Disorientation is a key early symptom of dementia, but why and how do people become disoriented? The Viney Group investigates neural circuit mechanisms underlying spatial orientation in the rodent and human brain. Our main focus of research is on the Papez circuit, a collection of subcortical and cortical brain areas important for spatial navigation, orientation, episodic memory, and cognition. We want to understand why parts of the Papez circuit show an early and selective vulnerability to Tau pathology and neurodegeneration.
Using in vivo recordings and molecular profiling, we define how the activity of individual nerve cells in the mammalian brain relates to their postsynaptic target neurons, and how this activity changes during different behavioural states, environmental contexts, and pathological conditions.
Alzheimer's disease, the most common form of dementia, is defined by the progressive spread of misfolded Tau proteins and the build-up of amyloid-beta plaques in the brain. We study the vulnerability of Papez circuit to pathology in the human brain and investigate the consequences of Tau pathology in mouse models. We are also investigating cell-type-specific biomarkers and biochemical pathways that are affected in neurodegenerative disease that may lead to treatments to prevent or slow disease progression.
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We are happy to support fellowship applications from interested postdoctoral candidates.
Information for DPhil (PhD) applications:
- Main Oxford DPhil applications: https://www.ox.ac.uk/admissions/graduate/courses/dphil-pharmacology. To be considered for Oxford Scholarships (full funding), application deadlines are usually around the start of December each year. However, the DPhil in Pharmacology applications are usually open until May.
- Doctoral Training Partnerships: Oxford Interdisciplinary Bioscience DTP. Main 4-year DTP studentships: https://www.biodtp.ox.ac.uk/main-dtp-studentships - deadlines are usually around the start of January each year.
Watch this space for announcements of open positions!
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NEWS
September 2024
- This month we start our new MRC-funded project, "Defining neural circuit mechanisms for disorientation in preclinical Alzheimer's disease"
- Congratulations to Aditi for a great result for her dissertation and completing the MSc Pharmacology degree!
July 2024
Fellowship success for Blaschko Fellow: Dr Sara Hijazi
Congratulations to Dr Sara Hijazi, the Department's current Blaschko Fellow, who has been awarded an MCSA Postdoctoral Fellowship for her proposal entitled: Defining how GABAergic inhibition coordinates the firing and tuning of head direction cell types across the anterodorsal nucleus of the thalamus.
The overarching goal of this proposal is to define the role of GABAergic inhibition in shaping the firing patterns of head direction cells in the thalamus, which are important for spatial navigation and memory.
“I would like to acknowledge the Department's support in facilitating my application,” said Sara. “I am very grateful for the Blaschko Fellowship, funded by the Department in collaboration with Linacre College, that allowed me to obtain preliminary data for this application. More importantly, the Blaschko Fellowship gave me the opportunity to explore and make new observations which were instrumental in writing the MCSA proposal. This would have not been possible without the excellent support from my mentor Dr Tim Viney and the very encouraging and nurturing environment in the Viney group. I am really looking forward to start working on this project and I am really glad I will be able to extend my stay in the Department of Pharmacology for another 2 years.”
June 2024
- New publication! We are delighted to announce that Barbara's paper, "Early and selective localization of tau filaments to glutamatergic subcellular domains within the human anterodorsal thalamus" is now published in Acta Neuropathologica. https://doi.org/10.1007/s00401-024-02749-3
- Tim gave an invited talk, entitled 'Vulnerability of neural encoding head direction in preclinical Alzheimer's disease', at a symposium on 'Astrocytes in Brain Function and Disease' at the Nobel Forum, Karolinska Institute, Stockholm. Programme can be found here: https://news.ki.se/calendar/symposium-astrocytes-in-brain-function-and-disease
May 2024
- The Viney Group were pleased to host Professor Michael Hasselmo, from Boston University, USA, who visited us and participated in our workshop on 'Mechanisms of Spatial Disorientation'. He also gave a talk at Cortex Club, entitled 'Egocentric and Allocentric Representations in Cortical Structures'
April 2024
- We are delighted to announce that the lab will receive major funding from the MRC to pursue a project on spatial disorientation in preclinical Alzheimer's disease. Further details will be announced later.
- At the stat of Trinity Term we welcome Aditi, who will investigate neuroinflammation in relation to tau pathology, and Mara, who will investigate cell types of the anterior thalamus
March 2024
- Tim gave an invited talk at the Tau2024 Global Conference in Washington DC, USA
- Tim's talk was entitled "Vulnerability of subcortical presynaptic terminals to Tau pathology", part of the Brain Micro-Environments session, and was attended by over 1,200 people.
Leading tau experts convened for the Tau2024 Global Conference to collaborate and discuss key issues impacting the tau research community. This in-person and online conference provided a forum for members of academia, industry, philanthropy and government to:
- Discuss tau-based biology, biomarkers, therapeutics and phenotypes.
- Attract talent and funding to the study of tauopathies, particularly among early career researchers.
- Increase interdisciplinary alignment and collaboration around challenges in tau research.
Topics included biomarkers, clinical manifestations, drug development, risk and environmental factors, genetics, molecular and cell biology, neuropathology, and more.
- Tim also gave a talk at the National Institutes of Health (NIH), MD, USA, and spent a couple of days interacting with various research groups.
October 2023
- Congratulations to Shan who was one of the 3 winners of the BRAINScapes Imaging Competition 2023. The prize was presented at the Autumn School for Cognitive Neuroscience
September 2023
- Shan was selected to attend the 'Advanced tools for data analysis in Neuroscience' summer school in Strasbourg
June 2023
- ***New preprint alert*** Pathway-specific progression of Tau pathology in the human thalamus
May 2023
"Wegovy and Ozempic: could the new weight-loss drug also treat dementia?" Tim and Barbara write for The Conversation. Also featured on 'Science Alert'. UPDATE: This article had more than 100,000 reads within the first month of being posted
April 2023
- A warm welcome to Katy and Natalia who start their projects on the mouse and human thalamus in Trinity term!
- Tim, Shan and Barbara attended EuroTau in Lille to find out about the latest research on Tau biology. Barbara's poster was selected from over 120 posters to give one of five 'flash talks' to promote the research
February 2023
- Tim gave an invited talk at the NeuroWire Virtual Club, entitled "Spread of pathological Tau within memory circuits of the mouse and human brain" https://www.neurowire.ca/invited-speakers-2023/
December 2022
- We are delighted to welcome Dr Sara Hijazi, who joins us as the Department's new Blaschko Fellow. Sara worked as a Postdoctoral Researcher in the group of Professor Steven Kushner at Erasmus MC in Rotterdam after completing her PhD at VU University in Amsterdam in 2020
November 2022
- 15/11/2022 Our paper entitled "Spread of pathological human Tau from neurons to oligodendrocytes and loss of high-firing pyramidal neurons in aging mice" has been published in Cell Reports today! https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01517-0
October 2022
- We are pleased to welcome Shan Jiang to the group as a new DPhil student. She will be investigating circuits of the anterior thalamus, and will initially be learning in vivo extracellular recordings and juxtacellular labelling
August 2022
- Barbara's winning image from the Alzheimer's Society 'Spotlight on Dementia' photography competition is featured in the BBC Science Focus Magazine
- Tim gave an invited talk ("Neuropeptides and rhythmic neuronal firing in brain networks") at RegPep24 in Stirling, Scotland
July 2022
- Tim and Barbara attended FENS Forum in Paris, the first in-person meeting since January 2020. Barbara presented a poster entitled "Accumulation and neuron-to-glia spread of human Tau proteins in ageing mice", which received very good attendance on the last day of the meeting
- Congratulations to Victoria for passing her FHS research project on "Effects of folate deficiency on spatial memory and Tau phosphorylation"
May 2022
- Welcome to Verena who starts her MSc Pharmacology research project in the lab this month
April 2022
- We welcome Dalya to the lab who will work on the human thalamus for her 8 week FHS project
- Tim gives an invited talk at the 39th Congress of International Union of Physiological Sciences in Beijing (which became a virtual meeting). The talk was entitled "Contribution of neuropeptide-expressing neuronal cell types to spatial memory processes" and was part of symposium on neuropeptides ("Uncovering peptides' role in brain function: from synaptic structure to oscillations and behaviour")
November 2021
- New preprint! "Consequences of human Tau aggregation in the hippocampal formation of ageing mice in vivo" https://doi.org/10.1101/2021.11.24.469849
CURRENT PROJECTS
Drivers of Tau pathology in the human brain
Synaptic targets of identified mouse thalamocortical neurons
Causes of the selectivity and sensitivity of 'limbic' neural circuits to neurodegeneration
Identification of GABAergic cell types in the mouse hippocampal formation
PAST/RELATED PROJECTS
Spread of pathological human Tau in a mouse tauopathy model and its effects on rhythmic brain activity (Viney et al Cell Reports 2022)
Postsynaptic targets and rhythmicity of GABAergic medial septal neurons (e.g. Salib et al 2019, Viney et al 2018)
Behavioural-state dependent activity of identified hippocampal GABAergic neurons (e.g. Viney et al 2013, Somogyi et al 2013)
INTERESTS / KEYWORDS
- Branched axons / efference copies
- Causes of sporadic Alzheimer's disease
- Thalamocortical and corticothalamic interactions
- Diversity of cortical and subcortical GABAergic neurons
- Spatial memory processing in the temporal cortex (e.g. cell assemblies, spatial modulation)
- Tauopathies
- Neuromodulation
- Neuropeptides
- Sleep-wake cycles
- Oscillations (e.g. theta, gamma, ripples)
TECHNIQUES
- Histology (immunohistochemistry, horseradish peroxidase-based diaminobenzidine reactions)
- Light microscopy
- Electron microscopy
- In vivo neurophysiology
- Single neuron extracellular recordings and juxtacellular labelling in awake and freely moving mice
- High density neuronal recordings in virtual environments
- Behavioural testing
- Viral tracing
Funding
- Alzheimer's Society
- John Fell Fund
- MRC
- Nuffield Benefaction for Medicine and the Wellcome Institutional Strategic Support Fund
Lab Alumni
- 2024 A Athreya (MSc in Pharmacology)
- 2024 M Wuelfing (FHS student)
- 2023 N Sypsa (MSc in Pharmacology)
- 2023 K Holland (FHS student)
- 2022 V Gautsch (MSc in Pharmacology) - Research Associate, Department of Oncology, University of Oxford
- 2022 D Glickman (FHS student)
- 2021 V Bagge (FHS student)
- 2021 H Hilton (MSc in Pharmacology) - PhD student, University of Cambridge
- 2021 D Brizee (BBSRC DTP rotation student) - DPhil student, University of Oxford
- 2015-2019 M Salib (MRC DTP DPhil) - Healthcare Management Consultant, Baden-Württemberg
Latest publications
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Early restoration of parvalbumin interneuron activity prevents memory loss and network hyperexcitability in a mouse model of Alzheimer's disease.
Journal article
Hijazi S. et al, (2020), Mol Psychiatry, 25, 3380 - 3398
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Hyperexcitable Parvalbumin Interneurons Render Hippocampal Circuitry Vulnerable to Amyloid Beta.
Journal article
Hijazi S. et al, (2020), iScience, 23
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Reducing hippocampal extracellular matrix reverses early memory deficits in a mouse model of Alzheimer's disease.
Journal article
Végh MJ. et al, (2014), Acta Neuropathol Commun, 2
Neurobiotin - by Lizzie Burns
This synthetic molecule is a derivative of a natural chemical, biotin, also known as Vitamin B7. The vitamin whose name refers to life (bio) is used in our cells for a wide range of metabolic processes. This synthetic derivative can be introduced into single brain cells in order to study their internal architecture and trace the fine processes - axons and dendrites – within and across different brain regions, revealing hidden details of the cellular diversity of the nervous system.