Investigating the activity dependent dynamics of synaptic structures using biologically realistic modelling of peripheral lesion experiments

Ankur Sinha's journal club session where he presents results from his Ph.D. research on the activity dependent dynamics of synaptic structures.

It is now well established that the brain retains its capacity to form and remove whole synapses in adulthood. This type of plasticity, termed structural plasticity, is capable of altering connectivity, and therefore function, of neuronal networks of the brain over periods of days and months. Although reports of disruptive effects of structural plasticity remain scarce, a number of lesion experiments have described the time course of synaptic structures during network reorganisation by homeostatic structural plasticity in great detail. The underlying mechanisms that drive these changes, however, are yet to be explained. To investigate the dynamics of synaptic structures reported in these lesion studies, we replicated a peripheral lesion in a biologically plausible spiking network model that exhibits cortical asynchronous irregular firing. Here, we present results from our computational modelling study.

Results from our simulations suggest that for activity to be restored to deprived neurons in the lesion projection zone (LPZ), excitatory and inhibitory post-synaptic structures must exhibit opposite activity dependent growth behaviours. Analysis of these growth regimes indicates that they contribute to the maintenance of optimal activity levels in individual neurons. Where a reduction in neuronal activity results in the sprouting of new excitatory post-synaptic structures, it is accompanied by the retraction of their inhibitory counterparts. Extra activity is similarly countered by a retraction of excitatory post-synaptic structures and sprouting of inhibitory ones. Our simulations also reproduce the ingrowth of excitatory axons into, and the outgrowth of inhibitory axons out from the LPZ that have been observed in lesion experiments. We find that the ingrowth of excitatory axons requires that sprouting of excitatory pre-synaptic structures be stimulated by extra excitatory neuron activity. The outgrowth of inhibitory axons, on the other hand, necessitates the sprouting of inhibitory pre-synaptic structures to be prompted by a loss in inhibitory neuron activity. In conclusion, by modelling repair following deafferentation that is faithful to experimental findings, we make testable predictions on the activity dependent dynamics of synaptic structures.

Date: 29/03/2019
Time: 16:00
Location: D118

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