Carey Megan R, Regehr Wade G
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Neuron. 2009 Apr 16;62(1):112-22. doi: 10.1016/j.neuron.2009.02.022.
Synapses throughout the brain are modified through associative mechanisms in which one input provides an instructive signal for changes in the strength of a second coactivated input. In cerebellar Purkinje cells, climbing fiber synapses provide an instructive signal for plasticity at parallel fiber synapses. Here, we show that noradrenaline activates alpha2-adrenergic receptors to control short-term and long-term associative plasticity of parallel fiber synapses. This regulation of plasticity does not reflect a conventional direct modulation of the postsynaptic Purkinje cell or presynaptic parallel fibers. Instead, noradrenaline reduces associative plasticity by selectively decreasing the probability of release at the climbing fiber synapse, which in turn decreases climbing fiber-evoked dendritic calcium signals. These findings raise the possibility that targeted presynaptic modulation of instructive synapses could provide a general mechanism for dynamic context-dependent modulation of associative plasticity.
大脑中的突触通过关联机制发生改变，在这种机制中，一个输入为第二个共同激活的输入的强度变化提供指导信号。在小脑浦肯野细胞中，攀缘纤维突触为平行纤维突触的可塑性提供指导信号。在这里，我们表明去甲肾上腺素激活α2-肾上腺素能受体，以控制平行纤维突触的短期和长期关联可塑性。这种可塑性调节并不反映对突触后浦肯野细胞或突触前平行纤维的传统直接调节。相反，去甲肾上腺素通过选择性降低攀缘纤维突触处的释放概率来降低关联可塑性，这反过来又减少了攀缘纤维诱发的树突状钙信号。这些发现增加了一种可能性，即对指导性突触进行靶向突触前调制可能为关联可塑性的动态上下文依赖性调制提供一种通用机制。
