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Traumatic brain injury (TBI) can lead to neurodegeneration in the injured circuitry, either through primary structural damage to the neuron or secondary effects that disrupt key cellular processes. Moreover, traumatic injuries can preferentially impact subpopulations of neurons, but the functional network effects of these targeted degeneration profiles remain unclear. Although isolating the consequences of complex injury dynamics and long-term recovery of the circuit can be difficult to control experimentally, computational networks can be a powerful tool to analyze the consequences of injury. Here, we use the Izhikevich spiking neuron model to create networks representative of cortical tissue. After an initial settling period with spike-timing-dependent plasticity (STDP), networks developed rhythmic oscillations similar to those seenin vivo. As neurons were sequentially removed from the network, population activity rate and oscillation dynamics were significantly reduced. In a successive period of network restructuring with STDP, network activity levels were returned to baseline for some injury levels and oscillation dynamics significantly improved. We next explored the role that specific neurons have in the creation and termination of oscillation dynamics. We determined that oscillations initiate from activation of low firing rate neurons with limited structural inputs. To terminate oscillations, high activity excitatory neurons with strong input connectivity activate downstream inhibitory circuitry. Finally, we confirm the excitatory neuron population role through targeted neurodegeneration. These results suggest targeted neurodegeneration can play a key role in the oscillation dynamics after injury.Author SummaryIn this study, we study the impact of neuronal degeneration – a process that commonly occurs after traumatic injury and neurodegenerative disease – on the neuronal dynamics in a cortical network. We create computational models of neural networks and include spike timing plasticity to alter the synaptic strength among connections as networks remodel after simulated injury. We find that spike-timing dependent plasticity helps recover the neural dynamics of an injured microcircuit, but it frequently cannot recover the original oscillation dynamics in an uninjured network. In addition, we find that selectively injuring excitatory neurons with the highest firing rate reduced the neuronal oscillations in a circuit much more than either random deletion or the removing neurons with the lowest firing rate. In all, these data suggest (a) plasticity reduces the consequences of neurodegeneration and (b) losing the most active neurons in the network has the most adverse effect on neural oscillations. |
