People diagnosed with an Autism Spectrum Disorder (ASD) are commonly assessed as having persistent difficulties with social communication and social interaction.
Preclinical ASD research focuses on developing rodent models, where pharmacological or other therapeutics can be tested. Notably, several recent studies have shown low success rates of translation of rodent model findings to therapeutics. A major bias of such studies is anthropomorphising rodent behaviours, often termed as “autism-like” in rodents, which leads to misinterpretation of experimental findings. There are fundamental anatomical differences between the rodent and human brain, such as the lack of a prominent prefrontal cortex in rodents. Taken together, these findings suggest that different brain regions and different neuronal ensembles may underlie complex behaviours, such as social behaviour in rodents and human. Thus, we reason that understanding the precise molecular and cellular mechanisms governing social behaviour in rodents is the best avenue to improve preclinical rodent models.
First, the student will use established and novel paradigms of social behaviour in rodents (examining social recognition, social memory, social hierarchy and social proximity), available in the Gkogkas and Morris labs, coupled with in vivo analysis of neuronal activity (Calcium imaging and activation of immediate early genes in freely moving/behaving rodents) to pinpoint the brain regions and cell-types which are recruited. Second, the student will analyse gene-expression with RNA sequencing after isolating activated cells either genetically, using cell-type specific gene expression analysis, or, by physically dissecting them (laser capture microdissection). The combination of those techniques will reveal which brain regions and cell-types underlie social behaviour in rodents, and will facilitate the design of optogenetic experiments to query the function of those circuits in vivo, during social behaviour.
In conclusion, this project will address a key question in neurobiology of behaviour, which is how social behaviour in rodents is regulated at the molecular/cellular/neuronal ensemble levels. This project will promote our understanding of the relation between rodent and human behaviour, and facilitate the development of therapeutics for autism based on solid preclinical rodent models.
Dr Christos Gkogkas
Prof Richard Morris