Understanding the dopamine signals triggered directly by striatal acetylcholine: The circuits, their timing and the actions of addictive drugs
Lead Research Organisation:
University of Oxford
Department Name: Physiology Anatomy and Genetics
Abstract
Context of the research: The chemical transmitter in the brain dopamine is critically involved in our ability to select our everyday actions and movements. Drugs that are addictive, like nicotine and cocaine, release too much dopamine, promoting the actions that underlie more drug seeking, and hence the cycle of addiction. Conversely, loss of dopamine in Parkinson's disease (PD) causes problems selecting and starting movements. But, we still do not fully understand how the dopamine release is controlled. We need to grasp the underlying neural mechanisms if we are to understand the functions of dopamine better and how to treat dopamine disorders.
It has long been assumed that the only trigger for dopamine release is the electrical impulses generated in the cell soma, and that these travel along the long cables, or axons, to axon endings where dopamine is released. However, we have new evidence that radically revises this thinking. Using state-of-the-art methods to drive specific neural circuits in the brains of mice engineered to respond to flashes of light, we have identified that a different set of neurons can trigger dopamine to be released. These neurons release the chemical acetylcholine directly onto dopaminergic axons which triggers dopamine release, equally as powerfully as impulses in dopamine cells themselves. These findings cause a paradigm shift in our current thinking and place cholinergic neurons central to the functions of dopamine. Here in this research grant we propose to advance our understanding of how acetylcholine neurons and their inputs evoke DA signals. Excitingly, new technology allows us for the first time to address this highly timely question.
Aims and objectives of the research: The broad aim of this research is to promote our understanding of how acetylcholine-producing neurons drive brain dopamine signals, and to understand whether these mechanisms contribute to the neural actions of drugs of addiction. We will address this through three specific aims.
Aim 1. Acetylcholine neurons in striatum powerfully trigger the release of dopamine from axons, but when does this happen? Our data suggest that this might happen when cholinergic neurons are excited by their inputs. If we could identify which inputs were important, we would understand which circuits we could target in dopamine dysfunction, and begin to understand what kinds of functions we might expect this dopamine signal to have. Therefore, in Aim 1, we will address - what are the inputs to cholinergic neurons that can drive dopamine release?
Aim 2. We already know that electrical impulses generated in the dopamine cell bodies themselves can trigger dopamine release. So which of these two triggers is the most important one and how do they interact? We will address this in Aim 2. The answers to this question will tell us a huge amount about the best way to drive dopamine release.
Aim 3. Addictive drugs like nicotine and cocaine are able to boost dopamine signals in the brain. But is acetylcholine-evoked dopamine release a mechanism targeted by these drugs? Our pilot data suggest it might be. We will address this in Aim 3. The answer to this question would have significant impact on our understanding of drug addiction.
Potential applications and benefits of the research: Through this work, we will build a more complete picture of the neural circuits that drive dopamine transmission. In turn, we will shed light on fundamental mechanisms of normal brain function that might be disrupted, and then targeted for therapeutic benefit, in disorders of dopamine neuron function, including addiction disorders and PD. In addition, the technical infrastructure that we will establish will be cutting-edge and an excellent investment for future studies to investigate dopamine function further e.g. in disease. Therefore, whatever the outcome, our work will provide a fundamental advance in knowledge and be of direct benefit to future work.
It has long been assumed that the only trigger for dopamine release is the electrical impulses generated in the cell soma, and that these travel along the long cables, or axons, to axon endings where dopamine is released. However, we have new evidence that radically revises this thinking. Using state-of-the-art methods to drive specific neural circuits in the brains of mice engineered to respond to flashes of light, we have identified that a different set of neurons can trigger dopamine to be released. These neurons release the chemical acetylcholine directly onto dopaminergic axons which triggers dopamine release, equally as powerfully as impulses in dopamine cells themselves. These findings cause a paradigm shift in our current thinking and place cholinergic neurons central to the functions of dopamine. Here in this research grant we propose to advance our understanding of how acetylcholine neurons and their inputs evoke DA signals. Excitingly, new technology allows us for the first time to address this highly timely question.
Aims and objectives of the research: The broad aim of this research is to promote our understanding of how acetylcholine-producing neurons drive brain dopamine signals, and to understand whether these mechanisms contribute to the neural actions of drugs of addiction. We will address this through three specific aims.
Aim 1. Acetylcholine neurons in striatum powerfully trigger the release of dopamine from axons, but when does this happen? Our data suggest that this might happen when cholinergic neurons are excited by their inputs. If we could identify which inputs were important, we would understand which circuits we could target in dopamine dysfunction, and begin to understand what kinds of functions we might expect this dopamine signal to have. Therefore, in Aim 1, we will address - what are the inputs to cholinergic neurons that can drive dopamine release?
Aim 2. We already know that electrical impulses generated in the dopamine cell bodies themselves can trigger dopamine release. So which of these two triggers is the most important one and how do they interact? We will address this in Aim 2. The answers to this question will tell us a huge amount about the best way to drive dopamine release.
Aim 3. Addictive drugs like nicotine and cocaine are able to boost dopamine signals in the brain. But is acetylcholine-evoked dopamine release a mechanism targeted by these drugs? Our pilot data suggest it might be. We will address this in Aim 3. The answer to this question would have significant impact on our understanding of drug addiction.
Potential applications and benefits of the research: Through this work, we will build a more complete picture of the neural circuits that drive dopamine transmission. In turn, we will shed light on fundamental mechanisms of normal brain function that might be disrupted, and then targeted for therapeutic benefit, in disorders of dopamine neuron function, including addiction disorders and PD. In addition, the technical infrastructure that we will establish will be cutting-edge and an excellent investment for future studies to investigate dopamine function further e.g. in disease. Therefore, whatever the outcome, our work will provide a fundamental advance in knowledge and be of direct benefit to future work.
Technical Summary
Striatal dopamine (DA) critically participates in the regulation of motivation and action selection. Dysregulation of DA signaling underlies a variety of psychomotor disorders, including addiction and Parkinson's disease. Surprisingly however, our grasp of the neuronal mechanisms that govern DA transmission remains incomplete. Activity in midbrain DA neurons has long been assumed to be its principal driver, but we have obtained new evidence for a radical shift to this paradigm, requiring us to rethink the mechanisms that govern DA release, and in turn, DA function and dysfunction.
Using an optogenetic strategy to light-activate striatal cholinergic interneurons (ChIs) that express channelrhodpsin2 (ChR2), and by detecting DA release at microelectrodes with subsecond resolution, we have identified that single action potentials in a population of ChIs triggers striatal DA release directly from DA axons by activating presynaptic nicotinic receptors (Threlfell et al, Neuron, in press). In addition, DA release was triggered by inputs to striatum from thalamus which coordinate ChI firing in vivo. Furthermore, ChI-evoked DA release overrode ascending activity in DA axons, suggesting that ChIs and their inputs might dominate as a trigger. These findings place ChIs central to our understanding of DA function and, potentially, dysfunction. It is imperative now to address key questions about how ChIs evoke DA release.
We will exploit optogenetic technologies to incorporate established and new light-activated channelrhodopsins (ChR2 and C1V1) in DA neurons, ChIs and/or their inputs to identify: (1) which inputs recruit ChIs to drive DA transmission?; (2) how do dynamic repertoires of activity in ChIs and DA neurons interact to govern DA transmission?; and (3) are these mechanisms targeted by addictive drugs? These studies are critical if we are to improve our knowledge of DA system function, and gain new insights about strategies for future therapies in DA dysfunction.
Using an optogenetic strategy to light-activate striatal cholinergic interneurons (ChIs) that express channelrhodpsin2 (ChR2), and by detecting DA release at microelectrodes with subsecond resolution, we have identified that single action potentials in a population of ChIs triggers striatal DA release directly from DA axons by activating presynaptic nicotinic receptors (Threlfell et al, Neuron, in press). In addition, DA release was triggered by inputs to striatum from thalamus which coordinate ChI firing in vivo. Furthermore, ChI-evoked DA release overrode ascending activity in DA axons, suggesting that ChIs and their inputs might dominate as a trigger. These findings place ChIs central to our understanding of DA function and, potentially, dysfunction. It is imperative now to address key questions about how ChIs evoke DA release.
We will exploit optogenetic technologies to incorporate established and new light-activated channelrhodopsins (ChR2 and C1V1) in DA neurons, ChIs and/or their inputs to identify: (1) which inputs recruit ChIs to drive DA transmission?; (2) how do dynamic repertoires of activity in ChIs and DA neurons interact to govern DA transmission?; and (3) are these mechanisms targeted by addictive drugs? These studies are critical if we are to improve our knowledge of DA system function, and gain new insights about strategies for future therapies in DA dysfunction.
Planned Impact
The wider impact of this work to non-academic beneficiaries could be far reaching in the longer term. This work is likely to impact upon a variety of non-academic groups including clinicians, sufferers and carers of a diverse group of DA-centred psychomotor diseases, the general public and pharmaceutical companies seeking new targets for drug development. The timescales over which this work is likely to impact these different groups of people will vary. Short-term benefits will be felt by all these groups as a result of increased understanding of neurotransmission in the brain, and progression of research into psychomotor disorders resulting from our findings. Longer-term societal and economic benefits may be felt by disease sufferers and pharmaceutical companies should new therapeutic targets emerge as a result of our research.
Organisations
- University of Oxford (Lead Research Organisation)
- University of Copenhagen (Collaboration)
- ETH Zurich (Collaboration)
- State University of New York (Collaboration)
- Karolinska Institute (Collaboration)
- Peking-Tsinghua Center for Life Sciences (Collaboration)
- Peking University (Collaboration)
- Boston University (Collaboration)
- Chalmers University of Technology (Collaboration)
- Stanford University (Collaboration)
- National University of Ireland, Maynooth (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- Cerevance Ltd (Collaboration)
- Chinese Institute for Brain Research, Beijing (Collaboration)
- Institute of Biomedical Research Alberto Sols (Collaboration)
Publications
Jennings KA
(2013)
A comparison of the subsecond dynamics of neurotransmission of dopamine and serotonin.
in ACS chemical neuroscience
Brimblecombe KR
(2015)
Gating of dopamine transmission by calcium and axonal N-, Q-, T- and L-type voltage-gated calcium channels differs between striatal domains.
in The Journal of physiology
Pristerà A
(2015)
Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice.
in Proceedings of the National Academy of Sciences of the United States of America
Jennings KA
(2015)
The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation.
in Neurobiology of disease
Brimblecombe KR
(2015)
Substance P Weights Striatal Dopamine Transmission Differently within the Striosome-Matrix Axis.
in The Journal of neuroscience : the official journal of the Society for Neuroscience
Brimblecombe KR
(2015)
Ni(2+) affects dopamine uptake which limits suitability as inhibitor of T-type voltage-gated Ca(2+) channels.
in ACS chemical neuroscience
Hunn BH
(2015)
Impaired intracellular trafficking defines early Parkinson's disease.
in Trends in neurosciences
Sulzer D
(2016)
Striatal dopamine neurotransmission: regulation of release and uptake.
in Basal ganglia
Dodson PD
(2016)
Representation of spontaneous movement by dopaminergic neurons is cell-type selective and disrupted in parkinsonism.
in Proceedings of the National Academy of Sciences of the United States of America
Title | Interview - Federation of European Neurosciences Forum, FENS Ambassador live interview |
Description | Interview to accompany conference presentation |
Type Of Art | Film/Video/Animation |
Year Produced | 2018 |
Impact | Promote interest in women in science, training as PhD student |
URL | https://www.facebook.com/FENSorg/videos/2118188164876552 |
Title | Video - "Pauses in Cholinergic Interneuron Activity Are Driven by Excitatory Input and Delayed Rectification, with Dopamine Modulation" Neuron, Cell Press |
Description | Video to explan and accompany manuscript published in Neuron - "Pauses in Cholinergic Interneuron Activity Are Driven by Excitatory Input and Delayed Rectification, with Dopamine Modulation" Neuron, Cell Press |
Type Of Art | Film/Video/Animation |
Year Produced | 2018 |
Impact | Promotes access to research paper |
URL | https://www.cell.com/cms/10.1016/j.neuron.2018.04.027/attachment/d84879f4-b0dc-459e-8158-b164e1ca09e... |
Description | Society for Neuroscience, Optogenetics Training Module |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
URL | https://neuronline.sfn.org/training/module-3-ex-vivo-applications-nuts-and-bolts |
Description | BBSRC DTP DPhil SVM |
Amount | £90,000 (GBP) |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2018 |
End | 09/2021 |
Description | Collaborative Award in Science |
Amount | £3,743,939 (GBP) |
Funding ID | 223202/Z/21/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 04/2022 |
End | 04/2027 |
Description | DPhil Studentship BR |
Amount | £110,000 (GBP) |
Organisation | University of Oxford |
Department | Clarendon Fund |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2016 |
End | 09/2019 |
Description | Exploring gabapentinoids for their potential to treat Parkinson's disease |
Amount | £326,682 (GBP) |
Funding ID | G-1803 |
Organisation | Parkinson's UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2019 |
End | 11/2023 |
Description | FORMA collaboration |
Amount | £300,000 (GBP) |
Organisation | FORMA Therapeutics |
Sector | Private |
Country | United States |
Start | 04/2019 |
End | 04/2021 |
Description | Grant title: Mapping the modulatory landscape governing striatal dopamine signaling and its dysregulation in Parkinson's disease |
Amount | $8,993,238 (USD) |
Funding ID | ASAP-020370 |
Organisation | Aligning Sciences Across Parkinson's |
Sector | Charity/Non Profit |
Country | United States |
Start | 11/2021 |
End | 10/2024 |
Description | Identifying mechanisms that govern synaptic dopamine transmission in the brain |
Amount | £80,000 (GBP) |
Funding ID | 2446134 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2020 |
End | 09/2024 |
Description | Identifying the regulation of striatal dopamine function by striatal astrocytes in health and parkinsonism |
Amount | £844,101 (GBP) |
Funding ID | MR/V013599/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2021 |
End | 04/2024 |
Description | MRC DTP DPhil studentship Bethan O'Connor |
Amount | £90,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2021 |
End | 09/2025 |
Description | MRC iCASE DPhil Studentship |
Amount | £120,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2018 |
End | 09/2022 |
Description | MRC-DTG Studentship 2014 |
Amount | £79,546 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2014 |
End | 09/2017 |
Description | MSD DPhil funding competition - Peter Kilfeather |
Amount | £85,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2016 |
End | 09/2020 |
Description | Monument Trust Discovery Award Renewal 2015 |
Amount | £5,800,000 (GBP) |
Funding ID | J-1403 |
Organisation | Parkinson's UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 02/2015 |
End | 02/2020 |
Description | NSF Fellowship LB |
Amount | $200,000 (USD) |
Organisation | National Science Foundation (NSF) |
Sector | Public |
Country | United States |
Start | 07/2018 |
End | 07/2021 |
Description | Natural Sciences and Engineering Research Council of Canada DPhil Scholarship |
Amount | $100,000 (CAD) |
Organisation | Natural Sciences and Engineering Research Council of Canada (NSERC) |
Sector | Public |
Country | Canada |
Start | 09/2019 |
End | 09/2022 |
Description | Parkinson's UK Project Grant 2015 |
Amount | £297,158 (GBP) |
Funding ID | G-1504 |
Organisation | Parkinson's UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2016 |
End | 12/2018 |
Description | Parkinson's UK Project Grant 2017 Magill PFFs |
Amount | £218,701 (GBP) |
Funding ID | G-1702 |
Organisation | Parkinson's UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2018 |
End | 02/2021 |
Description | Pump-Priming Award: Targetting nAChRs on dopamine axons as a potential treatment for Parkinson's disease |
Amount | £10,000 (GBP) |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2021 |
End | 12/2021 |
Description | Rhodes Scholarship |
Amount | £150,000 (GBP) |
Organisation | Rhodes Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2023 |
End | 09/2026 |
Description | Rhodes Scholarship 2013 |
Amount | £70,000 (GBP) |
Organisation | Rhodes Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2013 |
End | 09/2016 |
Title | ChI neuron model IKr |
Description | NEURON based model for a cholinergic interneuron, encompassing IKr |
Type Of Material | Computer model/algorithm |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | Published paper: Zhang et al (2018) Neuron, 98:918-925 |
URL | https://github.com/Yanfeng-Zhang/Pause-in-ChIs-Neuron-model |
Description | ASAP Team Cragg |
Organisation | Boston University |
Country | United States |
Sector | Academic/University |
PI Contribution | Team lead |
Collaborator Contribution | Co-Investigators and External Collaborators |
Impact | N/A |
Start Year | 2021 |
Description | ASAP Team Cragg |
Organisation | Karolinska Institute |
Country | Sweden |
Sector | Academic/University |
PI Contribution | Team lead |
Collaborator Contribution | Co-Investigators and External Collaborators |
Impact | N/A |
Start Year | 2021 |
Description | ASAP Team Cragg |
Organisation | Medical Research Council (MRC) |
Department | MRC Brain Network Dynamics Unit at the University of Oxford (BNDU) |
Country | United Kingdom |
Sector | Public |
PI Contribution | Team lead |
Collaborator Contribution | Co-Investigators and External Collaborators |
Impact | N/A |
Start Year | 2021 |
Description | ASAP Team Cragg |
Organisation | Peking University |
Department | College of Life Sciences |
Country | China |
Sector | Academic/University |
PI Contribution | Team lead |
Collaborator Contribution | Co-Investigators and External Collaborators |
Impact | N/A |
Start Year | 2021 |
Description | ASAP Team Cragg |
Organisation | Stanford University |
Country | United States |
Sector | Academic/University |
PI Contribution | Team lead |
Collaborator Contribution | Co-Investigators and External Collaborators |
Impact | N/A |
Start Year | 2021 |
Description | Bohacek ETH Zurich |
Organisation | ETH Zurich |
Country | Switzerland |
Sector | Academic/University |
PI Contribution | Collaboration to study optogenetic control of norepinephrine transmission |
Collaborator Contribution | Collaboration to study optogenetic control of norepinephrine transmission |
Impact | None yet |
Start Year | 2018 |
Description | Cerevance |
Organisation | Cerevance Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | Study of new pipeline ligands. Partner for MRC iCASE award |
Collaborator Contribution | Supply of new pipeline ligands Partner for MRC iCASE award |
Impact | New MRC iCASE studentship Manuscript in preparation Christie L, Brice NL, Rowland A, Dickson L, Anand R, Teall M, Doyle KJ, Lakshmi N, Mitchell C, Harvey JRM, Mulligan V, Dawson LA, Cragg SJ, Carlton M, Burli RW. (2023) Discovery of CVN417, a Novel Brain-Penetrant a6-Containing Nicotinic Receptor Antagonist for the Modulation of Motor Dysfunction, J Med Chem 66:11718-11731. https://doi.org/10.1021/acs.jmedchem.3c00630 |
Start Year | 2017 |
Description | Chinese partners conducting in vivo nachr studies |
Organisation | Chinese Institute for Brain Research, Beijing |
Country | China |
Sector | Academic/University |
PI Contribution | Designed experiments and acquired main data indicating the follow-on experiements for collaborators |
Collaborator Contribution | Conducted experiments with nachr antagonists in vivo |
Impact | Manuscript in preparation, Patent appliction in progress |
Start Year | 2020 |
Description | Collaboration Yetnikoff SUNY 2022-2023 |
Organisation | State University of New York |
Country | United States |
Sector | Academic/University |
PI Contribution | Identifying dopamine in corpus callosum |
Collaborator Contribution | Studying anatomy |
Impact | Caldwell M, Ayo-Jibunoh V, Criollo Mendoza J, Brimblecombe KR, Reynolds L, Zhu XY, Alarcon C, Fiore E, Hassan Z, Tomaio J, Phillips GR, Mingote S, Flores C, Casaccia P, Liu J, Cragg SJ, McCloskey DP, Yetnikoff L. (2023) Axo-glial interactions between midbrain dopamine neurons and oligodendrocyte lineage cells in the anterior corpus callosum. Brain Struct Func. 228:1993-2006 https://doi.org/10.1007/s00429-023-02695-y |
Start Year | 2020 |
Description | Design and supply of ASAP3 voltage sensors |
Organisation | Stanford University |
Country | United States |
Sector | Academic/University |
PI Contribution | Conceptualisation and acquisition of data for main study |
Collaborator Contribution | Design and supply of viral vectors for V imaging |
Impact | Manuscript in preparation |
Start Year | 2020 |
Description | Diabetes /Parkinson's link - Madrid collaboration |
Organisation | Institute of Biomedical Research Alberto Sols |
Country | Spain |
Sector | Academic/University |
PI Contribution | Analysis of diabetes model mice for deficits in dopamine transmission |
Collaborator Contribution | Initiatd the collaboration |
Impact | Pérez-Taboada I, Alberquilla S, Martín ED, Anand R, Vietti-Michelina S, Tebeka NN, Cantley J, Cragg SJ, Moratalla R, Vallejo M (2020). Diabetes causes dysfunctional dopamine neurotransmission favoring nigrostriatal degeneration in mice. Mov Disord 35:1636-1648 https://doi.org/10.1002/mds.28124 |
Start Year | 2019 |
Description | Ewing lab mass spec |
Organisation | Chalmers University of Technology |
Country | Sweden |
Sector | Academic/University |
PI Contribution | Supply of intellectual question, background data and brain tissue |
Collaborator Contribution | Mass spec analysis |
Impact | Threlfell S, Mohammadi AS, Ryan B, Platt NJ, Anand R, Serres F, Sharp T, Bengoa-Vergniory N, Wade-Martins R, Ewing A, Cragg SJ†*, Brimblecombe KR†* (2021) Striatal dopamine transporter function is facilitated by converging biology of a-synuclein and cholesterol, Front Cell Neurosci 15:658244 https://doi:10.3389/fncel.2021.658244 |
Start Year | 2017 |
Description | John Lowry |
Organisation | Maynooth University |
Country | Ireland |
Sector | Academic/University |
PI Contribution | Using new choline probes to explore striatal ACh function |
Collaborator Contribution | Manufacture and supply of choline probes |
Impact | New research effort and avenue |
Start Year | 2017 |
Description | Optogenetic constructs |
Organisation | Stanford University |
Department | Schools of Bioengineering and Medicine |
Country | United States |
Sector | Academic/University |
PI Contribution | Study of neural circuit function |
Collaborator Contribution | Provision of optogenetic gene constructs |
Impact | Publication PMID 22794260 Grant MR/K013866/1 Grant G-1305 |
Start Year | 2010 |
Description | University of Copenhagen, Perrier, spinal cord |
Organisation | University of Copenhagen |
Department | Department of Neuroscience and Pharmacology (DNP) |
Country | Denmark |
Sector | Academic/University |
PI Contribution | Study of 5-HT transmission in spinal cord |
Collaborator Contribution | Study of 5-HT actions |
Impact | Published paper PMID 23487756 |
Start Year | 2012 |
Description | Yulong Li GRAB sensors |
Organisation | Peking-Tsinghua Center for Life Sciences |
Country | China |
Sector | Academic/University |
PI Contribution | Exploring use of GRAB sensors to the study of neurotransmission in the CNS |
Collaborator Contribution | Developing and subsidising cost of supplying GRAB sensors |
Impact | Manuscripts in prepration, meetings abstracts |
Start Year | 2019 |
Title | Patent application - Treatments and Methods of increasing dopamine |
Description | Patent application |
IP Reference | GB2100053.4 |
Protection | Patent / Patent application |
Year Protection Granted | 2021 |
Licensed | Commercial In Confidence |
Impact | spinout company formed, and licensing to company underway. |
Description | (BOC) Public science event - IF-Oxford |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | IF Oxford science and ideas Festival, to educate and inspire young people ub science. Sparked inteerest, and enthusiasm. |
Year(s) Of Engagement Activity | 2022 |
URL | https://scienceoxford.com/events/if-oxford-2022 |
Description | (BOC) Volunteering at Science Saturdays, Museum of Natural History |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Volunteering at the Oxford Museum of Natural History's Science Saturdays events, hands-on science-based activities for families discussing the science of geology, entomology, microscopy and zoology |
Year(s) Of Engagement Activity | 2022 |
URL | https://oumnh.ox.ac.uk/event/science-saturdays-38 |
Description | (BOCO) Public Science event - DPAG Science in the Park |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Scientists frmo DPAG in a marquee in the University Parks, to answer questions and share fun facts about how bodies work. Exploring a range of topics, including blood, brain, DNA, heart, lungs, and the skeleton, using virtual reality (VR) augmented reality (AR) and hands-on activities. SParked much interest. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.dpag.ox.ac.uk/about-us/outreach/science-in-the-park |
Description | (KB) Primary School visit |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | A visit to a primaray school, to talk about the brain and body and how we study them, using body samples and microscopes. Sparked many questions, and excitement about the topics. Invited back the following year |
Year(s) Of Engagement Activity | 2023 |
Description | Blog post for Parkinson's UK on Threlfell et al 2021 |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | We wrote a lay version of our paper (Threlfell et al 2021) published in Frontiers in Cellular Neuroscience at https://www.dpag.ox.ac.uk/team/a-summary-of-threlfell-et-al-2021 and published an accompanying blog post for Parkinson's UK |
Year(s) Of Engagement Activity | 2021 |
URL | https://medium.com/parkinsons-uk/bridging-the-gap-between-basic-research-and-people-with-parkinsons-... |
Description | Discovery Award Participant Open Day' |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Participants in your research and patient groups |
Results and Impact | Sparked questions, discussion, interest in ongoing projects DOnations |
Year(s) Of Engagement Activity | 2014 |
Description | Discuss Parkinson's research with individual fundraisers (DB, EL, SB) |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Supporters |
Results and Impact | Engagement with small groups of charitable donors to promote fundraising into Parkinson's research |
Year(s) Of Engagement Activity | 2009,2016,2017 |
Description | Edinburgh International Science Festival |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Talk sparked questions and debate N/A |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.sciencefestival.co.uk/mediaLibrary/other/english/6285.pdf |
Description | FENS Ambassador interview |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Interview by an Ambassador to the Federation of European Neuroscience Societies for Facebook live interview, to give briefly discuss y lab's work and to give advice to postgraduate students |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.facebook.com/FENSorg/videos/2118188164876552 |
Description | Fundraising appeal for PUK 2014 |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | Yes |
Geographic Reach | National |
Primary Audience | Supporters |
Results and Impact | Raised funds for research of £150k |
Year(s) Of Engagement Activity | 2014 |
Description | Gave a Public Lecture (LB) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | Public online lecture |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.balliol.ox.ac.uk/events/2022/april/26/balliol-online-lecture |
Description | Guest speaker at 25th Anniversary tea party, Newbury Parkinson's group |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Guest speaker on disease research at anniversary tea party for Newbury Parkinson's group which sparked lively debate and questions and interest |
Year(s) Of Engagement Activity | 2017 |
Description | Host lab visits for Chinese students for Oxford Prospects Programme |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Undergraduate students |
Results and Impact | Host lab visits for Chinese students for Oxford Prospects Programme |
Year(s) Of Engagement Activity | 2017 |
Description | International Innovations article 2014 |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | Publication in internationally reaching magazine. results not yet clear. Not yet clear |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.internationalinnovation.com/hope-for-dopamine-disorders/ |
Description | KB Primary School visit (2022) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | A visit to a primaray school, to talk about the brain and body and how we study them, using body samples and microscopes. Sparked many questions, and excitement about the topics. Invited back the following year |
Year(s) Of Engagement Activity | 2022 |
Description | Keynote speaker on Career, DPAG Postdoc Day, Oxford |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Other audiences |
Results and Impact | Invited to discuss career path as part of a postdoctoral scientist development day |
Year(s) Of Engagement Activity | 2017 |
Description | Mentor on UNIQ+ Digital Programme |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | (JL) A mentor on the UNIQ+ Digital Programme, which aims to introduce undergraduate students from under-represented backgrounds to postgraduate study at Oxford. Mentored students interested in pursuing postgraduate study in neuroscience, based on discussing our current research |
Year(s) Of Engagement Activity | 2021 |
Description | Neuroscience exhibition in the Oxford museum of Science March 2014 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Neuroscience exhibition in the Oxford museum of Science March 2014 Unknown |
Year(s) Of Engagement Activity | 2014 |
Description | Parkinson's group talk Hereford |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Participants in your research and patient groups |
Results and Impact | Share knowledge, stimulate interest After the talk, audience asked to visit lab |
Year(s) Of Engagement Activity | 2015 |
Description | Primary school science talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Scientist attended a primary school to discuss science, which sparked questions and discussion afterwards |
Year(s) Of Engagement Activity | 2023 |
Description | School teaching BR MCS |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Catalysing interest in neuroscience |
Year(s) Of Engagement Activity | 2017,2018,2019 |
Description | School visit to lab - Akeley Wood |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | 20 pupils attended for a school visit to the research organisation which sparked questions and discussions |
Year(s) Of Engagement Activity | 2017 |
Description | Skype a scientist LB |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Undergraduate students |
Results and Impact | Inform about career in neuroscience |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.skypeascientist.com/ |
Description | Smarter UK |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | Yes |
Type Of Presentation | Workshop Facilitator |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | KS3 talks about cognitive enhancing drugs Not known |
Year(s) Of Engagement Activity | 2012 |
Description | Speaker and Opening of fundraising walk for Parkinson's UK, Oxford |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Supporters |
Results and Impact | Speaker and Opening of fundraising walk for Parkinson's UK, Oxford |
Year(s) Of Engagement Activity | 2016 |
URL | https://www.parkinsons.org.uk/content/walk-parkinsons |
Description | TV News interview ST 2013 |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Media (as a channel to the public) |
Results and Impact | TV description of PD work by ST Not known |
Year(s) Of Engagement Activity | 2013 |
Description | Talk at Stowe School to A-Level Medical Society on dopamine and careers in science |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | We attended a school to talk about science and careers in science which sparked questions and discussion |
Year(s) Of Engagement Activity | 2017 |
Description | UNIQ summer school 2013 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | Yes |
Type Of Presentation | Workshop Facilitator |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | 30 pupils attended a week-long course, I hosted a dinner and workshop with Q&A Not yet known |
Year(s) Of Engagement Activity | 2013 |
URL | http://www.uniq.ox.ac.uk/ |
Description | World Anatomy Day outreach event |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Celebration of World Anatomy Day through engagement of public in workshop 'Art of Anatomy: Explore, Create, Connect', Natural History Museum, Oxford |
Year(s) Of Engagement Activity | 2023 |
URL | http://www.dpag.ox.ac.uk/news/dpag-world-anatomy-day-event-success |
Description | Wow!How? Stall |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Type Of Presentation | Workshop Facilitator |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | science fair at the Oxford University of Museum of Natural History Not known |
Year(s) Of Engagement Activity | 2012 |