title: Selective expression of a constitutively active erythropoietin receptor in GABAergic neurons alters hippocampal network properties without affecting cognition.
abstract: We have previously shown that treatment with erythropoietin (EPO) improves cognition in patients with neuropsychiatric disorders as well as in healthy mice, and that transgenic expression of a constitutively active form of the EPO receptor (cEPOR) in glutamatergic neurons boosts higher cognitive functions in mice. In the present work, we examined whether selective activation of EPOR signaling in GABAergic neurons would also modulate cognitive performance. We generated transgenic mice that express cEPOR under the control of the vesicular inhibitory amino acid transporter (Viaat) promoter and subjected them to comprehensive behavioral, cognitive, and electrophysiological analyses. We demonstrate that transgenic expression of cEPOR in GABAergic neurons alters hippocampal gamma-oscillations and enhances long-term potentiation but neither impairs nor improves cognition. To conclude, constitutively active EPOR in GABAergic neurons changes hippocampal network properties without affecting cognition, which suggests that the effect of EPO on cognition is dominated by its effect on the glutamatergic system. Treatment with EPO improves cognitive performance. We previously demonstrated that this effect is replicated by constitutive autoactivation of cEPOR in glutamatergic neurons. By contrast, cEPOR in GABAergic neurons changes hippocampal network properties but neither impairs nor enhances cognition. Thus, EPO modulates neuronal plasticity, and the cognitive benefits may be mainly attributable to its effect on the glutamatergic system.
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Liane
authors.initials: L
authors.lastname: Wüstefeld
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.|DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Winkler
authors.affiliation: Department of Neurophysiology and Sensory Physiology, University Medical Center, Göttingen, Germany.
authors.forename: Oliwia A
authors.initials: OA
authors.lastname: Janc
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.|Physiology Unit, Zoology Department, Faculty of Science, Menoufia University, Shebin Elkom, Egypt.
authors.forename: Imam
authors.initials: I
authors.lastname: Hassouna
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Ronnenberg
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Ostmeier
authors.affiliation: DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.|Department of Neurophysiology and Sensory Physiology, University Medical Center, Göttingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.affiliation: DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.|Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.|DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Ehrenreich
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Sonja M
authors.initials: SM
authors.lastname: Wojcik
keywords: 
  EPO
  ; 
  LTP
  ; 
  PPF
  ; 
  cEPOR
  ; gamma-oscillations; mouse behavior