Disorientation is a key early symptom of dementia, but why and how do people become disoriented? We investigate the neural circuit mechanisms underlying spatial orientation in the rodent brain and study the same circuits in the 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.
The overall aim of our group is to understand how the activity of individual nerve cells in the mammalian brain relates to their postsynaptic target neurons (i.e. their connectivity / neural circuits), and how this activity changes during different behavioural states (e.g. sleep, movement), environmental contexts (e.g. spatial navigation, sensory stimulation), and pathological processes. We are currently defining the combined activity, molecular profiles and target regions of nerve cells within the so-called 'Papez circuit' and how they contribute to memory-related processes.
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 on rodent brain activity at the behavioural level (changes to memory), network level (oscillations), and cellular level (changes in single neuron activity). We are also investigating cell type specific biomarkers and biochemical pathways that are affected in memory-related conditions that may lead to treatments to prevent or slow disease progression.
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 - deadline 1st December 2023
- Doctoral Training Partnerships: Oxford Interdisciplinary Bioscience DTP. Main 4-year DTP studentships: https://www.biodtp.ox.ac.uk/main-dtp-studentships - deadline 5th January 2024
Watch this space for announcements of open positions!
- 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
- Shan was selected to attend the 'Advanced tools for data analysis in Neuroscience' summer school in Strasbourg
- ***New preprint alert*** Pathway-specific progression of Tau pathology in the human thalamus
- 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
- 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/
- 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
- 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
- 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
- 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
- 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"
- Welcome to Verena who starts her MSc Pharmacology research project in the lab this month
- 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")
- 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
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
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)
- Sleep-wake cycles
- Oscillations (e.g. theta, gamma, ripples)
- 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
- Alzheimer's Society
- John Fell Fund
- Nuffield Benefaction for Medicine and the Wellcome Institutional Strategic Support Fund
- 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
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.