RESEARCH

Motor and Non-Motor symptoms in Parkinson's disease


We use operant tests as well as hand tests to assess motor and non-motor deficits in animal models of Parkinson's disease. We are currently using several well established behavioural paradigms (5-choice reaction time task, Lateralised choice reaction time task, delayed alternation, progressive ratio) in rat Skinner and 9-hole operant chambers. We are assessing the effects of 6-OHDA lesions as well as over-expression of alpha-synuclein on behavioural performance to provide better models for therapeutic interventions like pharmacotherapy, neuroprotection, as well as cell replacement therapy.


Brain behaviour relationships


We are using electrochemical detection methods (Amperometry and Chronoamperometry; Calcium imaging) to measure the dopamine-release kinetics in freely-moving and anaesthetised rats. In combination with technologies that allow for the selective and reversible manipulation of cell activity (i.e. optogenetics and chemogenetics) in genetically defined cell populations we have started to study causal relationships between neurotransmitter release and behaviour. By measuring dopamine release/Cellular activity  from freely moving animals we can couple the results form behavioural studies to investigate changes in dopamine that are dynamilcally related to the behaviour.


Recently we have developed a 3D recording frame which enables us to track rodent movements using machine learning algorithms for rodent pose estimation (see techniques).



Cell replacement therapy / Gene therapy


With our past and present collaborators we assess the function of neural stem cell transplants, whether they are derived from rat primary fetal tissue or human embryonic ste cells or generated through iPS cell technology. Here we are mainly interested in the functions a graft can recover and how this recovery is achieved. We have used several methods from rabies-based tracing to electrochemical detection to investigate connectivity and function of dopaminergic transplants. By overexpression of neurotrophic factors we aim to test factors which might protect the surviving cells from degeneration.

COLLABORATIONS

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Prof. Magnus Johnsson (Kristianstad University)

Together with Magnus we apply associative self-organizing maps (A-SOMs) to recognise behavioural actions from rodent pose-estimation data.



A/Prof. Arezoo Sarkheyli-Hägele (Malmö University)

Together with Arezoo we aim to emply explainable AI and reasoning in cognitive systems to improve pose

estimation algorithms for rodent behaviour. 

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A/Prof. Gerard O'Keeffe (University College Cork)

Together with Dr. O'Keeffe we investigate neurotrophic factors as a potential therapeutic target in our recently developed AAV vector overexpression model of Parkinson's disease.



A/Prof. Frederic Manfredsson (Translational Neuroscience & Molecular Medicine, Barrow Neurological)

The Manfredsson laboratory and BNL teamed up to perform a behavioural characterisation of novel AAV-vector constructs.



Prof. Kathy Steece-Collier (Michigan State University)

The Steece-Collier lab is workin with us on developing a pose estimation algorithm for the automatic detection of abnormal involuntary movements in rodent models of Parkinson's disease.



Prof. Ronald Melki  (Institut des Neuroscience Paris-Saclay)

In collaboration with the Melki laboratory we assess the effects of preformed fibrils on aggravating the pathology induced by AAV-vector overexpression of human alpha-synuclein for the generation and behavioural phenotyping of novel preclinical rodent models of Parkinson's disease.


Prof. Anne E. Rosser and Dr. Claire Kelly (Brain Repair Group, Cardiff University)

In collaboration with the Brain Repair Group in Cardiff, UK we develop and  validate the "neonatal densensitisation" model, which allows for long-term xenograft survival without the need of pharmacological immune-suppression.


Prof. Greg Gerhardt (Kentucky University, KY,  USA)

Professor Gerhardt and his team are  assisting us in the implementation of electrochemical  detection methods for anaesthetised and freely-moving animals.

   

Funding

We are very greatful to receive support for our work from the following organisations

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