Role of mitochondrial uncoupling protein-2 (UCP2) in higher brain functions, neuronal plasticity and network oscillation

• Impairment of mitochondrial functions by removal of UCP2 has multiple behavioral and circuit impairments of animals.

Background/PurposeMajor psychiatric illnesses, affecting 36% of the world's population, are profound disorders of thought, mood and behavior associated with underlying impairments in synaptic plasticity and cellular resilience. Mitochondria support energy demanding processes like neural transmission and synaptogenesis and are thus points of broadening interest in the energetics underlying the neurobiology of mental illness. These experiments interrogated the importance of mitochondrial flexibility in behavior, synaptic and cortical activity in a mouse model.MethodsWe studied mice with ablated uncoupling protein-2 expression (UCP2 KO) and analyzed cellular, circuit and behavioral attributes of higher brain regions.ResultsWe found that mitochondrial impairment induced by UCP2 ablation produces an anxiety prone, cognitively impaired behavioral phenotype. Further, NMDA receptor blockade in the UCP2 KO mouse model resulted in changes in synaptic plasticity, brain oscillatory and sensory gating activities.ConclusionsWe conclude that disruptions in mitochondrial function may play a critical role in pathophysiology of mental illness. Specifically, we have shown that NMDA driven behavioral, synaptic, and brain oscillatory functions are impaired in UCP2 knockout mice.