The way(s) neurons integrate synaptic potentials generated throughout their elaborate dendritic arbors into a coded output signal lies at the heart of neuronal operation and so brain function. This question has been a focus of research for more than 50 years. Our work has provided new insights into this integrative process, highlighting the functional importance of interactions between synaptic potentials and dendritic voltage-activated ion channels. These studies have challenged classical ideas of neuronal integration and have revealed mechanisms that shape single neuron computation.||Our future work will provide a clear description of the computational role played by central neurons, and examine the dynamics of synaptic transmission between individual nerve cells in response to patterns of activity that occur in the working brain. We aim to untangle how disruption of the operation of single neurons and neuronal circuits leads to the aberrant neuronal activity characteristic of neurological diseases, such as the epilepsies, perhaps suggesting new avenues for their treatment.

Technical Abstract:
Our future studies will be focused on an understanding of the computational properties of central neurons and the dynamics of synaptic transmission. A deeper understanding of brain function and so insights into the formation of aberrant neuronal activity apparent in neurological disease states, of which the epilepsies are the clearest example, will only be gained from a clear description of the factors that shape the computational operations of central neurons and the dynamic operation of neuronal circuits. We will capitalize on groundwork laid by the establishment of a number of highly demanding experimental techniques that enable views of neuronal function from previously inaccessible thin dendritic processes. Our efforts will be focused on two key areas: i) to probe the computational operations performed by identified neuronal types; and ii) to investigate the dynamics of synaptic transmission at the level of unitary connections. The computational operation of neurons will be investigated using multi-site electrical recordings from neurons visualized in acute brain-slice preparations - coupled with experimentally constrained neuronal modelling techniques. This work will be supplemented by the use of light-activated ion channels expressed in central neurons allowing for the first time study of the operation of the finest and most inaccessible processes of neurons. The dynamics of synaptic transmission will be investigated by the simultaneous recording of groups of identified neocortical neurons in vitro. We will constrain these experiments by examining unitary synaptic responses generated by physiologically relevant patterns of action potential firing, that we will record from identified neurons in vivo in response to controlled natural stimuli. We plan to build a dynamic network model of the neocortex, using physiologically inspired neuronal elements, connected by dynamic synapses to examine information transfer in a physiologically constrained neuronal network.