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In theory, abnormal spines could lead to dysfunctional circuits and vice versa, so it is still not clear which problem comes first. Because of the tight structure-function relationships at the synapse, and given the significant overlap between signaling pathways that regulate spine shape\/dynamics and long-term synaptic plasticity (both of which involve proteins regulated by fragile X mental retardation protein [FMRP]), it is argued that the two defects cannot be separated. It will be critical to determine whether neurons that lack FMRP and demonstrate alterations in long-term potentiation\/depression also fail to undergo the expected enlargement\/shrinkage of dendritic spines associated with those forms of synaptic plasticity or to establish clear links from FMRP signaling to either spine instability or defective synaptic plasticity, especially during critical periods of brain development. The resulting data will be vital in guiding translational research that can identify novel molecular targets for therapy in this devastating disorder.<\/jats:p>","DOI":"10.1177\/1073858410395322","type":"journal-article","created":{"date-parts":[[2011,5,7]],"date-time":"2011-05-07T01:35:59Z","timestamp":1304732159000},"page":"28-44","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":59,"title":["Which Comes First in Fragile X Syndrome, Dendritic Spine Dysgenesis or Defects in Circuit Plasticity?"],"prefix":"10.1177","volume":"18","author":[{"given":"Carlos","family":"Portera-Cailliau","sequence":"first","affiliation":[{"name":"Departments of Neurology and Neurobiology, David Geffen School of Medicine at the University of California, Los Angeles, CA, 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