Laboratory of Neural Circuitry, Graduate School of Brain Science, Doshisha University, Kyotanabe, Japan.
Section of Viral Vector Development, National Institute for Physiological Sciences, Okazaki, Japan.
J Neurosci Res. 2018 Jul;96(7):1186-1207. doi: 10.1002/jnr.24214. Epub 2018 Jan 4.
In rodents, the dorsolateral striatum regulates voluntary movement by integrating excitatory inputs from the motor-related cerebral cortex and thalamus to produce contingent inhibitory output to other basal ganglia nuclei. Striatal parvalbumin (PV)-producing interneurons receiving this excitatory input then inhibit medium spiny neurons (MSNs) and modify their outputs. To understand basal ganglia function in motor control, it is important to reveal the precise synaptic organization of motor-related cortical and thalamic inputs to striatal PV interneurons. To examine which domains of the PV neurons receive these excitatory inputs, we used male bacterial artificial chromosome transgenic mice expressing somatodendritic membrane-targeted green fluorescent protein in PV neurons. An anterograde tracing study with the adeno-associated virus vector combined with immunodetection of pre- and postsynaptic markers visualized the distribution of the excitatory appositions on PV dendrites. Statistical analysis revealed that the density of thalamostriatal appositions along the dendrites was significantly higher on the proximal than distal dendrites. In contrast, there was no positional preference in the density of appositions from axons of the dorsofrontal cortex. Population observations of thalamostriatal and corticostriatal appositions by immunohistochemistry for pathway-specific vesicular glutamate transporters confirmed that thalamic inputs preferentially, and cortical ones less preferentially, made apposition on proximal dendrites of PV neurons. This axodendritic organization suggests that PV neurons produce fast and reliable inhibition of MSNs in response to thalamic inputs and process excitatory inputs from motor cortices locally and plastically, possibly together with other GABAergic and dopaminergic dendritic inputs, to modulate MSN inhibition.
在啮齿动物中,背外侧纹状体通过整合来自运动相关大脑皮层和丘脑的兴奋性输入,产生对其他基底神经节核团的条件性抑制输出,从而调节自主运动。接收这种兴奋性输入的纹状体内的γ-氨基丁酸(parvalbumin, PV)产生中间神经元随后抑制中等棘突神经元(medium spiny neurons, MSNs)并改变它们的输出。为了理解基底神经节在运动控制中的功能,揭示与运动相关的皮质和丘脑输入到纹状体内的 PV 中间神经元的精确突触组织是很重要的。为了研究哪些 PV 神经元的域接收这些兴奋性输入,我们使用了表达 somatodendritic 膜靶向绿色荧光蛋白的雄性细菌人工染色体转基因小鼠。与腺相关病毒载体结合的顺行示踪研究,以及突触前和突触后标记物的免疫检测,可视化了兴奋性突触前在 PV 树突上的分布。统计分析显示,在树突上,丘脑纹状体突触的密度在近端树突上明显高于远端树突上。相比之下,来自背侧额前皮质的轴突的突触密度没有位置偏好。通过对特定途径的囊泡谷氨酸转运体的免疫组织化学进行的丘脑纹状体和皮质纹状体突触的群体观察,证实了丘脑输入优先,而皮质输入则不太优先,在 PV 神经元的近端树突上形成突触。这种轴突树突组织表明,PV 神经元产生快速而可靠的 MSN 抑制,以响应丘脑输入,并局部和可塑性地处理来自运动皮质的兴奋性输入,可能与其他 GABA 能和多巴胺能树突输入一起,调节 MSN 抑制。