Circuit-level mechanisms of memory consolidation
Lead Research Organisation:
University of Oxford
Department Name: Clinical Neurosciences
Abstract
Understanding memory is a central goal of neuroscience, with potentially far-reaching consequences for treating Alzheimer's disease and other dementias. Memory formation requires 'offline consolidation', whereby the neuronal traces representing newly-acquired experiences are selectively stabilised during sleep. Following their retrieval, consolidated memories undergo an additional process of reconsolidation that further stabilizes them for long-term expression.
Damage to particular brain regions results in selective behavioural impairments. The hippocampus, for example, encodes new memories about specific events and places (episodic and spatial memories). We lack a comprehensive understanding of how new memories gain long-term expression but two distinctive patterns of hippocampal electrical activity could promote consolidation processes: sharp-wave ripples (SWRs) and 'dentate spikes'. SWRs have received much scientific attention, and disrupting SWRs impairs memory. In contrast, little is known about dentate spikes, a misleading term that refers not to the action potentials of individual dentate granule cells (DGCs) but to a large population event that recruits many DGCs. No one has ever silenced dentate spikes to determine their role in memory. Our proposed experiments will address this important gap in our knowledge, using cutting-edge technology to detect and silence dentate spikes in the mouse brain in post-learning sleep, thereby revealing their contribution to memory consolidation.
Our approach will utilise sophisticated genetic approaches that can deliver light-sensitive proteins into particular neurons (e.g. DGCs). When stimulated by light, these proteins will silence or activate those neurons. We will use real-time detection of dentate spikes to trigger light-stimulation, giving us precise control over neuronal activity during sleep.
We will assess the contribution of dentate spikes to two distinct forms of memory, both of which require the hippocampus. First we will investigate the effects of dentate spike silencing on associative memory, e.g. learning that cue A predicts outcome X. Ordinarily, learning simple associations does not require the hippocampus, but if the relationship is made ambiguous (e.g. such that outcome X only follows cue A on a subset of trials), the hippocampus then becomes necessary. Second, we will investigate the effects of silencing dentate spikes on non-associative memories, e.g. using the relative novelty or familiarity of mnemonic cues to guide behavioural choices. Consolidation is thought to be critical for associative but not non-associative memories. If silencing dentate spikes also affects non-associative memory, this would suggest a more general role in memory, rather than in consolidation per se. Moreover, in control conditions we will silence DGCs during sleep but NOT during dentate spikes to see whether this also affects memory consolidation.
Next, we will determine the neuronal inputs driving dentate spikes. We will use a recently developed technique to selectively target neurons in the neocortex that project directly to DGCs and determine how activating or silencing those neocortical cells alters dentate spikes.
Finally, we will test how inhibiting an already consolidated memory during 'reconsolidation' affects its long-term expression. We will use a special genetically-modified mouse line that can drive the expression of a light-sensitive neuronal inhibitor selectively in cells that were active during a particular learning episode. At a later time we will reactivate this memory, which places the memory in a labile state, and then determine how inhibiting dentate spikes following this reactivation affects the reconsolidation of this memory.
Collectively, our experiments will make a major contribution to a comprehensive understanding of the circuit-level mechanisms underlying the long-lasting expression of memory.
Damage to particular brain regions results in selective behavioural impairments. The hippocampus, for example, encodes new memories about specific events and places (episodic and spatial memories). We lack a comprehensive understanding of how new memories gain long-term expression but two distinctive patterns of hippocampal electrical activity could promote consolidation processes: sharp-wave ripples (SWRs) and 'dentate spikes'. SWRs have received much scientific attention, and disrupting SWRs impairs memory. In contrast, little is known about dentate spikes, a misleading term that refers not to the action potentials of individual dentate granule cells (DGCs) but to a large population event that recruits many DGCs. No one has ever silenced dentate spikes to determine their role in memory. Our proposed experiments will address this important gap in our knowledge, using cutting-edge technology to detect and silence dentate spikes in the mouse brain in post-learning sleep, thereby revealing their contribution to memory consolidation.
Our approach will utilise sophisticated genetic approaches that can deliver light-sensitive proteins into particular neurons (e.g. DGCs). When stimulated by light, these proteins will silence or activate those neurons. We will use real-time detection of dentate spikes to trigger light-stimulation, giving us precise control over neuronal activity during sleep.
We will assess the contribution of dentate spikes to two distinct forms of memory, both of which require the hippocampus. First we will investigate the effects of dentate spike silencing on associative memory, e.g. learning that cue A predicts outcome X. Ordinarily, learning simple associations does not require the hippocampus, but if the relationship is made ambiguous (e.g. such that outcome X only follows cue A on a subset of trials), the hippocampus then becomes necessary. Second, we will investigate the effects of silencing dentate spikes on non-associative memories, e.g. using the relative novelty or familiarity of mnemonic cues to guide behavioural choices. Consolidation is thought to be critical for associative but not non-associative memories. If silencing dentate spikes also affects non-associative memory, this would suggest a more general role in memory, rather than in consolidation per se. Moreover, in control conditions we will silence DGCs during sleep but NOT during dentate spikes to see whether this also affects memory consolidation.
Next, we will determine the neuronal inputs driving dentate spikes. We will use a recently developed technique to selectively target neurons in the neocortex that project directly to DGCs and determine how activating or silencing those neocortical cells alters dentate spikes.
Finally, we will test how inhibiting an already consolidated memory during 'reconsolidation' affects its long-term expression. We will use a special genetically-modified mouse line that can drive the expression of a light-sensitive neuronal inhibitor selectively in cells that were active during a particular learning episode. At a later time we will reactivate this memory, which places the memory in a labile state, and then determine how inhibiting dentate spikes following this reactivation affects the reconsolidation of this memory.
Collectively, our experiments will make a major contribution to a comprehensive understanding of the circuit-level mechanisms underlying the long-lasting expression of memory.
Technical Summary
First, in mice implanted with tetrodes and optic fibres in the dentate gyrus (DG) we will use a closed-loop brain-machine interface to detect dentate spikes and silence dentate granule cells (DGCs), virally transfected with the light-sensitive rapid neuronal silencer ArchT. We will use a transgenic mouse line (expressing Cre recombinase under the metabotropic glutamate receptor-2 promoter) which shows exquisite specificity for DGCs, with no observable expression in CA1-3 or the hilus. We will silence DGCs during sleep after learning events to determine the contribution of dentate spikes to the neuronal and behavioural correlates of memory.
Next we will investigate the neuronal inputs to DGCs that drive dentate spikes. We will use two transgenic mouse lines (Ai32 and Ai40D) that express the light-driven neuronal activator channelrhodopsin-2 (ChR2) and silencer ArchT, respectively, only in Cre-expressing cells. We will inject a retrograde adeno-associated viral vector into the DG to transduce DGC-projecting medial entorhinal cortex (MEC) cells with Cre recombinase. The presence of Cre in these MEC cells will drive ChR2 in Ai32 mice and ArchT in Ai40D mice. We will then test how stimulating DGC-projecting MEC cells during sleep alters the probability or amplitude of dentate spikes.
Finally, we will use 'TetTag' mice in which ArchT expression is driven by the immediate-early gene cFos. ArchT expression is controlled by an experimenter-defined window because it is suppressed by dietary doxycycline (dox). When dox is removed from the diet, neuronal activation induces cFos which then drives ArchT expression in those neurons. Thus we can 'tag' DGCs active during a specific memory episode. We will not interfere with the initial memory consolidation but will later 'reactivate' this memory by presenting retrieval cues which renders the memory labile. We will test how inhibiting the tagged DGCs during dentate spikes following this reactivation affects subsequent memory.
Next we will investigate the neuronal inputs to DGCs that drive dentate spikes. We will use two transgenic mouse lines (Ai32 and Ai40D) that express the light-driven neuronal activator channelrhodopsin-2 (ChR2) and silencer ArchT, respectively, only in Cre-expressing cells. We will inject a retrograde adeno-associated viral vector into the DG to transduce DGC-projecting medial entorhinal cortex (MEC) cells with Cre recombinase. The presence of Cre in these MEC cells will drive ChR2 in Ai32 mice and ArchT in Ai40D mice. We will then test how stimulating DGC-projecting MEC cells during sleep alters the probability or amplitude of dentate spikes.
Finally, we will use 'TetTag' mice in which ArchT expression is driven by the immediate-early gene cFos. ArchT expression is controlled by an experimenter-defined window because it is suppressed by dietary doxycycline (dox). When dox is removed from the diet, neuronal activation induces cFos which then drives ArchT expression in those neurons. Thus we can 'tag' DGCs active during a specific memory episode. We will not interfere with the initial memory consolidation but will later 'reactivate' this memory by presenting retrieval cues which renders the memory labile. We will test how inhibiting the tagged DGCs during dentate spikes following this reactivation affects subsequent memory.
Planned Impact
This proposal describes fundamental neuroscience research and therefore its main economic and societal impacts are likely to be increasing knowledge about brain function and effective information processing. As such, we do not anticipate any immediate commercially exploitable outputs or treatments for disease. Nevertheless, the potential consequences of better understanding the mechanisms underlying memory formation could have a significant impact on society at a later time. This proposal will also inform current research efforts in artificial intelligence and deep-learning networks.
Who will benefit?
In addition to the academic community (see Academic Beneficiaries), the main potential beneficiaries of our work will be the pharmaceutical industry, clinicians, and ultimately patient populations from within the general public.
How will they benefit?
Memory impairment is a major aspect of aging, which has considerable impact on the quality of life of individuals. As people live longer, Age-Associated Memory Impairment (AAMI) will become even more of an issue. The hippocampus is a brain region that is intimately associated with memory, and it exhibits important structural, physiological and neurochemical changes with aging. Hippocampus-dependent memories (e.g. episodic and spatial memories) appear to be particularly vulnerable to decline with aging, consistent with the neurobiological changes that occur in the hippocampus as individuals get older. Indeed, age-related cognitive decline has been strongly linked to impairments in hippocampal dependent forms of spatial and episodic memory. In addition, hippocampal dysfunction is a key feature of various other psychiatric and neurological disorders including anxiety, depression, schizophrenia and ischaemic brain injury. Thus, understanding how the hippocampus subserves memory function is likely to be of great importance to both pre-clinical and clinical researchers, the pharmaceutical industry, clinicians and ultimately to the patient population.
Our research is not designed to explicitly identify targets for drug development but, ultimately, a better understanding of the physiological processes that underlie memory formation could increase the likelihood of new treatments for dementia (not only in specific patients groups with conditions like Alzheimer's Disease, but also in the aging population more generally). Indeed, treatments that might restore hippocampal function could also be relevant for a variety of psychiatric disorders (e.g. schizophrenia, anxiety and depression). The development of novel treatment strategies and therapies will produce both economic and societal benefits, with the ultimate endpoint of improving human health.
The knowledge obtained from this proposal will also make an important contribution to the increased and timely interest on brain-machine interfaces, closed-loop systems and artificial intelligence. Indeed, offline consolidation processes have not yet been considered in these research areas while they are likely to greatly optimise information processing.
Finally, via our public-engagement activities, the general public will benefit from an increased knowledge and understanding of the physiological processes that underlie memory consolidation. Specifically, we will organise a public-focused event to discuss the concepts and technologies described in this proposal, and how they might lead to better treatments for age-associated memory impairments in humans (see pathways to impact).
Who will benefit?
In addition to the academic community (see Academic Beneficiaries), the main potential beneficiaries of our work will be the pharmaceutical industry, clinicians, and ultimately patient populations from within the general public.
How will they benefit?
Memory impairment is a major aspect of aging, which has considerable impact on the quality of life of individuals. As people live longer, Age-Associated Memory Impairment (AAMI) will become even more of an issue. The hippocampus is a brain region that is intimately associated with memory, and it exhibits important structural, physiological and neurochemical changes with aging. Hippocampus-dependent memories (e.g. episodic and spatial memories) appear to be particularly vulnerable to decline with aging, consistent with the neurobiological changes that occur in the hippocampus as individuals get older. Indeed, age-related cognitive decline has been strongly linked to impairments in hippocampal dependent forms of spatial and episodic memory. In addition, hippocampal dysfunction is a key feature of various other psychiatric and neurological disorders including anxiety, depression, schizophrenia and ischaemic brain injury. Thus, understanding how the hippocampus subserves memory function is likely to be of great importance to both pre-clinical and clinical researchers, the pharmaceutical industry, clinicians and ultimately to the patient population.
Our research is not designed to explicitly identify targets for drug development but, ultimately, a better understanding of the physiological processes that underlie memory formation could increase the likelihood of new treatments for dementia (not only in specific patients groups with conditions like Alzheimer's Disease, but also in the aging population more generally). Indeed, treatments that might restore hippocampal function could also be relevant for a variety of psychiatric disorders (e.g. schizophrenia, anxiety and depression). The development of novel treatment strategies and therapies will produce both economic and societal benefits, with the ultimate endpoint of improving human health.
The knowledge obtained from this proposal will also make an important contribution to the increased and timely interest on brain-machine interfaces, closed-loop systems and artificial intelligence. Indeed, offline consolidation processes have not yet been considered in these research areas while they are likely to greatly optimise information processing.
Finally, via our public-engagement activities, the general public will benefit from an increased knowledge and understanding of the physiological processes that underlie memory consolidation. Specifically, we will organise a public-focused event to discuss the concepts and technologies described in this proposal, and how they might lead to better treatments for age-associated memory impairments in humans (see pathways to impact).
Organisations
- University of Oxford (Lead Research Organisation)
- National Center for Scientific Research (Centre National de la Recherche Scientifique CNRS) (Collaboration)
- UNIVERSITY OF OXFORD (Collaboration)
- University College London (Collaboration)
- Heidelberg University (Collaboration)
- Tufts University (Collaboration)
- University of Calgary (Collaboration)
- École Normale Supérieure, Paris (Collaboration)
Publications
Barron HC
(2020)
Prediction and memory: A predictive coding account.
in Progress in neurobiology
Barron HC
(2021)
Neural inhibition for continual learning and memory.
in Current opinion in neurobiology
Barron HC
(2021)
Cross-species neuroscience: closing the explanatory gap.
in Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Barron HC
(2020)
Neuronal Computation Underlying Inferential Reasoning in Humans and Mice.
in Cell
Clarke-Williams C
(2024)
Coordinating brain-distributed network activities in memory resistant to extinction
in Cell
Fernandez-Ruiz A
(2023)
Over and above frequency: Gamma oscillations as units of neural circuit operations.
in Neuron
Gava GP
(2021)
Integrating new memories into the hippocampal network activity space.
in Nature neuroscience
Koolschijn RS
(2019)
The Hippocampus and Neocortical Inhibitory Engrams Protect against Memory Interference.
in Neuron
Koolschijn RS
(2021)
Memory recall involves a transient break in excitatory-inhibitory balance.
in eLife
Lima J
(2019)
Enhanced discriminative aversive learning and amygdala responsivity in 5-HT transporter mutant mice
in Translational Psychiatry
Description | We do not know how new experiences become consolidated into stable memories. One theory is that precisely-timed activation of hippocampal neurons during sleep is important for memory consolidation, and that there are particular 'signature' events that organize neuronal activation. One such event is called the dentate spike and, based on experiments in anaesthetized animals, it was believed that during these events, neuronal activity selectively increased in one type of hippocampal neuron (dentate granule cells) but decreased in others (CA3 and CA1 principal cells). However, our experiments in behaving mice have discovered that activity increases in all three of these neuron types during dentate spike events. Second, until now, we did not have a way to test whether neuronal activity during dentate spikes was necessary for consolidating new memories. Thus, one of our key objectives was to develop a system whereby we can silence neurons during dentate spikes. We have now developed this system and shown that we can significantly reduce neuronal activation specifically during dentate spike events. We are currently examining whether this affects memory. |
Exploitation Route | The selective silencing of dentate granule cells will be a valuable tool for many researchers throughout the world that are interested in the role of the hippocampus in learning in memory. |
Sectors | Education,Healthcare,Pharmaceuticals and Medical Biotechnology |
Description | Eco-friendly research |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Impact | We are assembling a European Network of research scientists from the field of Life sciences to assess ways to implement sustainable research. |
Description | Knowledge transfer about research practice with the scientific council of the French Embassy in London |
Geographic Reach | Europe |
Policy Influence Type | Influenced training of practitioners or researchers |
Description | Public Outreach Committee |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Research staff is being trained to share their knowledge to the general public, and notably to discuss animal related work in medical research. Notably, this allows changing public attitudes towards how scientific research is delivered and the use of animals in research. |
Description | Cross-Network Novelty Encoding along the VTA-Hippocampal Pathway |
Amount | £17,000 (GBP) |
Funding ID | 2445705 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2020 |
End | 09/2024 |
Description | UK DRI Grand Challenges Award Programme 2022 |
Amount | £1,690,295 (GBP) |
Funding ID | DRI-GCFA223 |
Organisation | UK Dementia Research Institute |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 06/2023 |
End | 07/2026 |
Title | Genetic construct for Cre-dependent expression of Flp recombinase pAAV-EF1a-DIO-FLPo-Myc |
Description | This genetic construct generated in my laboratory allows users to express the recombinase Flp conditioned to the expression of the recombinase Cre. This construct is used for cell-type-selective optogenetic manipulation of nerve cells in the mammalian brain. |
Type Of Material | Technology assay or reagent |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | This construct has allowed to identify the neural pathway supporting the behavioral expression of appetitive memories in the adult mammalian brain (https://www.mrcbndu.ox.ac.uk/publications/hippocampus-accumbens-tripartite-neuronal-motif-guides-appetitive-memory-space). This construct is available at Addgene (see URL below). |
URL | https://www.addgene.org/124641/ |
Title | Genetic construct for Cre-dependent expression of optogenetic silence ArchT pAAV-EF1a-FDIO-ArchT-GFP |
Description | This genetic construct generated in my laboratory allows users to express the neuronal silencer ArchT conditioned to the expression of the recombinase Flp. This construct is used for cell-type-selective optogenetic silencing of selective nerve cells in the mammalian brain. |
Type Of Material | Technology assay or reagent |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | This construct has allowed to identify the neural pathway supporting the behavioral expression of appetitive memories in the adult mammalian brain (https://www.mrcbndu.ox.ac.uk/publications/hippocampus-accumbens-tripartite-neuronal-motif-guides-appetitive-memory-space). |
URL | https://www.addgene.org/124640/ |
Title | analytical tool for network oscillations using Empirical Mode Decomposition |
Description | A set of Python programs to extract frequency content of network oscillations |
Type Of Material | Physiological assessment or outcome measure |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | This toolbox allows identifying non-linear and non-stationary oscillatory components of complex signals. |
URL | https://pypi.org/project/emd/ |
Title | theta-nested spectral components |
Description | A software and associated data-set to provide an analytical framework to reveal spectral components of theta-band brain waves |
Type Of Material | Physiological assessment or outcome measure |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | Analytical tool to identify transient spectral components nested in theta cycles |
URL | https://data.mrc.ox.ac.uk/data-set/tsc |
Title | Code used for analysis of task-relevant, time-resolved functional Magnetic Resonance Spectroscopy (fMRS) |
Description | This package contains code for: Preprocessing of fMRS data (matlab), fsl_mrs code for simulations of fMRS data (python), Code for analysis of behavioural data (matlab), Code to assess relationship between fMRI and fMRS data (matlab) and Plotting functions. |
Type Of Material | Data analysis technique |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | This research dataset and codes allow scientists to analyse functional Magnetic Resonance Spectroscopy acquired in humans. |
URL | https://data.mrc.ox.ac.uk/data-set/frms-code |
Title | Detection of cell assemblies |
Description | Development and refinement of analytical tools to detect coordinated neuronal activity forming functional cell assemblies |
Type Of Material | Data analysis technique |
Provided To Others? | No |
Impact | Validation to the behavioural relevance of short time-scale hippocampal assembly-patterns |
Title | Topological analysis of hippocampal CA1 co-firing graphs |
Description | This package allows applying a novel technique from graph-theory to neuronal networks. In the dataset provided, each matrix contains the hippocampal CA1 co-firing graphs computed using the spike trains of pyramidal cells recorded from mice during active exploratory behaviour (i.e., excluding immobility epochs and sharp-wave/ripples) in four different tasks: (i) conditioned place preference (CPP), (ii) exploration of a novel context (without reward), (iii) spontaneous place preference (SPP) for a novel context and (iv) rewarded exploration of an otherwise familiar context (without CPP). In these co firing graphs, each node represents one cell; the edge linking any two nodes represents the coactivity of that cell pair, with a weight computed as the Pearson correlation coefficient between their spike trains. Each co-firing graph is defined by its adjacency matrix, whose elements are the edges of the graph / co-firing relationships between pairs of neurons indexed by the rows and columns of the matrix. For each matrix, the code provided (python 3.6) analyses the co-firing relationships among pyramidal cells for the 6 sessions recorded on that task day. Graph-theoretical measures are obtained for each co-firing graph (one graph per task session) and their dynamics across the 6 task sessions are analysed. See the paper 'Integrating new memories into the hippocampal network activity space' for description of the task and detailed methods. Notably, these example co-firing graphs and codes relate to figures 1, 2 and extended data figure 2. |
Type Of Material | Data analysis technique |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | This package allows applying a novel technique from graph-theory to neuronal networks. |
URL | https://data.mrc.ox.ac.uk/data-set/topological-analysis-hippocampal-ca1-co-firing-graphs |
Description | Brain and behavioral dynamics of social interaction |
Organisation | École Normale Supérieure, Paris |
Country | France |
Sector | Academic/University |
PI Contribution | My laboratory is providing expertise in brain network physiology linked to social behaviour |
Collaborator Contribution | My collaborator is providing expertise in theoretical modelling of social dynamics |
Impact | This collaboration is multidisplinary, including experts in statistical physics and brain network physiology |
Start Year | 2020 |
Description | Graph theory and neuronal population activity |
Organisation | University of Oxford |
Department | Mathematical Institute Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | My laboratory is providing expertise and data about brain dynamics in memory |
Collaborator Contribution | My collaborators are helping supervising PhD students and to develop new methods to analyse brain function using graph theory |
Impact | design and test of new methods to analyse neuronal cooperation in the brain |
Start Year | 2022 |
Description | Molecular tagging of memory-bearing neurons |
Organisation | Tufts University |
Department | Department of Neuroscience |
Country | United States |
Sector | Academic/University |
PI Contribution | Using a tetTAG technology we labelled brain nece cells holding a memory representation of an environment paired with drug abuse. By controlling these tagged neurons, we have managed to alleviate the expression of a drug-place behaviour. |
Collaborator Contribution | Dr Reijmers provided the c-fos-tTA mouse line to implement the tetTAG technology. |
Impact | One peer-reviewed research article published: Nat Neurosci. 2016 Feb 22. doi: 10.1038/nn.4250. Recoding a cocaine-place memory engram to a neutral engram in the hippocampus. Trouche S, Perestenko PV, van de Ven GM, Bratley CT, McNamara CG, Campo-Urriza N, Black SL, Reijmers LG, Dupret D. |
Start Year | 2015 |
Description | Role of SWR in memory consolidation |
Organisation | Heidelberg University |
Country | Germany |
Sector | Academic/University |
PI Contribution | Interactive collaborative work to develop a closed loop interface to detect sharp wave/ripple events from the local field potential. This technology provides proof of principle for closed-loop manipulation of the neuronal representation of a memory trace. |
Collaborator Contribution | Interactive collaborative work to develop a closed loop interface to detect sharp wave/ripple events from the local field potential |
Impact | One peer-reviewed research article published: Hippocampal Offline Reactivation Consolidates Recently Formed Cell Assembly Patterns during Sharp Wave-Ripples. van de Ven GM, Trouche S, McNamara CG, Allen K, Dupret D. 2016. Neuron, 92(5): 968-974. |
Start Year | 2015 |
Description | Soft matter dynamics in the brain |
Organisation | University of Oxford |
Department | Department of Physics |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | My laboratory is providing expertise and data about brain dynamics with respect to learning processes |
Collaborator Contribution | My collaborators are providing methods and concepts about soft matter processes relevenat to neural tissue |
Impact | The collaboration is currently yielding grant applications, new analytical methods, PhD student co-supervision and design of new neural electrodes |
Start Year | 2022 |
Description | circuit-level biomarker of AD pathology |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The UK DRI Grand Challenge Award will support a collaboration between the Dupret Group at the MRC Unit and researchers based at University College London, and will be led by UK DRI Group Leader Dr. Marc Aurel Busche. The team will work together to develop a biomarker for Alzheimer's that can be used to identify and monitor early signs of the disease. My laboratory will leverage its leading expertise in the electrophysiological interrogation of brain functions underlying memory, focusing on state-of-the-art mouse models of Alzheimer's. |
Collaborator Contribution | The Award will also support parallel studies in human research participants at the UK DRI, offering a valuable opportunity for cross-species translation of research discoveries. |
Impact | The collaboration is about to officially start. |
Start Year | 2023 |
Description | hippocampal network physiology in the human brain |
Organisation | National Center for Scientific Research (Centre National de la Recherche Scientifique CNRS) |
Country | France |
Sector | Academic/University |
PI Contribution | In this collaboration, my laboratory is deploying expertise in brain network dynamics to analyse neural dynamics in the human hippocampus. Notably, we use state-of-the-art spectral decomposition of the local field potentials recorded from the human brain during memory tasks where participants use their memory abilities to draw conclusions. |
Collaborator Contribution | My collaborators are collecting the data at the hospital, running the memory task and brain recordings with the human participants. |
Impact | This collaboration is multi-disciplinary and cross-species: this project combines in vivo brain electrophysiology and medicine; rodents and humans. |
Start Year | 2022 |
Description | neural dynamics in AD |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | In this collaboration, my laboratory is deploying expertise in brain networks to reveal dysfunctional neural dynamics in Alzheimer Disease. Notably, we use state-of-the-art spectral decomposition of the local field potentials recorded from the brain during memory tasks where participants use their ability to continually learn new information to adjust their behaviour on a moment-by-moment basis. |
Collaborator Contribution | My collaborators are providing expertise in the neurobiological basis of AD pathology. |
Impact | This collaboration is multi-disciplinary and cross-species, allowing to combine multiple techniques (molecular biology, electrophysiology, imaging, medicine) to assess early biomarkers of AD onset in humans and rodents. |
Start Year | 2021 |
Description | neuromorphic chips |
Organisation | University of Calgary |
Country | Canada |
Sector | Academic/University |
PI Contribution | My laboratory is providing electrophysiological recording datasets of the spiking activity from hippocampal neurons during memory tasks to inform the design of novel neuromorphic chips. |
Collaborator Contribution | My colleague is providing the theoretical models and hard-ware implementation of the biologically-informed neuromorphic chips. |
Impact | This collaboration is multi-disciplinary, being at the nexus of neuroscience, machine learning and engineering. |
Start Year | 2019 |
Description | spectral analyses toolbox |
Organisation | University of Oxford |
Department | Oxford Centre for Human Brain Activity (OHBA) |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | My laboratory is providing expertise in brain network physiology and electrophysiological recording datasets of brain nerve cell activity during memory tasks. These datasets are used to develop and test innovative analytical frameworks of network oscillations. |
Collaborator Contribution | My collaborators are developing and implementing the analytical frameworks for spectral decomposition of network oscillations. |
Impact | A toolbox has been released: https://pypi.org/project/emd/ |
Start Year | 2019 |
Description | Featuring the brain in a museum exhibition |
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 | Research staff contributed to a large and new exhibition held at the Banbury Museum & Gallery (Oxforshire) by providing microscopic images to illuminate in beautiful details the circuits and cells of the mammalian brain. The exhibition, entitled "Your Amazing Brain: A User's Guide", ran from 12th February to 5th June 2022 and was an interactive, family-friendly experience offering the public an opportunity to journey inside the brain and discover more about what makes the brain so special. The Unit's images formed the core of a gallery piece "Zoom into your brain" that showcases, at increasing magnification, the organisation of the brain into regions, different types of neurons, and specialised structures such as axons, dendrites, and synaptic connections. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.banburymuseum.org/events/your-amazing-brain/ |
Description | General public documentary: The Symphony of the Brain |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | This documentary explains to the general public the notion of brain waves, and how this processs supports memory and movements. This documentary is available to anyone on the Youtube channel. It is a producion made in partnership with Oxford Sparks. Video Summary: "We can think of singers in a choir as neurons in the brain. Like these singers, neurons have to work together to create harmony, and once they do, the results are magnificent!" When neurons, or nerve cells, in the brain communicate with each other, they generate synchronised electrical activities known as brain waves. But what is the function of these brain waves? Can we 'see' them? What happens if these collective activities go 'out of sync'? In this video, Demi Brizee, a PhD student in the Medical Research Council Brain Network Dynamics Unit at the University of Oxford, introduces us to the fascinating world of brain waves, and explains how a better understanding of them could lead to new therapies for neurological conditions. |
Year(s) Of Engagement Activity | 2022,2023 |
URL | https://youtu.be/2YFHVyl8l1I |
Description | General public seminar about brain and memory |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | I discussed recent advances in the field of memort to the general public, annswering all questions from the audience. This event has allowed to clarify to the general public recent advances in the field of memory. |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.seh.ox.ac.uk/events/fellowship-lunchtime-lectures-professor-david-dupret |
Description | In2science 'virtual placement programme' |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | In July/August 2020, MRC BNDU continues to participate in the previously partnered with the charity In2science to host Year 12 school pupils enrolled on their STEM work-experience programme. Each summer, for the past 4 years, we have delivered personalised mentoring and rich STEM experiences for pupils from disadvantaged backgrounds. Charles Clarke-Williams from Dupret group together with some members of the Brown/Tan/Magill group took part in a research-based module "Interacting with the brain" that was jointly designed and delivered in support of In2scienceUK's Virtual Placement Programme. They organised webinars and research tasks (with real data!) for the students who took part. |
Year(s) Of Engagement Activity | 2020 |
URL | https://in2scienceuk.org/ |
Description | Locked-in: science on screen |
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 | I joined a group of University of Oxford neuroscientists for a film screening and discussion about The Diving Bell and the Butterfly, the true story of a former Elle editor, Jean-Dominique Bauby. Briefly, a major stroke leaves Bauby almost entirely paralysed, with the exception of his left eye. Bauby uses the experience to redeem himself for his less than exemplary life. In this event, I discussed the film's premise that consciousness is at the core of humanity and discussed scientific knowledge about locked-in syndrome, stroke and brain plasticity. This event contributed to the 2021 Oxford Science+ideas Festival (9-26October 2021), which comprised of 36 online and 67 face-to-face events with covid measures in place; a total of 35,000 people engaged with on-demand or live contents including 6,500 who came to 20 Oxford venues with 1.4 million social media users. |
Year(s) Of Engagement Activity | 2021 |
URL | https://if-oxford.com/wp-content/uploads/2021/08/IF-2021-PROGRAMME.pdf |
Description | MRC Festival School Visit to St Ebbes Primary School (19 June 2019) (Dupret) |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | On 19th June, Dr David Dupret and team of Unit members (Charlie Clarke-Williams, Gabrielle Leinhard (visiting student), and members from Magill/Sharott/Brown labs) went to St Ebbe's C. of E. (Aided) Primary School in central Oxford, where they visited Year 6 pupils and their teachers to help them learn more about science, researchers, and how the brain works to control memory and movement. Pupils were first given a brief introduction to the work of the Medical Research Council and the MRC Brain Network Dynamics Unit. Pupils, teachers and Unit members then engaged in a range of interactive discussions and hands-on activities that included looking at nerve cells under a microscope, reporting on observations by making model cells, measuring electrical activity from muscles to control a robotic claw, comparing the brains of different vertebrates, discovering different types of memories, and using a game version of a brain-machine interface. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.mrcbndu.ox.ac.uk/news/unit-goes-out-local-primary-school-mrc-festival-medical-research |
Description | Special Forum at FENS-Kavli Network of Excellence |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | 14 July 2020, at the FENS-Kavli Network of Excellence (FKNE), Professor David Dupret took part in a Session on Environmentally friendly Science. This special forum discussed what we can do to adopt a more sustainable model for life-sciences. The organizers presented the results of a small survey performed among neuroscientists and their research institutes to trigger the discussion on the environmental footprint of our community and to start identifying solutions. A panel of academics, activists and life-science industry representatives, among others, shared their viewpoints and experiences implementing concrete actions towards an environmentally friendly life-science framework. In addition to raising awareness on the impact of life sciences on the environment, they highlighted the need to better measure and document this impact, including plastic and Co2 emissions in scientific events and research centers. they also aim to draw up a list of concrete actions that define gold-standards of sustainability for our scientific community. |
Year(s) Of Engagement Activity | 2020 |
URL | https://forum2020.fens.org/event/sie05-towards-an-environmentally-friendly-model-for-life-sciences-1... |