Research

DREAM (Downstream Regulatory Element Antagonist Modulator) contributes to synaptic depression and contextual fear memory

Long-Jun Wu^1* , Britt Mellström^2* , Hansen Wang^1* , Ming Ren^1* , Sofia Domingo² , Susan S Kim¹ , Xiang-Yao Li¹ , Tao Chen¹ , Jose R Naranjo² and Min Zhuo^1,3

¹  Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada

²  Department of Molecular and Cellular Biology, National Centre of Biotechnology, Consejo Superior de Investigaciones Científicas, E-28049 Madrid, Spain

³  Department of Brain and Cognitive Sciences, Seoul National University, Seoul 151-746, Korea

author email corresponding author email* Contributed equally

Molecular Brain 2010, 3:3doi:10.1186/1756-6606-3-3

Published:	21 January 2010

Abstract

The downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca²⁺-binding protein, binds specifically to DNA and several nucleoproteins regulating gene expression and with proteins outside the nucleus to regulate membrane excitability or calcium homeostasis. DREAM is highly expressed in the central nervous system including the hippocampus and cortex; however, the roles of DREAM in hippocampal synaptic transmission and plasticity have not been investigated. Taking advantage of transgenic mice overexpressing a Ca²⁺-insensitive DREAM mutant (TgDREAM), we used integrative methods including electrophysiology, biochemistry, immunostaining, and behavior tests to study the function of DREAM in synaptic transmission, long-term plasticity and fear memory in hippocampal CA1 region. We found that NMDA receptor but not AMPA receptor-mediated current was decreased in TgDREAM mice. Moreover, synaptic plasticity, such as long-term depression (LTD) but not long-term potentiation (LTP), was impaired in TgDREAM mice. Biochemical experiments found that DREAM interacts with PSD-95 and may inhibit NMDA receptor function through this interaction. Contextual fear memory was significantly impaired in TgDREAM mice. By contrast, sensory responses to noxious stimuli were not affected. Our results demonstrate that DREAM plays a novel role in postsynaptic modulation of the NMDA receptor, and contributes to synaptic plasticity and behavioral memory.