Khan, SQ; (2017) Neurod6 and Neurod1 are required for the survival of a novel subset of midbrain dopaminergic neurons projecting to the lateral septum. Doctoral thesis , UCL (University College London).

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Abstract

Midbrain dopaminergic neurons are highly heterogeneous. They differ in their target and afferent projections and firing patterns, and therefore in their functional properties. The molecular underpinnings of this heterogeneity are largely unknown and there is a paucity of markers that distinguish these functional subsets. This thesis reports the identification and characterisation of a novel subset of midbrain dopaminergic neurons located in the ventral tegmental area that expresses the basic helix-loop-helix transcription factor, Neurogenic Differentiation Factor-6 (NEUROD6). Retrograde fluorogold tracing experiments demonstrate that Neurod6+ midbrain dopaminergic neurons project to two distinct septal regions, the dorsal lateral and intermediate region of the lateral septum. Loss-of-function studies in mice demonstrate that Neurod6 and the closely related family member Neurod1 are both specifically required for the survival of this lateral-septum projecting neuronal subset during development. These findings underscore the complex organisation of midbrain dopaminergic neurons and provide an entry point for future studies of the functions of the Neurod6+ subset of midbrain dopaminergic neurons

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