Research

synapses | circuits | plasticity | disease | decision-making

ORCID:  https://orcid.org/0000-0003-4141-339X

We work on a range of exciting and fundamental questions that aim to understand basic functions of neural circuits. Our research uses sensitive imaging methods, electrophysiology and ultrastructural analysis to tackle these important issues. Current areas of interest include:

Synaptic remodelling in learning and feeding circuits
Synapses are the key sites for information transfer in the mammalian brain. Importantly, they are not rigid in their function but highly adaptive – a change in synaptic strength is a critical step in memory formation and storage. We focus on how functional populations of synaptic vesicles – or pools – contribute to synaptic tuning in transmission and plasticity (Neuron 2010, Nature Comms 2011, Neuron 2012, Nature Comms 2015). We are now extending our findings from hippocampus into much more behaviourally-relevant circuits that underlie feeding control in hypothalamus in a collaboration with Tiago Branco at SWC, University College London.
Work with Evgeny Nikitin (Moscow) has been revealing how synaptic activity critically tunes ongoing neuronal function (Science Advances 2018).

Synaptic and neuronal dysfunction in disease
We are interested in how neural substrates are influenced by disease states. We collaborate with Keith Caldecott’s lab (Sussex) to examine neuronal defects in DNA damage repair models (Nature 2017 and BioRxiv 2018) and Louise Serpell’s lab (Sussex) to reveal key synaptic deficits in Alzheimer’s disease models (Sci Rep 2016).

Decision-making in simple circuits
We are interested in how simple invertebrates with limited numbers of neurons make complex decisions that aid their survival. We use the model molluscan system Lymnaea stagnalis which has a sophisticated rhythm-generating circuit that controls feeding behaviour. Our recent work in collaboration with George Kemenes (Sussex) has shown how this animal uses very few neurons to integrate information about internal hunger-state and external cues to make critical feeding decisions (Nature Comms 2016, BioRxiv and Science Advances 2018, in press).

Molecular targets for information signalling
We work with industrial partners, Janssen Pharmaceuticals and Syndesi Therapeutics, to look at novel targets for modulating vesicle recycling and information transmission. These substrates offer possible new therapies for treating seizures and Alzheimer’s-related cognitive defects.