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.
We are happy to support fellowship applications from interested postdoctoral candidates.
Watch this space for announcements of open positions!
- 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
- Investigating how expression of pathological Tau affects rhythmic cortical neuronal activity in a mouse model of tauopathy
- Vulnerability of human limbic thalamus cell types in relation to Tau pathology and ageing
- Identification of GABAergic cell types in the mouse hippocampal formation
- Causes of the selectivity and sensitivity of 'limbic' neural circuits to neurodegeneration
- 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
- Nuffield Benefaction for Medicine and the Wellcome Institutional Strategic Support Fund
- 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.