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

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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.