PhD Encoding of decision making by dopamine neurons in health and Parkinson’s disease

Closing Date

3 Dec 2018

Address

School of Physiology and Pharmacology, University of Bristol

Duration

3.5 years

Project Description

Third supervisor: Dr Jiaxiang Zhang , Cardiff University 

Understanding how we make decisions in the face of uncertainty and how we weigh risk and reward remains a central challenge for neuroscience. It is clear that signalling by dopamine plays a pivotal role in these calculations. However, the dopamine neurons responsible for these signals are diverse in terms of the anatomical connections they make, their molecular make-up, and their encoding of behaviour; it is not clear how these different populations generate the signals used for decision making. Furthermore, in Parkinson’s disease, not only are particular populations of dopamine neurons preferentially lost, but components of the decision making process are impaired. The focus of this PhD is to define how different populations of dopamine neurons encode aspects of decision-making and action, and how this is altered in models of Parkinson’s. We will use an innovative approach, combining: 1. Cutting-edge techniques To record from individual dopamine neurons in behaving animals we will take advantage of a new technique we recently developed (Dodson et al. 2015, 2016). This innovative approach not only allows one to identify the precise location and neurochemical identity of each recorded neuron, but also to interrogate which channels, receptors, and other proteins they express and which brain regions they innervate (and thus subdivide neurons into their different populations). 2. Advanced computational models To probe how the signals we record are related to different parts of the decision-making process, we will takeadvantage of powerful computational models. This multidisciplinary approach will not only maximise the potential of the experimental data, but also allow us to generate testable predictions for subsequent experiments (e.g. in the animal models of Parkinson’s). 3. Latest models of Parkinson’s We have previously demonstrated that the activity of dopamine neurons changes in models of Parkinson’s (e.g. Dodson et al. 2016); thus, we would predict that their encoding of choice would also be altered. To investigate how neural activity is altered during decision-making in disease, we will perform experiments in mouse models of Parkinson’s In addition to working in an interdisciplinary environment, the student will benefit from opportunities to collaborate with other groups (e.g. the Oxford Parkinson’s Disease Centre) through the host groups’ ongoing collaborations, to present at international conferences and to showcase their findings to the public (e.g. school children, clinicians, Parkinson’s patients, and their families) through our regular events. 

Deadline for applications: 5pm on Friday 23rd November 2018.

Funding Notes

Apply: You will need to complete both an application to the GW4 BioMed MRC DTP for an ‘offer of funding’ and to University of Bristol for an ‘offer to study’. Please see: View Website 

Funding is for 3.5 years and to be eligible for a full award (fees and stipend) from a Research Council, a UK or EU student must have no restrictions on how long they can stay in the UK and have been ordinarily resident in the UK for at least 3 years prior to the start of the studentship. For further details on eligibility: View Website 

References

References 
1. Zhang, J. et al. Different decision deficits impair response inhibition in progressive supranuclear palsy and Parkinson’s disease. Brain 139, 161–173 (2016). 
2. Dodson, P. D. et al. Representation of spontaneous movement by dopaminergic neurons is cell-type selective and disrupted in parkinsonism. Proc. Natl. Acad. Sci. 113, E2180–E2188 (2016). 
3. Sloan, M. et al. LRRK2 BAC transgenic rats develop progressive, L-DOPA-responsive motor impairment, and deficits in dopamine circuit function. Hum. Mol. Genet. 25, 951–963 (2016). 
4. Janezic, S. et al. Deficits in dopaminergic transmission precede neuron loss and dysfunction in a new Parkinson model. Proc. Natl. Acad. Sci. U. S. A. 110, E4016-25 (2013). 

For more information and to apply, click here