Summary:
Parkinson’s disease (PD) is mainly characterized by striatal dopamine (DA) depletion due to loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc). Progressive cell loss and greater nigro-striatal denervation are associated with increased motor deficits and suboptimal therapeutic control. Understanding the mechanisms that underlie the onset and progression of SNpc damage is a primary unmet goal in PD research, necessary to foster therapeutic strategies for stopping disease progression. There is relatively scarce information about the factors determining the vulnerability of the SNpc neurons that degenerate in PD. Possible factors include their large axonal arborisation, bursting activity with high Ca2+ inflow, high oxidative stress associated with DA metabolism and sensitivity to aging, among others. However, all of these factors are common for all SN neurons, whereas neurodegeneration begins specifically in the ventro-lateral tier. Such early loss of function leads to the engagement of other dopaminergic regions to compensate the motor deficits, triggering its progressive degeneration. The aim of this proposal is to identify the neuronal population and the functional factors that increase the vulnerability of the dopaminergic neurons in the vetro-lateral tier of the SNpc at the onset of PD. On the base of our preliminary results, we hypostatize that a subpopulation of dopaminergic neurons in the ventro-lateral tier generate higher level of activity and metabolism, which increase their vulnerability under some specific genetics, environmental or cellular metabolism factors. To answer our hypothesis, we will generate a mouse experimental model to study the specific neuronal subpopulations engaged in early stage of PD and define their intrinsic and external vulnerability factors that mark the neural degeneration. We will use the cutting-edge techniques combining optogenetics, electrophysiology, imaging, single cell sequencing, behavior and anatomy.
Job position description:
We are looking for a very responsible, enthusiastic and highly motivated candidate who want to develop an outstanding career in Neuroscience. Our ambitious project uses a vast number of different techniques which open a broader background. For this reason, interested candidates can hold: neuroscience, medicine, biological or pharmacological disciplines, psychology, physics, mathematics and/or statistics, or computer science degree. Nevertheless, the applicants should have a neurobiological background with skills in experimental laboratory research. The experiments to develop will combine optogenetics, in vivo and in vitro electrophysiology, behavior, tracking of the mouse movements, inmunohistochemistry, single cell sequence (Patch-seq), anatomical and morphological staining with confocal microscopy. We also currently use a very advance data analysis such as machine learning tools and theoretical characterization of the spontaneous activity propagation. The use of all of these different experimental and analytical techniques require continuous interactions between the lab members, and high degree of motivation and curiosity to learn new knowledge. Candidates also should have a skillful to collaborate and explain their research in an international scientific environment.
Our group aim to understand the functions and circuits of the basal ganglia together with their cortical and thalamic inputs in health and under some pathological conditions, such as Parkinson disease. To answer our questions, we use high-throughput approaches together with the cutting-edges techniques for neurophysiology and cell biology. In the proposed project and in order to get and holistic knowledge about Parkinson Disease, we collaborate with the movement disorders unit of Hospital Puerta del Sur, they are an international reference in the study of Parkinson’s disease.
How to apply ?
Link of the Grant: https://finder.lacaixafellowships.org/finder?position=5250
Research group: http://in.umh-csic.es/grupos-detalle.aspx?grupo=54
Contact: Dr. Ramon Reig (group leader): ramon.reig@umh.es