Whole-brain mapping of monosynaptic inputs to midbrain cholinergic neurons.

Whole-brain mapping of monosynaptic inputs to midbrain cholinergic neurons.
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中脑胆碱能神经元单突触输入的全脑映射。

DOI:
10.1038/s41598-021-88374-6
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发表时间:
2021-04-27
期刊:
影响因子:
4.6
通讯作者:
Mena-Segovia J
Mena-Segovia J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Huerta-Ocampo I;Dautan D;Gut NK;Khan B;Mena-Segovia J

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胆碱能中脑参与广泛的运动和认知过程。桥脚(PPN)和外侧背侧被核(LDT)的胆碱能神经元发送长距离轴突投射,以丘脑的感觉运动区和边缘区、多巴胺能中脑和纹状体复合体为目标,在那里它们影响一系列功能,包括注意力、强化学习和行动选择。然而,对PPN和LDT胆碱能神经元传入事件的全面检查仍然缺乏,部分原因是该区域的神经化学异质性。在这里,我们在ChAT::Cre雄性和雌性大鼠中使用条件跨突触逆行标记表征了不同功能域(即PPN与LDT)的全脑输入连接组对胆碱能神经元的特征。我们发现,输入神经元广泛分布在整个大脑,但分离到特定的功能域。运动相关区域优先支配PPN,而边缘相关区域优先支配LDT。输入神经元的量化显示,PPN和LDT都从上丘和基底神经节(即网状黑质)的输出接收相似的大量输入。值得注意的是,我们发现PPN胆碱能神经元接受基底神经节结构的优先输入,而LDT胆碱能神经元接受边缘皮质区域的优先输入。我们的研究结果首次提供了PPN和LDT胆碱能神经元输入的特征,并强调了脑胆碱能系统之间连接组的关键差异,从而支持了它们在行为中的不同作用。
The cholinergic midbrain is involved in a wide range of motor and cognitive processes. Cholinergic neurons of the pedunculopontine (PPN) and laterodorsal tegmental nucleus (LDT) send long-ranging axonal projections that target sensorimotor and limbic areas in the thalamus, the dopaminergic midbrain and the striatal complex following a topographical gradient, where they influence a range of functions including attention, reinforcement learning and action-selection. Nevertheless, a comprehensive examination of the afferents to PPN and LDT cholinergic neurons is still lacking, partly due to the neurochemical heterogeneity of this region. Here we characterize the whole-brain input connectome to cholinergic neurons across distinct functional domains (i.e. PPN vs LDT) using conditional transsynaptic retrograde labeling in ChAT::Cre male and female rats. We reveal that input neurons are widely distributed throughout the brain but segregated into specific functional domains. Motor related areas innervate preferentially the PPN, whereas limbic related areas preferentially innervate the LDT. The quantification of input neurons revealed that both PPN and LDT receive similar substantial inputs from the superior colliculus and the output of the basal ganglia (i.e. substantia nigra pars reticulata). Notably, we found that PPN cholinergic neurons receive preferential inputs from basal ganglia structures, whereas LDT cholinergic neurons receive preferential inputs from limbic cortical areas. Our results provide the first characterization of inputs to PPN and LDT cholinergic neurons and highlight critical differences in the connectome among brain cholinergic systems thus supporting their differential roles in behavior.
DOI: 10.3389/fnana.2010.00001
发表时间: 2016-01-22
影响因子: 2.9
作者:
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影响因子: --
作者:
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