Diverse serotonin 2C receptor mediated behaviours resulting from snoRNA regulated post-transcriptional modification

大脑中的化学信号高度依赖于特定的神经递质受体。这些受体的不同物理形式(异构体)可以极大地影响神经递质信号。2C受体(5HT2CR)是神经递质5-羟色胺结合的受体之一，以多种不同的形式(亚型)存在，具有不同的功能水平。不同的5HT2CR亚型的丰度取决于被称为转录后修饰的微妙分子变化的程度。初步研究表明，当转录后修饰的调节发生改变，产生功能较少的受体形式时，这可能会导致5HT2CR功能特有的行为影响。然而，5HT2CR调节行为的许多方面，这些分子变化和随后的受体变体对不同行为过程的贡献程度仍然不完全清楚。这项拟议的项目旨在通过观察5HT2CRs转录后修饰的程度在大脑中的变化来解决这个问题，并将这些分子发现与行为的影响联系起来。为了做到这一点，我们将检查缺乏转录后修饰机制的重要调控组件的动物。我们的工作将有助于更好地理解不同版本的5HT2CRs在大脑中的功能，并可能转化为治疗抑郁症、自杀和精神分裂症等临床疾病的更好方法，这些疾病与这种受体的变化有关。

Chemical signaling in the brain is highly dependent on specific neurotransmitter receptors. Different physical forms (isoforms) of these receptors can dramatically affect neurotransmitter signaling. One of the receptors to which the neurotransmitter serotonin binds, the 2C receptor (5HT2CR) exists in numerous different forms (isoforms) which have varying levels of functionality. The abundance of different 5HT2CR isoforms is dependent on the degree of subtle molecular changes known as post-transcriptional modifications. Preliminary studies have shown that when the regulation of post-transcriptional modification is altered and less functional forms of the receptor are generated, this can lead to behavioural effects that are specific to the function of the 5HT2CR. However, 5HT2CRs regulate many aspects of behaviour and the extent to which these molecular changes and the subsequent receptor variants contribute to different behavioural processes is still not fully understood. The proposed project aims to address this by looking at how the degree of post-transcriptional modification of 5HT2CRs varies through the brain and link these molecular findings to effects on behaviour. To do this we will examine animals lacking an important regulatory component of the post-transcription modification machinery. Our work will lead to a better understanding of how different versions of 5HT2CRs function in brain and may translate into better therapies for clinical conditions such as depression, suicide and schizophrenia, which have been linked to alterations in this receptor.