Neuron-specific Sumo1-3 knockdown in mice impairs episodic and fear memories.

Journal Article

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.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.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.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.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.

Full Text

Duke Authors

Cited Authors

  • Wang, L; Rodriguiz, RM; Wetsel, WC; Sheng, H; Zhao, S; Liu, X; Paschen, W; Yang, W

Published Date

  • July 2014

Published In

Volume / Issue

  • 39 / 4

Start / End Page

  • 259 - 266

PubMed ID

  • 24690371

Electronic International Standard Serial Number (EISSN)

  • 1488-2434

International Standard Serial Number (ISSN)

  • 1180-4882

Digital Object Identifier (DOI)

  • 10.1503/jpn.130148

Language

  • eng