Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, 16163 Genova, Italy; Life Science Department, University of Milan, 20133 Milano, Italy.
Cell Rep. 2015 Nov 17;13(7):1353-1365. doi: 10.1016/j.celrep.2015.10.009. Epub 2015 Nov 5.
The basal ganglia play a critical role in shaping motor behavior. For this function, the activity of medium spiny neurons (MSNs) of the striatonigral and striatopallidal pathways must be integrated. It remains unclear whether the activity of the two pathways is primarily coordinated by synaptic plasticity mechanisms. Using a model of Parkinson's disease, we determined the circuit and behavioral effects of concurrently regulating cell-type-specific forms of corticostriatal long-term synaptic depression (LTD) by inhibiting small-conductance Ca(2+)-activated K(+) channels (SKs) of the dorsolateral striatum. At striatopallidal synapses, SK channel inhibition rescued the disease-linked deficits in endocannabinoid (eCB)-dependent LTD. At striatonigral cells, inhibition of these channels counteracted a form of adenosine-mediated LTD by activating the ERK cascade. Interfering with eCB-, adenosine-, and ERK signaling in vivo alleviated motor abnormalities, which supports that synaptic modulation of striatal pathways affects behavior. Thus, our results establish a central role of coordinated synaptic plasticity at MSN subpopulations in motor control.
基底神经节在塑造运动行为方面起着关键作用。对于这一功能，纹状体苍白球和纹状体黑质通路的中间多棘神经元（MSN）的活动必须整合。目前尚不清楚两条通路的活动是否主要通过突触可塑性机制来协调。通过使用帕金森病模型，我们通过抑制外侧纹状体的小电导钙激活钾（SK）通道，确定了同时调节皮质纹状体长时程突触抑制（LTD）的细胞类型特异性形式的回路和行为效应。在纹状体苍白球突触上，SK 通道抑制挽救了与疾病相关的内源性大麻素（eCB）依赖性 LTD 的缺陷。在纹状体黑质神经元上，抑制这些通道通过激活 ERK 级联反应来拮抗一种由腺苷介导的 LTD。在体内干扰 eCB、腺苷和 ERK 信号通路缓解了运动异常，这支持了纹状体通路的突触调节对行为的影响。因此，我们的研究结果确立了 MSN 亚群在运动控制中协调的突触可塑性的核心作用。
