Susumu Tomita

GARLH regulates neuroligin preference for excitatory versus inhibitory synapses

Tokiwa Yamasaki, Kohtarou Konno, Dilja Krueger‐Burg, Yoav Noam et autres

Synaptic specificity is governed by precise combinations of cell adhesion proteins that stabilize pre- and postsynaptic sites and appropriate neurotransmitter receptors. The postsynaptic neuroligins NL1/3 and NL2/3/4 localize to excitatory and inhibitory synapses, respectively, and regulate the corresponding neurotransmitter receptors. However, the …

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Transmembrane AMPA receptor regulatory protein TARP ɣ-8 is a target of ethanol that regulates self-administration and relapse in mice

Sara Faccidomo, Jessica L. Hoffman, Julie Lee, Ciarra M. Whindleton et autres

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TARP ɣ-8 is a target of ethanol that regulates self-administration and relapse in mice

Sara Faccidomo, Jessica L. Hoffman, Julie Lee, Ciarra M. Whindleton et autres

Background: Behavioral pathologies that characterize alcohol use disorder (AUD) are driven by the powerful reinforcing, or rewarding, properties of the drug. We have shown that glutamate AMPA receptor (AMPAR) activity is both necessary and sufficient for alcohol (ethanol) reinforcement. Transmembrane AMPAR regulatory …

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Abundant extrasynaptic expression of α3β4-containing nicotinic acetylcholine receptors in the medial habenula–interpeduncular nucleus pathway in mice

Asuka Tsuzuki, Miwako Yamasaki, Kohtarou Konno, Taisuke Miyazaki et autres

Nicotinic acetylcholine receptors (nAChRs) in the medial habenula (MHb)-interpeduncular nucleus (IPN) pathway play critical roles in nicotine-related behaviors. This pathway is particularly enriched in nAChR α3 and β4 subunits, both of which are genetically linked to nicotine dependence. However, the cellular and …

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3-Hydroxykynurenine targets kainate receptors to promote defense against infection

Margarita Parada-Kusz, Anne E. Clatworthy, Emily Goering, Stephanie M. Blackwood et autres

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A tryptophan metabolite modulates the host response to bacterial infection via kainate receptors

Margarita Parada-Kusz, Anne E. Clatworthy, Emily Goering, Stephanie M. Blackwood et autres

SUMMARY Bacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host-pathogen dynamic, we conducted an in vivo …

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Chemogenetic regulation of the TARP-lipid interaction mimics LTP and reversibly modifies behavior

Joongkyu Park, Coralie Berthoux, Erika Hoyos, Lili Shan et autres

Long-term potentiation (LTP), a well-characterized form of synaptic plasticity, is believed to underlie memory formation. Hebbian, postsynaptically expressed LTP requires TARPγ-8 phosphorylation for synaptic insertion of AMPA receptors (AMPARs). However, it is unknown whether TARP-mediated AMPAR insertion alone is sufficient to modify …

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Glutamatergic Pathways and Receptors

Susumu Tomita

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Imaging of Transmembrane AMPA Receptor Regulatory Proteins by Positron Emission Tomography

Qingzhen Yu, Katsushi Kumata, Jian Rong, Zhen Chen et autres

The transmembrane α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptor regulatory protein γ-8 (TARP γ-8) constitutes an auxiliary subunit of AMPA receptors, which mediates various brain functions including learning and memory. TARP γ-8 has emerged as a promising therapeutic target for central nervous system disorders. Despite …

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Radiosynthesis of 6-(2-cyclobutyl-5-(methyl-11C)-3H-imidazo[4,5-b]pyridin-3-yl)benzo[d]thiazol-2(3H)-one and (2-cyclobutyl-3-(1H-indazol-5-yl)-5-[11C]methyl-3H-imidazo[4,5-b]pyridine for imaging γ-8 dependent transmembrane AMPA receptor regulatory protein

Qingzhen Yu, Katsushi Kumata, Thomas Collier, Susumu Tomita et autres

Identification of substrates of palmitoyl protein thioesterase 1 highlights roles of depalmitoylation in disulfide bond formation and synaptic function

Erica L. Gorenberg, Sofia Massaro Tieze, Betül Yücel, Helen R. Zhao et autres

Loss-of-function mutations in the depalmitoylating enzyme palmitoyl protein thioesterase 1 (PPT1) cause neuronal ceroid lipofuscinosis (NCL), a devastating neurodegenerative disease. The substrates of PPT1 are largely undescribed, posing a limitation on molecular dissection of disease mechanisms and therapeutic development. Here, we provide …

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Activation of Extrasynaptic Kainate Receptors Drives Hilar Mossy Cell Activity

Czarina Ramos, Stefano Lutzu, Miwako Yamasaki, Yuchio Yanagawa et autres

Mossy cells (MCs) of the dentate gyrus are key components of an excitatory associative circuit established by reciprocal connections with dentate granule cells (GCs). MCs are implicated in place field encoding, pattern separation, and novelty detection, as well as in brain disorders …

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