title: Erythropoietin enhances hippocampal long-term potentiation and memory.
abstract: BACKGROUND
  Erythropoietin (EPO) improves cognition of human subjects in the clinical setting by as yet unknown mechanisms. We developed a mouse model of robust cognitive improvement by EPO to obtain the first clues of how EPO influences cognition, and how it may act on hippocampal neurons to modulate plasticity.
  
  
  RESULTS
  We show here that a 3-week treatment of young mice with EPO enhances long-term potentiation (LTP), a cellular correlate of learning processes in the CA1 region of the hippocampus. This treatment concomitantly alters short-term synaptic plasticity and synaptic transmission, shifting the balance of excitatory and inhibitory activity. These effects are accompanied by an improvement of hippocampus dependent memory, persisting for 3 weeks after termination of EPO injections, and are independent of changes in hematocrit. Networks of EPO-treated primary hippocampal neurons develop lower overall spiking activity but enhanced bursting in discrete neuronal assemblies. At the level of developing single neurons, EPO treatment reduces the typical increase in excitatory synaptic transmission without changing the number of synaptic boutons, consistent with prolonged functional silencing of synapses.
  
  
  CONCLUSIONS
  We conclude that EPO improves hippocampus dependent memory by modulating plasticity, synaptic connectivity and activity of memory-related neuronal networks. These mechanisms of action of EPO have to be further exploited for treating neuropsychiatric diseases.
authors.affiliation: Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany. adamcio@em.mpg.de
authors.forename: Bartosz
authors.initials: B
authors.lastname: Adamcio
authors.forename: Derya
authors.initials: D
authors.lastname: Sargin
authors.forename: Alicja
authors.initials: A
authors.lastname: Stradomska
authors.forename: Lucian
authors.initials: L
authors.lastname: Medrihan
authors.forename: Christoph
authors.initials: C
authors.lastname: Gertler
authors.forename: Fabian
authors.initials: F
authors.lastname: Theis
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.forename: Imam
authors.initials: I
authors.lastname: Hassouna
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hannke
authors.forename: Swetlana
authors.initials: S
authors.lastname: Sperling
authors.forename: Konstantin
authors.initials: K
authors.lastname: Radyushkin
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Kordi
authors.forename: Lizzy
authors.initials: L
authors.lastname: Schulze
authors.forename: Anja
authors.initials: A
authors.lastname: Ronnenberg
authors.forename: Fred
authors.initials: F
authors.lastname: Wolf
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.forename: Jeong-Seop
authors.initials: JS
authors.lastname: Rhee
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zhang
authors.forename: Hannelore
authors.initials: H
authors.lastname: Ehrenreich
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004594:Electrophysiology; D004921:Erythropoietin / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D015151:Immunoblotting; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D018613:Microscopy, Confocal; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology
chemical_list: D004921:Erythropoietin
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