Synaptic circuit mechanisms of rhythmic oscillatory dynamics in the cerebral cortex
Lead Research Organisation:
University of Oxford
Department Name: Pharmacology
Abstract
Rhythmic brain activity governs behaviour through the coordination of large numbers of nerve cells within and amongst specialised brain regions. Of particular importance is the formation or recall of everyday memories, which requires the synchronised action of millions of nerve cells of the temporal lobe within about a tenth of a second. In mammals, including humans, such synchronisation is observed as a 'slow' oscillating electrical rhythm measured by electroencephalography (EEG). Embedded within each cycle of the slow EEG signal, higher frequency oscillations emerge in relation to cognitive processes. Brain disorders including dementia and age-related memory impairments are accompanied by perturbation of these brain rhythms, thus highlighting their biological importance. The mechanisms for establishing and maintaining such rhythmic brain activity at various time scales, and the specific roles of the hundreds of nerve cell varieties that cooperate to deliver such a feat of function, remain to be defined. Brain rhythmicity creates sequential "windows" of increased and decreased activity levels of large groups of nerve cells, which enables the cerebral cortex to encode and link actual sequences of real-life events that are represented on distinct oscillatory cycles. In the proposed project, we will exploit our discovery of three novel varieties of nerve cells for establishing their roles in rhythmic oscillatory neuronal activity and memory processing. The novel types of nerve cell are found in a subcortical area deep within the brain called the medial septum, and each type sends parallel projections to a select area or areas of the cerebral cortex that each plays a distinct role in the formation and recall of memories. These cooperative brain areas, including the hippocampus and entorhinal cortex, are the ones first affected by neurodegeneration in Alzheimer's disease. Using a novel technology for the molecular dissection of gene expression profiles of these and other nerve cells in the medial septum, we will provide a comprehensive definition of cell types in both the mouse and the human brain. Building on our recent discoveries, we will establish how the function of these types of nerve cells changes in a mouse model of Alzheimer's disease. We will then use external modulation of the activity of some of these specific pathways to test how to improve memory processing. This project will thus advance our understanding of the functional organisation of the mammalian brain in relation to memory processing.
Technical Summary
Neuronal rhythmic synchronous activity in the theta frequency range (4-10 Hz) modulates the frequency and amplitude of gamma frequency (30-120 Hz) synchronisation, reflecting cognitive processes in the cerebral cortex. Theta oscillations are generated in a network of brain stem and midbrain structures and are transmitted to the cortex by the medial septum and diagonal band nuclei (MS/DB), but the principles of organisation of this pathway remain undefined. To identify the cell types in the MS/DB, I propose to provide a comprehensive gene expression profile of neurons using a pioneering technique, in situ RNA sequencing, and compare cell types in the murine and human MS/DB. In the ongoing MRC programme, we discovered that individual neurons in the MS/DB are highly specialised in time and space. We have defined four groups of strongly rhythmic GABAergic neuronal types in vivo. Three of these novel cell types are characterised: the Orchid cells, the Teevra cells and the dentate gyrus-targeting cells. They differ in their cortical target regions and brain state dependent firing in awake mice. We propose to establish their functional roles and contributions to behavioural states in normal and in the THY-Tau22 mouse model of Alzheimer's disease, by analysing their activity and synaptic connections. Using pharmaco- and opto-genetic modulation of their activity, first we focus on Teevra cells that selectively innervate specific GABAergic neurons via GABAergic synapses in hippocampal CA3 area, which provides context-dependent drive to the CA1 area during memory representation. We will test the hypothesis that the disinhibitory temporal windows assisted by Teevra cells increase hippocampal pyramidal cell excitability, providing temporal windows of context dependent read-out of hippocampus-dependent memory traces to the cerebral cortex and subcortical systems. This project will advance understanding of the functional organisation of the brain in relation to memory processing.
Planned Impact
The results of the project and the training provided in it will have benefits to a wide range of stakeholders:
(1) Researchers: neuroscientists engaging in basic brain research, both experimentalists and theoretical, clinicians working with patients suffering from dementia, neuroimaging specialists researching the human brain (e.g. functional MRI, connectomics), engineers and technologists (e.g. those working on brain-machine interfaces), molecular biologists, biochemists.
(2) Private sector: pharmaceutical companies undertaking drug discovery and clinical trials relating to Alzheimer's disease.
(3) Organisations, Institutes and government: national policy makers assessing the medium and long-term impact of basic neuroscience on society, European brain science initiatives such as the Human Brain Project, international Institutes (e.g. Allen Institute, Peter Somogyi serves on the Advisory Council of the theme "Human cortical cell types").
(4) Public sector: Alzheimer's Research UK charity, schools and other educational establishments, care homes.
Each group will benefit from the research in different ways:
The short-term benefits will be the impact on the research carried out by other neuroscientists and clinicians within the same field. Once our data are disseminated (e.g. through peer-review publication), other laboratories will immediately be able to use the results to design, modify or further support their experiments or re-evaluate their previous findings. For example, for researchers using Alzheimer's disease mouse models, they will directly be able to determine whether our findings on cell types within the basal forebrain projecting to cortical areas that degenerate in Alzheimer's disease may explain their results. Since our research output includes both neuroanatomical (e.g. projections from subcortical regions to the cortex) and neurophysiological data (e.g. role of network oscillations), studies on the human brain (e.g. neuroimaging) will gain a deeper understanding of the link between neuronal communication across cortical areas and 'functional' connectivity. Within the first 6 months of the project, as it is a continuation of current research, we expect to have published significant progress explaining cellular and synaptic mechanisms of setting up and maintaining rhythmic synchronised brain activity in the cerebral cortex.
In the medium to long-term, our research will benefit human health, as our results will be incorporated into understanding and explaining information processing in the brain.
(1) Researchers: neuroscientists engaging in basic brain research, both experimentalists and theoretical, clinicians working with patients suffering from dementia, neuroimaging specialists researching the human brain (e.g. functional MRI, connectomics), engineers and technologists (e.g. those working on brain-machine interfaces), molecular biologists, biochemists.
(2) Private sector: pharmaceutical companies undertaking drug discovery and clinical trials relating to Alzheimer's disease.
(3) Organisations, Institutes and government: national policy makers assessing the medium and long-term impact of basic neuroscience on society, European brain science initiatives such as the Human Brain Project, international Institutes (e.g. Allen Institute, Peter Somogyi serves on the Advisory Council of the theme "Human cortical cell types").
(4) Public sector: Alzheimer's Research UK charity, schools and other educational establishments, care homes.
Each group will benefit from the research in different ways:
The short-term benefits will be the impact on the research carried out by other neuroscientists and clinicians within the same field. Once our data are disseminated (e.g. through peer-review publication), other laboratories will immediately be able to use the results to design, modify or further support their experiments or re-evaluate their previous findings. For example, for researchers using Alzheimer's disease mouse models, they will directly be able to determine whether our findings on cell types within the basal forebrain projecting to cortical areas that degenerate in Alzheimer's disease may explain their results. Since our research output includes both neuroanatomical (e.g. projections from subcortical regions to the cortex) and neurophysiological data (e.g. role of network oscillations), studies on the human brain (e.g. neuroimaging) will gain a deeper understanding of the link between neuronal communication across cortical areas and 'functional' connectivity. Within the first 6 months of the project, as it is a continuation of current research, we expect to have published significant progress explaining cellular and synaptic mechanisms of setting up and maintaining rhythmic synchronised brain activity in the cerebral cortex.
In the medium to long-term, our research will benefit human health, as our results will be incorporated into understanding and explaining information processing in the brain.
Organisations
- University of Oxford (Lead Research Organisation, Project Partner)
- Hungarian Academy of Sciences (MTA) (Collaboration)
- Aarhus University (Collaboration)
- University College London (Collaboration)
- Karolinska Institute (Collaboration, Project Partner)
- Mortimer B Zuckerman Mind Brain Behaviour Institute (Collaboration)
- National Institute for Health Research (Collaboration)
- John Radcliffe Hospital (Collaboration)
- MTA Institute of Experimental Medicine (Collaboration)
- Mental Health University Institute of Quebec (Collaboration)
- UNIVERSITY OF OXFORD (Collaboration)
- Stockholm University (Collaboration, Project Partner)
- University of Szeged (Collaboration)
- New York University (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- University College London (Project Partner)
- Hungarian Academy of Sciences (Project Partner)
Publications
Yuste R
(2020)
A community-based transcriptomics classification and nomenclature of neocortical cell type
in Nat Neurosci
Joshi A
(2020)
Changing phase relationship of the stepping rhythm to neuronal oscillatory theta activity in the septo-hippocampal network of mice.
in Brain structure & function
Harris KD
(2018)
Classes and continua of hippocampal CA1 inhibitory neurons revealed by single-cell transcriptomics.
in PLoS biology
Francavilla R
(2018)
Connectivity and network state-dependent recruitment of long-range VIP-GABAergic neurons in the mouse hippocampus.
in Nature communications
Lukacs IP
(2023)
Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex.
in Cerebral cortex (New York, N.Y. : 1991)
Sárkány B
(2024)
Early and selective localization of tau filaments to glutamatergic subcellular domains within the human anterodorsal thalamus.
in Acta neuropathologica
Salib M
(2019)
GABAergic Medial Septal Neurons with Low-Rhythmic Firing Innervating the Dentate Gyrus and Hippocampal Area CA3.
in The Journal of neuroscience : the official journal of the Society for Neuroscience
Bocchio M
(2018)
Group II Metabotropic Glutamate Receptors Mediate Presynaptic Inhibition of Excitatory Transmission in Pyramidal Neurons of the Human Cerebral Cortex.
in Frontiers in cellular neuroscience
Viney TJ
(2018)
Shared rhythmic subcortical GABAergic input to the entorhinal cortex and presubiculum.
in eLife
Description | John Fell Fund |
Amount | £3,880 (GBP) |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 05/2019 |
End | 01/2020 |
Description | Medical Sciences Division Pump Priming Fund |
Amount | £10,000 (GBP) |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 02/2020 |
End | 02/2021 |
Description | Nuffield Benefaction for Medicine and the Wellcome Institutional Strategic Support Fund |
Amount | £5,660 (GBP) |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 04/2021 |
End | 09/2022 |
Description | Nuffield Benefaction for Medicine and the Wellcome Institutional Strategic Support Fund |
Amount | £8,480 (GBP) |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 07/2019 |
End | 03/2020 |
Description | Oxford University V-C Diversity Returning Career Fund |
Amount | £5,000 (GBP) |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2021 |
End | 01/2022 |
Description | PhD Studentship |
Amount | £85,000 (GBP) |
Funding ID | 522 AS-PhD-19a-010 |
Organisation | Alzheimer's Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2020 |
End | 04/2024 |
Title | Extracellular recordings and juxtacellular labelling with glass electrodes in the mouse medial septum and hippocampus |
Description | This repository contains MAT files consisting of simultaneously recorded mouse medial septal and hippocampal local field potentials (20 kHz sampling rates) and spikes from single medial septal cells. Data were recorded with glass electrodes during spontaneous movement and rest periods, followed by juxtacellular labelling of the medial septal cell. Text files of the spike times and detected hippocampal CA1 theta (5-12 Hz) oscillation trough times are associated with each MAT file. The files are organised by cell (neuron) name. For further details, see the CSV file included with the dataset. These recorded and labelled single cells were originally reported in Joshi et al 2017, Viney et al 2018, and Salib et al 2019. Each MAT file contains the following channels, exported from the original Spike2 (smr) recording files: (1) Details of the recording (2) Detected spikes (in seconds) from the single medial septal cell (3) Movement detection (eg. accelerometer or rotary encoder) (4) Local field potential (medial septum), in mV (5) Local field potential (hippocampal CA1), in mV; see CSV file for precise location (e.g. within stratum pyramidale) This dataset is made available under a Creative Commons Attribution 4.0 International (CC BY 4.0) license: If you share or adapt these data you must give appropriate credit, provide a link to the license, and indicate if changes were made. |
Type Of Material | Database/Collection of data |
Year Produced | 2023 |
Provided To Others? | Yes |
URL | https://zenodo.org/record/8187902 |
Title | Glass electrode and silicon probe recordings from THY-Tau22 mice |
Description | This repository contains code used to analyse electrophysiological data obtained from THY-Tau22 mice. Example datasets are included. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | https://zenodo.org/record/7198897 |
Description | Dr David Dupret |
Organisation | Medical Research Council (MRC) |
Department | MRC Brain Network Dynamics Unit at the University of Oxford (BNDU) |
Country | United Kingdom |
Sector | Public |
PI Contribution | Data |
Collaborator Contribution | Data and analysis |
Impact | Bálint Király, Andor Domonkos, Márta Jelitai, Vítor Lopes-dos-Santos, Sergio Martínez-Bellver, Barnabás Kocsis, Dániel Schlingloff, Abhilasha Joshi, Minas Salib, Richárd Fiáth, Péter Barthó, István Ulbert, Tamás F. Freund, Tim J. Viney, David Dupret, Viktor Varga, Balázs Hangya, "The medial septum modulates hippocampal oscillations beyond the theta rhythm" Nature Communications (March 2023), Paper under second round of revision |
Start Year | 2018 |
Description | Dr Martin Gillies |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Data |
Collaborator Contribution | Acute human cortical surgeries for in vitro slice physiology |
Impact | Bocchio M, Lukacs IP, Stacey R, Plaha P, Apostolopoulos V, Livermore L, Argue S, Ansorge O, Gillies MJ, Somogyi P and Capogna, M. (2019) Group II metabotropic glutamate receptors mediate presynaptic inhibition of excitatory transmission in pyramidal neurons of the human cerebral cortex. Front Cell Neurosci. 12, 508. |
Start Year | 2018 |
Description | Dr Olaf Ansorge |
Organisation | John Radcliffe Hospital |
Department | Department of Neuropathology and Ocular Pathology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Data |
Collaborator Contribution | Data and analysis |
Impact | Bocchio M, Lukacs IP, Stacey R, Plaha P, Apostolopoulos V, Livermore L, Argue S, Ansorge O, Gillies MJ, Somogyi P and Capogna, M. (2019) Group II metabotropic glutamate receptors mediate presynaptic inhibition of excitatory transmission in pyramidal neurons of the human cerebral cortex. Front Cell Neurosci. 12, 508. Lukacs IP, Francavilla R, Field M, Hunter E, Howarth M, Horie S, Plaha P, Stacey R, Livermore L, Ansorge O, Tamas G, Somogyi P (2022) Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex. Cerebral Cort, Cerebral Cortex, bhac195, https://doi.org/10.1093/cercor/bhac195 Field M, Lukacs IP, Hunter E, Stacey R, Plaha P, Livermore L, Ansorge O, Somogyi P (2021) Tonic GABAA receptor mediated currents of human cortical GABAergic interneurons vary amongst cell types. J Neurosci 41:9702-9719. https://pubmed.ncbi.nlm.nih.gov/34667071/ |
Start Year | 2019 |
Description | Freund, T. F. |
Organisation | Hungarian Academy of Sciences (MTA) |
Department | Institute of Experimental Medicine |
Country | Hungary |
Sector | Academic/University |
PI Contribution | Experimental data and design |
Collaborator Contribution | experimental data and analysis |
Impact | Bálint Király, Andor Domonkos, Márta Jelitai, Vítor Lopes-dos-Santos, Sergio Martínez-Bellver, Barnabás Kocsis, Dániel Schlingloff, Abhilasha Joshi, Minas Salib, Richárd Fiáth, Péter Barthó, István Ulbert, Tamás F. Freund, Tim J. Viney, David Dupret, Viktor Varga, Balázs Hangya, "The medial septum modulates hippocampal oscillations beyond the theta rhythm" Nature Communications (March 2023), Paper under second round of revision |
Start Year | 2008 |
Description | G. Tamas |
Organisation | University of Szeged |
Department | Department of Pharmacology and Pharmacotherapy |
Country | Hungary |
Sector | Academic/University |
PI Contribution | Experimental data |
Collaborator Contribution | Experimental data and analysis |
Impact | Varga C, Tamas G, Barzo P, Olah S and Somogyi P. (2015) Molecular and electrophysiological characterization of GABAergic interneurons expressing the transcription factor COUP-TFII in the adult human temporal cortex. Cereb. Cortex. 25, 4430-4449. Lukacs IP, Francavilla R, Field M, Hunter E, Howarth M, Horie S, Plaha P, Stacey R, Livermore L, Ansorge O, Tamas G, Somogyi P (2022) Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex. Cerebral Cort, Cerebral Cortex, bhac195, https://doi.org/10.1093/cercor/bhac195 Yuste R, Hawrylycz M, Aalling N, Aguilar-Valles A, Arendt D, Arnedillo RA, Ascoli GA, Bielza C, Bokharaie V, Bergmann TB, Bystron I, Capogna M, Chang Y, Clemens A, de Kock CPJ, DeFelipe J, Dos Santos SE, Dunville K, Feldmeyer D, Fiáth R, Fishell GJ, Foggetti A, Gao X, Ghaderi P, Goriounova NA, Güntürkün O, Hagihara K, Hall VJ, Helmstaedter M, Herculano S, Hilscher MM, Hirase H, Hjerling-Leffler J, Hodge R, Huang J, Huda R, Khodosevich K, Kiehn O, Koch H, Kuebler ES, Kühnemund M, Larrañaga P, Lelieveldt B, Louth EL, Lui JH, Mansvelder HD, Marin O, Martinez-Trujillo J, Moradi Chameh H, Nath A, Nedergaard M, Nemec P, Ofer N, Pfisterer UG, Pontes S, Redmond W, Rossier J, Sanes JR, Scheuermann R, Serrano-Saiz E, Steiger JF, Somogyi P, Tamás G, Tolias AS, Tosches MA, García MT, Vieira HM, Wozny C, Wuttke TV, Yong L, Yuan J, Zeng H, Lein E. A (2020) Community-based transcriptomics classification and nomenclature of neocortical cell types. Nat Neurosci, 23:1456-1468. |
Start Year | 2012 |
Description | L. Topolnik |
Organisation | Mental Health University Institute of Quebec |
Department | Centre of Research |
Country | Canada |
Sector | Academic/University |
PI Contribution | Experimental data |
Collaborator Contribution | Experimental data and analysis |
Impact | Francavilla, R, Villette V, Luo X, Chamberland S, Muñoz-Pino E, Camiré O, Wagner K, Viktor K, Somogyi P and Topolnik L. (2018) Connectivity and network state-dependent recruitment of long-range VIP-GABAergic neurons in the mouse hippocampus. Nature Commun.,9, 5043. |
Start Year | 2018 |
Description | Mr James L Livermore |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Data |
Collaborator Contribution | Acute human cortical surgerioes for in vitro slice physiology |
Impact | Bocchio M, Lukacs IP, Stacey R, Plaha P, Apostolopoulos V, Livermore L, Argue S, Ansorge O, Gillies MJ, Somogyi P and Capogna, M. (2019) Group II metabotropic glutamate receptors mediate presynaptic inhibition of excitatory transmission in pyramidal neurons of the human cerebral cortex. Front Cell Neurosci. 12, 508. Field M, Lukacs IP, Hunter E, Stacey R, Plaha P, Livermore L, Ansorge O, Somogyi P (2021) Tonic GABAA receptor mediated currents of human cortical GABAergic interneurons vary amongst cell types. J Neurosci 41:9702-9719. https://pubmed.ncbi.nlm.nih.gov/34667071/ Lukacs IP, Francavilla R, Field M, Hunter E, Howarth M, Horie S, Plaha P, Stacey R, Livermore L, Ansorge O, Tamas G, Somogyi P (2022) Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex. Cerebral Cort, Cerebral Cortex, bhac195, https://doi.org/10.1093/cercor/bhac195 |
Start Year | 2018 |
Description | Prof Balazs Hangya |
Organisation | MTA Institute of Experimental Medicine |
Country | Hungary |
Sector | Public |
PI Contribution | Scientific exchange of data and analysis on medial septal cell types |
Collaborator Contribution | Advanced analysis of firing patterns and re-evaluation of data collected in Oxford |
Impact | Paper under second round of revision in Nature Communications (as of March 2023): "The medial septum modulates hippocampal oscillations beyond the theta rhythm" Bálint Király, Andor Domonkos, Márta Jelitai, Vítor Lopes-dos-Santos, Sergio Martínez-Bellver, Barnabás Kocsis, Dániel Schlingloff, Abhilasha Joshi, Minas Salib, Richárd Fiáth, Péter Barthó, István Ulbert, Tamás F. Freund, Tim J. Viney, David Dupret, Viktor Varga, Balázs Hangya |
Start Year | 2021 |
Description | Prof Gyorgy Buzsaki |
Organisation | New York University |
Country | United States |
Sector | Academic/University |
PI Contribution | Dr Tim Viney visited the research group in New York and provided advice and expertise on GABAergic neurons of the mouse cerebral cortex. Brains from a novel mouse line were transported back to the laboratory. The brains were sectioned and new cell types were defined using immunohistochemical and microscopic methods, resulting in a co-authorship publication (Valero et al Nat Neuro 2021). |
Collaborator Contribution | The collaborators provided expertise, designs and training for implementing novel recording and behavioural testing paradigms. Strategies for the analysis of 'multi-unit' data and the operation of silicon probes were instrumental in the completion of another research project (Viney et al Cell Reports 2022). The collaborators also provided intellectual / scientific feedback on ongoing research through lab meetings and presentations held by Dr Viney in their laboratory. Prof Buzsaki is listed in ongoing grant applications made by Dr Viney for futher collaboration on different projects. |
Impact | Valero, M., Viney, T.J., Machold, R., Mederos, S., Zutshi, I., Schuman, B., Senzai, Y., Rudy, B., and Buzsaki, G. (2021). Sleep down state-active ID2/Nkx2.1 interneurons in the neocortex. Nat Neurosci 24, 401-411. -multidisciplinary: high-density recording techniques, optogenetics, behavioural tasks, immunohistochemistry, in vitro slice recordings, and microscopy. |
Start Year | 2019 |
Description | Prof Jens Hjerling-Leffler |
Organisation | Karolinska Institute |
Country | Sweden |
Sector | Academic/University |
PI Contribution | Data |
Collaborator Contribution | In situ transcriptomic dissection of neuronal diversity |
Impact | Harris KD, Hochgerner H, Skene NG, Magno L, Katona L, Bengtsson Gonzales C, Somogyi P, Kessaris N, Linnarsson S and Hjerling-Leffler, J. (2018) Classes and continua of hippocampal CA1 inhibitory neurons revealed by single-cell transcriptomics. PLoS Biology, 16, e2006387. Yuste R, Hawrylycz M, Aalling N, Aguilar-Valles A, Arendt D, Arnedillo RA, Ascoli GA, Bielza C, Bokharaie V, Bergmann TB, Bystron I, Capogna M, Chang Y, Clemens A, de Kock CPJ, DeFelipe J, Dos Santos SE, Dunville K, Feldmeyer D, Fiáth R, Fishell GJ, Foggetti A, Gao X, Ghaderi P, Goriounova NA, Güntürkün O, Hagihara K, Hall VJ, Helmstaedter M, Herculano S, Hilscher MM, Hirase H, Hjerling-Leffler J, Hodge R, Huang J, Huda R, Khodosevich K, Kiehn O, Koch H, Kuebler ES, Kühnemund M, Larrañaga P, Lelieveldt B, Louth EL, Lui JH, Mansvelder HD, Marin O, Martinez-Trujillo J, Moradi Chameh H, Nath A, Nedergaard M, Nemec P, Ofer N, Pfisterer UG, Pontes S, Redmond W, Rossier J, Sanes JR, Scheuermann R, Serrano-Saiz E, Steiger JF, Somogyi P, Tamás G, Tolias AS, Tosches MA, García MT, Vieira HM, Wozny C, Wuttke TV, Yong L, Yuan J, Zeng H, Lein E. A (2020) Community-based transcriptomics classification and nomenclature of neocortical cell types. Nat Neurosci, 23:1456-1468. |
Start Year | 2018 |
Description | Prof Laszlo Acsady |
Organisation | MTA Institute of Experimental Medicine |
Country | Hungary |
Sector | Public |
PI Contribution | Histological analysis of pathological Tau proteins in human brain sections provided by their laboratory. |
Collaborator Contribution | Provided high quality human brain tissue for the project and use of facilities including light and electron microscopes |
Impact | A manuscript based on this collaboration is in the final stages of preparation for submission to a peer-reviewed journal (as of March 2023). Authors: B. Sarkany, Cs. David, P. Somogyi, L. Acsady, T. Viney. "Glutamatergic drivers of Tau pathology in the human thalamus". |
Start Year | 2020 |
Description | Professor Angus Silver |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Co-supervisotr of the thesis of Istvan Lukacs |
Collaborator Contribution | n/a |
Impact | n/a |
Start Year | 2018 |
Description | Professor Attila Losonczy |
Organisation | Mortimer B Zuckerman Mind Brain Behaviour Institute |
Country | United States |
Sector | Academic/University |
PI Contribution | Dr Viney visited the laboratory of Prof Losonczy in 2019 for a 5-week research collaboration. Dr Viney provided advice on the identification of GABAergic neurons and glutamatergic cortical pyramidal neurons. He trained staff in immunohistochemistry and the microscopic analysis of axons, and helped interpret the results of ongoing calcium imaging experiments based on his experience of in vivo electrophysiological recordings in the same brain regions (mostly hippocampus). |
Collaborator Contribution | The collaborator trained Dr Viney in two-photon calcium imaging in awake head-restrained mice, complementing the existing in vivo electrophysiological approaches in head-fixed mice carried out in the laboratory in Oxford (e.g. in Viney et al Cell Reports 2022). Dr Viney used the preliminary data in grant applications and in the creation of a new animal project licence. The collaborator also trained Dr Viney in how to use water restriction in mice, which was used in Viney et al Cell Report 2022. Dr Viney was also taught programming in Python, which is now implemented in his own group. Strategies to image cortical neurons in awake tauopathy model mice were discussed at lab meetings and other focused meetings during the research visit, and follow-up Zoom calls. The realisation of this would require further research visits but this was disrupted by the pandemic. Preliminary data obtained by Dr Viney and the collaborators was used in job applications. Dr Viney secured a competitive 5-year fellowship in the Department of Pharmacology, Oxford. |
Impact | This paper benefited from the training received by the collaborator: Viney, T.J., Sarkany, B., Ozdemir, A.T., Hartwich, K., Schweimer, J., Bannerman, D., and Somogyi, P. (2022). Spread of pathological human Tau from neurons to oligodendrocytes and loss of high-firing pyramidal neurons in aging mice. Cell Rep 41, 111646. |
Start Year | 2019 |
Description | Professor David Bannerman |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Design, data, analysis, interpretation, conclusion |
Collaborator Contribution | Data and analysis Behavioural testing of transgenic mice (tauoathy models) |
Impact | Viney TJ, Sarkany B, Ozdemir AT, Hartwich K, Schweimer J, Bannerman D, Somogyi P (2022) Spread of pathological human Tau from neurons to oligodendrocytes and loss of high-firing pyramidal neurons in ageing mice Cell Reports, 41:111646 |
Start Year | 2018 |
Description | Professor Frances Edwards |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Data |
Collaborator Contribution | Data and analysis Mouse models of mechanisms in tauopathies |
Impact | N/A |
Start Year | 2018 |
Description | Professor K D Harris |
Organisation | University College London |
Department | Neuroscience, Physiology & Pharmacology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Harris KD, Hochgerner H, Skene NG, Magno L, Katona L, Bengtsson Gonzales C, Somogyi P, Kessaris N, Linnarsson S and Hjerling-Leffler, J. (2018) Classes and continua of hippocampal CA1 inhibitory neurons revealed by single-cell transcriptomics. PLoS Biology, 16, e2006387. |
Collaborator Contribution | Data and analysis |
Impact | N/A |
Start Year | 2019 |
Description | Professor Marco Capogna |
Organisation | Aarhus University |
Department | Department of Biomedicine |
Country | Denmark |
Sector | Academic/University |
PI Contribution | Aarhus University |
Collaborator Contribution | Data |
Impact | Bocchio M, Lukacs IP, Stacey R, Plaha P, Apostolopoulos V, Livermore L, Argue S, Ansorge O, Gillies MJ, Somogyi P and Capogna, M. (2019) Group II metabotropic glutamate receptors mediate presynaptic inhibition of excitatory transmission in pyramidal neurons of the human cerebral cortex. Front Cell Neurosci. 12, 508. |
Start Year | 2018 |
Description | Professor Mats Nilsson |
Organisation | Stockholm University |
Department | Department of Biochemistry and Biophysics |
Country | Sweden |
Sector | Academic/University |
PI Contribution | data |
Collaborator Contribution | In situ transcriptomic dissection of neuronal diversity |
Impact | n/a |
Start Year | 2018 |
Description | Professor Nicoletta Kessaris |
Organisation | National Institute for Health Research |
Department | UCLH/UCL Biomedical Research Centre |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Data |
Collaborator Contribution | Molecular diversity of neurons in situ hybridisation |
Impact | Harris KD, Hochgerner H, Skene NG, Magno L, Katona L, Bengtsson Gonzales C, Somogyi P, Kessaris N, Linnarsson S and Hjerling-Leffler, J. (2018) Classes and continua of hippocampal CA1 inhibitory neurons revealed by single-cell transcriptomics. PLoS Biology, 16, e2006387. |
Start Year | 2019 |
Description | Puneet Plaha |
Organisation | John Radcliffe Hospital |
Country | United Kingdom |
Sector | Hospitals |
PI Contribution | Data |
Collaborator Contribution | Acute human cortical surgeries for in vitro slice phyiology |
Impact | Bocchio M, Lukacs IP, Stacey R, Plaha P, Apostolopoulos V, Livermore L, Argue S, Ansorge O, Gillies MJ, Somogyi P and Capogna, M. (2019) Group II metabotropic glutamate receptors mediate presynaptic inhibition of excitatory transmission in pyramidal neurons of the human cerebral cortex. Front Cell Neurosci. 12, 508. Lukacs IP, Francavilla R, Field M, Hunter E, Howarth M, Horie S, Plaha P, Stacey R, Livermore L, Ansorge O, Tamas G, Somogyi P (2022) Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex. Cerebral Cort, Cerebral Cortex, bhac195, https://doi.org/10.1093/cercor/bhac195 Field M, Lukacs IP, Hunter E, Stacey R, Plaha P, Livermore L, Ansorge O, Somogyi P (2021) Tonic GABAA receptor mediated currents of human cortical GABAergic interneurons vary amongst cell types. J Neurosci 41:9702-9719. https://pubmed.ncbi.nlm.nih.gov/34667071/ |
Start Year | 2019 |
Description | Z. Magloczky |
Organisation | Hungarian Academy of Sciences (MTA) |
Department | Institute of Experimental Medicine |
Country | Hungary |
Sector | Academic/University |
PI Contribution | Experimental data |
Collaborator Contribution | Experimental data and analysis |
Impact | n/a |
Start Year | 2018 |
Description | 2018 Brain Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Talk at the 2018 Brain Confeence - The Necesity of Cell Tupes for Brain Research "Brain Space and Time defines Neuron Types" |
Year(s) Of Engagement Activity | 2018 |
Description | Axons in the Hills |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Talk title Cortical axo-axonic cells in brain time and space |
Year(s) Of Engagement Activity | 2018 |
Description | Gordon Research Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Discussion leader at the Inhibition in the CNS conference |
Year(s) Of Engagement Activity | 2019 |
Description | IBRO-UM5, Rabat |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Undergraduate students |
Results and Impact | Module I: Neural substrates of cognitive functions Titles: Hippocampus - place and roles in brain networks (2) Hippocampus - intrinsic organization of time and space |
Year(s) Of Engagement Activity | 2019 |
Description | Practical microscopy and neuroanatomy |
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 | Small groups of secondary school pupils and teachers visited the laboratory and studied brain sections and the neurochemical diversity of brain cells under the microscope. They took images on a fluorescence microscope and took away printouts. We did similar open day / workshops for undergraduate and postgraduate students. |
Year(s) Of Engagement Activity | 2018,2019 |