Plasticity impairment alters community structure but permits successful pattern separation in a hippocampal network...

Patients who suffer from traumatic brain injury (TBI) often complain of learning and memory problems. Their symptoms are principally mediated by the hippocampus and the ability to adapt to stimulus, also known as neural plasticity. Therefore, one plausible injury mechanism is plasticity impairment, which currently lacks comprehensive investigation across TBI research. For these studies, we used a computational network model of the hippocampus that includes the dentate gyrus, CA3, and CA1 with neuron-scale resolution. We simulated mild injury through weakened spike-timing-dependent plasticity (STDP), which modulates synaptic weights according to causal spike timing. In preliminary work, we found functional deficits consisting of decreased firing rate and broadband power in areas CA3 and CA1 after STDP impairment. To address structural changes with these studies, we applied modularity analysis to evaluate how STDP impairment modifies community structure in the hippocampal network. We also studied the emergent function of network-based learning and found that impaired networks could acquire conditioned responses after training, but the magnitude of the response was significantly lower. Furthermore, we examined pattern separation, a prerequisite of learning, by entraining two overlapping patterns. Contrary to our initial hypothesis, impaired networks did not exhibit deficits in pattern separation with either population- or rate-based coding. Collectively, these results demonstrate how a mechanism of injury that operates at the synapse regulates circuit function.