title: Hunger States Control the Directions of Synaptic Plasticity via Switching Cell Type-Specific Subunits of NMDA Receptors.
abstract: It remains largely unknown whether and how hunger states control activity-dependent synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD). We here report that both LTP and LTD of excitatory synaptic strength within the appetite control circuits residing in hypothalamic arcuate nucleus (ARC) behave in a manner of hunger states dependence and cell type specificity. For instance, we find that tetanic stimulation induces LTP at orexigenic agouti-related protein (AgRP) neurons in ad libitum fed mice, whereas it induces LTD in food-deprived mice. In an opposite direction, the same induction protocol induces LTD at anorexigenic pro-opiomelanocortin (POMC) neurons in fed mice but weak LTP in deprived mice. Mechanistically, we also find that food deprivation increases the expressions of NR2C/NR2D/NR3-containing NMDA receptors (NMDARs) at AgRP neurons that contribute to the inductions of LTD, whereas it decreases their expressions at POMC neurons. Collectively, our data reveal that hunger states control the directions of activity-dependent synaptic plasticity by switching NMDA receptor subpopulations in a cell type-specific manner, providing insights into NMDAR-mediated interactions between energy states and associative memory. Significance statement: Based on the experiments performed in this study, we demonstrate that activity-dependent synaptic plasticity is also under the control of energy states by regulating NMDAR subpopulations in a cell type-specific manner. We thus propose a reversible memory configuration constructed from energy states-dependent cell type-specific bidirectional conversions of LTP and LTD. Together with the distinct functional roles played by NMDAR signaling in the control of food intake and energy states, these findings reveal a new reciprocal interaction between energy states and associative memory, one that might serve as a target for therapeutic treatments of the energy-related memory disorders or vice versa.
authors.affiliation: Department of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, New York 13210, and Zhengzhou University People's Hospital (He'nan Provincial People's Hospital), Zhengzhou 450003, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, New York 13210, and yangyun@upstate.edu.
authors.forename: Yunlei
authors.identifier: http://orcid.org/0000-0002-3722-840X
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000386:AIDS-Related Complex / Q000378:metabolism; D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology*; D003979:Diazonium Compounds / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006815:Hunger; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D059467:Transcriptome; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D003979:Diazonium Compounds; D018691:Excitatory Amino Acid Antagonists; D009478:Neuropeptide Y; D011725:Pyridines; D016194:Receptors, N-Methyl-D-Aspartate; C056729:4-(2'-pyridyldithio)benzyldiazoacetate; D011333:Pro-Opiomelanocortin; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; D015032:Zinc
keywords: AgRP neuron; LTD; LTP; NMDA receptor; POMC neuron; food deprivation