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) 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  from freely moving animals we can couple the results form behavioural studies to investigate changes in dopamine that are dynamilcally related to the behaviour.


Cell replacement 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.


COLLABORATIONS

Collaborations

Dr. Zisis Bimpisidis (Evolutionary Biology Centre, Uppsala University)

Together with Dr. Bimpisidis we investigate neural circuits involved in reward processing. Zisis has established several optogenetic paradigms to perturbate cell activity selectively in a genetically defined subset of dopaminergic neurons in the midbrain. Now we combine these technologies with electrochemical detection of neurotransmitter release to elucidate the release and reuptake kinetics of the neuronal ensembles. 



A/Prof. Tomas Bj√∂rklund (Molecular Neuromodulation Group, Lund University) 

We work closely with the Molecular Neuromodulation group who develops the viral vectors we use in our research. The main research overlap is the assessment of novel viral vectors to overexpress alpha-synuclein for the modelling of Parkinson's disease as well as optogenetic and chemogentics receptors to manipulate cell activity.



Prof. Angela Cenci-Nilsson (Basal Ganglia Patophysiology Group, Lund University)

We work together on the use of operant behavioural assessment of novel models in which we overexpress alpha-synuclein in the Prefrontal Cortex.



A/Prof. Lachlan Thompson (Neurogenesis and Neural Transplantation Laboratory, Melbourne University)

In collaboration with the group of Dr Thompson we work on human ES cell grafts and aim to study their dopamine release in freely-moving animals.


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

In collaboration with the Melki/Bousset 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.


A/Prof. Frederic Manfredsson (Translational Neuroscience & Molecular Medicine, Michigan State University)

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



Prof. Anne E. Rosser (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.

   

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