Research

synapses | circuits | plasticity | disease | decision-making

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

We work on exciting and fundamental questions that aim to understand basic functions of neural circuits, using imaging methods, electrophysiology and ultrastructural analysis. Current areas of interest include:

Synaptic remodelling in learning and feeding circuits
Synapses are 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, and their remodelling, contribute to synaptic tuning in transmission and plasticity (Neuron 2010, Nature Comms 2011, Neuron 2012, Nature Comms 2015, Cell Reports 2020).
Recent work with Evgeny Nikitin (Moscow) has considered how synaptic activity critically tunes ongoing neuronal function (Science Advances 2018). We are now extending our ideas about synaptic tuning towards understanding control mechanisms in behaviourally-relevant circuits – for example,feeding networks in hypothalamus (with Tiago Branco, SWC, UCL). To address these questions we utilize functional synaptic readouts and the latest generation of high-pressure freezing technologies and automated block-face EM (with Michael Hausser/Arnd Roth, WIBR, UCL).

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.