Network electrophysiology: exploring emerging properties in (dys)functional neuronal circuits in vitro
27 October 2016
UAntwerp, Stadscampus, Promotiezaal - Lange SInt-Annastraat 7 - 2000 Antwerp (route: UAntwerpen, Stadscampus
3:00 PM - 5:00 PM
PhD defence Rocco Pulizzi - Department of Biomedical Sciences
Beyond conventional correlative approaches in experimental Neuroscience research, there is an increasingly widespread drive toward causative approaches. Inspired by this and by the recent progress in Optogenetics, this PhD project has been focused on designing and validating experimental methods to study and control excitability and dynamical response properties of neuronal networks, under several physiopathological conditions.
In this work, cultures of primary neurons, grown on microelectrode arrays (MEAs) have been employed, implying the necessity to face some challenges, such as data collection, analysis, and interpretation. Therefore, I contributed to the development of 'QSpike Tools': a software platform that allows CPU-intensive operations, required for signal pre-processing, to be processed in parallel.
Focusing on the main goal, I showed how reverberating responses can be elicited by brief light pulses, dominated by oscillations in the physiological gamma frequency range, which were reliably manipulated in their frequency. Additionally, these oscillations likely emerge as in vivo and the light stimuli transiently facilitate excitatory synaptic transmission. Given the ability to steer the electric network activity and to alter its synaptic physiology by means of photostimulation, long-term plastic changes at the level of cell assemblies could be achieved. By repetitive photostimuli, the dynamics of spontaneous synchronized spiking activity was persistently changed together with increased pair-wise spike times cross-correlations.
Overall, these results advance our understanding on how network-level activity and its underlying synaptic physiology can be manipulated by photostimuli.
Being aware of the needs for translational research, also dysfunctional networks in vitro have been employed during my PhD. Specifically, I studied the spontaneous electric activity of cell assemblies when synaptic communication was impaired due to: i) accumulation of different alpha-synuclein aggregates within neurons, as in Parkinson’s disease; ii) hypoxia, as during strokes. The first investigation highlighted an increase in the average inter-spike intervals within the network-wide synchronization epochs, confirming a less efficient synaptic communication. In the second study, all neuronal networks showed a complete or partial suppression of spontaneous synchronized spiking activity during hypoxia. Interestingly, neurons restored synchronized spiking 24h following hypoxia, under control conditions.
Altogether, last results contribute to clarify network-level dysfunctions in specific neurological disorders.