In many species, including Syrian hamsters, male reproductive behavior depends on the perception of odor cues from conspecifics in the environment. Volatile odor cues are processed primarily by the main olfactory system, whereas non-volatile cues are processed primarily by the accessory olfactory system. Together, these two chemosensory systems mediate appetitive reproductive behaviors, such as attraction to female odors, and consummatory reproductive behaviors, such as copulation, in male Syrian hamsters. Main and accessory olfactory information are first integrated in the medial amygdala (MA), a limbic nucleus that is critical for the expression of reproductive behaviors. MA is densely interconnected with other ventral forebrain nuclei that receive chemosensory information and are sensitive to steroid hormones. Specifically, several lines of evidence suggest that MA may generate behavioral responses to socio-sexual odors via functional connections with the posterior bed nucleus of the stria terminalis (BNST) and medial preoptic area (MPOA). It is unknown, however, how these three nuclei act as functional circuit to adaptively regulate appetitive and consummatory reproductive behaviors. Therefore, the overarching goal of this dissertation was to determine how BNST and MPOA function, both uniquely and as a circuit with MA, to generate attraction to female odors and copulatory behaviors in male Syrian hamsters. We found that BNST is required for attraction to female odors, but not for copulation, in sexually-naïve males. In contrast, MPOA is required for both attraction to female odors and for copulation in sexually-naïve males. Surprisingly, prior sexual experience mitigated the requirement of BNST and MPOA for these behaviors. Next, we found that MA preferentially transmits female odor information to BNST and to MPOA, whereas BNST relays female and male odor information equivalently to MPOA. Finally, we found that the functional connections between MA and BNST are required for attraction to female odors but not for copulation, whereas the functional connections between MA and MPOA are required for copulation but not for attraction to female odors. Ultimately, these data may uncover a fundamental mechanism by which this ventral forebrain circuit regulates appetitive and consummatory reproductive behaviors across many species and modalities.

The salience of natural or drug-associated reward is mediated by phasic dopamine (DA) release in the nucleus accumbens (NAc) arising from DAergic cells in the ventral tegmental area (VTA). Circulating sex steroid hormones can modulate reward associated with drugs of abuse; yet, it still remains unclear which brain regions are responsible for this modulation. The medial preoptic area (mPOA) is a hypothalamic brain area involved in the expression of naturally rewarding behaviors as well as the regulation and reception of circulating sex steroid hormones in female rats. Considering its role in regulating naturally rewarding behaviors, its well-established anatomical connectivity with the VTA, and its responsiveness to circulating sex steroid hormones, the mPOA is an ideal neural node through which hormones could modulate the rewarding facets of drugs of abuse. Here I show that preoptotegmental efferents to the VTA are primarily GABAergic, that they appose putative DAergic cell bodies in the VTA that project to the NAc, and that they are capable of responding to sex steroid hormones and changes in DA release. Furthermore, cocaine influences neural activity in mPOA efferents that project to the VTA. Removal of the mPOA also enhanced cocaine-induced locomotion, Fos-immunoreactivity in the mesolimbic reward system, DA release in the NAc, and augmented conditioned place preference. Together these findings suggest that the mPOA modulates the release of DA in the mesolimbic reward circuitry via inhibitory connections with DA neurons residing in the VTA, and sex steroid hormones, in turn, may act in the mPOA to modulate response to cocaine. / text

Mice display robust and stereotyped behaviors towards pups: virgin males typically attack pups, while virgin females and sexually experienced males display parental care. I show here that virgin males that are genetically impaired in vomeronasal sensing do not attack pups and are parental, suggesting a key role of the vomeronasal system in controlling male infanticide. In addition, we have identified putative vomeronasal receptors (or receptor groups) for the detection of pup odors, thus uncovering new tools for the molecular and genetic dissection of male infanticide. Further, we have uncovered galanin-expressing neurons in the medial preoptic area (MPOA) as key regulators of male and female parental behavior. Genetic ablation of MPOA galanin- neurons results in dramatic impairment of parental responses in both virgin females and sexually experienced males. In addition, optogenetic activation of these cells in virgin males suppresses infanticide and induces pup grooming. Thus, MPOA galanin-expressing neurons emerge as an essential node of regulation of innate behavior in the hypothalamus that orchestrates male and female parenting while opposing vomeronasal circuits underlying infanticide. Our results provide an entry point for the genetic and circuit-level dissection of mouse parental behavior and its modulation by social experience.

ABSTRACT Evidence from knockout studies in male mice and from experiments in male rats,in which expression of the estrogen receptor alpha (ERα) gene was inhibited in the medial preoptic area (MPO), suggests that ERα is important in the control of male rat mating behavior. Therefore, in this experiment, we tested the hypothesis that activation of ERα in the MPO is sufficient to maintain mating behavior in castrated male rats receiving subcutaneously (s.c.) dihydrotestosterone (DHT), a non-aromatizable androgen. Accordingly, castrated rats treated with DHT s.c. received MPO implants of either: (i) propyl-pyrazole-triol (PPT) (Stauffer, et al 2000; Katzenellenbogen, et al 2000), a selective ERα agonist, (ii) E2 (positive controls) or (iii) cholesterol (negative controls)and sexual behavior was monitored. PPT was as effective as E2 at maintaining mating behavior suggesting that, in the MPO, ERα is sufficient to mediate responses to E2 that underlie male rat mating behavior.

Diss. (sammanfattning) Umeå : Univ., 2007. / Härtill 4 uppsatser.

Thesis (Ph.D.)--Indiana University, 2009. / Title from screen (viewed on August 27, 2009). Department of Medical Neuroscience, Indiana University-Purdue University Indianapolis (IUPUI). Advisor(s): Joseph DiMicco. Includes vita. Non-Latin script record Includes bibliographical references (leaves 123-140).

In the teleost brain, radial glial cells (RGCs) are the main macroglia and are stem- like progenitors that express key steroidogenic enzymes, including the estrogen- synthesizing enzyme, aromatase B (cyp19a1b). As a result, RGCs are integral to neurogenesis and neurosteroidogenesis in the brain, however little is known about the permissive factors and signaling mechanisms that control these functions. The aim of this thesis is to investigate if the secretogranin-derived neuropeptide secretoneurin (SN) can exert regulatory control over goldfish (Carassius auratus) RGCs. Immunohistochemistry revealed a close neuroanatomical relationship between RGCs and soma of SNa- immunoreactive magnocellular and parvocellular neurons in the preoptic nucleus in both goldfish and zebrafish (Danio rerio) models. Both intracerebroventricular injections of SNa into the third brain ventricle and SNa exposures of cultured goldfish RGCs in vitro show that SNa can reduce cyp19a1b expression, thus implicating SNa in the control of neuroestrogen production. RNA-sequencing was used to characterize the in vitro transcriptomic responses elicited by 1000 nM SNa in RGCs. These data revealed that gene networks related to central nervous system function (neurogenesis, glial cell development, synaptic plasticity) and immune function (immune system activation, leukocyte function, macrophage response) were increased by SNa. A dose-response study using quantitative proteomics indicates a low 10 nM dose of SNa increased expression of proteins involved in cell growth, proliferation, and migration whereas higher doses down- regulated proteins involved in these processes, indicating SNa has dose-dependent regulatory effects. Together, through these altered gene and protein networks, this thesis proposes SNa exerts trophic and immunogenic effects in RGCs. These datasets identified a total of 12,180 and 1,363 unique transcripts and proteins, respectively, and demonstrated that RGCs express a diverse receptor and signaling molecule profile. Therefore, RGCs can respond to and synthesize an array of hormones, peptides, cytokines, and growth factors, revealing a multiplicity of new functions critical to neuronal-glial interactions.

In the present work we evaluated the degree of sexual dimorphism in two cell groups of the medial preoptic-anterior hypothalamus (MPOA-AH) in monogamous and polygamous voles. Quantitative determinations were made of volume, cell number, and cell density for the anteroventral-periventriular nucleus (AVPV) and the sexually dimorphic nucleus of the preoptic area (SDN-POA). Polygamous montane voles (Microtus montanus) had a greater degree of sexual dimorphism in both cell groups than did monogamous prairie voles (M. ochrogaster). Most notable was the complete absence of the AVPV in male montane voles; male montane voles also had a significantly larger SDN-POA volume than did females. The only sexual dimorphism in prairie voles was a greater cell density in the female AVPV. In addition, prairie voles had larger relative brain size than did montane voles. Comparative behavioral studies have revealed a correlation between the degree of sexual dimorphism in external morphology and mating system, i.e., polygamous species display greater levels of dimorphism than do monogamous species. The present results indicate that the effects of sexual selection can also be seen in those brain regions, like the hypothalamus, that underlie social and reproductive behavior. Moreover, these results support the hypothesis that neuroanatomic dimorphisms in the MPOA-AH may be related to sex differences in behavior.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2013-04-19T16:45:21Z No. of bitstreams: 1 Diana Rodrigues de Cerqueira. Efeito antidipsogenico...pdf: 2541414 bytes, checksum: 91bafe7330198ea8c8a87c6c5f8f8fd6 (MD5) / Made available in DSpace on 2013-04-19T16:45:21Z (GMT). No. of bitstreams: 1 Diana Rodrigues de Cerqueira. Efeito antidipsogenico...pdf: 2541414 bytes, checksum: 91bafe7330198ea8c8a87c6c5f8f8fd6 (MD5) Previous issue date: 2012 / Universidade Federal da Bahia. Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz / Interleucina-1β (IL-1β) pode modular funções homeostáticas controladas pelo sistema nervoso central, incluindo a atividade do eixo hipotálamo-hipófise-adrenal, termorregulação, pressão arterial e comportamento ingestivo. Estudos anteriores do Laboratório de Neurociências mostram que IL-1β injetada no terceiro ventrículo cerebral inibe a ingestão de água em animais submetidos a diferentes protocolos e inibe o apetite por sódio em animais depletados deste íon. O núcleo pré-óptico mediano (MnPO) e o órgão subfornical (SFO) são áreas importantes no controle da homeostasia hidrossalina. Assim, a proposta deste estudo foi investigar o efeito de microinjeções de IL-1β no MnPO ou SFO sobre a ingestão de sal em animais depletados de sódio. Ratos Wistar (250-270g) foram anestesiados com cetamina/xilazina (80/7mg/kg) para cirurgia estereotáxica de implante de cânula guia no MnPO ou SFO. Quatro dias após a cirurgia os animais foram submetidos à depleção de sódio por injeções de furosemida (20 mg/kg, s.c) e mantidos com livre acesso a água destilada e dieta hipossódica. 24 horas após os animais receberam microinjeções de IL-1β, nas doses 1,6, 0,8 e 0,4 ng/rato. A ingestão de sal foi monitorada por 120 minutos e ao final das sessões experimentais, os animais foram anestesiados, submetidos à perfusão transcardíaca com salina 0,9% seguido de formol 10% e os encéfalos removidos para processamento histológico. Apenas os dados dos animais cuja cânula estava no MnPO ou SFO foram analisados. IL-1β injetada no MnPO e no SFO inibe a o apetite por sódio, em animais depletados deste íon, sendo o MnPO mais sensível a ação da IL-1β que o SFO. A ação da IL-1β no MnPO e no SFO no apetite por sódio foi específica e não associada a uma deficiência locomotora ou mal estar generalizado que impossibilitasse o animal a buscar da solução sacarina, uma vez que tanto a locomoção quanto a ingestão de sacarina 0,1% dos animais não foi alterada pela IL- 1β. Observou-se também aumento da temperatura corporal após tratamento com IL-1β, sendo a hipertermia mais expressiva após injeção no MnPO do que no SFO. Os resultados obtidos com este trabalho indicam que o MnPO é mais sensível a ação da IL-1β que o SFO e sugerem papel modulatório da IL-1β sobre a homeostasia hidrossalinana, mais especificamente, no apetite por sódio. / Interleukin-1β (IL-1β) may acts on the central nervous system integrating and modulating homeostatic functions including the activity of the hypothalamic-pituitary-adrenal axis, control of blood pressure and body temperature and ingestive behavior. Previous data from our laboratory showed that intracerebroventricular injection of IL-1β inhibits sodium appetite. However, the action of IL-1β in specific brain areas controlling this behavior is unknown. It is well documented that MnPO and SFO is an important brain sites involved in the control of water and salt intake. Therefore, the purpose of this study was to investigate the effect of IL- 1β microinjections into MnPO or SFO on salt intake in sodium-depleted rats. Wistar male rats (240-270g) were implanted with guide cannula in the MnPO or SFO under anesthesia with ketamine/xylazine (80/7 mg/kg i.p). The animals were submitted to sodium depletion by injection of furosemide (20 mg/kg, sc) and maintained with free access to distilled water and low sodium diet. Salt intake was monitored for 120 minutes after microinjection and at the end of the experiments the animals were anesthetized, submitted to a transcardiac perfusions with saline followed by 10% formalin and have their brain removed for histological procedure. Only data from animals whose guide cannulas were in the MnPO or SFO were considered. The results show that microinjection of IL-1β into MnPO and SFO inhibits the hypertonic saline intake throughout the experimental session. The inhibitory effect of IL-1β in MnPO on salt intake was more intense than SFO. Furthermore, the inhibition of sodium appetite seems not to be due to inhibition of locomotor activity or to any change in palatability, since microinjections of IL-1β in MnPO or SFO failed to modify the intake of a 0.1% saccharin solution when the animals were submitted to a "dessert test" or to induce any significant locomotor deficit in the open-field test. It was also observed a rise in body temperature after treatment with IL-1β and this hyperthermia was more significant after injection into MnPO than SFO. The results of this study indicate that the MnPO is more sensitive to IL-1β in MnPO than SFO and suggest modulatory role of IL-1β in this site on hydrosaline homeostasis especially in sodium appetite.

Indiana University-Purdue University Indianapolis (IUPUI) / Recent studies in anesthetized rats suggest that autonomic effects relating to thermoregulation that are evoked from the preoptic area (POA) may be mediated through activation of neurons in the dorsomedial hypothalamus (DMH). Disinhibition of neurons in the DMH produces not only cardiovascular changes but also increases in plasma adrenocorticotropic hormone (ACTH) and locomotor activity mimicking those evoked by microinjection of muscimol, a GABAA receptor agonist and neuronal inhibitor, into the POA. Therefore, I tested the hypothesis that all of these effects evoked from the POA are mediated through neurons in the DMH by assessing the effect of bilateral microinjection of muscimol into the DMH on the changes evoked by microinjection of muscimol into the POA in conscious rats. In addition, I tested the hypothesis that neurons in the DMH mediate a specific response that is thought to signal through the POA, the activation of the HPA axis evoked by systemic administration of the inflammatory cytokine IL-1β. After injection of vehicle into the DMH, injection of muscimol into the POA elicited marked increases in heart rate, arterial pressure, body temperature, plasma ACTH and locomotor activity and also increased Fos expression in the hypothalamic paraventricular nucleus (PVN), a region known to control the release of ACTH from the adenohypophysis, and the raphe pallidus, a medullary region known to mediate POA-evoked sympathetic responses. Prior microinjection of muscimol into the DMH produced a modest depression of baseline heart rate, arterial pressure, and body temperature but completely abolished all changes evoked from the POA. Microinjection of muscimol just anterior to the DMH had no effect on POA-evoked autonomic and neuroendocrine changes. Inhibition of neuronal activity in the DMH only partially attenuated the increased activity of the HPA axis following systemic injections of IL-1β. Thus, neurons in the DMH mediate a diverse array of physiological and behavioral responses elicited from the POA, suggesting that the POA represents an important source of inhibitory tone to key neurons in the DMH. However, it is clear that the inflammatory cytokine IL-1β must employ other pathways that are DMH-, and possibly POA-, independent to activate the HPA axis.