Our group studies the principles underlying synaptic circuit formation and plasticity. These processes are fundamental to normal brain function, and are implicated in disorders such as epilepsy, schizophrenia and dementia.
Evolution has invested heavily in synaptic connections. The human brain, for example, is estimated to contain 0.15 quadrillion synapses, each one taking up approximately 1 cubic micrometre. The type, strength, and distribution of synaptic connections determines the behavior of individual neurons within a neural network. For instance, experimental and computational modeling data demonstrate that the pattern of excitatory and inhibitory synaptic inputs across a neuron’s dendritic tree dictates how information is integrated and stored by the neuron. It is also widely believed that alterations in the formation and/or plasticity of synaptic connections underlie disorders such as epilepsy, schizophrenia and dementia.
These synaptic circuits develop through a combination of ‘hard-wired’ genetic mechanisms and ‘plastic’ activity-dependent processes. Understanding this interplay underlies many of the projects in our group. We are interested in establishing how the connectivity of an individual neuron becomes restricted during its development. But equally, how do synaptic plasticity mechanisms enable a neuron to adjust the weights of its connections, such as occur during learning? A related question is how neurons establish and maintain their correct balance of excitatory and inhibitory synaptic inputs. In this regard, we have described novel forms of inhibitory synaptic plasticity, in which local ionic changes can alter the strength of inhibitory synaptic transmission. We have shown that these have important implications during development and in epilepsy.
To study these questions, we combine electrophysiological assessment of synaptic transmission, single and multi-photon imaging of neural circuits, molecular-genetic manipulation techniques and computational approaches.
Area 1: Neuronal progenitors and synaptic circuit formation
- Ionic signalling in neuronal progenitor cells
- Influence of progenitor on synaptic connectivity
- Neuron-astrocyte interactions
Area 2: Excitatory-inhibitory balance
- Inhibitory synaptic transmission and plasticity
- Ionic dynamics and chloride regulation
- Relevance to epilepsy and network activity
Area 3: Synaptic plasticity and learning mechanisms
- Learning rules in synaptic networks
- Supervised and unsupervised forms of learning
- Synaptic plasticity in disease
Joining the Lab
We are always on the lookout for smart and highly-motivated people to join the lab. If you’re interested, please make contact (firstname.lastname@example.org). At the postdoc level, our research incorporates multiple approaches and so people with different backgrounds can excel in the group. Postdocs typically have a background in at least one key experimental approach (e.g. patch clamp electrophysiology, optogenetics, multiphoton imaging and/or computational modelling) and previous publications are normally viewed as evidence of your experience and productivity. At the PhD student level, the majority of students join the lab via one of the Oxford University programs, where they will have the opportunity to conduct a research project in the group during their first year: