The role of the D4a receptor in the genesis and function of spinal motorneurons

Project description

Project description

The process of development from a single fertilized egg cell to a fully functional organism, is an amazingly complex feat that is poorly understood and often taken for granted. Not surprisingly, errors in development or damage or disease lead to catastrophic consequences in adulthood.

Humans and other vertebrates share a common developmental template that builds the brain and spinal cord; at early stages, all vertebrate embryos are very similar. Thus, studying neural development in simpler, easier to study animals is instructive especially those capable of repairing the nervous system when it is damaged.

We will investigate the role of a neurotransmitter molecule, dopamine, and one of its receptors in the nervous system, the D4a receptor, in spinal cord development.

We will take two approaches, in St Andrews and Edinburgh, respectively. Firstly, we will investigate the how D4a receptors affect the electrical properties and synaptic connections of neurons within the spinal motor network of zebrafish. Secondly, the role of D4a receptors in the development of an amphibian locomotor circuit, that of Xenopus frog tadpoles will be explored.

The first set of experiments will extend a collaboration commenced under short-term BBSRC support and, by examining D4a receptor involvement at the level of individual spinal neurons, take our research to the next and more insightful level. The second set of experiments will address whether these dopaminergic mechanisms represent general principles of spinal circuit function and development by studying them in more detail in another vertebrate, the Xenopus frog tadpole.