reelin secreted by gabaergic neurons regulates glutamate receptor homeostasisreelin分泌gaba ergic神经元调节谷氨酸受体体内平衡.pdfVIP

Reelin Secreted by GABAergic Neurons Regulates Glutamate Receptor Homeostasis 1,2. ´ 1,2. ` 1,2 1,2 Cecilia Gonzalez Campo , Melanie Sinagra , Daniele Verrier , Olivier J. Manzoni , Pascale Chavis1,2* ´ 1 INSERM U862, Neurocentre Magendie, Pathophysiology of Synaptic Plasticity, Bordeaux, France, 2 Universite de Bordeaux, Bordeaux, France Abstract Background: Reelin is a large secreted protein of the extracellular matrix that has been proposed to participate to the etiology of schizophrenia. During development, reelin is crucial for the correct cytoarchitecture of laminated brain structures and is produced by a subset of neurons named Cajal-Retzius. After birth, most of these cells degenerate and reelin expression persists in postnatal and adult brain. The phenotype of neurons that bind secreted reelin and whether the continuous secretion of reelin is required for physiological functions at postnatal stages remain unknown. Methodology/Principal Findings: Combining immunocytochemical and pharmacological approaches, we first report that two distinct patterns of reelin expression are present in cultured hippocampal neurons. We show that in hippocampal cultures, reelin is secreted by GABAergic neurons displaying an intense reelin immunoreactivity (IR). We demonstrate that secreted reelin binds to receptors of the lipoprotein family on neurons with a punctate reelin IR. Secondly, using calcium imaging techniques, we examined the physiological consequences of reelin secretion blockade. Blocking protein secretion rapidly and reversib