Recent advances in understanding the mechanisms of cerebellar granule cell development and function and their contribution to behavior.
Recent advances in understanding the mechanisms of cerebellar granule cell development and function and their contribution to behavior.
复制标题
DOI：
10.12688/f1000research.15021.1
复制
发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Sillitoe, Roy V
中科院分区：
文献类型：
--
作者：
Lackey, Elizabeth P;Heck, Detlef H;Sillitoe, Roy V
小脑是一系列新兴争论的焦点，因为它的电路现在被认为编码了一个意想不到的功能多样性水平。小脑回路的灵活性使其不仅参与协调、学习和平衡等运动行为，还参与认知、情感和空间导航等非运动行为。根据小脑不同的功能角色，当这些回路因疾病或损伤而改变时，行为结果范围从神经系统疾病如共济失调、肌张力障碍和震颤到神经精神疾病，包括自闭症谱系障碍、精神分裂症和注意力缺陷/多动障碍。两个主要的问题出现了：什么类型的细胞介导这些正常和异常的过程，它们是如何完成这些看似不同的功能的？微小但数量众多的小脑颗粒细胞可能会回答这些问题。在这里，我们讨论了在理解颗粒细胞谱系如何在胚胎中出现以及当出生后小脑损伤时，补充颗粒细胞的干细胞生态位如何影响神经连接方面的最新进展。我们讨论了精确协调的发育程序、基因表达模式和表观遗传机制如何决定突触的形成，这些突触将多模态输入整合到单个颗粒细胞中。这些数据使我们考虑颗粒细胞突触异质性如何促进行为动物的感觉运动和非感觉运动信号。我们讨论了颗粒细胞使用超快神经传递的证据，可以在千赫兹频率下操作。总之，这些数据激发了一个新兴的观点，即颗粒细胞如何有助于形成复杂的动物行为。
The cerebellum is the focus of an emergent series of debates because its circuitry is now thought to encode an unexpected level of functional diversity. The flexibility that is built into the cerebellar circuit allows it to participate not only in motor behaviors involving coordination, learning, and balance but also in non-motor behaviors such as cognition, emotion, and spatial navigation. In accordance with the cerebellum's diverse functional roles, when these circuits are altered because of disease or injury, the behavioral outcomes range from neurological conditions such as ataxia, dystonia, and tremor to neuropsychiatric conditions, including autism spectrum disorders, schizophrenia, and attention-deficit/hyperactivity disorder. Two major questions arise: what types of cells mediate these normal and abnormal processes, and how might they accomplish these seemingly disparate functions? The tiny but numerous cerebellar granule cells may hold answers to these questions. Here, we discuss recent advances in understanding how the granule cell lineage arises in the embryo and how a stem cell niche that replenishes granule cells influences wiring when the postnatal cerebellum is injured. We discuss how precisely coordinated developmental programs, gene expression patterns, and epigenetic mechanisms determine the formation of synapses that integrate multi-modal inputs onto single granule cells. These data lead us to consider how granule cell synaptic heterogeneity promotes sensorimotor and non-sensorimotor signals in behaving animals. We discuss evidence that granule cells use ultrafast neurotransmission that can operate at kilohertz frequencies. Together, these data inspire an emerging view for how granule cells contribute to the shaping of complex animal behaviors.