Defining the role of ciliary BBS proteins in neuroplasticity

神经元可塑性是现代神经科学研究中最重要的领域之一，也是现存最好的学习和记忆细胞模型之一。海马体是一种对学习和记忆存储很重要的大脑结构。已有研究表明，即使在成年期间，海马区也有新的神经元诞生。新的神经元整合到现有的网络中，对发展新的技能和记忆非常重要。最近还发现，记忆和学习技能“储存”在树突中，树突是神经细胞树突上的蘑菇状突起。树突棘是非常“可塑性”的，也就是说，它们在短时间内在形状、体积和数量上都会发生显著的变化。由于脊柱主要由肌动蛋白细胞骨架组成，它们是动态的，大多数脊柱能够在肌动蛋白重塑后几秒钟到几分钟内改变形状。新的经历和学习会导致新的脊梁的形成。已经观察到脊柱畸形或脊柱数量减少与学习障碍有关。最近，纤毛/纤毛蛋白与成人神经发生之间出现了令人兴奋的联系。纤毛是细胞膜上的毛发状突起。它们存在于几乎所有的真核细胞中。在过去的十年里，它已经被证明是正常的人类功能，如视、听、嗅觉、呼吸、排泄、繁殖的能力，关键是依赖于正确的睫毛功能。研究还表明，纤毛对正常的大脑功能，如学习和记忆非常重要。正常的纤毛功能依赖于包括BBS在内的许多蛋白质的完整性。我们已经产生的初步数据表明，在BBS小鼠模型中，成年新生神经元的形成减少，树突棘的数量和密度也减少。这些小鼠缺乏具有功能的BBS蛋白，因此概括了人类BBS的主要特征，因此，我们建议研究单个BBS蛋白的突变如何导致神经可塑性的变化。我们假设，缺乏功能齐全的BBS蛋白会影响树突棘的形成，从而降低海马区信息存储和有效学习的能力。

Neuronal plasticity is among the most important areas of modern neuroscience research and one of the best existing cellular models for learning and memory. The hippocampus is a brain structure important for learning and the storage of memories. It has been shown that there is an area in hippocampus where new neurons are born even during adult life. New neurons integrate into existing networks and are important for developing new skills and memory. It has also recently emerged that memories and learning skills are "stored" in dendritic spines, mushroom like protrusions on the dendrites of nerve cells. Dendritic spines are very "plastic", that is, they change significantly in shape, volume, and number over a short time course. Because spines mostly comprise an actin cytoskeleton, they are dynamic, with the majority of spines able to change their shape within seconds to minutes following actin remodelling. New experiences and learning lead to the formation of new spines. It has been observed that malformed spines or reduced spine number can be associated with learning disabilities.Recently, an exciting link between cilia/ciliary proteins and adult neurogenesis has emerged. Cilia are hair-like projections from the cell membrane. They are found on almost all eukaryotic cells. In the last decade it has been shown normal human functions such as ability to see, hear, smell, breathe, excrete, reproduce critically depend on correct ciliary function. It has been also shown that cilia are important for normal brain functions such as learning and memory. Normal cilia function depends on integrity of many proteins including BBS. We have generated preliminary data indicating that there is a reduction in formation of adult new born neurons as well as reduction in dendritic spine number and density in Bbs mice model. These mice lack a functional BBS protein and therefore recapitulates the main features of human BBS and thus, will provide Here we propose to investigate how mutation in a single BBS protein might lead to the changes in neuroplasticity. We hypothesise that the absence of a fully functioning Bbs protein affects the formation of dendritic spines thus reducing the hippocampal capacity for information storage and effective learning.