My PhD examines how the neuromodulator adenosine affects activity in the neocortex.

The neocortex represents around 80% of the human brain and is associated with a range of cognitive functions including sensory perception, memory storage and the generation of motor commands. In recent years a wealth of data has been gathered exploring the microcircuitry that underlies these responses. These studies have uncovered canonical synaptic pathways that share similar efficacies, short-term dynamical properties and prevalence across cortical areas and even species.

However these circuits are under continual modulation by a host of chemicals released by neuronal and glial cells in the brain that transform both the properties of the synapses and the neurons. I am interested in a chemical called adenosine, which plays important neuroprotective roles in response to ischemia and epilepsy and is vital in the homeostasis of sleep.

I conduct patch-clamp recordings on multiple neurons simultaneously to gain unparalleled access to the properties of the neurons and the synaptic connections between them. I am investigating how adenosine modulates these synapses and the excitability of the neurons, and how these effects are integrated by the microcircuit to transform global activity patterns. This will help us further understand the development of the pathologies that can occur through dysfunction of this system.

A layer 5 pyramidal neuron with patch electrodes at the soma (right, with fluorescent dye) and on the apical dendrite (left, faint electrode). Using this challenging technique I can probe the effects of adenosine at the normally inaccessible apical dendrite, which acts as an important input integrator. scale bar = 50µm.