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

iScience (May 2023)

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

Journal volume & issue: Vol. 26, no. 5
p. 106664

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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