The 'limbic' thalamus, a group of anterior and midline nuclei in the rostral thalamus, is intricately connected to brain regions involved in spatial memory, cognition and emotion. The circuits of the limbic thalamus are composed by many distinct neuronal types, some of which are affected in neurodegenerative diseases such as Alzheimer's disease and are also involved in drug dependence. We study the structure and function of the limbic thalamus in rodents and humans using neuroanatomical and neurophysiological techniques.
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 (e.g. presence of hyperphosphorylated Tau proteins). We are particularly interested in defining the combined activity, molecular profiles and target regions of nerve cells of the 'limbic' thalamus and how they contribute to memory-related processes.
Alzheimer's disease, the most common form of dementia, is defined by the progressive spread of hyperphosphorylated Tau proteins and the build up of amyloid-beta plaques in the brain. We study the vulnerability of the human thalamus to Tau pathology 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.
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We are happy to support fellowship applications from interested postdoctoral candidates.
Watch this space for announcements of open positions!
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NEWS
June 2023
- ***New preprint alert***... link coming soon...
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'
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
- MRC
- Nuffield Benefaction for Medicine and the Wellcome Institutional Strategic Support Fund
Lab Alumni
- 2022 V Gautsch (MSc in Pharmacology)
- 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.