Dementia/Neurodegeneration Research Database - Research Projects

Project Aim(s): To support national and local Parkinson’s disease service planning by three linked work packages.

The first maps the prevalence of Parkinson’s disease and service availability for people with Parkinson’s, across each of the nine Community Healthcare Organisation regions in Ireland, to highlight mismatches between population needs and service provision.

The second develops quality indicators for Irish PD services and assesses existing services against these indicators, to demonstrate where extra resources are needed to provide a quality service.

The final work package explores the experience of people with Parkinson’s with respect to services they receive, and their priorities for service provision.

1. Overview of Research Plans.

The successful treatment of memory impairments and neurodegenerative disorders critically depends on our understanding of the storage and recollection of memory episodes. Specifically, an understanding of the interaction between amnesic and neurodegenerative syndromes would aid the development of effective treatments. One of the key questions in neuroscience is: how do brain networks encode experience-dependent memory? Answering this question will give us universal tool to treat multiple brain disorders. The anatomical focus of my current research interests is the interaction between limbic, basal forebrain and nigro-striatal circuits as a possible candidate for interregional coordination of spatial navigation and context-dependent components of episodic memory.
I plan to examine if 1) neuromodulation from cholinergic neurons in forebrain and pontine tegmentum and 2) neuromodulation from dopaminergic and GABA-ergic neurons from ventral tegmental area (VTA) and substantia nigra can regulate the properties of spatial experience-dependent spatial navigation to guide behavior. Understanding the fundamental principles of this inter-regional signal processing will allow me to address my next goal: to apply pharmacological, electrophysiological and genetic tools to treat memory and movement disorders. The cellular response to cholinergic and dopaminergic neurotransmitters in hippocampal region is largely explored, but little is known about the optimizing effect of extrinsic manipulation of the neuromodulatory projections on the encoding properties of hippocampal neurons and mnemonic function of the limbic system. Therefore, the present proposal addresses two broad questions: 1) Can we enhance the hippocampal spatial representation by activation of the cholinergic/dopaminergic systems? 2) Should medial temporal lobe amnesia and depression be regarded as independent syndromes, or are they interlinked?

2. Current Research.

My concurrent investigation targets the septal area, which is interconnected with 1) the hippocampus which mediates spatial memory 2) ventral dopaminergic tegmentum, which mediates reward-motivated behavior, and 3) medial cholinergic septal inputs, which regulate of the limbic excitability and network rhythmicity, that are crucially involved in the neuropathology of the Alzheimer’s disease. There is, however, limited information about how hippocampal spatial and tegmental reward systems maintain feedback loop to synchronize their activity for place and reward. I propose that septal neurons integrate spatial and context reward value, enabling episodic memory for past experience to support future adaptive behavior. Using electrophysiological recordings from rats performing spatial and reinforcement tasks I am currently identifying the signal processing of the space and reward for each septal sub-region (manuscript in preparation). My optognetic stimulation design also explores the role of pathophysiological alteration of septal cholinergic and tegmental dopaminergic inputs on septo-hippocampal neuronal responses and adaptive behaviour.

3. Next Research Aims.

PMSMatTrain focuses on gaining a comprehensive understanding of the progressive  phase of multiple sclerosis (PMS) from basics to translation, fully supported by eight beneficiaries (six research institutions and two SMEs).The consortium will develop a multi-modal “tuneable” hydrogel-based medical device designed to bring about biphasic release of anti-inflammatory molecules and neuroprotective drugs as well as generating a clinically-relevant in silico model of drug elution and dispersal within the central nervous system. Using “state-of-the-art” 3D organotypic cultures and disease-relevant oligodendrocytes produced from MS patient-derived stem cells, the project will allow investigation MS pathophysiology as well as analysing the role of therapeutic molecules in combatting inflammation and promoting regeneration and neuroprotection.  The industry partners will develop the end-device by providing standardised manufacturing protocols for scaled-up production and commercialisation of the final product.PMSMatTrain is a multidisciplinary European Training Network that will educate and train 15 Early Stage Researchers in functionalised biomaterials, materials science, stem cell biology, in vitro & pre-clinical models, molecular biology,  in silico modelling, functionalisation strategies  and prototype design.Programme fellows will experience both public and private sector research and development and will be best placed to secure employment as high calibre, innovative and well-trained graduates.

Five students will be based in the CÚRAM lab at NUIG, while the remaining 10 will be based in institutions in Denmark, Germany, France, Spain, Italy, Belgium and the Czech Republic. PIs involved are Prof Trevor Owens (Denmark), Dr Tanja Kuhlmann (Germany), Dr Bertrand Huard (France), Dr Damiana Pierogostina (Italy), Dr. Marlene Verhoye (Belgium), Dr Peter Ponsaerts (Belgium), Dr Martin Pravda (Czech Republic), Dr Anna Rodriguez (Spain).