title: Dual-phenotype GABA/glutamate neurons in adult preoptic area: sexual dimorphism and function.
abstract: It is generally assumed that the inhibitory neurotransmitter GABA and the stimulatory neurotransmitter glutamate are released from different neurons in adults. However, this tenet has made it difficult to explain how the same afferent signals can cause opposite changes in GABA and glutamate release. Such reciprocal release is a central mechanism in the neural control of many physiological processes including activation of gonadotropin-releasing hormone (GnRH) neurons, the neural signal for ovulation. Activation of GnRH neurons requires simultaneous suppression of GABA and stimulation of glutamate release, each of which occurs in response to a daily photoperiodic signal, but only in the presence of estradiol (E2). In rodents, E2 and photoperiodic signals converge in the anteroventral periventricular nucleus (AVPV), but it is unclear how these signals differentially regulate GABA and glutamate secretion. We now report that nearly all neurons in the AVPV of female rats express both vesicular glutamate transporter 2 (VGLUT2), a marker of hypothalamic glutamatergic neurons, as well as glutamic acid decarboxylase and vesicular GABA transporter (VGAT), markers of GABAergic neurons. These dual-phenotype neurons are the main targets of E2 in the region and are more than twice as numerous in females as in males. Moreover, dual-phenotype synaptic terminals contact GnRH neurons, and at the time of the surge, VGAT-containing vesicles decrease and VGLUT2-containing vesicles increase in these terminals. Thus, we propose a new model for ovulation that includes dual-phenotype GABA/glutamate neurons as central transducers of hormonal and neural signals to GnRH neurons.
authors.affiliation: Department of Biology, Center for Neuroendocrine Studies, University of Massachusetts-Amherst, Amherst, Massachusetts 01002, USA.
authors.forename: Erich N
authors.initials: EN
authors.lastname: Ottem
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Godwin
authors.forename: Sudha
authors.initials: S
authors.lastname: Krishnan
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Petersen
mesh_terms: D026905:Amino Acid Transport Systems / Q000032:analysis; D000818:Animals; D015415:Biomarkers; D002369:Castration; D002940:Circadian Rhythm / Q000502:physiology; D004343:Drug Implants; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D018698:Glutamic Acid / Q000032:analysis* / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000032:analysis; D017403:In Situ Hybridization; D008297:Male; D026901:Membrane Transport Proteins / Q000032:analysis; D008954:Models, Biological; D009411:Nerve Endings / Q000737:chemistry / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000737:chemistry / Q000145:classification* / Q000378:metabolism / Q000502:physiology; D010060:Ovulation / Q000502:physiology*; D010641:Phenotype; D011301:Preoptic Area / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D050599:Vesicular Glutamate Transport Protein 2; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D005680:gamma-Aminobutyric Acid / Q000032:analysis* / Q000378:metabolism
chemical_list: D026905:Amino Acid Transport Systems; D015415:Biomarkers; D004343:Drug Implants; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493475:Slc17a6 protein, rat; D050599:Vesicular Glutamate Transport Protein 2; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D007987:Gonadotropin-Releasing Hormone; D018698:Glutamic Acid; D004958:Estradiol; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase