Synaptic Function of Rab11Fip5: Selective Requirement for Hippocampal Long-Term Depression

摘要: Postsynaptic AMPA-type glutamate receptors (AMPARs) are among the major determinants of synaptic strength and can be trafficked into out synapses. Neuronal activity regulates AMPAR trafficking during plasticity to induce long-term changes in strength, including potentiation (LTP) depression (LTD). Rab family GTPases regulate most membrane eukaryotic cells; particularly, Rab11 its effectors implicated mediating postsynaptic insertion LTP. To explore function Rab11Fip5, a neuronal effector candidate autism-spectrum disorder gene, we performed shRNA-mediated knock-down genetic knock-out (KO) studies. Surprisingly, observed robust shRNA-induced phenotypes that were rescued by Rab11Fip5 cDNA but nevertheless not conditional KO neurons. Both cultured neurons acute slices, had no significant effect on basic parameters transmission, indicating is required for fundamental operations, such as neurotransmitter release or insertion. did, however, abolish hippocampal LTD measured both slices using chemical protocol did affect The mice normally several behavioral tasks, fear conditioning, showed enhanced contextual extinction. These first findings suggest requirement presumably Rab11, LTD.