title: Developmental changes in synaptic distribution in arcuate nucleus neurons.
abstract: Neurons coexpressing neuropeptide Y, agouti-related peptide, and GABA (NAG) play an important role in ingestive behavior and are located in the arcuate nucleus of the hypothalamus. NAG neurons receive both GABAergic and glutamatergic synaptic inputs, however, the developmental time course of synaptic input organization of NAG neurons in mice is unknown. In this study, we show that these neurons have low numbers of GABAergic synapses and that GABA is inhibitory to NAG neurons during early postnatal period. In contrast, glutamatergic inputs onto NAG neurons are relatively abundant by P13 and are comparatively similar to the levels observed in the adult. As mice reach adulthood (9-10 weeks), GABAergic tone onto NAG neurons increases. At this age, NAG neurons received similar numbers of inhibitory and EPSCs. To further differentiate age-associated changes in synaptic distribution, 17- to 18-week-old lean and diet-induced obesity (DIO) mice were studied. Surprisingly, NAG neurons from lean adult mice exhibit a reduction in the GABAergic synapses compared with younger adults. Conversely, DIO mice display reductions in the number of GABAergic and glutamatergic inputs onto NAG neurons. Based on these experiments, we propose that synaptic distribution in NAG neurons is continuously restructuring throughout development to accommodate the animals' energy requirements.
authors.affiliation: Division of Diabetes, Obesity, & Metabolism, Oregon National Primate Research Center (ONPRC), Beaverton, Oregon 97006 baqueroa@ohsu.edu.
authors.forename: Arian F
authors.initials: AF
authors.lastname: Baquero
authors.affiliation: Division of Diabetes, Obesity, & Metabolism, Oregon National Primate Research Center (ONPRC), Beaverton, Oregon 97006.
authors.forename: Melissa A
authors.identifier: http://orcid.org/0000-0002-2570-777X
authors.initials: MA
authors.lastname: Kirigiti
authors.affiliation: Division of Diabetes, Obesity, & Metabolism, Oregon National Primate Research Center (ONPRC), Beaverton, Oregon 97006.
authors.forename: Karalee C
authors.initials: KC
authors.lastname: Baquero
authors.affiliation: Division of Diabetes, Obesity, & Metabolism, Oregon National Primate Research Center (ONPRC), Beaverton, Oregon 97006.
authors.forename: Shin J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Division of Diabetes, Obesity, & Metabolism, Oregon National Primate Research Center (ONPRC), Beaverton, Oregon 97006.
authors.forename: M Susan
authors.identifier: http://orcid.org/0000-0002-3057-7009
authors.initials: MS
authors.lastname: Smith
authors.affiliation: Division of Diabetes, Obesity, & Metabolism, Oregon National Primate Research Center (ONPRC), Beaverton, Oregon 97006.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Grove
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology* / Q000254:growth & development*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005260:Female; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D009478:Neuropeptide Y; D026941:Sodium Channel Blockers; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C013411:biocytin; D008239:Lysine
keywords: NAG neurons; arcuate; development; obesity; synaptic inputs