Soler-Llavina Gilberto J, Sabatini Bernardo L
Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.
Nat Neurosci. 2006 Jun;9(6):798-806. doi: 10.1038/nn1698. Epub 2006 May 7.
Here we demonstrate that cerebellar stellate cells diffusionally isolate synaptically evoked signals in dendrites and are capable of input-specific synaptic plasticity. Sustained activity of parallel fibers induces a form of long-term depression that requires opening of calcium (Ca(2+))-permeable AMPA-type glutamate receptors (CP-AMPARs) and signaling through class 1 metabotropic glutamate receptors (mGluR1) and CB1 receptors. This depression is induced by postsynaptic increases in Ca(2+) concentration ([Ca(2+)]) and is limited to activated synapses. To understand how synapse-specific plasticity is induced by diffusible second messengers in aspiny dendrites, we examined diffusion of Ca(2+) and small molecules within stellate cell dendrites. Activation of a single parallel fiber opened CP-AMPARs, generating long-lived Ca(2+) transients that were confined to submicron dendritic stretches. The diffusion of Ca(2+) was severely retarded due to interactions with parvalbumin and a general restriction of small molecule mobility. Thus stellate cell dendrites spatially restrict signaling cascades that lead from CP-AMPAR activation to endocannabinoid production and trigger the selective regulation of active synapses.
在此我们证明，小脑星状细胞通过扩散隔离树突中突触诱发的信号，并且能够进行输入特异性的突触可塑性。平行纤维的持续活动诱导了一种形式的长时程抑制，这需要钙（Ca(2+)）通透型AMPA受体（CP-AMPARs）开放，并通过1类代谢型谷氨酸受体（mGluR1）和CB1受体进行信号传导。这种抑制是由突触后钙浓度（[Ca(2+)]）升高诱导的，并且仅限于激活的突触。为了理解无棘树突中可扩散的第二信使如何诱导突触特异性可塑性，我们研究了星状细胞树突内Ca(2+)和小分子的扩散。单个平行纤维的激活打开了CP-AMPARs，产生了局限于亚微米级树突段的长寿命Ca(2+)瞬变。由于与小白蛋白的相互作用以及小分子流动性的普遍限制，Ca(2+)的扩散受到严重阻碍。因此，星状细胞树突在空间上限制了从CP-AMPAR激活到内源性大麻素产生的信号级联反应，并触发了对活跃突触的选择性调节。
