, FMRP has little to no effect on long-term synaptic facilitation induced by repeated pulses of serotonin. Since other components of signaling pathways involved in plasticity appear to be conserved between Aplysia and mammalian neurons, our findings suggest that FMRP can participate in both pre- and postsynaptic regulation of enduring synaptic plasticity that underlies the storage of certain types of long-term memory.
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
authors.forename: Sally M
authors.initials: SM
authors.lastname: Till
authors.forename: Hsiu-Ling
authors.initials: HL
authors.lastname: Li
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Miniaci
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
authors.forename: Yun-Beom
authors.initials: YB
authors.lastname: Choi
mesh_terms: D000818:Animals; D001048:Aplysia / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D003001:Cloning, Molecular / Q000379:methods; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D019835:FMRFamide / Q000494:pharmacology; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D049990:Membrane Transport Modulators / Q000494:pharmacology; D018613:Microscopy, Confocal; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology
chemical_list: D019835:FMRFamide; D051860:Fragile X Messenger Ribonucleoprotein 1; D049990:Membrane Transport Modulators; D016376:Oligonucleotides, Antisense; D012701:Serotonin