Currently, I am working to understand the neuronal wiring of the hippocampus at the level of individual cells. Using a combination of multicellular patch-clamp recordings ('octuples') and various superresolution imaging approaches, we are working to determine the circuit arrangement in CA3 and how this influences information processing and storage.
This research has:
Begun to determine the distinct synaptic and circuit properties of the human hippocampus, using resected patient tissue (Watson et al. 2025a).
Demonstrated cell-specific wiring of heterogeneous pyramidal neuron populations in mouse CA3 (Watson et al. 2025b).
With Dr Ingo Greger & team at the MRC LMB, we worked to understand the molecular mechanisms of synaptic transmission, focussing on the glutamate-gated neurotransmitter receptor, the AMPA receptor. Our work:
Determined the requirements for receptor localisation at synapses, which controls synaptic strength (Watson et al. 2017, Watson, Pinggera et al. 2021).
Dissected the molecular interactions between AMPARs and their auxiliary subunits that control receptor activation (Herguedas et al. 2019, Zhang et al. 2021, Herguedas, Kohegyi et al. 2022, reviewed in Greger et al. 2017).
Characterised potential neurotherapeutics targetting the receptor complex (Dhorke et al. 2020, Zhang, Lape et al. 2022).
Investigated the mechanism of human patient mutations (Davies et al. 2017).
In collaboration with Garcia-Nafria Lab @ BIFI: A simple and refined molecular cloning approach for complex plasmid manipulation without expensive kits or special bacteria (Garcia-Nafria, Watson & Greger 2017, highlighted on Addgene). Based on a long-forgotten bacterial recombination pathway (reviewed in Watson & Garcia-Nafria 2019).
We optimised a protocol for inhalation anaesthesia of neonatal rodents to replace hypothermic anaesthesia for surgical procedures (Ho et al. 2020). This includes design of a 3D-printable mould for anaesthetic delivery.
Using simulated and experimental data, we have demonstrated the pitfalls with common approaches to mini (mPSC) analysis, and suggest a few means to improve it (Greger & Watson 2024).
The Danzl Lab @ IST Austria are developing new approaches for light microscopy based visualisation of complete brain tissue architecture. We are working to combine this with patch-clamp recordings for full structural/functional circuit mapping (Velicky et al. 2022, Michalska et al. 2022).