title: Feedback loops link odor and pheromone signaling with reproduction.
abstract: Pheromones can have profound effects on reproductive physiology and behavior in mammals. To investigate the neural circuits underlying these effects, we used a genetic transneuronal tracer to identify neurons that synapse with GnRH (LHRH) neurons, the key regulators of reproduction. We then asked whether the connected neurons are presynaptic or postsynaptic to GnRH neurons and analyzed their responses to chemosensory cues. Surprisingly, these experiments indicate that GnRH neurons receive pheromone signals from both odor and pheromone relays in the brain and may also receive common odor signals. Moreover, feedback loops are evident whereby GnRH neurons could influence both odor and pheromone processing. Remarkably, approximately 800 GnRH neurons communicate with approximately 50,000 neurons in 53 functionally diverse brain areas, with some connections exhibiting sexual dimorphism. These studies reveal a complex interplay between reproduction and other functions in which GnRH neurons appear to integrate information from multiple sources and modulate a variety of brain functions.
authors.affiliation: Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Boehm
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Zou
authors.forename: Linda B
authors.initials: LB
authors.lastname: Buck
mesh_terms: D000679:Amygdala / Q000737:chemistry / Q000166:cytology; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count; D050580:Excitatory Amino Acid Transporter 3 / Q000032:analysis; D030141:Feedback, Psychological / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009812:Odorants; D009833:Olfactory Pathways / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D037121:Plant Lectins / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012098:Reproduction / Q000502:physiology*; D012717:Sesquiterpenes / Q000494:pharmacology; D012724:Sex Attractants / Q000494:pharmacology / Q000502:physiology*; D012726:Sexual Behavior, Animal / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D050580:Excitatory Amino Acid Transporter 3; D037121:Plant Lectins; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012717:Sesquiterpenes; D012724:Sex Attractants; C493399:Slc1a1 protein, mouse; C076978:barley lectin; C050866:progonadoliberin I; D049452:Green Fluorescent Proteins; D007987:Gonadotropin-Releasing Hormone; C062672:alpha-farnesene