10th May: Barak Pearlmutter
The Slow Axon Blockade Hypothesis for DBS.
Deep brain stimulation (DBS) can ameliorate essential and Parkinsonian tremor. The detailed mechanism by which this is achieved is unclear, but clues to the mechanism may lie in the known destabilising influence of time delays upon closed-loop systems. We hypothesise that DBS tends to stabilise the system and reduce tremor oscillations by reducing time delays in motor control feedback loops. We posit that the reduction is associated with a partial blockade of axonal pathways by antidromic activation, with the blockade being less complete for axons with higher propagation velocities. The inverse relationship between blockade effectiveness and propagation velocity is due to the blocking pulses clearing the axon faster when their velocity is higher, leaving a larger fraction of the time for signalling activity. Two mathematical models have been used to illustrate the idea: a biomechanical model of arm movement and a random neuronal network. Both models exhibit changes of behaviour under simulated slow axon blockade that agree with several experimental observations of DBS. The hypothesis in general accounts for a variety of known features of DBS, especially regarding the target area and the stimulation frequency, and makes a number of testable predictions.
17th May: Martin Homer
The mathematical modelling of oscillatory dynamics in the accessory olfactory bulb
24th May: Jack Mellor
Modulation of hippocampal synaptic transmission and network oscillations
The hippocampus is sometimes referred to as a very large random access synaptic space where new information can be rapidly compared to existing memories. Networks of associated neurons form rapidly and interact with other networks by the processes of synaptic plasticity and network oscillations. We have been exploring how these processes interact and can be modulated by neuromodulatory input from the cholinergic system.