title: Neuron-specific Sumo1-3 knockdown in mice impairs episodic and fear memories.
abstract: BACKGROUND
  Growing evidence suggests that small ubiquitin-like modifier (SUMO) conjugation plays a key role in brain plasticity by modulating activity-dependent synaptic transmission. However, these observations are based largely on cell culture experiments. We hypothesized that episodic and fear memories would be affected by silencing SUMO1-3 expression.
  
  
  METHODS
  To investigate the role of SUMO conjugation in neuronal functioning in vivo, we generated a novel Sumo transgenic mouse model in which a Thy1 promoter drives expression of 3 distinct microRNAs to silence Sumo1-3 expression, specifically in neurons. Wild-type and Sumo1-3 knockdown mice were subjected to a battery of behavioural tests to elucidate whether Sumoylation is involved in episodic and emotional memory.
  
  
  RESULTS
  Expression of Sumo1-3 microRNAs and the corresponding silencing of Sumo expression were particularly pronounced in hippocampal, amygdala and layer V cerebral cortex neurons. The Sumo knockdown mice displayed anxiety-like responses and were impaired in episodic memory processes, contextual and cued fear conditioning and fear-potentiated startle.
  
  
  CONCLUSIONS
  Since expression of Sumo1-3 was silenced in this mouse model, we need to verify in future studies which of the SUMO paralogues play the pivotal role in episodic and emotional memory.
  
  
  CONCLUSIONS
  Our results indicate that a functional SUMO conjugation pathway is essential for emotionality and cognition. This novel Sumo knockdown mouse model and the technology used in generating this mutant may help to reveal novel mechanisms that underlie a variety of neuropsychiatric conditions associated with anxiety and impairment of episodic and emotional memory.
authors.affiliation: Department of Anesthesiology, Duke University, Durham, NC.
authors.forename: Liangli
authors.initials: L
authors.lastname: Wang
authors.affiliation: Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University, Durham, NC.
authors.forename: Ramona M
authors.initials: RM
authors.lastname: Rodriguiz
authors.affiliation: Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University, Durham, NC Departments of Psychiatry and Behavioral Sciences, and Cell Biology, Duke University, Durham, NC Department of Neurobiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Wetsel
authors.affiliation: Department of Anesthesiology, Duke University, Durham, NC.
authors.forename: Huaxin
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Shengli
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Duke University, Durham, NC.
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Duke University, Durham, NC.
authors.forename: Wulf
authors.initials: W
authors.lastname: Paschen
authors.affiliation: Department of Anesthesiology, Duke University, Durham, NC.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology; D003213:Conditioning, Psychological / Q000502:physiology; D003463:Cues; D004644:Emotions / Q000502:physiology; D005239:Fear / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D017403:In Situ Hybridization; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009483:Neuropsychological Tests; D013216:Reflex, Startle / Q000502:physiology
chemical_list: D035683:MicroRNAs