Crépel Francis
Pharmacologie de la Synapse, Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, Université Paris-Sud and Centre National de la Recherche Scientifique, 91405 Orsay Cedex, France.
J Neurophysiol. 2009 Aug;102(2):965-73. doi: 10.1152/jn.00269.2009. Epub 2009 Jun 17.
Until recently, except for A1 adenosine, N-methyl-d-aspartate, and cannabinoid receptors, little effort has been made to unravel possible roles of parallel fiber (PF) presynaptic receptors in long-term depression (LTD) of synaptic transmission at PF-Purkinje cell (PC) synapses. Presynaptic kainate (KA) receptors are also present on PFs and might also influence LTD induction by modulating glutamate (Glu) release at PF-PC synapses. This hypothesis was tested by comparing the efficacy of two pairing protocols in inducing LTD in adult wild-type and knock-out mice for the Glu receptor 6 (GluR6) subunit of KA receptors. Activation of presynaptic KA receptors was unnecessary for LTD induction when PF inputs were paired with climbing fiber (CF) stimulation but became crucial when CF input was replaced by direct depolarization of PCs. By comparing basal paired-pulse facilitation of PF-excitatory postsynaptic currents (EPSCs) and depolarization-induced suppression of excitation in adult wild-type and GluR6 knock-out mice, it was shown that the participation of PF presynaptic KA receptors in LTD induction was likely to mainly result from their tonic activation by basal extracellular Glu, rather than from their activation by retrograde release of Glu by PCs during pairing protocols. Finally, this study suggests that, in adult mice, CFs not only participate in LTD induction by depolarizing postsynaptic cells but also by activating postsynaptic mGluR1alpha metabotropic glutamate receptors at CF-PC synapses.
直到最近，除了A1腺苷、N-甲基-D-天冬氨酸和大麻素受体外，人们很少致力于揭示平行纤维（PF）突触前受体在PF-浦肯野细胞（PC）突触传递的长时程抑制（LTD）中的可能作用。PF上也存在突触前海人藻酸（KA）受体，其也可能通过调节PF-PC突触处的谷氨酸（Glu）释放来影响LTD的诱导。通过比较两种配对方案在成年野生型和KA受体Glu受体6（GluR6）亚基基因敲除小鼠中诱导LTD的效果，对这一假设进行了验证。当PF输入与攀爬纤维（CF）刺激配对时，突触前KA受体的激活对于LTD的诱导并非必需，但当CF输入被PC的直接去极化取代时则变得至关重要。通过比较成年野生型和GluR6基因敲除小鼠中PF兴奋性突触后电流（EPSC）的基础配对脉冲易化和去极化诱导的兴奋抑制，结果表明PF突触前KA受体参与LTD诱导可能主要是由于基础细胞外Glu对其的持续性激活，而非配对方案期间PC逆行释放Glu对其的激活。最后，这项研究表明，在成年小鼠中，CF不仅通过使突触后细胞去极化参与LTD诱导，还通过激活CF-PC突触处的突触后代谢型谷氨酸受体mGluR1α来参与。
