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Graded lines: using genetic variation in neuronal projections to understand functional organization



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Phillips, James William  ORCID logo


In this thesis, I investigated the interactions between brain regions in mice, with an emphasis on the motor system. Whilst brain areas are typically studied in isolation, they exist to act upon one other, and we lack even relatively basic principles of how brain areas interact. Here, my colleagues and I used new genetic techniques to investigate this topic. There were two major focuses. Firstly, I investigated how thalamic pathways vary, using genetic sequencing to produce a high dimensional transcriptomic profile of forebrain communication pathways. This revealed a strikingly simple organisational system in rodent thalamus, with pathways serving diverse modalities varying in a common manner. Pathways serving systems as variable as vision, navigation, motor control and somatosensation showed a similar variation in gene expression, which was functionally relevant. This establishes a common reference frame for diverse modalities of cognition. Secondly, I began an ongoing investigation of the signals that motor cortex send to subcortical motor structures. This revealed a separation of signals that project to the basal ganglia and cerebellum, opposite to existing predictions. Basal Ganglia-projecting signals encoded motor execution, whilst cerebellar projecting pathways encoded preparation- and reward-related information. These experiments motivated further investigation of these pathways, which are described within. Together, these results demonstrate the utility of focussing upon interactions between network nodes to reveal the contribution of individual nodes.





Edgley, Steve


Thalamus, Thalamocortical, cortex, genetics, RNAseq, microscopy


Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge