title: Role of mitochondrial uncoupling protein-2 (UCP2) in higher brain functions, neuronal plasticity and network oscillation.
abstract: OBJECTIVE
  Major 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.
  
  
  METHODS
  We studied mice with ablated uncoupling protein-2 expression (UCP2 KO) and analyzed cellular, circuit and behavioral attributes of higher brain regions.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  We 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.
authors.affiliation: Yale School of Medicine, Department of Psychiatry, 300 George St., Suite 901, New Haven, CT 06511, USA. Electronic address: gretchen.hermes@yale.edu.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Hermes
authors.affiliation: Yale School of Medicine, Section of Comparative Medicine, 310 Cedar St., BML 330, P.O. Box 208016, New Haven, CT 06520-8016, USA. Electronic address: david.nagy@yale.edu.
authors.forename: David
authors.initials: D
authors.lastname: Nagy
authors.affiliation: Yale School of Medicine, Section of Comparative Medicine, 310 Cedar St., BML 330, P.O. Box 208016, New Haven, CT 06520-8016, USA. Electronic address: mike.waterson@yale.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Waterson
authors.affiliation: Yale School of Medicine, Section of Comparative Medicine, 310 Cedar St., BML 330, P.O. Box 208016, New Haven, CT 06520-8016, USA. Electronic address: zsarnovszky.attila@aotk.szie.hu.
authors.forename: Attila
authors.initials: A
authors.lastname: Zsarnovszky
authors.affiliation: Yale School of Medicine, Section of Comparative Medicine, 310 Cedar St., BML 330, P.O. Box 208016, New Haven, CT 06520-8016, USA. Electronic address: luis.varela@yale.edu.
authors.forename: Luis
authors.initials: L
authors.lastname: Varela
authors.affiliation: Yale School of Medicine, Section of Comparative Medicine, 310 Cedar St., BML 330, P.O. Box 208016, New Haven, CT 06520-8016, USA. Electronic address: mihaly.hajos@yale.edu.
authors.forename: Mihaly
authors.initials: M
authors.lastname: Hajos
authors.affiliation: Yale School of Medicine, Section of Comparative Medicine, 310 Cedar St., BML 330, P.O. Box 208016, New Haven, CT 06520-8016, USA. Electronic address: tamas.horvath@yale.edu.
authors.forename: Tamas L
authors.initials: TL
authors.lastname: Horvath
keywords: Auditory gating; Behavioral phenotype; Mental illness; Mitochondria; NMDA receptor antagonism; Uncoupling proteins