Neuronal SNAP-23 is critical for synaptic plasticity and spatial memory independently of NMDA receptor regulation
Mengjia Huang,
Na-Ryum Bin,
Jayant Rai,
Ke Ma,
Chun Hin Chow,
Sarah Eide,
Hidekiyo Harada,
Jianbing Xiao,
Daorong Feng,
Hong-Shuo Sun,
Zhong-Ping Feng,
Herbert Y. Gaisano,
Jeffrey E. Pessin,
Philippe P. Monnier,
Kenichi Okamoto,
Liang Zhang,
Shuzo Sugita
Affiliations
Mengjia Huang
Division of Experimental & Translational Neuroscience, Krembil Brain Institute, University Health Network, Toronto, ON M5T 0S8, Canada; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
Na-Ryum Bin
Division of Experimental & Translational Neuroscience, Krembil Brain Institute, University Health Network, Toronto, ON M5T 0S8, Canada; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
Jayant Rai
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G1X5, Canada; Department of Molecular Genetics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
Ke Ma
Division of Experimental & Translational Neuroscience, Krembil Brain Institute, University Health Network, Toronto, ON M5T 0S8, Canada; Department of Pediatrics, The First Hospital of Jilin University, Changchun 130021, China
Chun Hin Chow
Division of Experimental & Translational Neuroscience, Krembil Brain Institute, University Health Network, Toronto, ON M5T 0S8, Canada; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
Sarah Eide
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
Hidekiyo Harada
Donald K. Johnson Eye Institute, University Health Network, Toronto, ON M5T 0S8, Canada
Jianbing Xiao
Division of Experimental & Translational Neuroscience, Krembil Brain Institute, University Health Network, Toronto, ON M5T 0S8, Canada; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Anatomy, Harbin Medical University, Harbin 150081, China
Daorong Feng
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Hong-Shuo Sun
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Anatomy, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
Zhong-Ping Feng
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
Herbert Y. Gaisano
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada; Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
Jeffrey E. Pessin
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Philippe P. Monnier
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Donald K. Johnson Eye Institute, University Health Network, Toronto, ON M5T 0S8, Canada; Department of Ophthalmology & Vision Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada
Kenichi Okamoto
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G1X5, Canada; Department of Molecular Genetics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
Liang Zhang
Division of Experimental & Translational Neuroscience, Krembil Brain Institute, University Health Network, Toronto, ON M5T 0S8, Canada; Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
Shuzo Sugita
Division of Experimental & Translational Neuroscience, Krembil Brain Institute, University Health Network, Toronto, ON M5T 0S8, Canada; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Corresponding author
Summary: SNARE-mediated membrane fusion plays a crucial role in presynaptic vesicle exocytosis and also in postsynaptic receptor delivery. The latter is considered particularly important for synaptic plasticity and learning and memory, yet the identity of the key SNARE proteins remains elusive. Here, we investigate the role of neuronal synaptosomal-associated protein-23 (SNAP-23) by analyzing pyramidal-neuron specific SNAP-23 conditional knockout (cKO) mice. Electrophysiological analysis of SNAP-23 deficient neurons using acute hippocampal slices showed normal basal neurotransmission in CA3-CA1 synapses with unchanged AMPA and NMDA currents. Nevertheless, we found theta-burst stimulation-induced long-term potentiation (LTP) was vastly diminished in SNAP-23 cKO slices. Moreover, unlike syntaxin-4 cKO mice where both basal neurotransmission and LTP decrease manifested changes in a broad set of behavioral tasks, deficits of SNAP-23 cKO are more limited to spatial memory. Our data reveal that neuronal SNAP-23 is selectively crucial for synaptic plasticity and spatial memory without affecting basal glutamate receptor function.
