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Sample records for stria terminalis induces

  1. Nicotine self-administration induces CB1-dependent LTP in the bed nucleus of the stria terminalis.

    PubMed

    Reisiger, Anne-Ruth; Kaufling, Jennifer; Manzoni, Olivier; Cador, Martine; Georges, François; Caillé, Stephanie

    2014-03-19

    Nicotine addiction is characterized by repetitive drug taking and drug seeking, both tightly controlled by cannabinoid CB1 receptors. The responsiveness of neurons of the bed nucleus of the stria terminalis (BNST) to infralimbic cortex (ILCx) excitatory inputs is increased in rats with active, but not passive, nicotine taking. Therefore, we hypothesize that acquisition of the learned association between nicotine infusion and a paired cue light permits the strengthening of the ILCx-BNST synapses after ILCx tetanic stimulation. We exposed rats to intravenous nicotine self-administration for 2 months. Using a combination of in vivo protocols (electrical stimulations, extracellular recordings, and pharmacological manipulations), we characterized the effects of 10 Hz stimulation of the ILCx on BNST excitatory responses, under different conditions of exposure to nicotine. In addition, we tested whether the effects of the stimulation were CB1 receptor-dependent. The results show that nicotine self-administration supports the induction of evoked spike potentiation in the BNST in response to 10 Hz stimulation of ILCx afferents. Although not altered by nicotine abstinence, this cellular adaptation was blocked by CB1 receptor antagonism. Moreover, blockade of BNST CB1 receptors prevented increases in time-out responding subsequent to ILCx stimulation and decreased cue-induced reinstatement. Thus, the synaptic potentiation within the BNST in response to ILCx stimulation seems to contribute to the cue-elicited responding associated with nicotine self-administration and is tightly controlled by CB1 receptors. PMID:24647948

  2. Temporary inactivation of the anterior part of the bed nucleus of the stria terminalis blocks alarm pheromone-induced defensive behavior in rats

    PubMed Central

    Breitfeld, Tino; Bruning, Johann E. A.; Inagaki, Hideaki; Takeuchi, Yukari; Kiyokawa, Yasushi; Fendt, Markus

    2015-01-01

    Rats emit an alarm pheromone in threatening situations. Exposure of rats to this alarm pheromone induces defensive behaviors, such as head out behavior, and increases c-Fos expression in brain areas involved in the mediation of defensive behaviors. One of these brain areas is the anterior bed nucleus of the stria terminalis (aBNST). The goal of the present study was to investigate if pharmacological inactivation of the aBNST by local microinjections of the GABAA receptor-agonist muscimol modulates alarm pheromone-induced defensive behaviors. We first established the behavioral paradigm of alarm pheromone-induced defensive behaviors in Sprague-Dawley rats in our laboratory. In a second experiment, we inactivated the aBNST, then exposed rats to one of four different odors (neck odor, female urine, alarm pheromone, fox urine) and tested the effects of the aBNST inactivation on the behavior in response to these odors. Our data show that temporary inactivation of the aBNST blocked head out behavior in response to the alarm pheromone. This indicates that the aBNST plays an important role in the mediation of the alarm pheromone-induced defensive behavior in rats. PMID:26441496

  3. Suckling induces a daily rhythm in the preoptic area and lateral septum but not in the bed nucleus of the stria terminalis in lactating rabbit does.

    PubMed

    Meza, Enrique; Aguirre, Juan; Waliszewski, Stefan; Caba, Mario

    2015-01-01

    Maternal behavior in the rabbit is restricted to a brief nursing period every day. Previously, we demonstrated that this event induces daily rhythms of Period1 (PER1) protein, the product of the clock gene Per1, in oxytocinergic and dopaminergic populations in the hypothalamus of lactating rabbit does. This is significant for the periodic production and ejection of milk, but the activation of other areas of the brain has not been explored. Here, we hypothesised that daily suckling would induce a rhythm in the preoptic area, lateral septum, and bed nucleus of the stria terminalis, which are important areas for the expression of maternal behavior in mammals, including the rabbit. To this end, we analysed PER1 expression in those areas through a complete 24-h cycle at lactation day 7. Does were scheduled to nurse during either the day at 10:00 h [zeitgeber time (ZT)03] or the night at 02:00 h (ZT19). Non-pregnant, non-lactating females were used as controls. In contrast to control females, lactating does showed a clear, significant rhythm of PER1 that shifted in parallel with the timing of nursing in the preoptic area and lateral septum. We determined that the maximal expression of PER1 at 8 h after scheduled nursing decreased significantly at 24 and 48 h after the absence of suckling. This effect was more pronounced in the lateral septum than in the preoptic area. We conclude that daily suckling is a powerful stimulus inducing rhythmic activity in brain structures in the rabbit that appear to form part of a maternal entrainable circuit. PMID:25370159

  4. Androgen Receptors in the Posterior Bed Nucleus of the Stria Terminalis Increase Neuropeptide Expression and the Stress-Induced Activation of the Paraventricular Nucleus of the Hypothalamus

    PubMed Central

    Bingham, Brenda; Myung, Clara; Innala, Leyla; Gray, Megan; Anonuevo, Adam; Viau, Victor

    2011-01-01

    The posterior bed nuclei of the stria terminalis (BST) are important neural substrate for relaying limbic influences to the paraventricular nucleus (PVN) of the hypothalamus to inhibit hypothalamic-pituitary-adrenal (HPA) axis responses to emotional stress. Androgen receptor-expressing cells within the posterior BST have been identified as projecting to the PVN region. To test a role for androgen receptors in the posterior BST to inhibit PVN motor neurons, we compared the effects of the non-aromatizable androgen dihydrotestosterone (DHT), the androgen receptor antagonist hydroxyflutamide (HF), or a combination of both drugs implanted unilaterally within the posterior BST. Rats bearing unilateral implants were analyzed for PVN Fos induction in response to acute-restraint stress and relative levels of corticotrophin-releasing hormone and arginine vasopressin (AVP) mRNA. Glutamic acid decarboxylase (GAD) 65 and GAD 67 mRNA were analyzed in the posterior BST to test a local involvement of GABA. There were no changes in GAD expression to support a GABA-related mechanism in the BST. For PVN neuropeptide expression and Fos responses, basic effects were lateralized to the sides of the PVN ipsilateral to the implants. However, opposite to our expectations of an inhibitory influence of androgen receptors in the posterior BST, PVN AVP mRNA and stress-induced Fos were augmented in response to DHT and attenuated in response to HF. These results suggest that a subset of androgen receptor-expressing cells within the posterior BST region may be responsible for increasing the biosynthetic capacity and stress-induced drive of PVN motor neurons. PMID:21412226

  5. Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis

    PubMed Central

    Greenberg, Gian D.; Laman-Maharg, Abigail; Campi, Katharine L.; Voigt, Heather; Orr, Veronica N.; Schaal, Leslie; Trainor, Brian C.

    2014-01-01

    Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus), a species in which both males and females defend territories. We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF) protein but not mRNA in the bed nucleus of the stria terminalis (BNST) in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc). The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB) antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naïve to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females. PMID:24409132

  6. Functional Heterogeneity in the Bed Nucleus of the Stria Terminalis.

    PubMed

    Gungor, Nur Zeynep; Paré, Denis

    2016-08-01

    Early work stressed the differing involvement of the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST) in the genesis of fear versus anxiety, respectively. In 2009, Walker, Miles, and Davis proposed a model of amygdala-BNST interactions to explain these functional differences. This model became extremely influential and now guides a new wave of studies on the role of BNST in humans. Here, we consider evidence for and against this model, in the process highlighting central principles of BNST organization. This analysis leads us to conclude that BNST's influence is not limited to the generation of anxiety-like responses to diffuse threats, but that it also shapes the impact of discrete threatening stimuli. It is likely that BNST-CeA interactions are involved in modulating responses to such threats. In addition, whereas current views emphasize the contributions of the anterolateral BNST region in anxiety, accumulating data indicate that the anteromedial and anteroventral regions also play a critical role. The presence of multiple functional subregions within the small volume of BNST raises significant technical obstacles for functional imaging studies in humans. PMID:27488624

  7. Inactivation of the bed nucleus of the stria terminalis suppresses the innate fear responses of rats induced by the odor of cat urine.

    PubMed

    Xu, H-Y; Liu, Y-J; Xu, M-Y; Zhang, Y-H; Zhang, J-X; Wu, Y-J

    2012-09-27

    In this study, we investigated whether two brain regions, the bed nucleus of the stria terminalis (BNST) and the basolateral amygdala (BLA), affected male rats' (Rattus norvigicus) ability to innately discriminate between a predator odor (cat urine) and female rat urine. Muscimol, a GABAa receptor agonist, was bilaterally microinjected into either the BNST or BLA of rats through implanted stainless-steel guide cannulas to temporarily inactivate these brain nuclei. The behavioral responses of the treated rats to female rat urine and cat urine were then tested in an experimental arena. Compared to a saline infusion control, the injection of muscimol into the BNST strongly reversed the innate aversion of rats to cat urine but the injection of muscimol into the BLA had no effect. Furthermore, intra-BNST infusion of muscimol caused rats to be equally attracted to urine from cats and female rats but intra-BLA infusion did not stop rats manifesting fear on exposure to cat urine and exploratory behavior on exposure to female rat urine. We conclude that the BNST plays a more crucial role in modulating innate fear responses in rats than the BLA. PMID:22766237

  8. Neuronal Correlates of Fear Conditioning in the Bed Nucleus of the Stria Terminalis

    ERIC Educational Resources Information Center

    Haufler, Darrell; Nagy, Frank Z.; Pare, Denis

    2013-01-01

    Lesion and inactivation studies indicate that the central amygdala (CeA) participates in the expression of cued and contextual fear, whereas the bed nucleus of the stria terminalis (BNST) is only involved in the latter. The basis for this functional dissociation is unclear because CeA and BNST form similar connections with the amygdala and…

  9. Regulation of bed nucleus of the stria terminalis PACAP expression by stress and corticosterone.

    PubMed

    Lezak, Kimberly R; Roman, Carolyn W; Braas, Karen M; Schutz, Kristin C; Falls, William A; Schulkin, Jay; May, Victor; Hammack, Sayamwong E

    2014-11-01

    Single-nucleotide polymorphisms (SNPs) in the genes for pituitary adenylyl cyclase-activating peptide (PACAP) and the PAC1 receptor have been associated with stress-related psychiatric disorders. Although, from recent work, we have argued that stress-induced PACAP expression in the bed nucleus of the stria terminalis (BNST) may mediate stress-related psychopathology, it is unclear whether stress-induced increases in BNST PACAP expression require acute or repeated stressor exposure and whether increased BNST PACAP expression is related to stress-induced increases in circulating glucocorticoids. In the current work, we have used real-time quantitative polymerase chain reaction (qPCR) to assess transcript expression in brain punches from rats after stressor exposure paradigms or corticosterone injection. BNST PACAP and PAC1 receptor transcript expression was increased only after 7 days of repeated stressor exposure; no changes in transcript levels were observed 2 or 24 hours after a single-restraint session. Moreover, repeated corticosterone treatment for 7 days was not sufficient to reliably increase BNST PACAP transcript levels, suggesting that stress-induced elevations in corticosterone may not be the primary drivers of BNST PACAP expression. These results may help clarify the mechanisms and temporal processes that underlie BNST PACAP induction for intervention in stress-related anxiety disorders. PMID:24614974

  10. Role of Bed Nucleus of the Stria Terminalis Corticotrophin-Releasing Factor Receptors in Frustration Stress-Induced Binge-Like Palatable Food Consumption in Female Rats with a History of Food Restriction

    PubMed Central

    Micioni Di Bonaventura, Maria Vittoria; Ciccocioppo, Roberto; Romano, Adele; Bossert, Jennifer M.; Rice, Kenner C.; Ubaldi, Massimo; St. Laurent, Robyn; Gaetani, Silvana; Massi, Maurizio; Shaham, Yavin

    2014-01-01

    We developed recently a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after 15 min exposure to the sight of the palatable food. This “frustration stress” manipulation also activates the hypothalamic–pituitary–adrenal stress axis. Here, we determined the role of the stress neurohormone corticotropin-releasing factor (CRF) in stress-induced binge eating in our model. We also assessed the role of CRF receptors in the bed nucleus of the stria terminalis (BNST), a brain region implicated in stress responses and stress-induced drug seeking, in stress-induced binge eating. We used four groups that were first exposed or not exposed to repeated intermittent cycles of regular chow food restriction during which they were also given intermittent access to high-caloric palatable food. On the test day, we either exposed or did not expose the rats to the sight of the palatable food for 15 min (frustration stress) before assessing food consumption for 2 h. We found that systemic injections of the CRF1 receptor antagonist R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7 dipropylamino pyrazolo[1,5-a]pyrimidine) (10–20 mg/kg) and BNST (25–50 ng/side) or ventricular (1000 ng) injections of the nonselective CRF receptor antagonist d-Phe-CRF(12–41) decreased frustration stress-induced binge eating in rats with a history of food restriction. Frustration stress also increased Fos (a neuronal activity marker) expression in ventral and dorsal BNST. Results demonstrate a critical role of CRF receptors in BNST in stress-induced binge eating in our rat model. CRF1 receptor antagonists may represent a novel pharmacological treatment for bingeing-related eating disorders. PMID:25143612

  11. Vasopressin-immunoreactive cell bodies in the bed nucleus of the stria terminalis of the rat.

    PubMed

    van Leeuwen, F; Caffé, R

    1983-01-01

    In the dorsal and ventral portions of the bed nucleus of the stria terminalis of the rat numerous cell bodies immunoreactive for vasopressin and neurophysin II were found after colchicin pretreatment. These cells are predominantly multipolar but sometimes also bipolar, and have a width and length of approximately 9 and 16 microns, respectively. In the homozygous Brattleboro rat, which is deficient in vasopressin, no immunoreactive vasopressin was found in these cells. Following incubation with anti-oxytocin and anti-bovine neurophysin I, only magnocellular immunoreactive cell bodies were found in the septal region. The consequences of these results concerning the vasopressin fiber pathways in the brain are discussed. PMID:6339062

  12. The bed nucleus of the stria terminalis regulates ethanol-seeking behavior in mice.

    PubMed

    Pina, Melanie M; Young, Emily A; Ryabinin, Andrey E; Cunningham, Christopher L

    2015-12-01

    Drug-associated stimuli are considered important factors in relapse to drug use. In the absence of drug, these cues can trigger drug craving and drive subsequent drug seeking. One structure that has been implicated in this process is the bed nucleus of the stria terminalis (BNST), a chief component of the extended amygdala. Previous studies have established a role for the BNST in cue-induced cocaine seeking. However, it is unclear if the BNST underlies cue-induced seeking of other abused drugs such as ethanol. In the present set of experiments, BNST involvement in ethanol-seeking behavior was assessed in male DBA/2J mice using the conditioned place preference procedure (CPP). The BNST was inhibited during CPP expression using electrolytic lesions (Experiment 1), co-infusion of GABAA and GABAB receptor agonists muscimol and baclofen (M+B; Experiment 2), and activation of inhibitory designer receptors exclusively activated by designer drugs (hM4Di-DREADD) with clozapine-N-oxide (CNO; Experiment 3). The magnitude of ethanol CPP was reduced significantly by each of these techniques. Notably, infusion of M+B (Exp. 2) abolished CPP altogether. Follow-up studies to Exp. 3 showed that ethanol cue-induced c-Fos immunoreactivity in the BNST was reduced by hM4Di activation (Experiment 4) and in the absence of hM4Di, CNO did not affect ethanol CPP (Experiment 5). Combined, these findings demonstrate that the BNST is involved in the modulation of cue-induced ethanol-seeking behavior. PMID:26302652

  13. Effects of hypocretin and norepinephrine interaction in bed nucleus of the stria terminalis on arterial pressure.

    PubMed

    Ciriello, J; Caverson, M M; Li, Z

    2013-01-01

    Forebrain neuronal circuits containing hypocretin-1 (hcrt-1) and norepinephrine (NE) are important components of central arousal-related processes. Recently, these two systems have been shown to have an overlapping distribution within the bed nucleus of the stria terminalis (BST), a limbic structure activated by stressful challenges, and which functions to adjust arterial pressure (AP) and heart rate (HR) to the stressor. However, whether hcrt-1 and NE interact in BST to alter cardiovascular function is unknown. Experiments were done in urethane-α-chloralose anesthetized, paralyzed, and artificially ventilated male Wistar rats to investigate the effect of hcrt-1 and NE on the cardiovascular responses elicited by l-glutamate (Glu) stimulation of BST neurons. Microinjections of hcrt-1, NE or tyramine into BST attenuated the decrease in AP and HR to Glu stimulation of BST. Additionally, combined injections of hcrt-1 with NE or tyramine did not elicit a greater attenuation than either compound alone. Furthermore, injections into BST of the α2-adrenergic receptor (α2-AR) antagonist yohimbine, but not the α1-AR antagonist 2-{[β-(4-hydroxyphenyl)ethyl]aminomethyl}-1-tetralone hydrochloride, blocked both the hcrt-1 and NE-induced inhibition of the BST cardiovascular depressors responses. Finally, injections into BST of the GABAA receptor antagonist bicuculline, but not the GABAB receptor antagonist phaclofen, blocked the hcrt-1 and NE attenuation of the BST Glu-induced depressor and bradycardia responses. These data suggest that hcrt-1 effects in BST are mediated by NE neurons, and hcrt-1 likely acts to facilitate the synaptic release of NE. NE neurons, acting through α2-AR may activate Gabaergic neurons in BST, which in turn through the activation of GABAA receptors inhibit a BST sympathoinhibitory pathway. Taken together, these data suggest that hcrt-1 pathways to BST through their interaction with NE and Gabaergic neurons may function in the coordination of

  14. Immune Challenge Activates Neural Inputs to the Ventrolateral Bed Nucleus of the Stria Terminalis

    PubMed Central

    Bienkowski, Michael S.; Rinaman, Linda

    2011-01-01

    Hypothalamo-pituitary-adrenal (HPA) axis activation in response to infection is an important mechanism by which the nervous system can suppress inflammation. HPA output is controlled by the hypothalamic paraventricular nucleus (PVN). Previously, we determined that noradrenergic inputs to the PVN contribute to, but do not entirely account for, the ability of bacterial endotoxin (i.e., lipopolysacharide, LPS) to activate the HPA axis. The present study investigated LPS-induced recruitment of neural inputs to the ventrolateral bed nucleus of the stria terminalis (vlBNST). GABAergic projections from the vlBNST inhibit PVN neurons at the apex of the HPA axis; thus, we hypothesize that LPS treatment activates inhibitory inputs to the vlBNST to thereby “disinhibit” the PVN and increase HPA output. To test this hypothesis, retrograde neural tracer was iontophoretically delivered into the vlBNST of adult male rats to retrogradely label central sources of axonal input. After one week, rats were injected i.p. with either LPS (200 µg/kg BW) or saline vehicle, and then perfused with fixative 2.5 hours later. Brains were processed for immunohistochemical localization of retrograde tracer and the immediate-early gene product, Fos (a marker of neural activation). Brain regions that provide inhibitory input to the vlBNST (e.g., caudal nucleus of the solitary tract, central amygdala, dorsolateral BNST) were preferentially activated by LPS, whereas sources of excitatory input (e.g., paraventricular thalamus, medial prefrontal cortex) were not activated or were activated less robustly. These results suggest that LPS treatment recruits central neural systems that actively suppress vlBNST neural activity, thereby removing a potent source of inhibitory control over the HPA axis. PMID:21402087

  15. Electrical stimulation in the bed nucleus of the stria terminalis alleviates severe obsessive-compulsive disorder.

    PubMed

    Luyten, L; Hendrickx, S; Raymaekers, S; Gabriëls, L; Nuttin, B

    2016-09-01

    In 1998, we proposed deep brain stimulation as a last-resort treatment option for patients suffering from severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, 24 OCD patients were included in a long-term follow-up study to evaluate the effects of electrical stimulation in the anterior limbs of the internal capsule (ALIC) and bed nucleus of the stria terminalis (BST). We find that electrical stimulation in the ALIC/BST area is safe and significantly decreases obsessions, compulsions, and associated anxiety and depressive symptoms, and improves global functioning in a blinded crossover trial (n=17), after 4 years (n=18), and at last follow-up (up to 171 months, n=24). Moreover, our data indicate that BST may be a better stimulation target compared with ALIC to alleviate OCD symptoms. We conclude that electrical stimulation in BST is a promising therapeutic option for otherwise treatment-resistant OCD patients. PMID:26303665

  16. Ethanol induced adaptations in 5-HT2c receptor signaling in the bed nucleus of the stria terminalis: implications for anxiety during ethanol withdrawal.

    PubMed

    Marcinkiewcz, Catherine A; Dorrier, Cayce E; Lopez, Alberto J; Kash, Thomas L

    2015-02-01

    One of the hallmarks of alcohol dependence is the presence of a withdrawal syndrome during abstinence, which manifests as physical craving for alcohol accompanied by subjective feelings of anxiety. Using a model of chronic intermittent ethanol (CIE) vapor in mice, we investigated the role of serotonin2c receptor (5HT2c-R) signaling in the BNST as a neural substrate underlying ethanol-induced anxiety during withdrawal. Mice were subjected to a 5-day CIE regimen of 16 h of ethanol vapor exposure followed by an 8 h "withdrawal" period between exposures. After the 5th and final exposure, mice were withdrawn for 24 h or 1 week before experiments began. Anxiety-like behavior was assessed in the social approach, light dark, and open field tests with mice showing deficits in social, but not general anxiety-like behavior that was alleviated by pretreatment with the 5HT2c-R antagonist SB 242,084 (3 mg/kg, i.p.) 24 h and 1 week post-CIE. Using immunohistochemistry and whole cell patch clamp electrophysiology, we also found that CIE increased FOS-IR and enhanced neuronal excitability in the ventral BNST (vBNST) 24 h into withdrawal in a 5HT2c-R dependent manner. This enhanced excitability persisted for 1 week post-CIE. We also found that mCPP, a 5HT2c/b agonist, induced a more robust depolarization in cells of the vBNST in CIE mice, confirming that 5HT2c-R signaling is upregulated in the vBNST following CIE. Taken together, these results suggest that CIE upregulates 5HT2c-R signaling in the vBNST, leading to increased excitability. This enhanced excitability of the vBNST may drive increased anxiety-like behavior during ethanol withdrawal. PMID:25229718

  17. ASIC1A in the bed nucleus of the stria terminalis mediates TMT-evoked freezing

    PubMed Central

    Taugher, Rebecca J.; Ghobbeh, Ali; Sowers, Levi P.; Fan, Rong; Wemmie, John A.

    2015-01-01

    Mice display an unconditioned freezing response to TMT, a predator odor isolated from fox feces. Here we found that in addition to freezing, TMT caused mice to decrease breathing rate, perhaps because of the aversive smell. Consistent with this possibility, olfactory bulb lesions attenuated this effect of TMT, as well as freezing. Interestingly, butyric acid, another foul odor, also caused mice to reduce breathing rate. However, unlike TMT, butyric acid did not induce freezing. Thus, although these aversive odors may affect breathing, the unpleasant smell and suppression of breathing by themselves are insufficient to cause freezing. Because the acid-sensing ion channel-1A (ASIC1A) has been previously implicated in TMT-evoked freezing, we tested whether Asic1a disruption also altered breathing. We found that TMT reduced breathing rate in both Asic1a+/+ and Asic1a−/− mice, suggesting that ASIC1A is not required for TMT to inhibit breathing and that the absence of TMT-evoked freezing in the Asic1a−/− mice is not due to an inability to detect TMT. These observations further indicate that ASIC1A must affect TMT freezing in another way. Because the bed nucleus of the stria terminalis (BNST) has been critically implicated in TMT-evoked freezing and robustly expresses ASIC1A, we tested whether ASIC1A in the BNST plays a role in TMT-evoked freezing. We disrupted ASIC1A in the BNST of Asic1aloxP/loxP mice by delivering Cre recombinase to the BNST with an adeno-associated virus (AAV) vector. We found that disrupting ASIC1A in the BNST reduced TMT-evoked freezing relative to control mice in which a virus expressing eGFP was injected. To test whether ASIC1A in the BNST was sufficient to increase TMT-evoked freezing, we used another AAV vector to express ASIC1A in the BNST of Asic1a−/− mice. We found region-restricted expression of ASIC1A in the BNST increased TMT-elicited freezing. Together, these data suggest that the BNST is a key site of ASIC1A action in TMT

  18. Vasopressin cells in the bed nucleus of the stria terminalis of the rat: sex differences and the influence of androgens.

    PubMed

    van Leeuwen, F W; Caffe, A R; De Vries, G J

    1985-01-28

    A sex difference in the number of vasopressin-immunoreactive cells was found in the bed nucleus of the stria terminalis of the rat. The number of cells found in males exceeded the female corresponding value. A sharp decrease in the number of vasopressin-immunoreactive cells was noted 21 weeks after the castration of adult male rats. This decline could be reversed completely by a 5-week testosterone substitution therapy. PMID:3978433

  19. Ventromedial prefrontal cortex damage alters resting blood flow to the bed nucleus of stria terminalis

    PubMed Central

    Motzkin, Julian C.; Philippi, Carissa L.; Oler, Jonathan A.; Kalin, Ned H.; Baskaya, Mustafa K.; Koenigs, Michael

    2014-01-01

    The ventromedial prefrontal cortex (vmPFC) plays a key role in modulating emotional responses, yet the precise neural mechanisms underlying this function remain unclear. vmPFC interacts with a number of subcortical structures involved in affective processing, including the amygdala, hypothalamus, periaqueductal gray, ventral striatum, and bed nucleus of stria terminalis (BNST). While a previous study of non-human primates shows that vmPFC lesions reduce BNST activity and anxious behavior, no such causal evidence exists in humans. In this study, we used a novel application of MRI in neurosurgical patients with focal, bilateral vmPFC damage to determine whether vmPFC is indeed critical for modulating BNST function in humans. Relative to neurologically healthy subjects, who exhibited robust rest-state functional connectivity between vmPFC and BNST, the vmPFC lesion patients had significantly lower resting-state perfusion of the right BNST. No such perfusion differences were observed for the amygdala, striatum, hypothalamus, or periaqueductal gray. This study thus provides unique data on the relationship between vmPFC and BNST, suggesting that vmPFC serves to promote BNST activity in humans. This finding is relevant for neural circuitry models of mood and anxiety disorders. PMID:25569763

  20. Neuregulin 1-ErbB4 signaling in the bed nucleus of the stria terminalis regulates anxiety-like behavior.

    PubMed

    Geng, Fei; Zhang, Jie; Wu, Jian-Lin; Zou, Wen-Jun; Liang, Zhi-Ping; Bi, Lin-Lin; Liu, Ji-Hong; Kong, Ying; Huang, Chu-Qiang; Li, Xiao-Wen; Yang, Jian-Ming; Gao, Tian-Ming

    2016-08-01

    The bed nucleus of the stria terminalis (BNST), a nucleus defined as part of the extended amygdala, is involved in the expression of anxiety disorders. However, the regulatory mechanisms of BNST inhibitory activity that is involved in anxiety are unknown. Here, we showed that blocking neuregulin 1 (NRG1)-ErbB4 signaling in the BNST of mice, by either neutralizing endogenous NRG1 with ecto-Erbb4 or antagonizing the ErbB4 receptor with its specific inhibitor, produced anxiogenic responses. Interestingly, application of exogenous NRG1 into the BNST induced no anxiolytic effects, suggesting saturating activity of endogenous NRG1. While infusion of the GABAA receptor antagonist bicuculline into the BNST also led to anxiety-related behaviors, it did not worsen the anxiogenic effects produced by blocking NRG1-ErbB4 signaling, suggesting possible involvement of GABAergic neurotransmission. Further, in vitro electrophysiological recordings showed that BNST NRG1-ErbB4 signaling regulated the presynaptic GABA release. Together, these results suggest that NRG1-ErbB4 signaling in the BNST may play an important role in regulating anxiety-like behaviors. PMID:27189883

  1. Stress increases GABAergic neurotransmission in CRF neurons of the central amygdala and bed nucleus stria terminalis.

    PubMed

    Partridge, John G; Forcelli, Patrick A; Luo, Ruixi; Cashdan, Jonah M; Schulkin, Jay; Valentino, Rita J; Vicini, Stefano

    2016-08-01

    Corticotrophin Releasing Factor (CRF) is a critical stress-related neuropeptide in major output pathways of the amygdala, including the central nucleus (CeA), and in a key projection target of the CeA, the bed nucleus of the stria terminalis (BnST). While progress has been made in understanding the contributions and characteristics of CRF as a neuropeptide in rodent behavior, little attention has been committed to determine the properties and synaptic physiology of specific populations of CRF-expressing (CRF(+)) and non-expressing (CRF(-)) neurons in the CeA and BnST. Here, we fill this gap by electrophysiologically characterizing distinct neuronal subtypes in CeA and BnST. Crossing tdTomato or channelrhodopsin-2 (ChR2-YFP) reporter mice to those expressing Cre-recombinase under the CRF promoter allowed us to identify and manipulate CRF(+) and CRF(-) neurons in CeA and BnST, the two largest areas with fluorescently labeled neurons in these mice. We optogenetically activated CRF(+) neurons to elicit action potentials or synaptic responses in CRF(+) and CRF(-) neurons. We found that GABA is the predominant co-transmitter in CRF(+) neurons within the CeA and BnST. CRF(+) neurons are highly interconnected with CRF(-) neurons and to a lesser extent with CRF(+) neurons. CRF(+) and CRF(-) neurons differentially express tonic GABA currents. Chronic, unpredictable stress increase the amplitude of evoked IPSCs and connectivity between CRF(+) neurons, but not between CRF(+) and CRF(-) neurons in both regions. We propose that reciprocal inhibition of interconnected neurons controls CRF(+) output in these nuclei. PMID:27016019

  2. Allopregnanolone in the bed nucleus of the stria terminalis modulates contextual fear in rats

    PubMed Central

    Nagaya, Naomi; Acca, Gillian M.; Maren, Stephen

    2015-01-01

    Trauma- and stress-related disorders are among the most common types of mental illness affecting the U.S. population. For many of these disorders, there is a striking sex difference in lifetime prevalence; for instance, women are twice as likely as men to be affected by posttraumatic stress disorder (PTSD). Gonadal steroids and their metabolites have been implicated in sex differences in fear and anxiety. One example, allopregnanolone (ALLO), is a neuroactive metabolite of progesterone that allosterically enhances GABAA receptor activity and has anxiolytic effects. Like other ovarian hormones, it not only occurs at different levels in males and females but also fluctuates over the female reproductive cycle. One brain structure that may be involved in neuroactive steroid regulation of fear and anxiety is the bed nucleus of the stria terminalis (BNST). To explore this question, we examined the consequences of augmenting or reducing ALLO activity in the BNST on the expression of Pavlovian fear conditioning in rats. In Experiment 1, intra-BNST infusions of ALLO in male rats suppressed freezing behavior (a fear response) to the conditioned context, but did not influence freezing to a discrete tone conditioned stimulus (CS). In Experiment 2, intra-BNST infusion of either finasteride (FIN), an inhibitor of ALLO synthesis, or 17-phenyl-(3α,5α)-androst-16-en-3-ol, an ALLO antagonist, in female rats enhanced contextual freezing; neither treatment affected freezing to the tone CS. These findings support a role for ALLO in modulating contextual fear via the BNST and suggest that sex differences in fear and anxiety could arise from differential steroid regulation of BNST function. The susceptibility of women to disorders such as PTSD may be linked to cyclic declines in neuroactive steroid activity within fear circuitry. PMID:26300750

  3. Allopregnanolone in the bed nucleus of the stria terminalis modulates contextual fear in rats.

    PubMed

    Nagaya, Naomi; Acca, Gillian M; Maren, Stephen

    2015-01-01

    Trauma- and stress-related disorders are among the most common types of mental illness affecting the U.S. population. For many of these disorders, there is a striking sex difference in lifetime prevalence; for instance, women are twice as likely as men to be affected by posttraumatic stress disorder (PTSD). Gonadal steroids and their metabolites have been implicated in sex differences in fear and anxiety. One example, allopregnanolone (ALLO), is a neuroactive metabolite of progesterone that allosterically enhances GABAA receptor activity and has anxiolytic effects. Like other ovarian hormones, it not only occurs at different levels in males and females but also fluctuates over the female reproductive cycle. One brain structure that may be involved in neuroactive steroid regulation of fear and anxiety is the bed nucleus of the stria terminalis (BNST). To explore this question, we examined the consequences of augmenting or reducing ALLO activity in the BNST on the expression of Pavlovian fear conditioning in rats. In Experiment 1, intra-BNST infusions of ALLO in male rats suppressed freezing behavior (a fear response) to the conditioned context, but did not influence freezing to a discrete tone conditioned stimulus (CS). In Experiment 2, intra-BNST infusion of either finasteride (FIN), an inhibitor of ALLO synthesis, or 17-phenyl-(3α,5α)-androst-16-en-3-ol, an ALLO antagonist, in female rats enhanced contextual freezing; neither treatment affected freezing to the tone CS. These findings support a role for ALLO in modulating contextual fear via the BNST and suggest that sex differences in fear and anxiety could arise from differential steroid regulation of BNST function. The susceptibility of women to disorders such as PTSD may be linked to cyclic declines in neuroactive steroid activity within fear circuitry. PMID:26300750

  4. Development of sexually dimorphic vasotocinergic system in the bed nucleus of stria terminalis in chickens.

    PubMed

    Jurkevich, A; Barth, S W; Kuenzel, W J; Köhler, A; Grossmann, R

    1999-05-24

    The bed nucleus of stria terminalis (BnST) of the domestic fowl contains two groups of parvicellular vasotocinergic neurons that are sexually dimorphic. In adult cockerels, arginine vasotocin (AVT) synthesis is well expressed in the dorsolateral and ventromedial portions of the BnST, whereas in corresponding brain areas of hens, AVT synthesis is completely lacking. In the present study, in situ hybridization and immunocytochemical methods were used to compare the ontogeny of sexually dimorphic AVT gene expression in the BnST of male and female chickens from day 12 of embryonic development (E12) until the onset of sexual maturation. By E12, both parvicellular groups of AVT-immunoreactive (AVT-ir) perikarya in the developing BnST can be distinguished in some males, whereas in females their presence is questionable. A quantitative analysis, beginning at E14, showed that the parvicellular dorsolateral portion of the BnST of male embryos had more AVT perikarya compared with females. In contrast, no evident sex difference in distribution pattern and number of AVT mRNA containing neurons in this BnST portion was observable by in situ hybridization at E15. At E18, as well as on the first and second days posthatch (D1 and D2), no differences in the number of AVT synthesizing cells and intensity of immunoreactive staining in male versus female chickens were found. Between D2 and D7, the number of AVT-ir cells in the BnST declined rapidly in both sexes until it disappeared completely in females before D35. In males, another increase in sexually dimorphic AVT-ir cells and innervation of the lateral septum was associated with the onset of puberty and fully matched a pattern observed in adult fowls. These results demonstrate that the sexually dimorphic part of the AVT system undergoes sexual differentiation during early stages of ontogeny. PMID:10331579

  5. CGRP inhibits neurons of the bed nucleus of the stria terminalis: implications for the regulation of fear and anxiety.

    PubMed

    Gungor, Nur Zeynep; Pare, Denis

    2014-01-01

    The bed nucleus of the stria terminalis (BNST) is thought to generate anxiety-like states via its projections to autonomic and neuroendocrine regulatory structures of the brain. However, because most BNST cells are GABAergic, they are expected to inhibit target neurons. In contrast with this, infusion of calcitonin gene-related peptide (CGRP) into BNST was reported to potentiate anxiety while activating BNST targets. The present study aimed to shed light on this paradox. The CGRP innervation of BNST originates in the pontine parabrachial nucleus and targets its anterolateral sector (BNST-AL). Thus, we investigated the effects of CGRP on BNST-AL neurons using patch recordings in vitro in male rats. CGRP did not alter the passive properties of BNST-AL cells but increased the amplitude of IPSPs evoked by stimulation of the stria terminalis (ST). However, IPSP paired-pulse ratios were unchanged by CGRP, and there was no correlation between IPSP potentiation and variance, suggesting that CGRP acts postsynaptically. Consistent with this, CGRP hyperpolarized the GABA-A reversal of BNST-AL cells. These results indicate that CGRP increases ST-evoked GABA-A IPSPs and hyperpolarizes their reversal potential through a postsynaptic change in Cl(-) homeostasis. Overall, our findings suggest that CGRP potentiates anxiety-like behaviors and increases neural activity in BNST targets, by inhibiting BNST-AL cells, supporting the conclusion that BNST-AL exerts anxiolytic effects. PMID:24381268

  6. Role of the lateral preoptic area and the bed nucleus of stria terminalis in the regulation of penile erection.

    PubMed

    Iwasaki, Hiroshi; Jodo, Eiichi; Kawauchi, Akihiro; Miki, Tsuneharu; Kayama, Yukihiko; Koyama, Yoshimasa

    2010-10-21

    To elucidate the role of the preoptic area (POA) in the regulation of penile erection, we examined the effects of electrical stimulation in and around the POA on penile erection in rats, which was assessed by changes in pressure in the corpus spongiosum of the penis (CSP) and electromyography (EMG) of the bulbospongiosus (BS) muscle. In unanesthetized and anesthetized rats, four types of responses were induced by stimulation in and around the POA; (1) normal type responses, which were similar to spontaneously occurring erections, characterized by slow increase in CSP pressure and sharp peaks concurrent with BS muscle bursting; (2) muscular type responses, which included sharp CSP pressure peaks (muscular component) with almost no vascular component; (3) mixed type responses, which included a sequence of high-frequency CSP peaks followed by low-frequency CSP peaks; and (4) micturition type responses, which had higher-frequency and lower-amplitude CSP peaks than other responses which were identical to those of normal micturition. In unanesthetized condition, erections were evoked by stimulation of the lateral preoptic area (LPOA), medial preoptic area (MPOA), bed nucleus of the stria terminalis (BST), paraventricular nucleus (PVN), reuniens thalamic nucleus (Re) and lateral septum (LS). Lower-intensity stimulation evoked erections from the LPOA, BST, PVN and RE, but not the MPOA. In anesthetized condition, stronger stimuli were required and effective sites were restricted to the LPOA, MPOA and BST. These findings suggest that the lateral and medial subdivisions of the preoptic area play different roles in mediating penile erection. PMID:20705064

  7. Serotonin Transporter Availability in the Amygdala and Bed Nucleus of the Stria Terminalis Predicts Anxious Temperament and Brain Glucose Metabolic Activity

    PubMed Central

    Oler, Jonathan A; Fox, Andrew S; Shelton, Steven E; Christian, Bradley T; Murali, Dhanabalan; Oakes, Terrence R; Davidson, Richard J; Kalin, Ned H

    2009-01-01

    The serotonin transporter (5-HTT) plays a critical role in regulating serotonergic neurotransmission and is implicated in the pathophysiology of anxiety and affective disorders. PET scans using [C-11]DASB to measure 5-HTT availability (an index of receptor density and binding) were performed in 34 rhesus monkeys in which the relation between regional brain glucose metabolism and anxious temperament was previously established. 5-HTT availability in the amygdalohippocampal area and bed nucleus of the stria terminalis correlated positively with individual differences in a behavioral and neuroendocrine composite of anxious temperament. 5-HTT availability also correlated positively with stress-induced metabolic activity within these regions. Collectively, these findings suggest that serotonergic modulation of neuronal excitability in the neural circuitry associated with anxiety mediates the developmental risk for affect-related psychopathology. PMID:19675230

  8. CGRP Antagonist Infused into the Bed Nucleus of the Stria Terminalis Impairs the Acquisition and Expression of Context but Not Discretely Cued Fear

    ERIC Educational Resources Information Center

    Sink, Kelly S.; Davis, Michael; Walker, David L.

    2013-01-01

    Calcitonin gene-related peptide (CGRP) infusions into the bed nucleus of the stria terminalis (BNST) evoke increases in startle amplitude and increases in anxiety-like behavior in the plus maze. Conversely, intra-BNST infusions of the CGRP antagonist CGRP[subscript 8-37] block unconditioned startle increases produced by fox odor. Here we evaluate…

  9. Mechanisms in the Bed Nucleus of the Stria Terminalis Involved in Control of Autonomic and Neuroendocrine Functions: A Review

    PubMed Central

    Crestani, Carlos C; Alves, Fernando HF; Gomes, Felipe V; Resstel, Leonardo BM; Correa, Fernando MA; Herman, James P

    2013-01-01

    The bed nucleus of the stria terminalis (BNST) is a heterogeneous and complex limbic forebrain structure, which plays an important role in controlling autonomic, neuroendocrine and behavioral responses. The BNST is thought to serve as a key relay connecting limbic forebrain structures to hypothalamic and brainstem regions associated with autonomic and neuroendocrine functions. Its control of physiological and behavioral activity is mediated by local action of numerous neurotransmitters. In the present review we discuss the role of the BNST in control of both autonomic and neuroendocrine function. A description of BNST control of cardiovascular and hypothalamus-pituitary-adrenal axisactivity at rest and during physiological challenges (stress and physical exercise) is presented. Moreover, evidence for modulation of hypothalamic magnocellular neurons activity is also discussed. We attempt to focus on the discussion of BNST neurochemical mechanisms. Therefore, the source and targets of neurochemical inputs to BNST subregions and their role in control of autonomic and neuroendocrine function is discussed in details. PMID:23997750

  10. Overshadowed by the amygdala: the bed nucleus of the stria terminalis emerges as key to psychiatric disorders.

    PubMed

    Lebow, M A; Chen, A

    2016-04-01

    The bed nucleus of the stria terminalis (BNST) is a center of integration for limbic information and valence monitoring. The BNST, sometimes referred to as the extended amygdala, is located in the basal forebrain and is a sexually dimorphic structure made up of between 12 and 18 sub-nuclei. These sub-nuclei are rich with distinct neuronal subpopulations of receptors, neurotransmitters, transporters and proteins. The BNST is important in a range of behaviors such as: the stress response, extended duration fear states and social behavior, all crucial determinants of dysfunction in human psychiatric diseases. Most research on stress and psychiatric diseases has focused on the amygdala, which regulates immediate responses to fear. However, the BNST, and not the amygdala, is the center of the psychogenic circuit from the hippocampus to the paraventricular nucleus. This circuit is important in the stimulation of the hypothalamic-pituitary-adrenal axis. Thus, the BNST has been largely overlooked with respect to its possible dysregulation in mood and anxiety disorders, social dysfunction and psychological trauma, all of which have clear gender disparities. In this review, we will look in-depth at the anatomy and projections of the BNST, and provide an overview of the current literature on the relevance of BNST dysregulation in psychiatric diseases. PMID:26878891

  11. Amygdala projections to the lateral bed nucleus of the stria terminalis in the Macaque: comparison with ventral striatal afferents

    PubMed Central

    deCampo, Danielle M.; Fudge, Julie L.

    2013-01-01

    The lateral bed nucleus of the stria terminalis (BSTL) is involved in mediating anxiety-related behaviors to sustained aversive stimuli. The BSTL forms part of the central extended amygdala, a continuum composed of the BSTL, the amygdala central nucleus, and cell columns running between the two. The central subdivision (BSTLcn), and the juxtacapsular subdivision (BSTLJ) are two BSTL regions that lie above the anterior commissure, near the ventral striatum. The amygdala, a heterogeneous structure that encodes emotional salience, projects to both the BSTL and ventral striatum. We placed small injections of retrograde tracers into the BSTL, focusing on the BSTLcn and BSTLJ, and analyzed the distribution of labeled cells in amygdala subregions. We compared this to the pattern of labeled cells following injections into the ventral striatum. All retrograde results were confirmed by anterograde studies. We found that the BSTLcn receives stronger amygdala inputs relative to the BSTLJ. Furthermore, the BSTLcn is defined by inputs from the corticoamygdaloid transition area and central nucleus, while the BSTLJ receives inputs mainly from the magnocellular accessory basal and basal nucleus. In the ventral striatum, the dorsomedial shell receives inputs that are similar, but not identical, to inputs to the BSTLcn. In contrast, amygdala projections to the ventral shell/core are similar to projections to the BSTLJ. These findings indicate that the BSTLcn and BSTLJ receive distinct amygdala afferent inputs and that the dorsomedial shell is a transition zone with the BSTLcn, while the ventral shell/core are transition zones with the BSTLJ. PMID:23696521

  12. Genetic cell targeting uncovers specific neuronal types and distinct subregions in the bed nucleus of the stria terminalis.

    PubMed

    Nguyen, Amanda Q; Dela Cruz, Julie A D; Sun, Yanjun; Holmes, Todd C; Xu, Xiangmin

    2016-08-15

    The bed nucleus of the stria terminalis (BNST) plays an important role in fear, stress, and anxiety. It contains a collection of subnuclei delineated by gross cytoarchitecture features; however, there has yet to be a systematic examination of specific BNST neuronal types and their associated neurochemical makeup. The present study focuses on improved characterization of the anterior BNST based on differing molecular and chemical expression aided by mouse genetics. Specific Cre driver lines crossed with a fluorescent reporter line were used for genetic cell targeting and immunochemical staining. Using this new approach, we were able to robustly identify specific excitatory and inhibitory cell types in the BNST. The presence and distribution of excitatory neurons were firmly established; glutamatergic neurons in the anterior BNST accounted for about 14% and 31% of dorsal and ventral BNST cells, respectively. GABAergic neurons expressing different isoforms of glutamic acid decarboxylase were found to have differential subregional distributions. Almost no parvalbumin-expressing cells were found in the BNST, while somatostatin-expressing cells and calretinin-expressing cells account for modest proportions of BNST cells. In addition, vasoactive intestinal peptide-expressing axonal plexuses were prominent in the oval and juxtacapsular subregions. In addition, we discovered that corticotropin-releasing hormone-expressing cells contain GABAergic and glutamatergic subpopulations. Together, this study reveals new information on excitatory and inhibitory neurons in the BNST, which will facilitate genetic dissection and functional studies of BNST subregions. J. Comp. Neurol. 524:2379-2399, 2016. © 2016 Wiley Periodicals, Inc. PMID:26718312

  13. Overshadowed by the amygdala: the bed nucleus of the stria terminalis emerges as key to psychiatric disorders

    PubMed Central

    Lebow, M A; Chen, A

    2016-01-01

    The bed nucleus of the stria terminalis (BNST) is a center of integration for limbic information and valence monitoring. The BNST, sometimes referred to as the extended amygdala, is located in the basal forebrain and is a sexually dimorphic structure made up of between 12 and 18 sub-nuclei. These sub-nuclei are rich with distinct neuronal subpopulations of receptors, neurotransmitters, transporters and proteins. The BNST is important in a range of behaviors such as: the stress response, extended duration fear states and social behavior, all crucial determinants of dysfunction in human psychiatric diseases. Most research on stress and psychiatric diseases has focused on the amygdala, which regulates immediate responses to fear. However, the BNST, and not the amygdala, is the center of the psychogenic circuit from the hippocampus to the paraventricular nucleus. This circuit is important in the stimulation of the hypothalamic–pituitary–adrenal axis. Thus, the BNST has been largely overlooked with respect to its possible dysregulation in mood and anxiety disorders, social dysfunction and psychological trauma, all of which have clear gender disparities. In this review, we will look in-depth at the anatomy and projections of the BNST, and provide an overview of the current literature on the relevance of BNST dysregulation in psychiatric diseases. PMID:26878891

  14. Importance of CRF Receptor-Mediated Mechanisms of the Bed Nucleus of the Stria Terminalis in the Processing of Anxiety and Pain

    PubMed Central

    Tran, Lee; Schulkin, Jay; Greenwood-Van Meerveld, Beverley

    2014-01-01

    Corticotropin-releasing factor (CRF)-mediated mechanisms in the bed nucleus of the stria terminalis (BNST) have a pivotal role in stress-induced anxiety and hyperalgesia. Although CRF is known to activate two receptor subtypes, CRF1 and CRF2, attempts to delineate the specific role of each subtype in modulating anxiety and nociception have been inconsistent. Here we test the hypothesis that CRF1 and CRF2 receptor activation in the anteriolateral BNST (BNSTAL) facilitates divergent mechanisms modulating comorbid anxiety and hyperalgesia. Microinfusions of the specific antagonists CP376395 and Astressin2B into the BNSTAL were used to investigate CRF1 and CRF2 receptor functions, respectively. We found that CRF1 and CRF2 receptors in the BNSTAL had opposing effects on exploratory behavior in the elevated plus-maze, somatic mechanical threshold, and the autonomic and endocrine response to stress. However, CRF1 or CRF2 receptor antagonism in the BNSTAL revealed complementary roles in facilitating the acoustic startle and visceromotor reflexes. Our results suggest that the net effect of CRF1 and CRF2 receptor activation in the BNSTAL is pathway-dependent and provides important insight into the CRF receptor-associated circuitry that likely underpins stress-induced pathologies. PMID:24853772

  15. Whole-brain mapping of afferent projections to the bed nucleus of the stria terminalis in tree shrews.

    PubMed

    Ni, Rong-Jun; Luo, Peng-Hao; Shu, Yu-Mian; Chen, Ju-Tao; Zhou, Jiang-Ning

    2016-10-01

    The bed nucleus of the stria terminalis (BST) plays an important role in integrating and relaying input information to other brain regions in response to stress. The cytoarchitecture of the BST in tree shrews (Tupaia belangeri chinensis) has been comprehensively described in our previous publications. However, the inputs to the BST have not been described in previous reports. The aim of the present study was to investigate the sources of afferent projections to the BST throughout the brain of tree shrews using the retrograde tracer Fluoro-Gold (FG). The present results provide the first detailed whole-brain mapping of BST-projecting neurons in the tree shrew brain. The BST was densely innervated by the prefrontal cortex, entorhinal cortex, ventral subiculum, amygdala, ventral tegmental area, and parabrachial nucleus. Moreover, moderate projections to the BST originated from the medial preoptic area, supramammillary nucleus, paraventricular thalamic nucleus, pedunculopontine tegmental nucleus, dorsal raphe nucleus, locus coeruleus, and nucleus of the solitary tract. Afferent projections to the BST are identified in the ventral pallidum, nucleus of the diagonal band, ventral posteromedial thalamic nucleus, posterior complex of the thalamus, interfascicular nucleus, retrorubral field, rhabdoid nucleus, intermediate reticular nucleus, and parvicellular reticular nucleus. In addition, the different densities of BST-projecting neurons in various regions were analyzed in the tree shrew brains. In summary, whole-brain mapping of direct inputs to the BST is delineated in tree shrews. These brain circuits are implicated in the regulation of numerous physiological and behavioral processes including stress, reward, food intake, and arousal. PMID:27436534

  16. The response of neurons in the bed nucleus of the stria terminalis to serotonin: implications for anxiety.

    PubMed

    Hammack, Sayamwong E; Guo, Ji-Dong; Hazra, Rimi; Dabrowska, Joanna; Myers, Karyn M; Rainnie, Donald G

    2009-11-13

    Substantial evidence has suggested that the activity of the bed nucleus of the stria terminalis (BNST) mediates many forms of anxiety-like behavior in human and non-human animals. These data have led many investigators to suggest that abnormal processing within this nucleus may underlie anxiety disorders in humans, and effective anxiety treatments may restore normal BNST functioning. Currently some of the most effective treatments for anxiety disorders are drugs that modulate serotonin (5-HT) systems, and several decades of research have suggested that the activation of 5-HT can modulate anxiety-like behavior. Despite these facts, relatively few studies have examined how activity within the BNST is modulated by 5-HT. Here we review our own investigations using in vitro whole-cell patch-clamp electrophysiological methods on brain sections containing the BNST to determine the response of BNST neurons to exogenous 5-HT application. Our data suggest that the response of BNST neurons to 5-HT is complex, displaying both inhibitory and excitatory components, which are mediated by 5-HT(1A), 5-HT(2A), 5-HT(2C) and 5-HT(7) receptors. Moreover, we have shown that the selective activation of the inhibitory response to 5-HT reduces anxiety-like behavior, and we describe data suggesting that the activation of the excitatory response to 5-HT may be anxiogenic. We propose that in the normal state, the function of 5-HT is to dampen activity within the BNST (and consequent anxiety-like behavior) during exposure to threatening stimuli; however, we suggest that changes in the balance of the function of BNST 5-HT receptor subtypes could alter the response of BNST neurons to favor excitation and produce a pathological state of increased anxiety. PMID:19467288

  17. α2A-Adrenergic Receptors Filter Parabrachial Inputs to the Bed Nucleus of the Stria Terminalis

    PubMed Central

    Flavin, Stephanie A.; Matthews, Robert T.; Wang, Qin; Muly, E. Chris

    2014-01-01

    α2-adrenergic receptors (AR) within the bed nucleus of the stria terminalis (BNST) reduce stress–reward interactions in rodent models. In addition to their roles as autoreceptors, BNST α2A-ARs suppress glutamatergic transmission. One prominent glutamatergic input to the BNST originates from the parabrachial nucleus (PBN) and consists of asymmetric axosomatic synapses containing calcitonin gene-related peptide (CGRP) and vGluT2. Here we provide immunoelectron microscopic data showing that many asymmetric axosomatic synapses in the BNST contain α2A-ARs. Further, we examined optically evoked glutamate release ex vivo in BNST from mice with virally delivered channelrhodopsin2 (ChR2) expression in PBN. In BNST from these animals, ChR2 partially colocalized with CGRP, and activation generated EPSCs in dorsal anterolateral BNST neurons that elicited two cell-type-specific outcomes: (1) feedforward inhibition or (2) an EPSP that elicited firing. We found that the α2A-AR agonist guanfacine selectively inhibited this PBN input to the BNST, preferentially reducing the excitatory response in ex vivo mouse brain slices. To begin to assess the overall impact of α2A-AR control of this PBN input on BNST excitatory transmission, we used a Thy1-COP4 mouse line with little postsynaptic ChR2 expression nor colocalization of ChR2 with CGRP in the BNST. In slices from these mice, we found that guanfacine enhanced, rather than suppressed, optogenetically initiated excitatory drive in BNST. Thus, our study reveals distinct actions of PBN afferents within the BNST and suggests that α2A-AR agonists may filter excitatory transmission in the BNST by inhibiting a component of the PBN input while enhancing the actions of other inputs. PMID:25009265

  18. α(2A)-adrenergic receptors filter parabrachial inputs to the bed nucleus of the stria terminalis.

    PubMed

    Flavin, Stephanie A; Matthews, Robert T; Wang, Qin; Muly, E Chris; Winder, Danny G

    2014-07-01

    α2-adrenergic receptors (AR) within the bed nucleus of the stria terminalis (BNST) reduce stress-reward interactions in rodent models. In addition to their roles as autoreceptors, BNST α(2A)-ARs suppress glutamatergic transmission. One prominent glutamatergic input to the BNST originates from the parabrachial nucleus (PBN) and consists of asymmetric axosomatic synapses containing calcitonin gene-related peptide (CGRP) and vGluT2. Here we provide immunoelectron microscopic data showing that many asymmetric axosomatic synapses in the BNST contain α(2A)-ARs. Further, we examined optically evoked glutamate release ex vivo in BNST from mice with virally delivered channelrhodopsin2 (ChR2) expression in PBN. In BNST from these animals, ChR2 partially colocalized with CGRP, and activation generated EPSCs in dorsal anterolateral BNST neurons that elicited two cell-type-specific outcomes: (1) feedforward inhibition or (2) an EPSP that elicited firing. We found that the α(2A)-AR agonist guanfacine selectively inhibited this PBN input to the BNST, preferentially reducing the excitatory response in ex vivo mouse brain slices. To begin to assess the overall impact of α(2A)-AR control of this PBN input on BNST excitatory transmission, we used a Thy1-COP4 mouse line with little postsynaptic ChR2 expression nor colocalization of ChR2 with CGRP in the BNST. In slices from these mice, we found that guanfacine enhanced, rather than suppressed, optogenetically initiated excitatory drive in BNST. Thus, our study reveals distinct actions of PBN afferents within the BNST and suggests that α(2A)-AR agonists may filter excitatory transmission in the BNST by inhibiting a component of the PBN input while enhancing the actions of other inputs. PMID:25009265

  19. Role of bed nucleus of the stria terminalis and amygdala AMPA receptors in the development and expression of context conditioning and sensitization of startle by prior shock

    PubMed Central

    Davis, Michael

    2013-01-01

    A core symptom of post-traumatic stress disorder is hyper-arousal—manifest in part by increases in the amplitude of the acoustic startle reflex. Gewirtz et al. (Prog Neuropsychopharmacol Biol Psychiatry 22:625–648, 1998) found that, in rats, persistent shock-induced startle increases were prevented by pre-test electrolytic lesions of the bed nucleus of the stria terminalis (BNST). We used reversible inactivation to determine if similar effects reflect actions on (a) BNST neurons themselves versus fibers-of-passage, (b) the development versus expression of such increases, and (c) associative fear versus non-associative sensitization. Twenty-four hours after the last of three shock sessions, startle was markedly enhanced when rats were tested in a non-shock context. These increases decayed over the course of several days. Decay was unaffected by context exposure, and elevated startle was restored when rats were tested for the first time in the original shock context. Thus, both associative and non-associative components could be measured under different conditions. Pre-test intra-BNST infusions of the AMPA receptor antagonist NBQX (3 μg/side) blocked the non-associative (as did infusions into the basolateral amygdala) but not the associative component, whereas pre-shock infusions disrupted both. NBQX did not affect baseline startle or shock reactivity. These results indicate that AMPA receptors in or very near to the BNST are critical for the expression and development of non-associative shock-induced startle sensitization, and also for context fear conditioning, but not context fear expression. More generally, they suggest that treatments targeting the BNST may be clinically useful for treating trauma-related hyper-arousal and perhaps for retarding its development. PMID:23934654

  20. Role of the bed nucleus of the stria terminalis in cardiovascular changes following chronic treatment with cocaine and testosterone: a role beyond drug seeking in addiction?

    PubMed

    Cruz, F C; Alves, F H F; Leão, R M; Planeta, C S; Crestani, C C

    2013-12-01

    Neural plasticity has been observed in the bed nucleus of the stria terminalis (BNST) following exposure to both cocaine and androgenic-anabolic steroids. Here we investigated the involvement of the BNST on changes in cardiovascular function and baroreflex activity following either single or combined administration of cocaine and testosterone for 10 consecutive days in rats. Single administration of testosterone increased values of arterial pressure, evoked rest bradycardia and reduced baroreflex-mediated bradycardia. These effects of testosterone were not affected by BNST inactivation caused by local bilateral microinjections of the nonselective synaptic blocker CoCl2. The single administration of cocaine as well as the combined treatment with testosterone and cocaine increased both bradycardiac and tachycardiac responses of the baroreflex. Cocaine-evoked baroreflex changes were totally reversed after BNST inactivation. However, BNST inhibition in animals subjected to combined treatment with cocaine and testosterone reversed only the increase in reflex tachycardia, whereas facilitation of reflex bradycardia was not affected by local BNST treatment with CoCl2. In conclusion, the present study provides the first direct evidence that the BNST play a role in cardiovascular changes associated with drug abuse. Our findings suggest that alterations in cardiovascular function following subchronic exposure to cocaine are mediated by neural plasticity in the BNST. The single treatment with cocaine and the combined administration of testosterone and cocaine had similar effects on baroreflex activity, however the association with testosterone inhibited cocaine-induced changes in the BNST control of reflex bradycardia. Testosterone-induced cardiovascular changes seem to be independent of the BNST. PMID:23994153

  1. Sex dimorphism in the avian arginine vasotocin system with special emphasis to the bed nucleus of the stria terminalis.

    PubMed

    Grossmann, Roland; Jurkevich, Aleksandr; Köhler, Almut

    2002-04-01

    The avian neuropeptide arginine vasotocin (AVT) originally characterized as the antidiuretic hormone (, Endocrinol. 66, 860-871) is produced by neurosecretory cells within the brain. Numerous neuroanatomical studies that employed immunocytochemical and in situ hybridization techniques revealed such cells in the following anatomical brain locations: (a) preoptic area including supraoptic nucleus; (b) paraventricular nucleus; (c) the bed nucleus of the stria terminalis (BnST) (, J. Hirnforsch. 27, 559-566;, J. Neuroendcrinol. 5, 281-288;, Cell Tiss. Res. 287, 69-77;, J. Comp. Neurol. 369, 141-157). The BnST which influences reproduction and sexual behavior shows sex differences in morphology, steroid responsiveness and synthesis of neuropeptides including AVT (, Brain Res. 657, 171-184). AVT is the main endocrine regulator of fluid balance in avian species and, in addition, is involved in oviposition in these species. Our recent studies clearly demonstrated that AVT secretion after osmotic stimulation is sexually dimorphic. In order to investigate whether AVT is expressed and synthesized in the BnST in a sexually dimorphic manner we have used in situ hybridization technique and immunocytochemistry to analyze AVT gene expressing neurons in the parvocellular (small-celled nulei) BnST of adult male and female chickens. In cocks, AVT peptide-containing neurons were detected in the parvocellular BnST and the lateral septal area, whereas no AVT immunoreactive neurons were detected in the corresponding regions of the hen. Even after osmotic stimulation AVT gene expression in neurons of the parvocellular BnST of hens was not upregulated (, Cell Tiss. Res. 287, 69-77). These results demonstrate: (a) AVT gene expression in the BnST of chickens; and (b) a strong sexual dimorphism in this region. Furthermore, AVT synthesis is regulated on the transcriptional level independent from osmotic stimuli. Thus, sex steroids might be the main regulator of AVT gene expression in the Bn

  2. Effects of neural androgen receptor disruption on aggressive behavior, arginine vasopressin and galanin systems in the bed nucleus of stria terminalis and lateral septum.

    PubMed

    Marie-Luce, Clarisse; Raskin, Kalina; Bolborea, Matei; Monin, Marion; Picot, Marie; Mhaouty-Kodja, Sakina

    2013-07-01

    In the present study, we investigated the role of the androgen receptor (AR) in the nervous system in the regulation of aggressive behavior and arginine vasopressin and galanin systems by testosterone. For this purpose, we used a conditional mouse line selectively lacking AR gene in the nervous system, backcrossed onto the C57BL/6J strain. Adult males were gonadectomized and supplemented with similar amounts of testosterone. When tested on two consecutive days in the resident intruder paradigm, fewer males of the mutant group exhibited aggressive behavior compared to their control littermates. In addition, a high latency to the first offensive attack was observed for the few animals that exhibited fighting behavior. This alteration was associated with a normal anogenital chemoinvestigation of intruder males. In olfactory discrimination tasks, sexual experience enhanced preference towards female-soiled bedding rather than male-soiled bedding and estrus females rather than intact males, regardless of genotype. This indicated that the behavioral alteration induced by neural AR mutation occurs in brain areas located downstream from the olfactory bulb. Quantification of the sexually dimorphic cell populations expressing preprovasopressin and galanin mRNAs in the bed nucleus of stria terminalis (BNST) and vasopressin-neurophysin 2 and galanin immunoreactivity in the lateral septum showed no significant differences between the two genotypes. The present findings indicate that the neural AR is required in the expression of aggressive behavior but not in the sexual differentiation of AVP and galanin cell number in the BNST and fiber immunoreactivity in the lateral septum. They also suggest that AR in the nervous system could mediate activational effects of testosterone in the regulation of aggressive behavior during adulthood. PMID:23583766

  3. CRF1 and CRF2 receptors in the bed nucleus of the stria terminalis modulate the cardiovascular responses to acute restraint stress in rats.

    PubMed

    Oliveira, Leandro A; Almeida, Jeferson; Benini, Ricardo; Crestani, Carlos C

    2015-01-01

    The corticotropin-releasing factor (CRF) is involved in behavioral and physiological responses to emotional stress through its action in several limbic structures, including the bed nucleus of the stria terminalis (BNST). Nevertheless, the role of CRF1 and CRF2 receptors in the BNST in cardiovascular adjustments during aversive threat is unknown. Therefore, in the present study we investigated the involvement of CRF receptors within the BNST in cardiovascular responses evoked by acute restraint stress in rats. For this, we evaluated the effects of bilateral treatment of the BNST with selective agonists and antagonists of either CRF1 or CRF2 receptors in the arterial pressure and heart rate increase and the decrease in tail skin temperature induced by restraint stress. Microinjection of the selective CRF1 receptor antagonist CP376395 into the BNST reduced the pressor and tachycardiac responses caused by restraint. Conversely, BNST treatment with the selective CRF1 receptor agonist CRF increased restraint-evoked arterial pressure and HR responses and reduced the fall in tail skin temperature response. All effects of CRF were inhibited by local BNST pretreatment with CP376395. The selective CRF2 receptor antagonist antisalvagine-30 reduced the arterial pressure increase and the fall in tail skin temperature. The selective CRF2 receptor agonist urocortin-3 increased restraint-evoked pressor and tachycardiac responses and reduced the drop in cutaneous temperature. All effects of urocortin-3 were abolished by local BNST pretreatment with antisalvagine-30. These findings indicate an involvement of both CRF1 and CRF2 receptors in the BNST in cardiovascular adjustments during emotional stress. PMID:25829333

  4. Reversible Inactivation of the Bed Nucleus of the Stria Terminalis Prevents Reinstatement But Not Renewal of Extinguished Fear1,2,3

    PubMed Central

    Goode, Travis D.; Kim, Janice J.

    2015-01-01

    Abstract The extinction of conditioned fear is labile. For example, fear to an extinguished conditioned stimulus (CS) returns after presentation of an aversive stimulus (“reinstatement”) or a change in context (“renewal”). Substantial research implicates the bed nucleus of the stria terminalis (BNST) in the stress-induced relapse of extinguished behaviors, such as in instrumental drug seeking, but its role in the relapse of extinguished fear responses is not clear. Here, we explored the role of the BNST in both the reinstatement and renewal of fear, two forms of relapse that are differentially triggered by stress. In Experiment 1, rats received pairings of an auditory CS and footshock unconditioned stimulus (US) followed by an extinction procedure. After extinction, rats received an unsignaled US to reinstate fear to the extinguished CS. Twenty-four hours later, they were infused with either muscimol or vehicle into the BNST immediately prior to a CS retrieval test. In Experiment 2, rats were conditioned and extinguished in two distinct contexts. Twenty-four hours after extinction, the rats were infused with muscimol, NBQX, or vehicle immediately prior to a CS retrieval test in either the extinction context or a different (but familiar) context. In both experiments, freezing behavior served as the index of conditioned fear. The results revealed that BNST inactivation prevented reinstatement (Experiment 1), but not renewal (Experiment 2), of conditioned freezing to the extinguished CS. Hence, the BNST is critical for the reinstatement of extinguished fear in an aversive context, but not for the contextual retrieval processes that mediate fear renewal. PMID:26464990

  5. Sex chromosome complement determines sex differences in aromatase expression and regulation in the stria terminalis and anterior amygdala of the developing mouse brain.

    PubMed

    Cisternas, Carla D; Tome, Karina; Caeiro, Ximena E; Dadam, Florencia M; Garcia-Segura, Luis M; Cambiasso, María J

    2015-10-15

    Aromatase, which converts testosterone in estradiol, is involved in the generation of brain sex dimorphisms. Here we used the "four core genotypes" mouse model, in which the effect of gonadal sex and sex chromosome complement is dissociated, to determine if sex chromosomes influence the expression of brain aromatase. The brain of 16 days old XY mouse embryos showed higher aromatase expression in the stria terminalis and the anterior amygdaloid area than the brain of XX embryos, independent of gonadal sex. Furthermore, estradiol or dihydrotestosterone increased aromatase expression in cultures of anterior amygdala neurons derived from XX embryos, but not in those derived from XY embryos. This effect was also independent of gonadal sex. The expression of other steroidogenic molecules, estrogen receptor-α and androgen receptor was not influenced by sex chromosomes. In conclusion, sex chromosomes determine sex dimorphisms in aromatase expression and regulation in the developing mouse brain. PMID:26231585

  6. Activation of corticotropin releasing factor-containing neurons in the rat central amygdala and bed nucleus of the stria terminalis following exposure to two different anxiogenic stressors.

    PubMed

    Butler, Ryan K; Oliver, Elisabeth M; Sharko, Amanda C; Parilla-Carrero, Jeffrey; Kaigler, Kris F; Fadel, Jim R; Wilson, Marlene A

    2016-05-01

    Rats exposed to the odor of a predator or to the elevated plus maze (EPM) express unique unconditioned fear behaviors. The extended amygdala has previously been demonstrated to mediate the response to both predator odor and the EPM. We seek to determine if divergent amygdalar microcircuits are associated with the different behavioral responses. The current experiments compared activation of corticotropin-releasing factor (CRF)-containing neuronal populations in the central amygdala and bed nucleus of the stria terminalis (BNST) of rats exposed to either the EPM (5 min) versus home cage controls, or predator (ferret) odor versus butyric acid, or no odor (30 min). Sections of the brains were prepared for dual-labeled immunohistochemistry and counts of c-Fos co-localized with CRF were made in the centrolateral and centromedial amygdala (CLA and CMA) as well as the dorsolateral (dl), dorsomedial (dm), and ventral (v) BNST. Ferret odor-exposed rats displayed an increase in duration and a decrease in latency of defensive burying versus control rats. Exposure to both predator stress and EPM induced neuronal activation in the BNST, but not the central amygdala, and similar levels of neuronal activation were seen in both the high and low anxiety groups in the BNST after EPM exposure. Dual-labeled immunohistochemistry showed a significant increase in the percentage of CRF/c-Fos co-localization in the vBNST of ferret odor-exposed rats compared to control and butyric acid-exposed groups as well as EPM-exposed rats compared to home cage controls. In addition, an increase in the percentage of CRF-containing neurons co-localized with c-Fos was observed in the dmBNST after EPM exposure. No changes in co-localization of CRF with c-Fos was observed with these treatments in either the CLA or CMA. These results suggest that predator odor and EPM exposure activates CRF neurons in the BNST to a much greater extent than CRF neurons of the central amygdala, and indicates unconditioned

  7. The bed nucleus of the stria terminalis has developmental and adult forms in mice, with the male bias in the developmental form being dependent on testicular AMH.

    PubMed

    Wittmann, Walter; McLennan, Ian S

    2013-09-01

    Canonically, the sexual dimorphism in the brain develops perinatally, with adult sexuality emerging due to the activating effects of pubescent sexual hormones. This concept does not readily explain why children have a gender identity and exhibit sex-stereotypic behaviours. These phenomena could be explained if some aspects of the sexual brain networks have childhood forms, which are transformed at puberty to generate adult sexuality. The bed nucleus of stria terminalis (BNST) is a dimorphic nucleus that is sex-reversed in transsexuals but not homosexuals. We report here that the principal nucleus of the BNST (BNSTp) of mice has developmental and adult forms that are differentially regulated. In 20-day-old prepubescent mice, the male bias in the principal nucleus of the BNST (BNSTp) was moderate (360 ± 6 vs 288 ± 12 calbindin(+ve) neurons, p < 0.0001), and absent in mice that lacked a gonadal hormone, AMH. After 20 days, the number of BNSTp neurons increased in the male mice by 25% (p < 0.0001) and decreased in female mice by 15% (p = 0.0012), independent of AMH. Adult male AMH-deficient mice had a normal preference for sniffing female pheromones (soiled bedding), but exhibited a relative disinterest in both male and female pheromones. This suggests that male mice require AMH to undergo normal social development. The reported observations provide a rationale for examining AMH levels in children with gender identity disorders and disorders of socialization that involve a male bias. PMID:24012942

  8. Corticotropin releasing factor type-1 receptor antagonism in the dorsolateral bed nucleus of the stria terminalis disrupts contextually conditioned fear, but not unconditioned fear to a predator odor.

    PubMed

    Asok, Arun; Schulkin, Jay; Rosen, Jeffrey B

    2016-08-01

    The bed nucleus of the stria terminalis (BNST) plays a critical role in fear and anxiety. The BNST is important for contextual fear learning, but the mechanisms regulating this function remain unclear. One candidate mechanism is corticotropin-releasing-factor (CRF) acting at CRF type 1 receptors (CRFr1s). Yet, there has been little progress in elucidating if CRFr1s in the BNST are involved in different types of fear (conditioned and/or unconditioned). Therefore, the present study investigated the effect of antalarmin, a potent CRFr1 receptor antagonist, injected intracerebroventricularly (ICV) and into the dorsolateral BNST (LBNST) during single trial contextual fear conditioning or exposure to the predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT). Neither ICV nor LBNST antalarmin disrupted unconditioned freezing to TMT. In contrast, ICV and LBNST antalarmin disrupted the retention of contextual fear when tested 24h later. Neither ICV nor LBNST antalarmin affected baseline or post-shock freezing-indicating antalarmin does not interfere with the early phases of contextual fear acquisition. Antalarmin did not (1) permanently affect the ability to learn and express contextual fear, (2) change responsivity to footshocks, or (3) affect the ability to freeze. Our findings highlight an important role for CRFr1s within the LBNST during contextually conditioned fear, but not unconditioned predator odor fear. PMID:27153520

  9. Cardiovascular and single-unit responses to microinjection of angiotensin II into the bed nucleus of the stria terminalis in rat.

    PubMed

    Kafami, M; Nasimi, A

    2015-08-01

    The bed nucleus of the stria terminalis (BST) is part of the limbic system located in the rostral forebrain. BST is involved in behavioral, neuroendocrine and autonomic functions, including cardiovascular regulation. The angiotensin II (Ang II) receptor, AT1, was found in the BST, however its effects on the cardiovascular system and on single-unit responses have not been studied yet. In the present study, Ang II was microinjected into the BST of anesthetized rats and cardiovascular and single-unit responses were recorded simultaneously. Furthermore the responses were re-tested after the microinjection of a blocker of the AT1 receptor, losartan, into the BST. We found that microinjection of Ang II into the BST produced a pressor response of 11±1mmHg for a duration of 2-8min. Ang II had no consistent effect on heart rate. It also produced two types of single-unit responses in the BST, short excitatory and long inhibitory. Blockade of AT1 receptors abolished both the cardiovascular and single-unit responses, indicating that the responses were mediated through AT1 receptors. These findings imply that Ang II may be utilized as a neurotransmitter and may play a role in returning blood pressure toward normal during hypotension. PMID:26026681

  10. Vasopressin and sympathetic system mediate the cardiovascular effects of the angiotensin II in the bed nucleus of the stria terminalis in rat.

    PubMed

    Nasimi, Ali; Kafami, Marzieh

    2016-07-01

    The bed nucleus of the stria terminalis (BST) is involved in cardiovascular regulation. The angiotensin II (Ang II) receptor (AT1), and angiotensinogen were found in the BST. In our previous study we found that microinjection of Ang II into the BST produced a pressor response. This study was performed to find the mechanisms mediating this response in anesthetized rats. Ang II was microinjected into the BST and the cardiovascular responses were re-tested after systemic injection of a blocker of autonomic or vasopressin V1 receptor. The ganglionic nicotinic receptor blocker, hexamethonium dichloride, attenuated the pressor response to Ang II, indicating that the cardiovascular sympathetic system is involved in the pressor effect of Ang II. A selective vasopressin V1 receptor antagonist greatly attenuated the pressor effect of Ang II, indicating that the Ang II increases the arterial pressure via stimulation of vasopressin release as well. In conclusion, in the BST, Ang II as a neurotransmitter increases blood pressure by exciting cardiovascular sympathetic system and directly or indirectly causing vasopressin to release into bloodstream by VPN. This is an interesting new finding that not only circulating Ang II but also brain Ang II makes vasopressin release. PMID:26820216

  11. Central stress-integrative circuits: Forebrain glutamatergic and GABAergic projections to the dorsomedial hypothalamus, medial preoptic area, and bed nucleus of the stria terminalis

    PubMed Central

    Myers, Brent; Dolgas, C. Mark; Kasckow, John; Cullinan, William E.; Herman, James P.

    2013-01-01

    Central regulation of hypothalamo-pituitary-adrenocortical (HPA) axis stress responses is mediated by a relatively circumscribed group of projections to the paraventricular hypothalamus (PVN). The dorsomedial hypothalamus (DMH), medial preoptic area (mPOA), and bed nucleus of the stria terminalis (BST) provide direct, predominantly inhibitory, innervation of the PVN. These PVN-projecting neurons are controlled by descending information from limbic forebrain structures, including the prefrontal cortex, amygdala, hippocampus, and septum. The neurochemical phenotype of limbic circuits targeting PVN relays has not been systematically analyzed. The current study combined retrograde tracing and immunohistochemistry/in situ hybridization to identify the specific sites of glutamatergic and GABAergic inputs to the DMH, mPOA, and BST. Following Flouro-Gold (FG) injections in the DMH, retrogradely-labeled cells co-localized with vesicular glutamate transporter mRNA in the prefrontal cortex, ventral hippocampus, and paraventricular thalamus. Co-localization of FG and glutamic acid decarboxylase mRNA was present throughout the central and medial amygdaloid nuclei and septal area. Additionally, the mPOA received predominantly GABAergic input from the septum, amygdala, and BST. The BST received glutamatergic projections from the hippocampus and basomedial amygdala, whereas GABAergic inputs arose from central and medial amygdaloid nuclei. Thus, discrete sets of neurons in the hypothalamus and BST are positioned to summate limbic inputs into PVN regulation and may play a role in HPA dysfunction and stress-related illness. PMID:23661182

  12. Projections from Bed Nuclei of the Stria Terminalis, Magnocellular Nucleus: Implications for Cerebral Hemisphere Regulation of Micturition, Defecation, and Penile Erection

    PubMed Central

    DONG, HONG-WEI; SWANSON, LARRY W.

    2008-01-01

    The basic structural organization of axonal projections from the small but distinct magnocellular and ventral nuclei (of the bed nuclei of the stria terminalis) were analyzed with the PHAL anterograde tract tracing method in adult male rats. The former's overall projection pattern is complex, with over 80 distinct terminal fields ipsilateral to injection sites. Innervated regions in the cerebral hemisphere and brainstem fall into 9 general functional categories: cerebral nuclei, behavior control column, orofacial motor-related, humorosensory/thirst-related, brainstem autonomic control network, neuroendocrine, hypothalamic visceromotor pattern generator network, thalamocortical feedback loops, and behavioral state control. The most novel findings indicate that the magnocellular nucleus projects to virtually all known major parts of the brain network that controls pelvic functions including micturition, defecation, and penile erection—as well as to brain networks controlling nutrient and body water homeostasis. This and other evidence suggests that the magnocellular nucleus is part of a cortico-striatopallidal differentiation modulating and coordinating pelvic functions with the maintenance of nutrient and body water homeostasis. Projections of the ventral nucleus are a subset of those generated by the magnocellular nucleus, with the obvious difference that the ventral nucleus does not project detectably to Barrington's nucleus, the subfornical organ, the median preoptic and parastrial nuclei, the neuroendocrine system, and midbrain orofacial motor-related regions. PMID:16304682

  13. The effect of angiotensin II microinjection into the bed nucleus of the stria terminalis on serum lipid peroxidation and nitric oxide metabolite levels

    PubMed Central

    Kafami, Marzieh

    2016-01-01

    Background: Overactivity of renin-angiotensin system is involved in the pathophysiology of renal and cardiovascular diseases. It is suggested that endothelial cells can release nitric oxide (NO) and reactive oxygen species in response to angiotensin II (Ang II). Angiotensin type 1 (AT1) receptor of Ang II has been found in the bed nucleus of the stria terminalis (BST). BST is involved in autonomic function. This study was performed to find the role of central Ang II in serum lipid peroxidation product and in releasing NO into circulation. Materials and Methods: Twenty-one catheterized rats were placed in stereotaxic instrument. A hole was drilled above BST. In the control group, saline 0.9% (100 nl) was microinjected into the BST. In the second group, Ang II (100 μM, 100–150 nl) was microinjected into the BST. In the third group losartan (an AT1 antagonist) was microinjected (100 μM, 200 nl) before Ang II into the BST. Systolic blood pressure was recorded. The NO metabolite (nitrite) and malondialdehyde (MDA) were measured in the rat's serum. Results: The data indicated that microinjection of Ang II into the BST produced a pressor response (P < 0.0001). It also increased MDA and nitrite levels of the serum significantly (P < 0.001, P < 0.0001). Pretreatment with losartan before Ang II microinjection attenuated serum's levels of MDA and nitrite (P < 0.001, P < 0.0001). Conclusion: Our findings suggest that central effect of Ang II on blood pressure is accompanied with increased levels of MDA and nitrite in the circulation. PMID:27376045

  14. A Switch in the Neuromodulatory Effects of Dopamine in the Oval Bed Nucleus of the Stria Terminalis Associated with Cocaine Self-Administration in Rats

    PubMed Central

    Krawczyk, Michal; Sharma, Robyn; Mason, Xenos; DeBacker, Julian; Jones, Andrea A.; Dumont, Éric C.

    2014-01-01

    Chronic exposure to drugs of abuse alters brain reward circuits and produces functional changes in the dopamine (DA) system. However, it is not known whether these changes are directly related to drug-driven behaviors or whether they simply are adaptive responses to long-term drug exposure. Here, we combined the rat model of cocaine self-administration with brain slice electrophysiology to identify drug-use related alterations in the neuromodulatory effects of DA in the oval bed nucleus of the stria terminalis (ovBST), a robust DA terminal field. Long–Evans rats self-administered cocaine intravenously (0.75 mg/kg/injection) for an average of 15 d, on reward-lean or -rich schedules of reinforcement. Brain slice recordings conducted 20 h after the last self-administration session revealed a reversal of the neuromodulatory effect of DA on GABAA-IPSCs. Specifically, the effect of DA switched from a D2-mediated decrease in drug-naive rats to a D1-receptor-mediated increase in GABAA-IPSC in cocaine self-administering rats. Furthermore, the switch in DA modulation of GABAA-IPSC remained after a 30 d withdrawal period. In contrast, this switch was not observed after the acquisition phase of cocaine self-administration, when rats received cocaine passively, or in rats maintaining sucrose self-administration. Therefore, our study reveals a reversal in the effects of DA on inhibitory transmission, from reduction to enhancement, in the ovBST of cocaine self-administering rats. This change was unique to voluntary intake of cocaine and maintained after a withdrawal period, suggesting a mechanism underlying the maintenance of cocaine self-administration and perhaps craving during drug-free periods. PMID:21677176

  15. Noradrenergic alpha-2 receptor modulators in the ventral bed nucleus of the stria terminalis – effects on anxiety behavior in postpartum and virgin female rats

    PubMed Central

    Smith, Carl D.; Piasecki, Christopher C.; Weera, Marcus; Olszewicz, Joshua; Lonstein, Joseph S.

    2014-01-01

    Emotional hyper-reactivity can inhibit maternal responsiveness in female rats and other animals. Maternal behavior in postpartum rats is disrupted by increasing norepinephrine release in the ventral bed nucleus of the stria terminalis (BSTv) with the α2-autoreceptor antagonist, yohimbine, or the more selective α2-autoreceptor antagonist, idazoxan (Smith et al., 2012). Because high noradrenergic activity in the BSTv can also increase anxiety-related behaviors, increased anxiety may underlie the disrupted mothering of dams given yohimbine or idazoxan. To assess this possibility, anxiety-related behaviors in an elevated plus maze were assessed in postpartum rats after administration of yohimbine or idazoxan. It was further assessed if the α2-autoreceptor agonist clonidine (which decreases norepinephrine release) would, conversely, reduce dams’ anxiety. Groups of diestrous virgins were also examined. It was found that peripheral or intra-BSTv yohimbine did increase anxiety-related behavior in postpartum females. However, BSTv infusion of idazoxan did not reproduce yohimbine’s anxiogenic effects and anxiety was not reduced by peripheral or intra-BSTv clonidine. Because yohimbine is a weak 5HT1A receptor agonist, other groups of females received BSTv infusion of the 5HT1A receptor agonist 8OH-DPAT, but it did not alter their anxiety-related behavior. Lastly, levels of norepinephrine and serotonin in tissue punches from the BSTv did not differ between postpartum and diestrous rats, but serotonin turnover was lower in mothers. These results suggest that the impaired maternal behavior after BSTv infusion of yohimbine or idazoxan cannot both be readily explained by an increase in dams’ anxiety, and that BSTv α2-autoreceptor modulation alone has little influence anxiety-related behaviors in postpartum or diestrous rats. PMID:23796237

  16. A switch in the neuromodulatory effects of dopamine in the oval bed nucleus of the stria terminalis associated with cocaine self-administration in rats.

    PubMed

    Krawczyk, Michal; Sharma, Robyn; Mason, Xenos; Debacker, Julian; Jones, Andrea A; Dumont, Eric C

    2011-06-15

    Chronic exposure to drugs of abuse alters brain reward circuits and produces functional changes in the dopamine (DA) system. However, it is not known whether these changes are directly related to drug-driven behaviors or whether they simply are adaptive responses to long-term drug exposure. Here, we combined the rat model of cocaine self-administration with brain slice electrophysiology to identify drug-use related alterations in the neuromodulatory effects of DA in the oval bed nucleus of the stria terminalis (ovBST), a robust DA terminal field. Long-Evans rats self-administered cocaine intravenously (0.75 mg/kg/injection) for an average of 15 d, on reward-lean or -rich schedules of reinforcement. Brain slice recordings conducted 20 h after the last self-administration session revealed a reversal of the neuromodulatory effect of DA on GABA(A)-IPSCs. Specifically, the effect of DA switched from a D2-mediated decrease in drug-naive rats to a D1-receptor-mediated increase in GABA(A)-IPSC in cocaine self-administering rats. Furthermore, the switch in DA modulation of GABA(A)-IPSC remained after a 30 d withdrawal period. In contrast, this switch was not observed after the acquisition phase of cocaine self-administration, when rats received cocaine passively, or in rats maintaining sucrose self-administration. Therefore, our study reveals a reversal in the effects of DA on inhibitory transmission, from reduction to enhancement, in the ovBST of cocaine self-administering rats. This change was unique to voluntary intake of cocaine and maintained after a withdrawal period, suggesting a mechanism underlying the maintenance of cocaine self-administration and perhaps craving during drug-free periods. PMID:21677176

  17. GABAergic neurons in the ventral tegmental area receive dual GABA/enkephalin-mediated inhibitory inputs from the bed nucleus of the stria terminalis.

    PubMed

    Kudo, Takehiro; Konno, Kohtarou; Uchigashima, Motokazu; Yanagawa, Yuchio; Sora, Ichiro; Minami, Masabumi; Watanabe, Masahiko

    2014-06-01

    Activation of mu-opioid receptor (MOR) disinhibits dopaminergic neurons in the ventral tegmental area (VTA) through inhibition of γ-aminobutyric acid (GABA)ergic neurons. This mechanism is thought to play a pivotal role in mediating reward behaviors. Here, we characterised VTA-projecting enkephalinergic neurons in the anterior division of the bed nucleus of the stria terminalis (BST) and investigated their targets by examining MOR expression in the VTA. In the BST, neurons expressing preproenkephalin mRNA were exclusively GABAergic, and constituted 37.2% of the total GABAergic neurons. Using retrograde tracer injected into the VTA, 21.6% of VTA-projecting BST neurons were shown to express preproenkephalin mRNA. Enkephalinergic projections from the BST exclusively formed symmetrical synapses onto the dendrites of VTA neurons. In the VTA, 74.1% of MOR mRNA-expressing neurons were GABAergic, with the rest being glutamatergic neurons expressing type-2 vesicular glutamate transporter mRNA. However, MOR mRNA was below the detection threshold in dopaminergic neurons. By immunohistochemistry, MOR was highly expressed on the extrasynaptic membranes of dendrites in GABAergic VTA neurons, including dendrites innervated by BST-VTA projection terminals. MOR was also expressed weakly on GABAergic and glutamatergic terminals in the VTA. Given that GABAA α1 is expressed at GABAergic BST-VTA synapses on dendrites of GABAergic neurons [T. Kudo et al. (2012) J. Neurosci., 32, 18035-18046], our results collectively indicate that the BST sends dual inhibitory outputs targeting GABAergic VTA neurons; GABAergic inhibition via 'wired' transmission, and enkephalinergic inhibition via 'volume' transmission. This dual inhibitory system provides the neural substrate underlying the potent disinhibitory control over dopaminergic VTA neurons exerted by the BST. PMID:24580812

  18. GluN2B-containing NMDA receptors blockade rescues bidirectional synaptic plasticity in the bed nucleus of the stria terminalis of cocaine self-administering rats.

    PubMed

    deBacker, Julian; Hawken, Emily R; Normandeau, Catherine P; Jones, Andrea A; Di Prospero, Cynthia; Mechefske, Elysia; Gardner Gregory, James; Hayton, Scott J; Dumont, Éric C

    2015-01-01

    Drugs of abuse have detrimental effects on homeostatic synaptic plasticity in the motivational brain network. Bidirectional plasticity at excitatory synapses helps keep neural circuits within a functional range to allow for behavioral flexibility. Therefore, impaired bidirectional plasticity of excitatory synapses may contribute to the behavioral hallmarks of addiction, yet this relationship remains unclear. Here we tracked excitatory synaptic strength in the oval bed nucleus of the stria terminalis (ovBNST) using whole-cell voltage-clamp recordings in brain slices from rats self-administering sucrose or cocaine. In the cocaine group, we measured both a persistent increase in AMPA to NMDA ratio (A:N) and slow decay time of NMDA currents throughout the self-administration period and after withdrawal from cocaine. In contrast, the sucrose group exhibited an early increase in A:N ratios (acquisition) that returned toward baseline values with continued self-administration (maintenance) and after withdrawal. The sucrose rats also displayed a decrease in NMDA current decay time with continued self-administration (maintenance), which normalized after withdrawal. Cocaine self-administering rats exhibited impairment in NMDA-dependent long-term depression (LTD) that could be rescued by GluN2B-containing NMDA receptor blockade. Sucrose self-administering rats demonstrated no impairment in NMDA-dependent LTD. During the maintenance period of self-administration, in vivo (daily intraperitoneally for 5 days) pharmacologic blockade of GluN2B-containing NMDA receptors did not reduce lever pressing for cocaine. However, in vivo GluN2B blockade did normalize A:N ratios in cocaine self-administrating rats, and dissociated the magnitude of ovBNST A:N ratios from drug-seeking behavior after protracted withdrawal. Altogether, our data demonstrate when and how bidirectional plasticity at ovBNST excitatory synapses becomes dysfunctional with cocaine self-administration and that NMDA

  19. GluN2B-Containing NMDA Receptors Blockade Rescues Bidirectional Synaptic Plasticity in the Bed Nucleus of the Stria Terminalis of Cocaine Self-Administering Rats

    PubMed Central

    deBacker, Julian; Hawken, Emily R; Normandeau, Catherine P; Jones, Andrea A; Di Prospero, Cynthia; Mechefske, Elysia; Gardner Gregory, James; Hayton, Scott J; Dumont, Éric C

    2015-01-01

    Drugs of abuse have detrimental effects on homeostatic synaptic plasticity in the motivational brain network. Bidirectional plasticity at excitatory synapses helps keep neural circuits within a functional range to allow for behavioral flexibility. Therefore, impaired bidirectional plasticity of excitatory synapses may contribute to the behavioral hallmarks of addiction, yet this relationship remains unclear. Here we tracked excitatory synaptic strength in the oval bed nucleus of the stria terminalis (ovBNST) using whole-cell voltage-clamp recordings in brain slices from rats self-administering sucrose or cocaine. In the cocaine group, we measured both a persistent increase in AMPA to NMDA ratio (A:N) and slow decay time of NMDA currents throughout the self-administration period and after withdrawal from cocaine. In contrast, the sucrose group exhibited an early increase in A:N ratios (acquisition) that returned toward baseline values with continued self-administration (maintenance) and after withdrawal. The sucrose rats also displayed a decrease in NMDA current decay time with continued self-administration (maintenance), which normalized after withdrawal. Cocaine self-administering rats exhibited impairment in NMDA-dependent long-term depression (LTD) that could be rescued by GluN2B-containing NMDA receptor blockade. Sucrose self-administering rats demonstrated no impairment in NMDA-dependent LTD. During the maintenance period of self-administration, in vivo (daily intraperitoneally for 5 days) pharmacologic blockade of GluN2B-containing NMDA receptors did not reduce lever pressing for cocaine. However, in vivo GluN2B blockade did normalize A:N ratios in cocaine self-administrating rats, and dissociated the magnitude of ovBNST A:N ratios from drug-seeking behavior after protracted withdrawal. Altogether, our data demonstrate when and how bidirectional plasticity at ovBNST excitatory synapses becomes dysfunctional with cocaine self-administration and that NMDA

  20. DISTRIBUTION OF CATECHOLAMINERGIC AND PEPTIDERGIC CELLS IN THE GERBIL MEDIAL AMYGADALA, CAUDAL PREOPTIC AREA AND CAUDAL BED NUCLEI OF THE STRIA TERMINALIS WITH A FOCUS ON AREAS ACTIVATED AT EJACULATION

    PubMed Central

    Simmons, Danielle A.; Yahr, Pauline

    2010-01-01

    The posterodorsal preoptic nucleus (PdPN), lateral part of the posterodorsal medial amygdala (MeApd) and medial part of the medial preoptic nucleus (MPNm) are activated at ejaculation in male gerbils as assessed by Fos expression. We sought to immunocytochemically visualize substance P (SP), cholecystokinin (CCK), oxytocin, vasopressin and tyrosine hydroxylase (TH), a catecholaminergic marker, in the mating-activated cells, but the need for colchicine precluded behavioral testing. Instead, we detailed distributions of cells containing these molecules in the medial amygdala, caudal preoptic area and caudal bed nuclei of the stria terminalis (BST) and quantified their densities in the PdPN, MPNm and lateral MeApd for comparison to densities previously assessed for mating-activated efferents from these sites. TH cells were as dense in the PdPN and lateral MeApd as activated efferents to the anteroventral periventricular nucleus. In the lateral MeApd, TH cells were grouped where cells activated at ejaculation are clustered and where CCK cells form a ball. Lateral MeApd CCK cells and PdPN SP cells were as dense as activated efferents to the principal BST. Oxytocinergic PdPN cells and SP cells in the MPNm were as dense as mating-activated efferents to the lateral MeApd. If some oxytocin cells in the PdPN project to the neurohypophysis, as in rats, they could be a source of the oxytocin secreted at ejaculation. Since gerbils are monogamous and biparental, it was also interesting that, unlike monogamous prairie voles, they had few TH cells in the MeApd or dorsal BST, resembling promiscuous rats, hamsters and meadow voles. PMID:21087661

  1. A circadian rhythm in the expression of PERIOD2 protein reveals a novel SCN-controlled oscillator in the oval nucleus of the bed nucleus of the stria terminalis.

    PubMed

    Amir, Shimon; Lamont, Elaine Waddington; Robinson, Barry; Stewart, Jane

    2004-01-28

    Circadian rhythms in mammals are regulated not only globally by the master clock in the suprachiasmatic nucleus (SCN), but also locally by widely distributed populations of clock cells in the brain and periphery that control tissue-specific rhythmic outputs. Here we show that the oval nucleus of the bed nucleus of the stria terminalis (BNST-OV) exhibits a robust circadian rhythm in expression of the Period2 (PER2) clock protein. PER2 expression is rhythmic in the BNST-OV in rats housed under a light/dark cycle or in constant darkness, in blind rats, and in mice, and is in perfect synchrony with the PER2 rhythm of the SCN. Constant light or bilateral SCN lesions abolish the rhythm of PER2 in the BNST-OV. Large abrupt shifts in the light schedule transiently uncouple the BNST-OV rhythm from that of the SCN. Re-entrainment of the PER2 rhythm is faster in the SCN than in the BNST-OV, and it is faster after a delay than an advance shift. Bilateral adrenalectomy blunts the PER2 rhythm in the BNST-OV. Thus, the BNST-OV contains circadian clock cells that normally oscillate in synchrony with the SCN, but these cells appear to require both input from the SCN and circulating glucocorticoids to maintain their circadian oscillation. Taken together with what is known about the functional organization of the connections of the BNST-OV with systems of the brain involved in stress and motivational processes, these findings place BNST-OV oscillators in a position to influence specific physiological and behavioral rhythms downstream from the SCN clock. PMID:14749422

  2. Distribution of catecholaminergic and peptidergic cells in the gerbil medial amygdala, caudal preoptic area and caudal bed nuclei of the stria terminalis with a focus on areas activated at ejaculation.

    PubMed

    Simmons, Danielle A; Yahr, Pauline

    2011-01-01

    The posterodorsal preoptic nucleus (PdPN), lateral part of the posterodorsal medial amygdala (MeApd) and medial part of the medial preoptic nucleus (MPNm) are activated at ejaculation in male gerbils as assessed by Fos expression. We sought to immunocytochemically visualize substance P (SP), cholecystokinin (CCK), oxytocin, vasopressin and tyrosine hydroxylase (TH), a catecholaminergic marker, in the mating-activated cells, but the need for colchicine precluded behavioral testing. Instead, we detailed distributions of cells containing these molecules in the medial amygdala, caudal preoptic area and caudal bed nuclei of the stria terminalis (BST) and quantified their densities in the PdPN, MPNm and lateral MeApd for comparison to densities previously assessed for mating-activated efferents from these sites. TH cells were as dense in the PdPN and lateral MeApd as activated efferents to the anteroventral periventricular nucleus. In the lateral MeApd, TH cells were grouped where cells activated at ejaculation are clustered and where CCK cells form a ball. Lateral MeApd CCK cells and PdPN SP cells were as dense as activated efferents to the principal BST. Oxytocinergic PdPN cells and SP cells in the MPNm were as dense as mating-activated efferents to the lateral MeApd. If some oxytocin cells in the PdPN project to the neurohypophysis, as in rats, they could be a source of the oxytocin secreted at ejaculation. Since gerbils are monogamous and biparental, it was also interesting that, unlike monogamous prairie voles, they had few TH cells in the MeApd or dorsal BST, resembling promiscuous rats, hamsters and meadow voles. PMID:21087661

  3. Appetitive and consummatory sexual and agonistic behaviour elicits FOS expression in aromatase and vasotocin neurones within the preoptic area and bed nucleus of the stria terminalis of male domestic chickens.

    PubMed

    Xie, J; Kuenzel, W J; Sharp, P J; Jurkevich, A

    2011-03-01

    Some components of male sexual and agonistic behaviours are considered to be regulated by the same neurocircuitry in the medial preoptic nucleus (POM) and the medial portion of bed nucleus of the stria terminalis (BSTM). To better understand this neurocircuitry, numbers of aromatase- (ARO) or arginine vasotocin- (AVT) immunoreactive (ir) neurones expressing immediate early gene protein FOS were compared in the POM and BSTM of male chickens following sexual or agonistic behaviours. Observations were made on males showing: (i) appetitive (courtship) and consummatory (copulation) sexual behaviours; (ii) only appetitive sexual behaviour, or (iii) displaying agonistic behaviour toward other males. Control males were placed on their own in the observation pen, or only handled. In the POM, appetitive sexual behaviour increased ARO+FOS colocalisation, whereas agonistic behaviour decreased the number of visible ARO-ir cells. In the dorsolateral subdivision of BSTM (BSTM1), appetitive sexual behaviour also increased ARO+FOS colocalisation, although the numbers of visible ARO-ir and AVT-ir cells were not altered by sexual or agonistic behaviours. In the ventromedial BSTM (BSTM2), appetitive sexual behaviour increased ARO+FOS and AVT+FOS colocalisation, and all behaviours decreased the number of visible ARO-ir cells, particularly in males expressing consummatory sexual behaviour. Positive correlations were found between numbers of cells with ARO+FOS and AVT+FOS colocalisation in both subdivisions of the BSTM. Waltzing frequency was positively correlated with ARO+FOS colocalisation in the lateral POM, and in both subdivisions of the BSTM in males expressing sexual behaviour. Waltzing frequency in males expressing agonistic behaviour was negatively correlated with the total number of visible ARO-ir cells in the lateral POM and BSTM2. These observations suggest a key role for ARO and AVT neurones in BSTM2 in the expression of appetitive sexual behaviour, and differential roles

  4. Regional brain c-fos activation associated with penile erection and other symptoms induced by the spider toxin Tx2-6.

    PubMed

    Troncone, Lanfranco R P; Ravelli, Katherine G; Magnoli, Fabio C; Lebrun, Ivo; Hipolide, Debora C; Raymond, Roger; Nobrega, José N

    2011-08-01

    Brain areas expressing c-fos messenger RNA were mapped by quantitative in situ hybridization after 1-2 h of intoxication with 10 μg/kg Tx2-6, a toxin obtained from the venom of the spider Phoneutria nigriventer. Relative to saline-treated controls, brains from toxin-treated animals showed pronounced c-fos activation in many brain areas, including the supraoptic nucleus, the paraventricular nucleus of the hypothalamus, the motor nucleus of the vagus, area postrema, paraventricular and paratenial nuclei of the thalamus, locus coeruleus, central amydaloid nucleus and the bed nucleus of the stria terminalis. The paraventricular hypothalamus and the bed nucleus of the stria terminalis have been implicated in erectile function in other studies. A possible role for central NO is considered. Acute stress also activates many brain areas activated by Tx2-6 as well as with NOstimulated Fos transcription. Brain areas that appear to be selectively activated by Tx2-6, include the paratenial and paraventricular thalamic nuclei, the bed nucleus of the stria terminalis and the area postrema and the dorsal motor n. of vagus in the medulla. However, direct injections of different doses of the toxin into the paraventricular hypothalamic n. failed to induce penile erection, arguing against CNS involvement in this particular effect. PMID:21684302

  5. Angiotensin II-Induced Hypertension Is Attenuated by Overexpressing Copper/Zinc Superoxide Dismutase in the Brain Organum Vasculosum of the Lamina Terminalis

    PubMed Central

    Collister, John P.; Taylor-Smith, Heather; Drebes, Donna; Nahey, David; Tian, Jun; Zimmerman, Matthew C.

    2016-01-01

    Angiotensin II (AngII) can access the brain via circumventricular organs (CVOs), including the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), to modulate blood pressure. Previous studies have demonstrated a role for both the SFO and OVLT in the hypertensive response to chronic AngII, yet it is unclear which intracellular signaling pathways are involved in this response. Overexpression of copper/zinc superoxide dismutase (CuZnSOD) in the SFO has been shown to attenuate the chronic hypertensive effects of AngII. Presently, we tested the hypothesis that elevated levels of superoxide (O2∙−) in the OVLT contribute to the hypertensive effects of AngII. To facilitate overexpression of superoxide dismutase, adenoviral vectors encoding human CuZnSOD or control adenovirus (AdEmpty) were injected directly into the OVLT of rats. Following 3 days of control saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Blood pressure increased 33 ± 8 mmHg in AdEmpty rats (n = 6), while rats overexpressing CuZnSOD (n = 8) in the OVLT demonstrated a blood pressure increase of only 18 ± 5 mmHg after 10 days of AngII infusion. These results support the hypothesis that overproduction of O2∙− in the OVLT plays an important role in the development of chronic AngII-dependent hypertension. PMID:26881025

  6. Chronic food restriction and streptozotocin-induced diabetes differentially alter prodynorphin mRNA levels in rat brain regions.

    PubMed

    Berman, Y; Devi, L; Spangler, R; Kreek, M J; Carr, K D

    1997-06-01

    It was previously reported that chronic food restriction and streptozotocin-induced diabetes lead to brain region-specific changes in levels of Prodyn-derived peptides. These changes parallel behavioral adaptations that are reversed by opioid antagonists. In the present study, effects of food restriction and diabetes on Prodyn gene expression were measured in rat brain regions using a quantitative solution hybridization mRNA assay. Picogram amounts of Prodyn mRNA were determined in extracts of five brain regions. The highest density of Prodyn mRNA was observed in extracts of nucleus accumbens (4.68 pg/microg total RNA), bed nucleus of the stria terminalis (4.18 pg/microg), and in caudate nucleus (3.51 pg/microg). Lower levels were observed in the lateral hypothalamus (1.87 pg/microg) and central nucleus of the amygdala (1.22 pg/microg). Food restriction and diabetes both markedly increased the levels of Prodyn mRNA in the central amygdala (163% and 93%, respectively). Levels in the lateral hypothalamus were also increased (35% and 29%, respectively), though only the food-restriction effect was statistically significant. Neither treatment altered prodynorphin mRNA levels in the caudate nucleus, nucleus accumbens or bed nucleus of the stria terminalis. These results suggest that dynorphin neurons in central amygdala and lateral hypothalamus may be involved in behavioral or physiological adaptations to sustained metabolic need. PMID:9191075

  7. Freeze fracturing of the human stria vascularis.

    PubMed

    Bagger-Sjöbäck, D; Engström, B; Steinholtz, L; Hillerdal, M

    1987-01-01

    The stria vascularis is an important functional element in the mammalian cochlea. This special tissue is considered to be the source of the endocochlear potential and thus the driving force for the production of a receptor response to the auditory stimulus. In order to maintain its function, the stria vascularis needs to be separated from the endolymphatic space by a tight seal. This seal is comprised of tight junctions in the marginal cell layer. The junctional arrangement in the stria vascularis is described, utilizing the freeze-fracturing technique which allows the visualization of large expansions of plasma membrane. The marginal cells are generally separated by tight junctions of the moderately tight to tight type. In places, however, even so-called leaky junctions with only a few sealing strands are present. Whereas the intermediate cell layer seems to lack tight junctions, the basal cells are connected by extensive tight junctions more or less covering the entire cell. These junctions seem to form an extremely tight barrier against the spiral ligament. Gap junctions are also present in the tissue. Intermediate cells as well as the basal cells are coupled by gap junctions. In the basal cell layer, gap junctional elements may also be found inside the large tight junctions comprising so-called mixed junctions. PMID:3564929

  8. Upregulated iNOS and oxidative damage to the cochlear stria vascularis due to noise stress.

    PubMed

    Shi, Xiaorui; Nuttall, Alfred L

    2003-03-28

    Our previous work has revealed increased nitric oxide (NO) production in the cochlear perilymph following noise stress. However, it is not clear if the increase of NO is related to iNOS and whether NO-related oxidative stress can cause vascular tissue damage. In this study, iNOS immunoreactivity, NO production, and reactive oxygen species (ROS) in the lateral wall were examined in normal mice and compared with similar animals exposed to 120 dBA broadband noise, 3 h/day, for 2 consecutive days. In the normal animals, iNOS expression was not observed in the vascular endothelium of the stria vascularis and only weak iNOS immunoactivity was detected in the marginal cells. However, expression of iNOS in the wall of the blood vessels of stria vascularis and marginal cells was observed after loud sound stress (LSS). Relatively low levels of NO production and low ROS activity were detected in the stria vascularis in the unstimulated condition. In contrast, NO production was increased and ROS activity was elevated in the stria vascularis after LSS. These changes were attenuated by the iNOS inhibitor, GW 274150. To explore whether noise induces apoptotic processes in the stria vascularis, we examined morphological changes in endothelial- and marginal-cells. In vitro, annexin-V phosphatidylserine (PS) (to label and detect early evidence of apoptosis) was combined with propidium iodide (PI) (to probe plasma membrane integrity). PI alone was used in fixed tissues to detect later stage apoptotic cells by morphology of the nuclei. Following LSS, PS was expressed on cell surfaces of endothelial cells of blood vessels and marginal cells of the stria vascularis. Later stage apoptosis, characterized by irregular nuclei and condensation of nuclei, was also observed in these cells. The data indicate that increased iNOS expression and production of both NO and ROS following noise stress may lead to marginal cell pathology, and the dysfunction of cochlear microcirculation by inducing

  9. The goldfish nervus terminalis: a luteinizing hormone-releasing hormone and molluscan cardioexcitatory peptide immunoreactive olfactoretinal pathway.

    PubMed Central

    Stell, W K; Walker, S E; Chohan, K S; Ball, A K

    1984-01-01

    Antisera to two putative neurotransmitters, luteinizing hormone-releasing hormone (LHRH) and molluscan cardioexcitatory tetrapeptide (H-Phe-Met-Arg-Phe-NH2; FMRF-amide), bind specifically to neurites in the inner nuclear and inner plexiform layers of the goldfish retina. Retrograde labeling showed that intraocular axon terminals originate from the nervus terminalis, whose cell bodies are located in the olfactory nerves. Double immunocytochemical and retrograde labeling showed that some terminalis neurons project to the retina; others may project only within the brain. All terminalis neurons having proven retinal projections were both LHRH- and FMRF-amide-immunoreactive. The activity of retinal ganglion cells was recorded with microelectrodes in isolated superfused goldfish retinas. In ON- and OFF-center double-color-opponent cells, micromolar FMRF-amide and salmon brain gonadotropin-releasing factor ( [Trp7, Leu8] LHRH) caused increased spontaneous activity in the dark, loss of light-induced inhibition, and increased incidence of light-entrained pulsatile response. The nervus terminalis is therefore a putatively peptidergic retinopetal projection. Sex-related olfactory stimuli may act through it, thereby modulating the output of ganglion cells responsive to color contrast. Images PMID:6199789

  10. Renal responses produced by microinjection of the kappa opioid receptor agonist, U50-488H, into sites within the rat lamina terminalis.

    PubMed

    Franklin, Cynthia; Fortepiani, Lourdes; Nguyen, Tin; Rangel, Yolanda; Strong, Randy; Gottlieb, Helmut B

    2015-03-01

    Activation of central kappa opioid receptors (KOR) has been demonstrated to produce marked free water diuresis with a concurrent increase in renal sympathetic nerve activity (RSNA). This study investigated the cardiovascular (CV) and renal effects evoked by central activation of KOR in two lamina terminalis sites, the median preoptic area (MPA) and anterolateral division of the bed nuclei of the stria terminalis (BST). Rats anesthetized with urethane alpha-chloralose were instrumented to record mean arterial pressure, heart rate, RSNA, and urine output (V). Rats were infused with isotonic saline (25 μL/min) and urine samples were collected during two 10-min control periods and six consecutive 10-min experimental periods following microinjection of vehicle, U50-448H (U50, KOR agonist) alone or norbinaltorphimine (nor-BNI, KOR antagonist) plus U50. Microinjection of U50 into the BST increased V (peak at 30 min, 84.8 ± 12.9 μL/min) as compared to its respective control, vehicle, or nor-BNI plus U50. This diuretic effect occurred without any significant changes in CV parameters, RSNA, or urinary sodium excretion. In contrast, U50 injection into the MPA significantly increased RSNA (peak at 20 mins: 129 ± 9.9) without increasing the other parameters. This study demonstrated novel sites through which activation of KOR selectively increases V and RSNA. The ability of U50 to increase V without affecting sodium excretion and RSNA raises the possibility that LT neurons could be an important substrate through which drugs targeting KOR could selectively facilitate water excretion in sodium-retaining diseases such as congestive heart failure. PMID:26038693

  11. Renal responses produced by microinjection of the kappa opioid receptor agonist, U50-488H, into sites within the rat lamina terminalis

    PubMed Central

    Franklin, Cynthia; Fortepiani, Lourdes; Nguyen, Tin; Rangel, Yolanda; Strong, Randy; Gottlieb, Helmut B

    2015-01-01

    Activation of central kappa opioid receptors (KOR) has been demonstrated to produce marked free water diuresis with a concurrent increase in renal sympathetic nerve activity (RSNA). This study investigated the cardiovascular (CV) and renal effects evoked by central activation of KOR in two lamina terminalis sites, the median preoptic area (MPA) and anterolateral division of the bed nuclei of the stria terminalis (BST). Rats anesthetized with urethane alpha-chloralose were instrumented to record mean arterial pressure, heart rate, RSNA, and urine output (V). Rats were infused with isotonic saline (25 μL/min) and urine samples were collected during two 10-min control periods and six consecutive 10-min experimental periods following microinjection of vehicle, U50-448H (U50, KOR agonist) alone or norbinaltorphimine (nor-BNI, KOR antagonist) plus U50. Microinjection of U50 into the BST increased V (peak at 30 min, 84.8 ± 12.9 μL/min) as compared to its respective control, vehicle, or nor-BNI plus U50. This diuretic effect occurred without any significant changes in CV parameters, RSNA, or urinary sodium excretion. In contrast, U50 injection into the MPA significantly increased RSNA (peak at 20 mins: 129 ± 9.9) without increasing the other parameters. This study demonstrated novel sites through which activation of KOR selectively increases V and RSNA. The ability of U50 to increase V without affecting sodium excretion and RSNA raises the possibility that LT neurons could be an important substrate through which drugs targeting KOR could selectively facilitate water excretion in sodium-retaining diseases such as congestive heart failure. PMID:26038693

  12. Neurohumoral Integration of Cardiovascular Function by the Lamina Terminalis.

    PubMed

    Cancelliere, Nicole M; Black, Emily A E; Ferguson, Alastair V

    2015-12-01

    The mechanisms involved in cardiovascular regulation, such as vascular tone, fluid volume and blood osmolarity, are quite often mediated by signals circulating in the periphery, such as angiotensin II and sodium concentration. Research has identified areas within the lamina terminalis (LT), specifically the sensory circumventricular organs (CVOs), the subfornical organ and the organum vasculosum of the lamina terminalis, as playing crucial roles detecting and integrating information derived from these circulating signals. The median preoptic nucleus (MnPO) is a third integrative structure within the LT that influences cardiovascular homeostasis, although to date, its role is not as clearly elucidated. More recent studies have demonstrated that the CVOs are not only essential in the detection of traditional cardiovascular signals but also signals primarily considered to be important in the regulation of metabolic, reproductive and inflammatory processes that have now also been implicated in cardiovascular regulation. In this review, we highlight the critical roles played by the LT in the detection and integration of circulating signals that provide critical feedback control information contributing to cardiovascular regulation. PMID:26531751

  13. The microanatomical structure of the cistern of the lamina terminalis.

    PubMed

    Wang, Shou-Sen; Zheng, He-Ping; Zhang, Fa-Hui; Wang, Ru-Mi

    2011-02-01

    Microanatomical dissection was performed on 14 formalin-fixed human cadaveric head specimens to provide information relevant for surgical procedures involving the cistern of the lamina terminalis (LT). The cistern of the LT was located in the midline of the telencephalon and was tent-shaped. The superior wall was located between the septal areas bilaterally, the lateral walls leaned laterally downwards, the anterior wall was the integrated line of the bilateral leptomeninges, the posterior and the inferoposterior walls were composed of the LT, the inferior margin was the arachnoid membrane between the optic nerves, and the inferoanterior wall usually formed a recess in front of the optic chiasm. In summary, the shape of the cistern of the LT is relatively constant, which is helpful for predicting the direction of hemorrhage of an aneurysm of the anterior communicating artery; in distinguishing its neural, vascular, and fibrous contents; and guiding surgical procedures. PMID:20926296

  14. Anatomical organization of the rat organum vasculosum laminae terminalis.

    PubMed

    Prager-Khoutorsky, Masha; Bourque, Charles W

    2015-08-15

    The organum vasculosum of the laminae terminalis (OVLT) is a circumventricular organ located along the ventral part of the anterior wall of the third ventricle. Because it lacks a complete blood-brain barrier (BBB), blood-borne signals detected in the OVLT provide the brain with information from the periphery and contribute to the generation of centrally mediated responses to humoral feedback and physiological stressors. Experimental studies on the rat OVLT are hindered by a poor understanding of its precise anatomical dimensions and cellular organization. In this study, we use histological techniques to characterize the spatial outline of the rat OVLT and to examine the location of neurons, astrocytes, tanycytes, and ependymocytes within its confines. Our data reveal that OVLT neurons are embedded in a dense network of tanycyte processes. Immunostaining against the neuronal marker NeuN revealed that neurons are distributed throughout the OVLT, except for a thick midline septum, which comprises densely packed cells of unknown function or lineage. Moreover, the most ventral aspect of the OVLT is devoid of neurons and is occupied by a dense network of glial cell processes that form a thick layer between the neurons and the pial surface on the ventral aspect of the nucleus. Lastly, combined detection of NeuN and c-Fos protein following systemic injection of hypertonic NaCl revealed that neurons responsive to this stimulus are located along the entire midline core of the OVLT, extending from its most anterior ventral aspect to the more caudally located "dorsal cap" region. PMID:26017494

  15. Altered responsiveness of BNST and amygdala neurons in trauma-induced anxiety.

    PubMed

    Rodríguez-Sierra, O E; Goswami, S; Turesson, H K; Pare, D

    2016-01-01

    A highly conserved network of brain structures regulates the expression of fear and anxiety in mammals. Many of these structures display abnormal activity levels in post-traumatic stress disorder (PTSD). However, some of them, like the bed nucleus of the stria terminalis (BNST) and amygdala, are comprised of several small sub-regions or nuclei that cannot be resolved with human neuroimaging techniques. Therefore, we used a well-characterized rat model of PTSD to compare neuronal properties in resilient vs PTSD-like rats using patch recordings obtained from different BNST and amygdala regions in vitro. In this model, a persistent state of extreme anxiety is induced in a subset of susceptible rats following predatory threat. Previous animal studies have revealed that the central amygdala (CeA) and BNST are differentially involved in the genesis of fear and anxiety-like states, respectively. Consistent with these earlier findings, we found that between resilient and PTSD-like rats were marked differences in the synaptic responsiveness of neurons in different sectors of BNST and CeA, but whose polarity was region specific. In light of prior data about the role of these regions, our results suggest that control of fear/anxiety expression is altered in PTSD-like rats such that the influence of CeA is minimized whereas that of BNST is enhanced. A model of the amygdalo-BNST interactions supporting the PTSD-like state is proposed. PMID:27434491

  16. Oxytocin Reduces Cocaine Seeking and Reverses Chronic Cocaine-Induced Changes in Glutamate Receptor Function

    PubMed Central

    Zhou, Luyi; Sun, Wei-Lun; Young, Amy B.; Lee, Kunhee; McGinty, Jacqueline F.

    2015-01-01

    Background: Oxytocin, a neurohypophyseal neuropeptide, is a potential mediator and regulator of drug addiction. However, the cellular mechanisms of oxytocin in drug seeking remain unknown. Methods: In the present study, we used a self-administration/reinstatement model to study the effects of oxytocin on cocaine seeking and its potential interaction with glutamate function at the receptor level. Results: Systemic oxytocin dose-dependently reduced cocaine self-administration during various schedules of reinforcement, including fixed ratio 1, fixed ratio 5, and progressive ratio. Oxytocin also attenuated reinstatement to cocaine seeking induced by cocaine prime or conditioned cues. Western-blot analysis indicated that oxytocin increased phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor GluA1 subunit at the Ser 845 site with or without accompanying increases in phosphorylation of extracellular signal-regulated kinase, in several brain regions, including the prefrontal cortex, bed nucleus of the stria terminalis, amygdala, and dorsal hippocampus. Immunoprecipitation of oxytocin receptor and GluA1 subunit receptors further demonstrated a physical interaction between these 2 receptors, although the interaction was not influenced by chronic cocaine or oxytocin treatment. Oxytocin also attenuated sucrose seeking in a GluA1- or extracellular-signal-regulated kinase-independent manner. Conclusions: These findings suggest that oxytocin mediates cocaine seeking through interacting with glutamate receptor systems via second messenger cascades in mesocorticolimbic regions. PMID:25539504

  17. Adolescent nicotine induces persisting changes in development of neural connectivity.

    PubMed

    Smith, Robert F; McDonald, Craig G; Bergstrom, Hadley C; Ehlinger, Daniel G; Brielmaier, Jennifer M

    2015-08-01

    Adolescent nicotine induces persisting changes in development of neural connectivity. A large number of brain changes occur during adolescence as the CNS matures. These changes suggest that the adolescent brain may still be susceptible to developmental alterations by substances which impact its growth. Here we review recent studies on adolescent nicotine which show that the adolescent brain is differentially sensitive to nicotine-induced alterations in dendritic elaboration, in several brain areas associated with processing reinforcement and emotion, specifically including nucleus accumbens, medial prefrontal cortex, basolateral amygdala, bed nucleus of the stria terminalis, and dentate gyrus. Both sensitivity to nicotine, and specific areas responding to nicotine, differ between adolescent and adult rats, and dendritic changes in response to adolescent nicotine persist into adulthood. Areas sensitive to, and not sensitive to, structural remodeling induced by adolescent nicotine suggest that the remodeling generally corresponds to the extended amygdala. Evidence suggests that dendritic remodeling is accompanied by persisting changes in synaptic connectivity. Modeling, electrophysiological, neurochemical, and behavioral data are consistent with the implication of our anatomical studies showing that adolescent nicotine induces persisting changes in neural connectivity. Emerging data thus suggest that early adolescence is a period when nicotine consumption, presumably mediated by nicotine-elicited changes in patterns of synaptic activity, can sculpt late brain development, with consequent effects on synaptic interconnection patterns and behavior regulation. Adolescent nicotine may induce a more addiction-prone phenotype, and the structures altered by nicotine also subserve some emotional and cognitive functions, which may also be altered. We suggest that dendritic elaboration and associated changes are mediated by activity-dependent synaptogenesis, acting in part

  18. The role of PKC signaling in CRF-induced modulation of startle

    PubMed Central

    M, Toth; JE, Gresack; RL, Hauger; AL, Halberstadt; VB, Risbrough

    2013-01-01

    Rationale Hypersignaling of corticotropin releasing factor (CRF) has been implicated in stress disorders, however many of its downstream mechanisms of action remain unclear. In vitro, CRF1 receptor activation initiates multiple cell signaling cascades, including protein kinase A (PKA), protein kinase C (PKC) and mitogen-activated protein kinase kinase MEK1/2 signaling. It is unclear however, which of these signaling cascades mediate CRF-induced behaviors during stress. Objectives We examined the role of PKA, PKC and MEK1/2 signaling pathways in CRF-induced anxiety as measured by startle hyperreactivity. Methods Mice treated with intracerbroventricular (ICV) ovine CRF (oCRF) were pretreated with the PKA inhibitor Rp-cAMPS, PKC inhibitor BIM (bisindolylmaleimide) or MEK1/2 inhibitor PD98059 (ICV) and assessed for acoustic startle reactivity. Results The PKC inhibitor BIM significantly attenuated CRF-induced increases in startle. BIM was also able to block startle increases induced by oCRF when both compounds were infused directly into the bed nucleus of stria terminalis (BNST). PKA and MEK1/2 inhibition had no significant effects on CRF-induced changes in startle at the dose ranges tested. CRF-induced disruption of PPI was not significantly reversed by any of the 3 pretreatments at the dose ranges tested. Conclusions PKC signaling is required for CRF-induced increases in startle, and this effect is mediated at least in part at the BNST. These findings suggest PKC signaling cascades: 1) may be important for the acute effects of CRF to induce startle hyperreactivity, and 2) support further research of the role of PKC signaling in startle abnormalities relevant to disorders such as posttraumatic stress disorder. PMID:23722830

  19. Neurokinin-1 receptor antagonism attenuates neuronal activity triggered by stress-induced reinstatement of alcohol seeking.

    PubMed

    Schank, J R; Nelson, B S; Damadzic, R; Tapocik, J D; Yao, M; King, C E; Rowe, K E; Cheng, K; Rice, K C; Heilig, M

    2015-12-01

    Substance P (SP) and its cognate neurokinin-1 receptor (NK1R) are involved in alcohol-related behaviors. We have previously reported that NK1R antagonism attenuates stress-induced reinstatement of alcohol seeking and suppresses escalated alcohol self-administration, but does not affect primary reinforcement or cue-induced reinstatement. Here, we administered an NK1R antagonist or vehicle prior to footshock-induced reinstatement of alcohol seeking, and mapped the resulting neuronal activation using Fos immunohistochemistry. As expected, vehicle treated animals exposed to footshock showed induction of Fos immunoreactivity in several regions of the brain stress circuitry, including the amygdala (AMG), nucleus accumbens (NAC), dorsal raphe nucleus (DR), prefrontal cortex (PFC), and bed nucleus of the stria terminalis (BNST). NK1R antagonism selectively suppressed the stress-induced increase in Fos in the DR and NAC shell. In the DR, Fos-induction by stress largely overlapped with tryptophan hydroxylase (TrpH), indicating activation of serotonergic neurons. Of NAC shell neurons activated during stress-induced reinstatement of alcohol seeking, about 30% co-expressed dynorphin (DYN), while 70% co-expressed enkephalin (ENK). Few (<1%) activated NAC shell neurons coexpressed choline acetyltransferase (ChAT), which labels the cholinergic interneurons of this region. Infusion of the NK1R antagonist L822429 into the NAC shell blocked stress-induced reinstatement of alcohol seeking. In contrast, L822429 infusion into the DR had no effect, suggesting that the influence of NK1R signaling on neuronal activity in the DR is indirect. Taken together, our results outline a potential pathway through which endogenous NK1R activation mediates stress-induced alcohol seeking. PMID:26188146

  20. Pathways to relapse: the neurobiology of drug- and stress-induced relapse to drug-taking.

    PubMed Central

    Stewart, J

    2000-01-01

    Relapse is a major characteristic of drug addiction, and remains the primary problem in treating drug abuse. Without an understanding of the factors that determine renewed drug-seeking, the urge to use drugs, and the persistent craving for them, it is unlikely that health care professionals can provide effective treatment. Using an animal model of relapse, the author and her team are studying factors that induce reinstatement of drug-taking behaviour after short and long periods of abstinence, and they are exploring the neurobiological basis of these effects. In their experiments, rats are trained to self-administer drugs intravenously by pressing 1 of 2 levers. During a subsequent period, the drug is no longer available, but the rats are free to try to obtain the drug (a period of "extinction training"). After extinction of responding, the investigators test for the ability of various events to reinitiate drug-seeking. On this background of renewed drug-seeking or relapse, the investigators search for pharmacological and neurochemical manipulations that might block or attenuate such behaviour. They have found that the 2 most effective events for reinstating responding after both short and long drug-free periods are re-exposure to the drug itself and exposure to a brief period of stress. The critical neurochemical pathways mediating drug-induced relapse are not identical to those mediating stress-induced relapse. Relapse induced by "priming" injections of heroin or cocaine involves activation of the mesolimbic dopaminergic pathways, whereas relapse induced by stress involves actions of corticotropin-releasing factor (CRF) in the brain, and of brain noradrenergic (NE) systems. In addition, evidence shows that CRF and NE may interact at the level of the bed nucleus of the stria terminalis in stress-induced relapse. By contrast, relapse induced by "priming" injections of drugs is relatively unaffected by manipulation of CRF and NE systems of the brain. PMID:10740986

  1. Knockdown of BNST GluN2B-containing NMDA receptors mimics the actions of ketamine on novelty-induced hypophagia

    PubMed Central

    Louderback, K M; Wills, T A; Muglia, L J; Winder, D G

    2013-01-01

    Administration of a single low dose of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has been demonstrated to elicit long-lasting antidepressant effects in humans with depression, as well as in rodent models of depression. Although pharmacological studies have implicated the GluN2B subunit of the NMDA receptor in these effects, drugs targeting this subunit have off-target actions, and systemic administration of these compounds does not allow for delineation of specific brain regions involved. In this study, we assessed the role of GluN2B in the bed nucleus of the stria terminalis (BNST) in novelty-induced hypophagia (NIH) in mice. First, we verified that ketamine, as well as the GluN2B antagonist Ro25–6981, decreased the latency to consume food in a novel environment in a version of the NIH test. We then hypothesized that GluN2B-containing receptors within the BNST may be a target of systemic ketamine and contribute to behavioral effects. Through the combination of a GluN2B-floxed mouse line and stereotaxic delivery of lentiviral Cre recombinase, we found that targeted knockdown of this subunit within the BNST mimicked the reduction in affective behavior observed with systemic ketamine or Ro25–6981 in the NIH test. These data suggest a role for GluN2B-containing NMDARs within the BNST in the affective effects of systemic ketamine. PMID:24301649

  2. The complete mitochondrial genome of the hybrid of Megalobrama terminalis (♀) × Megalobrama amblycephala (♂).

    PubMed

    Zhang, Weizhuo; Zhao, Yan; Guan, Ningnan; Nie, Chunhong; Zhang, Xiujie; Gao, Zexia

    2016-07-01

    In this study, the complete mitochondrial genome of the hybrid of Megalobrama terminalis (♀) × Megalobrama amblycephala (♂) was determined. The total length of the genome was 16,622 bp in accordance with the female parent, and the overall base composition was 31.13% A, 24.94% T, 27.72% C and 16.21% G, with a slight A + T bias. The genome contained 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 2 main non-coding regions (the control region and the origin of the light strand replication). The 99.48% sequence identity between the hybrid and its female parent, M. terminalis, confirmed the maternal inheritance pattern followed by the mitochondrial genome of the hybrid bream; however, it was interesting to find a total of 86 mutation sites in 12 genes or regions. The phylogenetic analysis indicated that the studied hybrid was relatively more close to M. terminalis, and the result was in agreement with their conventional taxonomic relationship. The genome information reported here may provide important information for further studies on the mitochondrial inheritance mechanisms in hybrids. PMID:26075479

  3. Cisplatin induces neuronal activation and increases central AMPA and NMDA receptor subunit gene expression in mice.

    PubMed

    Holland, Ruby A; Leonard, John J; Kensey, Nicholas A; Hannikainen, Paavali A; De Jonghe, Bart C

    2014-09-01

    Although rats and mice do not vomit, these species are widely studied as models of energy balance and sickness behavior. Previous work has shown that rats exhibit similar neuroanatomical activation of brain and visceral afferent pathways following cisplatin chemotherapy compared to vomiting species. However, the neural response to cisplatin in mice is understudied. Here, food intake, body weight, and central c-Fos immunofluorescence were analyzed in the hindbrains of male C57BL/6 mice following IP saline or cisplatin (5mg/kg, and 20mg/kg doses). As glutamate receptor signaling is classically linked to inhibitory feeding pathways in the rodent, gene expression of selected α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartic acid (NMDA) receptor subunits were assessed in the dorsal vagal complex (DVC), parabrachial nucleus (PBN), amygdala, and bed nucleus of the stria terminalis (BNST). Our results show dose-dependent reductions in food intake and body weight following cisplatin treatment, as well as increases in cisplatin-induced c-Fos in the PBN and throughout the DVC. Quantitative PCR analysis shows cisplatin-induced increases in NMDA receptor subunit expression, particularly NR2B, in the DVC, PBN, BNST, and amygdala. In addition, upregulation of AMPA receptor subunits (GluA1 and/or GluA2) were observed in all regions examined except the amygdala. Taken together, these results suggest similar neural pathways mediating cisplatin effects in mice compared to other well-studied species, which are likely mediated by central upregulation of AMPA and NMDA receptors. PMID:24582677

  4. Is unpredictable chronic mild stress (UCMS) a reliable model to study depression-induced neuroinflammation?

    PubMed

    Farooq, Rai Khalid; Isingrini, Elsa; Tanti, Arnaud; Le Guisquet, Anne-Marie; Arlicot, Nicolas; Minier, Frederic; Leman, Samuel; Chalon, Sylvie; Belzung, Catherine; Camus, Vincent

    2012-05-16

    Unipolar depression is one of the leading causes of disability. The pathophysiology of depression is poorly understood. Evidence suggests that inflammation is associated with depression. For instance, pro-inflammatory cytokines are found to be elevated in the peripheral blood of depressed subjects. Cytokine immunotherapy itself is known to induce depressive symptoms. While the epidemiological and biochemical relationship between inflammation and depression is strong, little is known about the possible existence of neuroinflammation in depression. The use of animal models of depression such as the Unpredictable Chronic Mild Stress (UCMS) has already contributed to the elucidation of the pathophysiological mechanisms of depression such as decreased neurogenesis and HPA axis alterations. We used this model to explore the association of depressive-like behavior in mice with changes in peripheral pro-inflammatory cytokines IL-1β, TNFα and IL-6 level as well as the neuroinflammation by quantifying CD11b expression in brain areas known to be involved in the pathophysiology of depression. These areas include the cerebral cortex, the nucleus accumbens, the bed nucleus of the stria terminalis, the caudate putamen, the amygdala and the hippocampus. The results indicate that microglial activation is significantly increased in the infralimbic, cingulate and medial orbital cortices, nucleus accumbens, caudate putamen, amygdala and hippocampus of the mouse brain as a function of UCMS, while levels of pro-inflammatory cytokines did not differ among the groups. This finding suggests that neuroinflammation occurs in depression and may be implicated in the subject's behavioral response. They also suggest that UCMS could be a potentially reliable model to study depression-induced neuroinflammation. PMID:22465167

  5. Ascending caudal medullary catecholamine pathways drive sickness-induced deficits in exploratory behavior: brain substrates for fatigue?

    PubMed

    Gaykema, Ronald P A; Goehler, Lisa E

    2011-03-01

    Immune challenges can lead to marked behavioral changes, including fatigue, reduced social interest, anorexia, and somnolence, but the precise neuronal mechanisms that underlie sickness behavior remain elusive. Part of the neurocircuitry influencing behavior associated with illness likely includes viscerosensory nuclei located in the caudal brainstem, based on findings that inactivation of the dorsal vagal complex (DVC) can prevent social withdrawal. These brainstem nuclei contribute multiple neuronal projections that target different components of autonomic and stress-related neurocircuitry. In particular, catecholaminergic neurons in the ventrolateral medulla (VLM) and DVC target the hypothalamus and drive neuroendocrine responses to immune challenge, but their particular role in sickness behavior is not known. To test whether this catecholamine pathway also mediates sickness behavior, we compared effects of DVC inactivation with targeted lesion of the catecholamine pathway on exploratory behavior, which provides an index of motivation and fatigue, and associated patterns of brain activation assessed by immunohistochemical detection of c-Fos protein. LPS treatment dramatically reduced exploratory behavior, and produced a pattern of increased c-Fos expression in brain regions associated with stress and autonomic adjustments paraventricular hypothalamus (PVN), bed nucleus of the stria terminalis (BST), central amygdala (CEA), whereas activation was reduced in regions involved in exploratory behavior (hippocampus, dorsal striatum, ventral tuberomammillary nucleus, and ventral tegmental area). Both DVC inactivation and catecholamine lesion prevented reductions in exploratory behavior and completely blocked the inhibitory LPS effects on c-Fos expression in the behavior-associated regions. In contrast, LPS-induced activation in the CEA and BST was inhibited by DVC inactivation but not by catecholamine lesion. The findings support the idea that parallel pathways from

  6. Addictive and non-addictive drugs induce distinct and specific patterns of ERK activation in mouse brain.

    PubMed

    Valjent, Emmanuel; Pagès, Christiane; Hervé, Denis; Girault, Jean-Antoine; Caboche, Jocelyne

    2004-04-01

    A major goal of research on addiction is to identify the molecular mechanisms of long-lasting behavioural alterations induced by drugs of abuse. Cocaine and delta-9-tetrahydrocannabinol (THC) activate extracellular signal-regulated kinase (ERK) in the striatum and blockade of the ERK pathway prevents establishment of conditioned place preference to these drugs. However, it is not known whether activation of ERK in the striatum is specific for these two drugs and/or this brain region. We studied the appearance of phospho-ERK immunoreactive neurons in CD-1 mouse brain following acute administration of drugs commonly abused by humans, cocaine, morphine, nicotine and THC, or of other psychoactive compounds including caffeine, scopolamine, antidepressants and antipsychotics. Each drug generated a distinct regional pattern of ERK activation. All drugs of abuse increased ERK phosphorylation in nucleus accumbens, lateral bed nucleus of the stria terminalis, central amygdala and deep layers of prefrontal cortex, through a dopamine D1 receptor-dependent mechanism. Although some non-addictive drugs moderately activated ERK in a few of these areas, they never induced this combined pattern of strong activation. Antidepressants and caffeine activated ERK in hippocampus and cerebral cortex. Typical antipsychotics mildly activated ERK in dorsal striatum and superficial prefrontal cortex, whereas clozapine had no effect in the striatum, but more widespread effects in cortex and amygdala. Our results outline a subset of structures in which ERK activation might specifically contribute to the long-term effects of drugs of abuse, and suggest mapping ERK activation in brain as a way to identify potential sites of action of psychoactive drugs. PMID:15078556

  7. Slc26a4-Insufficiency Causes Fluctuating Hearing Loss and Stria Vascularis Dysfunction

    PubMed Central

    Ito, Taku; Li, Xiangming; Kurima, Kiyoto; Choi, Byung Yoon; Wangemann, Philine; Griffith, Andrew J.

    2014-01-01

    SLC26A4 mutations can cause a distinctive hearing loss phenotype with sudden drops and fluctuation in patients. Existing Slc26a4 mutant mouse lines have a profound loss of hearing and vestibular function, with severe inner ear malformations that do not model this human phenotype. In this study, we generated Slc26a4-insufficient mice by manipulation of doxycycline administration to a transgenic mouse line in which all Slc26a4 expression was under the control of doxycycline. Doxycycline was administered from conception to embryonic day 17.5, and then discontinued. Auditory brainstem response thresholds showed significant fluctuation of hearing loss from 1 through 3 months of age. The endocochlear potential, which is required for inner ear sensory cell function, correlated with auditory brainstem response thresholds. We observed degeneration of stria vascularis intermediate cells, the cells that generate the endocochlear potential, but no other abnormalities within the cochlea. We conclude that fluctuations of hearing result from fluctuations of the endocochlear potential and stria vascularis dysfunction in Slc26a4-insufficient mouse ears. This model can now be used to test potential interventions to reduce or prevent sudden hearing loss or fluctuation in human patients. Our strategy to generate a hypomorphic mouse model utilizing the tet-on system will be applicable to other diseases in which a hypomorphic allele is needed to model the human phenotype. PMID:24561068

  8. ATP-containing vesicles in stria vascular marginal cell cytoplasms in neonatal rat cochlea are lysosomes

    PubMed Central

    Liu, Jun; Liu, Wenjing; Yang, Jun

    2016-01-01

    We confirmed that ATP is released from cochlear marginal cells in the stria vascular but the cell organelle in which ATP stores was not identified until now. Thus, we studied the ATP-containing cell organelles and suggest that these are lysosomes. Primary cultures of marginal cells of Sprague-Dawley rats aged 1–3 days was established. Vesicles within marginal cells stained with markers were identified under confocal laser scanning microscope and transmission electron microscope (TEM). Then ATP release from marginal cells was measured after glycyl-L-phenylalanine-ß- naphthylamide (GPN) treatment using a bioluminescent assay. Quinacrine-stained granules within marginal cells were labeled with LysoTracker, a lysosome tracer, and lysosomal-associated membrane protein 1(LAMP1), but not labeled with the mitochondrial tracer MitoTracker. Furthermore, LysoTracker-labelled puncta showed accumulation of Mant-ATP, an ATP analog. Treatment with 200 μM GPN quenched fluorescently labeled puncta after incubation with LysoTracker or quinacrine, but not MitoTracker. Quinacrine-labeled organelles observed by TEM were lysosomes, and an average 27.7 percent increase in ATP luminescence was observed in marginal cells extracellular fluid after GPN treatment. ATP-containing vesicles in cochlear marginal cells of the stria vascular from neonatal rats are likely lysosomes. ATP release from marginal cells may be via Ca2+-dependent lysosomal exocytosis. PMID:26864824

  9. Slc26a4-insufficiency causes fluctuating hearing loss and stria vascularis dysfunction.

    PubMed

    Ito, Taku; Li, Xiangming; Kurima, Kiyoto; Choi, Byung Yoon; Wangemann, Philine; Griffith, Andrew J

    2014-06-01

    SLC26A4 mutations can cause a distinctive hearing loss phenotype with sudden drops and fluctuation in patients. Existing Slc26a4 mutant mouse lines have a profound loss of hearing and vestibular function, with severe inner ear malformations that do not model this human phenotype. In this study, we generated Slc26a4-insufficient mice by manipulation of doxycycline administration to a transgenic mouse line in which all Slc26a4 expression was under the control of doxycycline. Doxycycline was administered from conception to embryonic day 17.5, and then it was discontinued. Auditory brainstem response thresholds showed significant fluctuation of hearing loss from 1 through 3months of age. The endocochlear potential, which is required for inner ear sensory cell function, correlated with auditory brainstem response thresholds. We observed degeneration of stria vascularis intermediate cells, the cells that generate the endocochlear potential, but no other abnormalities within the cochlea. We conclude that fluctuations of hearing result from fluctuations of the endocochlear potential and stria vascularis dysfunction in Slc26a4-insufficient mouse ears. This model can now be used to test potential interventions to reduce or prevent sudden hearing loss or fluctuation in human patients. Our strategy to generate a hypomorphic mouse model utilizing the tet-on system will be applicable to other diseases in which a hypomorphic allele is needed to model the human phenotype. PMID:24561068

  10. CRF-R1 activation in the anterior-dorsal BNST induces maternal neglect in lactating rats via an HPA axis-independent central mechanism

    PubMed Central

    Klampfl, Stefanie M.; Brunton, Paula J.; Bayerl, Doris S.; Bosch, Oliver J.

    2016-01-01

    Adequate maternal behavior in rats requires minimal corticotropin-releasing factor receptor (CRF-R) activation in the medial-posterior bed nucleus of the stria terminalis (mpBNST). Based on the architectural heterogeneity of the BNST and its distinct inter-neural connectivity, we tested whether CRF-R manipulation in another functional part, the anterior-dorsal BNST (adBNST), differentially modulates maternal behavior. We demonstrate that in the adBNST, activation of CRF-R1 reduced arched back nursing (ABN) and nursing, whereas activation of CRF-R2 resulted in an initial reduction in nursing but significantly increased the incidence of ABN 5 h after the treatment. Following stressor exposure, which is detrimental to maternal care, ABN tended to be protected by CRF-R1 blockade. Maternal motivation, maternal aggression, and anxiety were unaffected by any manipulation. Furthermore, under basal and stress conditions, activation of adBNST CRF-R1 increased plasma ACTH and corticosterone concentrations, whereas stimulation of adBNST CRF-R2 increased basal plasma ACTH and corticosterone concentrations, but blocked the stress-induced increase in plasma corticosterone secretion. Moreover, both the CRF-R1 and -R2 antagonists prevented the stress-induced increase in plasma corticosterone secretion. Importantly, elevated levels of circulating corticosterone induced by intra-adBNST administration of CRF-R1 or -R2 agonist did not impact maternal care. Finally, Crf mRNA expression in the adBNST was increased during lactation; however, Crfr1 mRNA expression was similar between lactating and virgin rats. In conclusion, maternal care is impaired by adBNST CRF-R1 activation, and this appears to be the result of a central action, rather than an effect of elevated circulating levels of CORT. These data provide new insights into potential causes of disturbed maternal behavior postpartum. PMID:26630389

  11. Ventral lamina terminalis mediates enhanced cardiovascular responses of rostral ventrolateral medulla neurons during increased dietary salt.

    PubMed

    Adams, Julye M; Bardgett, Megan E; Stocker, Sean D

    2009-08-01

    Increased dietary salt enhances sympathoexcitatory and sympathoinhibitory responses evoked from the rostral ventrolateral medulla (RVLM). The purpose of the present study was to determine whether neurons of the forebrain lamina terminalis (LT) mediated these changes in the RVLM. Male Sprague-Dawley rats with and without LT lesions were fed normal chow and given access to water or 0.9% NaCl for 14 to 15 days. Unilateral injection of l-glutamate into the RVLM produced significantly larger increases in renal sympathetic nerve activity and arterial blood pressure of sham rats ingesting 0.9% NaCl versus water. However, these differences were not observed between ventral LT-lesioned rats drinking 0.9% NaCl versus water. Similar findings were observed when angiotensin II or gamma-aminobutyric acid was injected into the RVLM. Interestingly, a subset of animals drinking 0.9% but with damage restricted to the organum vasculosum of the lamina terminalis did not show enhanced responses to l-glutamate or gamma-aminobutyric acid. In marked contrast, RVLM injection of l-glutamate or gamma-aminobutyric acid produced exaggerated sympathetic nerve activity and arterial blood pressure responses in animals drinking 0.9% NaCl versus water after an acute ventral LT lesion or chronic lesion of the subfornical organ. Additional experiments demonstrated that plasma sodium concentration and osmolality were increased at night in rats ingesting 0.9% NaCl. These findings suggest that neurons of the ventral LT mediate the ability of increased dietary salt to enhance the responsiveness of RVLM sympathetic neurons. PMID:19506102

  12. Effects of prostaglandin E2 on cells cultured from the rat organum vasculosum laminae terminalis and median preoptic nucleus.

    PubMed

    Simm, B; Ott, D; Pollatzek, E; Murgott, J; Gerstberger, R; Rummel, C; Roth, J

    2016-01-28

    The time course of the induction of enzymes responsible for the formation of prostaglandin E2 (PGE2) after an inflammatory insult, in relation to the concomitant febrile response, suggests that peripherally generated PGE2 is involved in the induction of the early phase of fever, while centrally produced PGE2 exerts pyrogenic capacities during the later stages of fever within the hypothalamic median preoptic nucleus (MnPO). The actions of peripherally derived PGE2 on the brain might occur at the level of the organum vasculosum laminae terminalis (OVLT), which lacks a tight blood-brain barrier and is implicated in fever, while the effects of PGE2 within the MnPO might interfere with glutamatergic neurotransmission within a recently characterized central efferent pathway for the activation of cold-defence reactions. Using the fura-2 ratio imaging technique we, therefore, measured changes of the intracellular Ca(2+)-concentration in primary neuroglial microcultures of rat OVLT and MnPO stimulated with PGE2 and/or glutamate. In cultures from the OVLT, as opposed to those derived from the MnPO, substantial numbers of neurons (8% of 385), astrocytes (19% of 645) and microglial cells (28% of 43) directly responded to PGE2 with a transient increase of intracellular Ca(2+). The most pronounced effect of PGE2 on cells from MnPO microcultures was its modulatory influence on the strength of glutamate-induced Ca(2+)-signals. In 72 out of 512 neurons and in 105 out of 715 astrocytes PGE2 significantly augmented glutamate-induced Ca(2+)-signals. About 30% of these neurons were GABAergic. These observations are in agreement with putative roles of peripheral PGE2 as a directly acting circulating agent at the level of the OVLT, and of central MnPO-intrinsic PGE2 as an enhancer of glutamatergic neurotransmission, which causes disinhibition of thermogenic heat production, a crucial component for the manifestation of fever. In microcultures from both brain sites investigated incubation

  13. Neural correlates of cat odor-induced anxiety in rats: region-specific effects of the benzodiazepine midazolam.

    PubMed

    McGregor, Iain S; Hargreaves, Garth A; Apfelbach, Raimund; Hunt, Glenn E

    2004-04-28

    Cat odor elicits a profound defensive reaction in rats that is reduced by benzodiazepine drugs. The neural correlates of this phenomenon were investigated here using Fos immunohistochemistry. Rats received either midazolam (0.75 mg/kg, s.c.) or vehicle and were exposed to pieces of a collar that had been worn by a domestic cat or an unworn (dummy) collar. Cat odor caused midazolam-sensitive defensive behavioral responses, including avoidance of collar contact, inhibition of grooming, and prolonged rearing. Cat odor exposure induced Fos expression in the posterior accessory olfactory bulb (glomerular, mitral, and granule cell layers), with granule cell layer activation attenuated by midazolam. High basal Fos expression, and some cat odor-associated Fos expression, was evident in the main olfactory bulb (glomerular cell layer), and midazolam exerted a strong inhibitory effect in this region. Midazolam inhibited Fos expression in key limbic regions involved in pheromone transduction (medial amygdala and bed nucleus of the stria terminalis) and defensive behavior (prelimbic cortex, lateral septum, lateral and medial preoptic areas, and dorsal premammillary nucleus). However, midazolam failed to affect cat odor-related Fos expression in a range of key defense-related sites, including the ventromedial hypothalamic nucleus, paraventricular nucleus of the hypothalamus, periaqueductal gray, and cuneiform nucleus. These results indicate that midazolam exerts a region-specific effect on the neural substrates activated by predator odor, with effects in the lateral septum and dorsal premammillary nucleus likely to be of major importance. These findings also suggest the intriguing hypothesis that cat odor is processed by rats as a "pheromone-like" stimulus. PMID:15115808

  14. The Role of the Hypothalamic Paraventricular Nucleus and the Organum Vasculosum Lateral Terminalis in the Control of Sodium Appetite in Male Rats

    PubMed Central

    Takacs, Anne E.; Yee, Daniel K.; Flanagan-Cato, Loretta M.

    2014-01-01

    Angiotensin II (AngII) and aldosterone cooperate centrally to produce a robust sodium appetite. The intracellular signaling and circuitry that underlie this interaction remain unspecified. Male rats pretreated with both deoxycorticosterone (DOC; a synthetic precursor of aldosterone) and central AngII exhibited a marked sodium intake, as classically described. Disruption of inositol trisphosphate signaling, but not extracellular-regulated receptor kinase 1 and 2 signaling, prevented the cooperativity of DOC and AngII on sodium intake. The pattern of expression of the immediate early gene product cFos was used to identify key brain regions that may underlie this behavior. In the paraventricular nuclei (PVN) of the hypothalamus, DOC pretreatment diminished both AngII-induced cFos induction and neurosecretion of oxytocin, a peptide expressed in the PVN. Conversely, in the organum vasculosum lateral terminalis (OVLT), DOC pretreatment augmented cFos expression. Immunohistochemistry identified a substantial presence of oxytocin fibers in the OVLT. In addition, when action potentials in the PVN were inhibited with intraparenchymal lidocaine, AngII-induced sodium ingestion was exaggerated. Intriguingly, this treatment also increased the number of neurons in the OVLT expressing AngII-induced cFos. Collectively, these results suggest that the behavioral cooperativity between DOC and AngII involves the alleviation of an inhibitory oxytocin signal, possibly relayed directly from the PVN to the OVLT. PMID:25009258

  15. Corticotropin-Releasing Factor Modulation of Forebrain GABAergic Transmission has a Pivotal Role in the Expression of Anabolic Steroid-Induced Anxiety in the Female Mouse

    PubMed Central

    Oberlander, Joseph G; Henderson, Leslie P

    2012-01-01

    Increased anxiety is commonly observed in individuals who illicitly administer anabolic androgenic steroids (AAS). Behavioral effects of steroid abuse have become an increasing concern in adults and adolescents of both sexes. The dorsolateral bed nucleus of the stria terminalis (dlBnST) has a critical role in the expression of diffuse anxiety and is a key site of action for the anxiogenic neuromodulator, corticotropin releasing factor (CRF). Here we demonstrate that chronic, but not acute, exposure of female mice during adolescence to AAS augments anxiety-like behaviors; effects that were blocked by central infusion of the CRF receptor type 1 antagonist, antalarmin. AAS treatment selectively increased action potential (AP) firing in neurons of the central amygdala (CeA) that project to the dlBnST, increased the frequency of GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in dlBnST target neurons, and decreased both c-FOS immunoreactivity (IR) and AP frequency in these postsynaptic cells. Acute application of antalarmin abrogated the enhancement of GABAergic inhibition induced by chronic AAS exposure whereas application of CRF to brain slices of naïve mice mimicked the actions of this treatment. These results, in concert with previous data demonstrating that chronic AAS treatment results in enhanced levels of CRF mRNA in the CeA and increased CRF-IR in the dlBnST neuropil, are consistent with a mechanism in which the enhanced anxiety elicited by chronic AAS exposure involves augmented inhibitory activity of CeA afferents to the dlBnST and CRF-dependent enhancement of GABAergic inhibition in this brain region. PMID:22298120

  16. REGION-SPECIFIC MECHANISMS FOR TESTOSTERONE-INDUCED FOS IN HAMSTER BRAIN

    PubMed Central

    Nagypál, Anita; Wood, Ruth I.

    2007-01-01

    Hamsters self-administer androgens. Previously, we determined that testosterone (T) activates select steroid- and opiate-sensitive brain regions. Is T-stimulated neuronal activation androgenic? 35 castrated males with physiologic T replacement (n=7/group) were pre-treated with the androgen antagonist flutamide (15 mg/kg sc) or ethanol (0.25 ml), and infused into the lateral ventricle (ICV) for 4h with 40 μg T (TF and TE, respectively) or 40 μl vehicle (VF and VE). To determine if androgens and opiates activate overlapping brain areas, 7 additional males received 20 μg morphine sulfate ICV following ethanol injection (ME). Immediately after ICV infusion, animals were perfused. 60 μm coronal brain slices were stained for Fos. Fos-positive neurons were counted in a 0.3 mm2 area from 5 regions previously shown to express T-induced Fos: the posteromedial bed nucleus of the stria terminalis (BSTPM), posteromedial amygdala (MeP), lateral habenula (LHb), ventral tegmental area, and lateral pontine nucleus. T induced Fos in all areas reported previously (TE vs. VE, p<0.05), except LHb (p>0.05). Morphine induced Fos in all 5 brain regions (ME vs. VE, p<0.05), indicating that androgens and opiates activate overlapping brain regions. Flutamide alone did not induce Fos (VF vs. VE, p>0.05). Moreover, flutamide treatment blocked T-induced Fos expression only in the steroid-sensitive BSTPM, suggesting that androgens mediate neuronal activation in this area (mean±SEM: TF: 68.4±13.2 vs. TE: 137.9±17.6, p<0.05). The absence of flutamide effects on T-induced Fos in the steroid-sensitive MeP (TE: 210.6±50.0 vs. TF: 215.3±28.2, p>0.05) suggests that distinct mechanisms activate Fos in individual androgen-responsive nuclei. PMID:17276422

  17. In vivo capillary diameters in the stria vascularis and spiral ligament of the guinea pig cochlea.

    PubMed

    Miles, F P; Nuttall, A L

    1988-05-01

    Blood microvessels in the membraneous lateral wall of the cochlea were examined using intravital microscopic techniques. A video analysis system made serial diameter measurements at 1 micron intervals along the length of selected vessel segments during four experimental conditions. For each vessel segment, the serial measurements were statistically converted into a single diameter estimate, such that the flow resistance in a uniform vessel of this diameter would equal the resistance of the real non-uniform vessel. Nominal vessel diameters found (spiral ligament: 9-12 micron; stria vascularis: 12-16 micron) were nearly double those reported earlier in histological observations (Axelsson, 1968). During stimulation the largest diameter change seen was a 3.7% dilation (about 0.5 micron) in response to breathing 5% CO2 in oxygen. Theoretically, this change could reduce vascular fluid resistance by 16%, nearly enough to explain the observed flow increase of 20%. No diameter changes occurred for 5% CO2 in air despite a 50% flow increase, nor for air pressure pulses applied at the tympanic membrane. Round window electrical stimulation of 50 microA also produced dilation (less than 2.5%), but higher current levels were ineffective. In general, blood flow increases seen in this study could not adequately be attributed to the small lateral wall vessel diameter increases nor systemic causes, suggesting that lateral wall blood flow in these instances is dependent on control within the modiolus. PMID:3135284

  18. FMRFamide-like immunoreactive nervus terminalis innervation to the pituitary in the catfish, Clarias batrachus (Linn.): demonstration by lesion and immunocytochemical techniques

    NASA Technical Reports Server (NTRS)

    Krishna, N. S.; Subhedar, N.; Schreibman, M. P.

    1992-01-01

    Certain thick FMRFamide-like immunoreactive fibers arising from the ganglion cells of nervus terminalis in the olfactory bulb of Clarias batrachus can be traced centripetally through the medial olfactory tract, telencephalon, lateral preoptic area, tuberal area, and hypothalamohypophysial tract to the pituitary. Following 6 days of bilateral olfactory tract transection, the immunoreactivity in the thick fibers, caudal to the lesion site, was partially eliminated, whereas after 10 and 14 days, it was totally abolished in the processes en route to the pituitary. The results indicate a direct innervation of the pituitary gland by the FMRFamide-like peptide containing fibers of the nervus terminalis.

  19. A case of transient hypothermia after trans-lamina terminalis and third ventricle clipping of an extremely high-position basilar tip aneurysm

    PubMed Central

    Ikawa, Fusao; Hamasaki, Osamu; Kurokawa, Yasuharu; Yonezawa, Ushio; Kurisu, Kaoru

    2015-01-01

    Reports on the trans-lamina terminalis and trans-third ventricular approach are rare. The risk associated with this approach is unknown. After an unsuccessful endovascular surgery, we performed direct surgical clipping via the third ventricle on a 78-year-old woman presenting with an extremely high-positioned, ruptured basilar tip aneurysm. She experienced transient hypothermia for 5 days, and it was considered that this was due to hypothalamic dysfunction. It is necessary to recognize that there is the potential for hypothermia after surgery via the lamina terminalis and third ventricle, even though the mechanisms of hypothalamic thermoregulation are still unclear. PMID:27489684

  20. Phytophthora terminalis sp. nov. and Phytophthora occultans sp. nov., two invasive pathogens of ornamental plants in Europe.

    PubMed

    Man In 't Veld, Willem A; Rosendahl, Karin C H M; van Rijswick, Patricia C J; Meffert, Johan P; Westenberg, Marcel; van de Vossenberg, Bart T L H; Denton, Geoff; van Kuik, Fons A J

    2015-01-01

    In the past decade several Phytophthora strains were isolated from diseased Pachysandra terminalis plants suffering stem base and root rot, originating from the Netherlands and Belgium. All isolates were homothallic and had a felt-like colony pattern, produced semi-papillate sporangia, globose oogonia and had a maximum growth at ~ 27 C. Several additional Phytophthora strains were isolated from diseased Buxus sempervirens plants, originating from the Netherlands and Belgium, which had sustained stem base and root rot; similar strains also were isolated from Acer palmatum, Choisya ternata and Taxus in the United Kingdom. All isolates were homothallic and had a stellate colony pattern, produced larger semi-papillate sporangia and smaller globose oogonia than the isolates from Pa. terminalis and had a maximum growth temperature of ~ 30 C. Phylogenetic analyses of both species using the internal transcribed spacer region of the nuc rDNA (ITS), mt cytochrome oxidases subunit I gene (CoxI) and nuc translation elongation factor 1-α gene (TEF1α) revealed that all sequences of each species were identical at each locus and unique to that species, forming two distinct clusters in subclade 2a. Sequence analysis of partial β-tubulin genes showed that both taxa share an identical sequence that is identical to that of Ph. himalsilva, a species originating from Asia, suggesting a common Asian origin. Pathogenicity trials demonstrated disease symptoms on their respective hosts, and re-isolation and re-identification of the inoculated pathogens confirmed Koch's postulates. PMID:25261495

  1. Patterns of Brain Activation and Meal Reduction Induced by Abdominal Surgery in Mice and Modulation by Rikkunshito.

    PubMed

    Wang, Lixin; Mogami, Sachiko; Yakabi, Seiichi; Karasawa, Hiroshi; Yamada, Chihiro; Yakabi, Koji; Hattori, Tomohisa; Taché, Yvette

    2015-01-01

    Abdominal surgery inhibits food intake and induces c-Fos expression in the hypothalamic and medullary nuclei in rats. Rikkunshito (RKT), a Kampo medicine improves anorexia. We assessed the alterations in meal microstructure and c-Fos expression in brain nuclei induced by abdominal surgery and the modulation by RKT in mice. RKT or vehicle was gavaged daily for 1 week. On day 8 mice had no access to food for 6-7 h and were treated twice with RKT or vehicle. Abdominal surgery (laparotomy-cecum palpation) was performed 1-2 h before the dark phase. The food intake and meal structures were monitored using an automated monitoring system for mice. Brain sections were processed for c-Fos immunoreactivity (ir) 2-h after abdominal surgery. Abdominal surgery significantly reduced bouts, meal frequency, size and duration, and time spent on meals, and increased inter-meal interval and satiety ratio resulting in 92-86% suppression of food intake at 2-24 h post-surgery compared with control group (no surgery). RKT significantly increased bouts, meal duration and the cumulative 12-h food intake by 11%. Abdominal surgery increased c-Fos in the prelimbic, cingulate and insular cortexes, and autonomic nuclei, such as the bed nucleus of the stria terminalis, central amygdala, hypothalamic supraoptic (SON), paraventricular and arcuate nuclei, Edinger-Westphal nucleus (E-W), lateral periaqueduct gray (PAG), lateral parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius (NTS). RKT induced a small increase in c-Fos-ir neurons in the SON and E-W of control mice, and in mice with surgery there was an increase in the lateral PAG and a decrease in the NTS. These findings indicate that abdominal surgery inhibits food intake by increasing both satiation (meal duration) and satiety (meal interval) and activates brain circuits involved in pain, feeding behavior and stress that may underlie the alterations of meal pattern and food intake inhibition. RKT improves

  2. Patterns of Brain Activation and Meal Reduction Induced by Abdominal Surgery in Mice and Modulation by Rikkunshito

    PubMed Central

    Wang, Lixin; Mogami, Sachiko; Yakabi, Seiichi; Karasawa, Hiroshi; Yamada, Chihiro; Yakabi, Koji; Hattori, Tomohisa; Taché, Yvette

    2015-01-01

    Abdominal surgery inhibits food intake and induces c-Fos expression in the hypothalamic and medullary nuclei in rats. Rikkunshito (RKT), a Kampo medicine improves anorexia. We assessed the alterations in meal microstructure and c-Fos expression in brain nuclei induced by abdominal surgery and the modulation by RKT in mice. RKT or vehicle was gavaged daily for 1 week. On day 8 mice had no access to food for 6–7 h and were treated twice with RKT or vehicle. Abdominal surgery (laparotomy-cecum palpation) was performed 1–2 h before the dark phase. The food intake and meal structures were monitored using an automated monitoring system for mice. Brain sections were processed for c-Fos immunoreactivity (ir) 2-h after abdominal surgery. Abdominal surgery significantly reduced bouts, meal frequency, size and duration, and time spent on meals, and increased inter-meal interval and satiety ratio resulting in 92–86% suppression of food intake at 2–24 h post-surgery compared with control group (no surgery). RKT significantly increased bouts, meal duration and the cumulative 12-h food intake by 11%. Abdominal surgery increased c-Fos in the prelimbic, cingulate and insular cortexes, and autonomic nuclei, such as the bed nucleus of the stria terminalis, central amygdala, hypothalamic supraoptic (SON), paraventricular and arcuate nuclei, Edinger-Westphal nucleus (E-W), lateral periaqueduct gray (PAG), lateral parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius (NTS). RKT induced a small increase in c-Fos-ir neurons in the SON and E-W of control mice, and in mice with surgery there was an increase in the lateral PAG and a decrease in the NTS. These findings indicate that abdominal surgery inhibits food intake by increasing both satiation (meal duration) and satiety (meal interval) and activates brain circuits involved in pain, feeding behavior and stress that may underlie the alterations of meal pattern and food intake inhibition. RKT

  3. A Switch in Keystone Seed-Dispersing Ant Genera between Two Elevations for a Myrmecochorous Plant, Acacia terminalis

    PubMed Central

    Thomson, Fiona J.; Auld, Tony D.; Ramp, Daniel; Kingsford, Richard T.

    2016-01-01

    The dispersal capacity of plant species that rely on animals to disperse their seeds (biotic dispersal) can alter with changes to the populations of their keystone dispersal vectors. Knowledge on how biotic dispersal systems vary across landscapes allows better understanding of factors driving plant persistence. Myrmecochory, seed dispersal by ants, is a common method of biotic dispersal for many plant species throughout the world. We tested if the seed dispersal system of Acacia terminalis (Fabaceae), a known myrmecochore, differed between two elevations in the Greater Blue Mountains World Heritage Area, in southeastern Australia. We compared ant assemblages, seed removal rates of ants and other vertebrates (bird and mammal) and the dominant seed-dispersing ant genera. At low elevations (c. 200 m a.s.l) seed removal was predominantly by ants, however, at high elevation sites (c. 700 m a.s.l) vertebrate seed dispersers or seed predators were present, removing over 60% of seeds from experimental depots when ants were excluded. We found a switch in the keystone seed-dispersing ant genera from Rhytidoponera at low elevations sites to Aphaenogaster at high elevation sites. This resulted in more seeds being removed faster at low elevation sites compared to high elevation sites, however long-term seed removal rates were equal between elevations. Differences in the keystone seed removalist, and the addition of an alternate dispersal vector or seed predator at high elevations, will result in different dispersal and establishment patterns for A. terminalis at different elevations. These differences in dispersal concur with other global studies that report myrmecochorous dispersal systems alter with elevation. PMID:27310262

  4. A Switch in Keystone Seed-Dispersing Ant Genera between Two Elevations for a Myrmecochorous Plant, Acacia terminalis.

    PubMed

    Thomson, Fiona J; Auld, Tony D; Ramp, Daniel; Kingsford, Richard T

    2016-01-01

    The dispersal capacity of plant species that rely on animals to disperse their seeds (biotic dispersal) can alter with changes to the populations of their keystone dispersal vectors. Knowledge on how biotic dispersal systems vary across landscapes allows better understanding of factors driving plant persistence. Myrmecochory, seed dispersal by ants, is a common method of biotic dispersal for many plant species throughout the world. We tested if the seed dispersal system of Acacia terminalis (Fabaceae), a known myrmecochore, differed between two elevations in the Greater Blue Mountains World Heritage Area, in southeastern Australia. We compared ant assemblages, seed removal rates of ants and other vertebrates (bird and mammal) and the dominant seed-dispersing ant genera. At low elevations (c. 200 m a.s.l) seed removal was predominantly by ants, however, at high elevation sites (c. 700 m a.s.l) vertebrate seed dispersers or seed predators were present, removing over 60% of seeds from experimental depots when ants were excluded. We found a switch in the keystone seed-dispersing ant genera from Rhytidoponera at low elevations sites to Aphaenogaster at high elevation sites. This resulted in more seeds being removed faster at low elevation sites compared to high elevation sites, however long-term seed removal rates were equal between elevations. Differences in the keystone seed removalist, and the addition of an alternate dispersal vector or seed predator at high elevations, will result in different dispersal and establishment patterns for A. terminalis at different elevations. These differences in dispersal concur with other global studies that report myrmecochorous dispersal systems alter with elevation. PMID:27310262

  5. Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain

    PubMed Central

    Van Bockstaele, Elisabeth J.; Qian, Yaping; Sterling, Robert C.; Page, Michelle E.

    2009-01-01

    The administration of low dose opioid antagonists has been explored as a potential means of detoxification in opiate dependence. Previous results from our laboratory have shown that concurrent administration of low dose naltrexone in the drinking water of rats implanted with subcutaneous morphine pellets attenuates behavioral and biochemical signs of withdrawal in brainstem noradrenergic nuclei. Noradrenergic projections originating from the nucleus tractus solitarius (NTS) and the locus coeruleus (LC) have previously been shown to be important neural substrates involved in the somatic expression of opiate withdrawal. The hypothesis that low dose naltrexone treatment attenuates noradrenergic hyperactivity typically associated with opiate withdrawal was examined in the present study by assessing norepinephrine tissue content and norepinephrine efflux using in vivo microdialysis coupled to high performance liquid chromatography (HPLC) with electrochemical detection (ED). The frontal cortex (FC), amygdala, bed nucleus of the stria terminalis (BNST) and cerebellum were analyzed for tissue content of norepinephrine following withdrawal in morphine dependent rats. Naltrexone precipitated withdrawal elicited a significant decrease in tissue content of norepinephrine in the BNST and amygdala. This decrease was significantly attenuated in the BNST of rats that received low dose naltrexone pretreatment compared to controls. No significant difference was observed in the other brain regions examined. In a separate group of rats, norepinephrine efflux was assessed with in vivo microdialysis in the BNST or the FC of morphine dependent rats or placebo treated rats subjected to naltrexone-precipitated withdrawal that received either naltrexone in their drinking water (5 mg/L) or unadulterated water. Following baseline dialysate collection, withdrawal was precipitated by injection of naltrexone and sample collection continued for an additional four hours. At the end of the

  6. Regional Fos-expression induced by γ-hydroxybutyrate (GHB): comparison with γ-butyrolactone (GBL) and effects of co-administration of the GABAB antagonist SCH 50911 and putative GHB antagonist NCS-382.

    PubMed

    van Nieuwenhuijzen, P S; McGregor, I S; Chebib, M; Hunt, G E

    2014-09-26

    γ-Hydroxybutyrate (GHB) has a complex array of neural actions that include effects on its own high-affinity GHB receptor, the release of neuroactive steroids, and agonist actions at GABAA and GABAB receptors. We previously reported partial overlap in the c-Fos expression patterns produced by GHB and the GABAB agonist, baclofen in rats. The present study extends these earlier findings by examining the extent to which GHB Fos expression and behavioral sedation are prevented by (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911), a GABAB antagonist, and NCS-382, a putative antagonist at the high-affinity GHB receptor. We also compare Fos expression caused by GHB and its precursor γ-butyrolactone (GBL), which is a pro-drug for GHB but lacks the high sodium content of the parent GHB molecule. Both GHB (1,000 mg/kg) and GBL (600 mg/kg) induced rapid sedation in rats that lasted over 90 min and caused similar Fos expression patterns, albeit with GBL causing greater activation of the nucleus accumbens (core and shell) and dentate gyrus (granular layer). Pretreatment with SCH 50911 (100mg/kg) partly reversed the sedative effects of GHB and significantly reduced GHB-induced Fos expression in only four regions: the tenia tecta, lateral habenula, dorsal raphe and laterodorsal tegmental nucleus. NCS-382 (50mg/kg) had no effect on GHB-induced sedation or Fos expression. When given alone, both NCS-382 and SCH 50911 increased Fos expression in the bed nucleus of the stria terminalis, central amygdala, parasubthalamic nucleus and nucleus of the solitary tract. SCH 50911 alone affected the Islands of Calleja and the medial, central and paraventricular thalamic nuclei. Overall, this study shows a surprising lack of reversal of GHB-induced Fos expression by two relevant antagonists, both of which have marked intrinsic actions. This may reflect the limited doses tested but also suggests that GHB Fos expression reflects mechanisms independent of GHB and GABAB receptors. PMID

  7. Hypertonicity sensing in organum vasculosum lamina terminalis neurons: a mechanical process involving TRPV1 but not TRPV4.

    PubMed

    Ciura, Sorana; Liedtke, Wolfgang; Bourque, Charles W

    2011-10-12

    Primary osmosensory neurons in the mouse organum vasculosum lamina terminalis (OVLT) transduce hypertonicity via the activation of nonselective cation channels that cause membrane depolarization and increased action potential discharge, and this effect is absent in mice lacking expression of the transient receptor potential vanilloid 1 (Trpv1) gene (Ciura and Bourque, 2006). However other experiments have indicated that channels encoded by Trpv4 also contribute to central osmosensation in mice (Liedtke and Friedman, 2003; Mizuno et al., 2003). At present, the mechanism by which hypertonicity modulates cation channels in OVLT neurons is unknown, and it remains unclear whether Trpv1 and Trpv4 both contribute to this process. Here, we show that physical shrinking is necessary and sufficient to mediate hypertonicity sensing in OVLT neurons isolated from adult mice. Steps coupling progressive decreases in cell volume to increased neuronal activity were quantitatively equivalent whether shrinking was evoked by osmotic pressure or mechanical aspiration. Finally, modulation of OVLT neurons by tonicity or mechanical stimulation was unaffected by deletion of trpv4 but was abolished in cells lacking Trpv1 or wild-type neurons treated with the TRPV1 antagonist SB366791. Thus, hypertonicity sensing is a mechanical process requiring Trpv1, but not Trpv4. PMID:21994383

  8. The organum vasculosum laminae terminalis in immune-to-brain febrigenic signaling: a reappraisal of lesion experiments.

    PubMed

    Romanovsky, Andrej A; Sugimoto, Naotoshi; Simons, Christopher T; Hunter, William S

    2003-08-01

    The organum vasculosum laminae terminalis (OVLT) has been proposed to serve as the interface for blood-to-brain febrigenic signaling, because ablation of this structure affects the febrile response. However, lesioning the OVLT causes many "side effects" not fully accounted for in the fever literature. By placing OVLT-lesioned rats on intensive rehydration therapy, we attempted to prevent these side effects and to evaluate the febrile response in their absence. After the OVLT of Sprague-Dawley rats was lesioned electrolytically, the rats were given access to 5% sucrose for 1 wk to stimulate drinking. Sucrose consumption and body mass were monitored. The animals were examined twice a day for signs of dehydration and treated with isotonic saline (50 ml/kg sc) when indicated. This protocol eliminated mortality but not several acute and chronic side effects stemming from the lesion. The acute effects included adipsia and gross (14% of body weight) emaciation; chronic effects included hypernatremia, hyperosmolality, a suppressed drinking response to hypertonic saline, and previously unrecognized marked (by approximately 2 degrees C) and long-lasting (>3 wk) hyperthermia. Because the hyperthermia was not accompanied by tail skin vasoconstriction, it likely reflected increased thermogenesis. After the rats recovered from the acute (but not chronic) side effects, their febrile response to IL-1beta (500 ng/kg iv) was tested. The sham-operated rats developed typical monophasic fevers ( approximately 0.5 degrees C), the lesioned rats did not. However, the absence of the febrile response in the OVLT-lesioned rats likely resulted from the untreatable side effects. For example, hyperthermia at the time of pyrogen injection was high enough (39-40 degrees C) to solely prevent fever from developing. Hence, the changed febrile responsiveness of OVLT-lesioned animals is given an alternative interpretation, unrelated to febrigenic signaling to the brain. PMID:12714358

  9. Neuroanatomical relationships between FMRFamide-immunoreactive components of the nervus terminalis and the topology of olfactory bulbs in teleost fish.

    PubMed

    D'Aniello, Biagio; Polese, Gianluca; Luongo, Luciano; Scandurra, Anna; Magliozzi, Laura; Aria, Massimo; Pinelli, Claudia

    2016-04-01

    The nervus terminalis (NT) is the most anterior of the vertebrate cranial nerves. In teleost fish, the NT runs across all olfactory components and shows high morphological variability within this taxon. We compare the anatomical distribution, average number and size of the FMRFamide-immunoreactive (ir) NT cells of fourteen teleost species with different positions of olfactory bulbs (OBs) with respect to the ventral telencephalic area. Based on the topology of the OBs, three different neuroanatomical organizations of the telencephalon can be defined, viz., fish having sessile (Type I), pseudosessile (short stalked; Type II) or stalked (Type III) OBs. Type III topology of OBs appears to be a feature associated with more basal species, whereas Types I and II occur in derived and in basal species. The displacement of the OBs is positively correlated with the peripheral distribution of the FMRFamide-ir NT cells. The number of cells is negatively correlated with the size of the cells. A dependence analysis related to the type of OB topology revealed a positive relationship with the number of cells and with the size of the cells, with Type I and II topologies of OBs showing significantly fewer cells and larger cells than Type III. A dendrogram based on similarities obtained by taking into account all variables under study, i.e., the number and size of the FMRFamide-ir NT cells and the topology of OBs, does not agree with the phylogenetic relationships amongst species, suggesting that divergent or convergent evolutionary phenomena produced the olfactory components studied. PMID:26453401

  10. Differential co-localization with choline acetyltransferase in nervus terminalis suggests functional differences for GnRH isoforms in bonnethead sharks (Sphyrna tiburo).

    PubMed

    Moeller, John F; Meredith, Michael

    2010-12-17

    The nervus terminalis (NT) is a vertebrate cranial nerve whose function in adults is unknown. In bonnethead sharks, the nerve is anatomically independent of the olfactory system, with two major cell populations within one or more ganglia along its exposed length. Most cells are immunoreactive for either gonadotropin-releasing hormone (GnRH) or RF-amide-like peptides. To define further the cell populations and connectivity, we used double-label immunocytochemistry with antisera to different isoforms of GnRH and to choline acetyltransferase (ChAT). The labeling patterns of two GnRH antisera revealed different populations of GnRH-immunoreactive (ir) cell profiles in the NT ganglion. One antiserum labeled a large group of cells and fibers, which likely contain mammalian GnRH (GnRH-I) as described in previous studies and which were ChAT immunoreactive. The other antiserum labeled large club-like structures, which were anuclear, and a sparse number of fibers, but with no clear labeling of cell bodies in the ganglion. These club structures were choline acetyltrasferase (ChAT)-negative, and preabsorption control tests suggest they may contain chicken-GnRH-II (GnRH-II) or dogfish GnRH. The second major NT ganglion cell-type was immunoreactive for RF-amides, which regulate GnRH release in other vertebrates, and may provide an intraganglionic influence on GnRH release. The immunocytochemical and anatomical differences between the two GnRH-immunoreactive profile types indicate possible functional differences for these isoforms in the NT. The club-like structures may be sites of GnRH release into the general circulation since these structures were observed near blood vessels and resembled structures seen in the median eminence of rats. PMID:20950589

  11. Combined effects of dietary fructooligosaccharide and Bacillus licheniformis on innate immunity, antioxidant capability and disease resistance of triangular bream (Megalobrama terminalis).

    PubMed

    Zhang, Chun-Nuan; Li, Xiang-Fei; Xu, Wei-Na; Jiang, Guang-Zhen; Lu, Kang-Le; Wang, Li-Na; Liu, Wen-Bin

    2013-11-01

    This study was conducted to investigate the effects of fructooligosaccharide (FOS) and Bacillus licheniformis (B. licheniformis) and their interaction on innate immunity, antioxidant capability and disease resistance of triangular bream Megalobrama terminalis (average initial weight 30.5 ± 0.5 g). Nine experimental diets were formulated to contain three FOS levels (0, 0.3% and 0.6%) and three B. licheniformis levels (0, 1 × 10(7), 5 × 10(7) CFU g(-1)) according to a 3 × 3 factorial design. At the end of the 8-week feeding trial, fish were challenged by Aeromonas hydrophila (A. hydrophila) and survival rate was recorded for the next 7 days. The results showed that leucocyte counts, alternative complement activity as well as total serum protein and globulin contents all increased significantly (P < 0.05) as dietary B. licheniformis levels increased from 0 to 1 × 10(7) CFU g(-1), while little difference (P > 0.05) was observed in these parameters in terms of dietary FOS levels. Both plasma alkaline phosphatase and phenoloxidase activities were significantly (P < 0.05) affected only by dietary FOS levels with the highest values observed in fish fed 0.6 and 0.3% FOS, respectively. Both immunoglobulin M content and liver superoxide dismutase (SOD) activity were significantly affected (P > 0.05) by both FOS and B. licheniformis. Liver catalase, glutathione peroxidase as well as plasma SOD activities of fish fed 1 × 10(7) CFU g(-1)B. licheniformis were all significantly (P < 0.05) higher than that of the other groups, whereas the opposite was true for malondialdehyde content. After A. hydrophila challenge, survival rate was not affected (P > 0.05) by either FOS levels or B. licheniformis contents, whereas a significant (P < 0.05) interaction between these two substances was observed with the highest value observed in fish fed 0.3% FOS and 1 × 10(7) CFU g(-1)B. licheniformis. The results of this study indicated that dietary FOS and B. licheniformis could

  12. Enhanced anxiety and stress-induced corticosterone release are associated with increased Crh expression in a mouse model of Rett syndrome

    PubMed Central

    McGill, Bryan E.; Bundle, Sharyl F.; Yaylaoglu, Murat B.; Carson, James P.; Thaller, Christina; Zoghbi, Huda Y.

    2006-01-01

    Rett syndrome (RTT), a postnatal neurodevelopmental disorder, is caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Children with RTT display cognitive and motor abnormalities as well as autistic features. We studied mice bearing a truncated Mecp2 allele (Mecp2308/Y mice) and found evidence of increased anxiety-like behavior and an abnormal stress response as evidenced by elevated serum corticosterone levels. We found increased corticotropin-releasing hormone (Crh) gene expression in the paraventricular nucleus of the hypothalamus, the central amygdala, and the bed nucleus of the stria terminalis. Finally, we discovered that MeCP2 binds the Crh promoter, which is enriched for methylated CpG dinucleotides. In contrast, the MeCP2308 protein was not detected at the Crh promoter. This study identifies Crh as a target of MeCP2 and implicates Crh overexpression in the development of specific features of the Mecp2308/Y mouse, thereby providing opportunities for clinical investigation and therapeutic intervention in RTT. PMID:17108082

  13. Unbiased Stereological Estimation of the Spiral Ligament and Stria Vascularis Volumes in Aging and Ménière’s Disease Using Archival Human Temporal Bones

    PubMed Central

    Ishiyama, Gail; Tokita, Joshua; Lopez, Ivan; Tang, Yong

    2006-01-01

    The present study applies the unbiased stereological technique—Cavalieri principle to measure the volumes of the stria vascularis (SV) and the spiral ligament (SL) using postmortem archival human temporal bones from normal young and older subjects and subjects with Ménière’s disease. Normative data was obtained from subjects without ages ranging from 15 to 84 years old who had no history of audiovestibular disease (N = 25). For comparison purposes, the normative specimens were divided into three groups: group 1 (n = 8) had ages ranging from 15 to 38 years old, average age = 23.9; group 2 (n = 8) had ages ranging from 51 to 59 years old, average age = 55.1; group 3 (n = 9) had ages ranging from 64 to 84 years old, average age = 74.3. The average SV volume of group 3 (0.479 mm3) was significantly lower than that of group 1 (0.705 mm3) (p < 0.0005) and was significantly lower than that of group 2 (0.603 mm3) (p = 0.01). The average SL volume of group 3 (8.42 mm3) was significantly lower than that of group 1 (9.54 mm3) (p<0.05), but was not significantly lower than that of group 2 (8.58 mm3). Five subjects with Ménière’s disease, confirmed by histopathological examination (ages ranging from 63 to 91 years old, average age = 73.4), were studied. The average SV volume in Ménière’s subjects (0.378 mm3) was significantly lower than age-matched controls (p<0.05). The average SL volume in Ménière’s subjects (7.01 mm3) was also significantly lower than age-matched controls (p<0.05). The SV and SL volumes were unaffected by gender. The present study demonstrates for the first time the use of the unbiased stereological technique—Cavalieri principle—as a reliable and efficient method to obtain volumetric estimates of the SV and the SL by using archival human temporal bone specimens. PMID:17160359

  14. Unexpected presence of graminan- and levan-type fructans in the evergreen frost-hardy eudicot Pachysandra terminalis (Buxaceae): purification, cloning, and functional analysis of a 6-SST/6-SFT enzyme.

    PubMed

    Van den Ende, Wim; Coopman, Marlies; Clerens, Stefan; Vergauwen, Rudy; Le Roy, Katrien; Lammens, Willem; Van Laere, André

    2011-01-01

    About 15% of flowering plants accumulate fructans. Inulin-type fructans with β(2,1) fructosyl linkages typically accumulate in the core eudicot families (e.g. Asteraceae), while levan-type fructans with β(2,6) linkages and branched, graminan-type fructans with mixed linkages predominate in monocot families. Here, we describe the unexpected finding that graminan- and levan-type fructans, as typically occurring in wheat (Triticum aestivum) and barley (Hordeum vulgare), also accumulate in Pachysandra terminalis, an evergreen, frost-hardy basal eudicot species. Part of the complex graminan- and levan-type fructans as accumulating in vivo can be produced in vitro by a sucrose:fructan 6-fructosyltransferase (6-SFT) enzyme with inherent sucrose:sucrose 1-fructosyltransferase (1-SST) and fructan 6-exohydrolase side activities. This enzyme produces a series of cereal-like graminan- and levan-type fructans from sucrose as a single substrate. The 6-SST/6-SFT enzyme was fully purified by classic column chromatography. In-gel trypsin digestion led to reverse transcription-polymerase chain reaction-based cDNA cloning. The functionality of the 6-SST/6-SFT cDNA was demonstrated after heterologous expression in Pichia pastoris. Both the recombinant and native enzymes showed rather similar substrate specificity characteristics, including peculiar temperature-dependent inherent 1-SST and fructan 6-exohydrolase side activities. The finding that cereal-type fructans accumulate in a basal eudicot species further confirms the polyphyletic origin of fructan biosynthesis in nature. Our data suggest that the fructan syndrome in P. terminalis can be considered as a recent evolutionary event. Putative connections between abiotic stress and fructans are discussed. PMID:21037113

  15. Unexpected Presence of Graminan- and Levan-Type Fructans in the Evergreen Frost-Hardy Eudicot Pachysandra terminalis (Buxaceae): Purification, Cloning, and Functional Analysis of a 6-SST/6-SFT Enzyme1[W

    PubMed Central

    Van den Ende, Wim; Coopman, Marlies; Clerens, Stefan; Vergauwen, Rudy; Le Roy, Katrien; Lammens, Willem; Van Laere, André

    2011-01-01

    About 15% of flowering plants accumulate fructans. Inulin-type fructans with β(2,1) fructosyl linkages typically accumulate in the core eudicot families (e.g. Asteraceae), while levan-type fructans with β(2,6) linkages and branched, graminan-type fructans with mixed linkages predominate in monocot families. Here, we describe the unexpected finding that graminan- and levan-type fructans, as typically occurring in wheat (Triticum aestivum) and barley (Hordeum vulgare), also accumulate in Pachysandra terminalis, an evergreen, frost-hardy basal eudicot species. Part of the complex graminan- and levan-type fructans as accumulating in vivo can be produced in vitro by a sucrose:fructan 6-fructosyltransferase (6-SFT) enzyme with inherent sucrose:sucrose 1-fructosyltransferase (1-SST) and fructan 6-exohydrolase side activities. This enzyme produces a series of cereal-like graminan- and levan-type fructans from sucrose as a single substrate. The 6-SST/6-SFT enzyme was fully purified by classic column chromatography. In-gel trypsin digestion led to reverse transcription-polymerase chain reaction-based cDNA cloning. The functionality of the 6-SST/6-SFT cDNA was demonstrated after heterologous expression in Pichia pastoris. Both the recombinant and native enzymes showed rather similar substrate specificity characteristics, including peculiar temperature-dependent inherent 1-SST and fructan 6-exohydrolase side activities. The finding that cereal-type fructans accumulate in a basal eudicot species further confirms the polyphyletic origin of fructan biosynthesis in nature. Our data suggest that the fructan syndrome in P. terminalis can be considered as a recent evolutionary event. Putative connections between abiotic stress and fructans are discussed. PMID:21037113

  16. Aggression- and sex-induced neural activity across vasotocin populations in the brown anole.

    PubMed

    Kabelik, David; Alix, Veronica C; Burford, Emily R; Singh, Leah J

    2013-03-01

    Activity within the social behavior neural network is modulated by the neuropeptide arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin (AVP). However, central AVT/AVP release causes different behavioral effects across species and social environments. These differences may be due to the activation of different neuronal AVT/AVP populations or to similar activity patterns causing different behavioral outputs. We examined neural activity (assessed as Fos induction) within AVT neurons in male brown anole lizards (Anolis sagrei) participating in aggressive or sexual encounters. Lizards possess simple amniote nervous systems, and their examination provides a comparative framework to complement avian and mammalian studies. In accordance with findings in other species, AVT neurons in the anole paraventricular nucleus (PVN) were activated during aggressive encounters; but unlike in other species, a positive correlation was found between aggression levels and activation. Activation of AVT neurons within the supraoptic nucleus (SON) occurred nonspecifically with participation in either aggressive or sexual encounters. Activation of AVT neurons in the preoptic area (POA) and bed nucleus of the stria terminalis (BNST) was associated with engagement in sexual behaviors. The above findings are congruent with neural activation patterns observed in other species, even when the behavioral outputs (i.e., aggression level) differed. However, aggressive encounters also increased activation of AVT neurons in the BNST, which is incongruous with findings in other species. Thus, some species differences involve the encoding of social stimuli as different neural activation patterns within the AVT/AVP network, whereas other behavioral differences arise downstream of this system. PMID:23201179

  17. Sexual dimorphism of arg-vasotocin gene expressing neurons in the telencephalon and dorsal diencephalon of the domestic fowl. An immunocytochemical and in situ hybridization study.

    PubMed

    Jurkevich, A; Barth, S W; Grossmann, R

    1997-01-01

    A strong sex dimorphism in the distribution of immunoreactive arginine-vasotocin (AVT) and AVT mRNA was observed in telencephalic and dorsal diencephalic areas of the domestic fowl using immunocytochemistry and in situ hybridization. Two subgroups of immunoreactive parvocellular perikarya surrounded by dense plexus of immunoreactive fibres were found within the bed nucleus of the stria terminalis and the dorsal part of the diencephalic paraventricular region of males. No signs of immunoreactivity were observed within corresponding regions of the female brain. Instead, in females a few scattered weakly stained perikarya were observed rostrally to the level of the anterior commissure, juxtapositioned to the nucleus accumbens and the floor of the lateral ventricle. The distribution of AVT mRNA containing cell profiles fully confirmed the immunocytochemical findings. Osmotic stress induced by water deprivation for 48 h had no influence on the number of immunoreactive or AVT mRNA containing parvocellular cell bodies. However, it resulted in an increase of immunoreactive cell area in the bed nucleus of the stria terminalis and dorsal diencephalon of 5. 9 and 11.7%, respectively. We suggest that the sexually dimorphic vasotocinergic circuit may be involved in the co-ordination of behavioural and autonomic functions in response to environmental stress. PMID:9011403

  18. A non-peptide oxytocin receptor agonist, WAY-267,464, alleviates novelty-induced hypophagia in mice: insights into changes in c-Fos immunoreactivity.

    PubMed

    Olszewski, Pawel K; Ulrich, Christine; Ling, Nicholas; Allen, Kerry; Levine, Allen S

    2014-09-01

    Anxiety caused by the novelty of food or of the environment where the food is presented leads to suppression of consumption (hyponeophagia) reflected by an increased latency to begin feeding and decreased food intake. Studies suggest that some anxiolytics, mainly benzodiazepines and SSRIs, resolve hyponeophagia. Though the neurohormone oxytocin (OT) affects both anxiety responsiveness and feeding-related homeostasis, the link between OT and hyponeophagia has not been established. The current experiments examined the effect of OT receptor stimulation on hyponeophagia in mice and associated changes in brain activity. We found that the OT receptor agonist, WAY-267,464, at 10 and 30 mg/kg b. wt. IP, reduced the latency to approach food and increased the amount of food eaten in hyponeophagia tests differing in animals' motivation to eat (hunger, reward) and the anxiogenic context of environmental novelty (illumination and type of the cage). This effect was abolished by the pretreatment with the OT receptor antagonist, L-368,899, at 10mg/kg b. wt. The antagonist also suppressed social transmission of preference for novel food. Mice subjected to novelty conditions causing hypophagia showed significant changes in c-Fos immunoreactivity in the hippocampus, lateral septum, cingulate and piriform cortex and in the bed nucleus of the stria terminalis, lateral division, posterolateral part (STLP). The pretreatment with WAY-267,464 restored c-Fos levels in the STLP to values detected in control animals subjected to non-anxiogenic conditions. We conclude that OT plays a role in shaping the magnitude of the novelty stress-provoked hypophagia and the activity of the relevant neural networks. PMID:25038444

  19. Alcohol consumption increases locomotion in an open field and induces Fos-immunoreactivity in reward and approach/withdrawal-related neurocircuitries.

    PubMed

    Wscieklica, Tatiana; de Barros Viana, Milena; Le Sueur Maluf, Luciana; Pouza, Kathlein Cristiny Peres; Spadari, Regina Célia; Céspedes, Isabel Cristina

    2016-02-01

    Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take the drug, loss of control in limiting intake and, eventually, the emergence of a negative emotional state when access to the drug is prevented. Both dopamine and corticotropin-releasing factor (CRF)-mediated systems seem to play important roles in the modulation of alcohol abuse and dependence. The present study investigated the effects of alcohol consumption on anxiety and locomotor parameters and on the activation of dopamine and CRF-innervated brain regions. Male Wistar rats were given a choice of two bottles for 31 days, one containing water and the other a solution of saccharin + alcohol. Control animals only received water and a solution of 0.2% saccharin. On the 31st day, animals were tested in the elevated plus-maze and open field, and euthanized immediately after the behavioral tests. An independent group of animals was treated with ethanol and used to measure blood ethanol concentration. Results showed that alcohol intake did not alter behavioral measurements in the plus-maze, but increased the number of crossings in the open field, an index of locomotor activity. Additionally, alcohol intake increased Fos-immunoreactivity (Fos-ir) in the prefrontal cortex, in the shell region of the nucleus accumbens, in the medial and central amygdala, in the bed nucleus of the stria terminalis, in the septal region, and in the paraventricular and dorsomedial hypothalamus, structures that have been linked to reward and to approach/withdrawal behavior. These observations might be relevant to a better understanding of the behavioral and physiological alterations that follow alcohol consumption. PMID:26786746

  20. Anti-clarin-1 AAV-delivered ribozyme induced apoptosis in the mouse cochlea.

    PubMed

    Aarnisalo, A A; Pietola, L; Joensuu, J; Isosomppi, J; Aarnisalo, P; Dinculescu, A; Lewin, A S; Flannery, J; Hauswirth, W W; Sankila, E-M; Jero, J

    2007-08-01

    Usher syndrome type 3 is caused by mutations in the USH3A gene, which encodes the protein clarin-1. Clarin-1 is a member of the tetraspanin superfamily (TM4SF) of transmembrane proteins, expressed in the organ of Corti and spiral ganglion cells of the mouse ear. We have examined whether the AAV-mediated anti-clarin ribozyme delivery causes apoptotic cell death in vivo in the organ of Corti. We used an AAV-2 vector delivered hammerhead ribozyme, AAV-CBA-Rz, which specifically recognizes and cleaves wild type mouse clarin-1 mRNA. Cochleae of CD-1 mice were injected either with 1mul of the AAV-CBA-Rz, or control AAV vectors containing the green fluorescent protein (GFP) marker gene (AAV-CBA-GFP). Additional controls were performed with saline only. At one-week and one-month post-injection, the animals were sacrificed and the cochleae were studied by histology and fluorescence imaging. Mice injected with AAV-CBA-GFP displayed GFP reporter expression of varying fluorescence intensity throughout the length of the cochlea in the outer and inner hair cells and stria vascularis, and to a lesser extent, in vestibular epithelial cells. GFP expression was not detectable in the spiral ganglion. The pro-apoptotic effect of AAV-CBA-delivered anti-clarin-1 ribozymes was evaluated by TUNEL-staining. We observed in the AAV-CBA-Rz, AAV-CBA-GFP and saline control groups apoptotic nuclei in the outer and inner hair cells and in the stria vascularis one week after the microinjection. The vestibular epithelium was also observed to contain apoptotic cells. No TUNEL-positive spiral ganglion neurons were detected. After one-month post-injection, the AAV-CBA-Rz-injected group had significantly more apoptotic outer and inner hair cells and cells of the stria vascularis than the AAV-CBA-GFP group. In this study, we demonstrate that AAV-CBA mediated clarin-1 ribozyme may induce apoptosis of the cochlear hair cells and cells of the stria vascularis. Surprisingly, we did not observe apoptosis in

  1. The paracrine effect of mesenchymal human stem cells restored hearing in β-tubulin induced autoimmune sensorineural hearing loss.

    PubMed

    Yoo, T J; Du, Xiaoping; Zhou, Bin

    2015-12-01

    The aim of this study was to examine the activities of hASCs (Human Adipose tissue Derived Stem Cells) on experimental autoimmune hearing loss (EAHL) and how human stem cells regenerated mouse cochlea cells. We have restored hearing in 19 years old white female with autoimmune hearing loss with autologous adipose tissue derived stem cells and we wish to understand the mechanism of restoration of hearing in animal model. BALB/c mice underwent to develop EAHL; mice with EAHL were given hASCs intraperitoneally once a week for 6 consecutive weeks. ABR were examined over time. The helper type 1 autoreactive responses and T-reg cells were examined. H&E staining or immunostaining with APC conjugated anti-HLA-ABC antibody were conducted. The organ of Corti, stria vascularis, spira ligament and spiral ganglion in stem cell group are normal. In control group, without receiving stem cells, the organ of Corti is replaced by a single layer of cells, atrophy of stria vascularis. Systemic infusion of hASCs significantly improved hearing function and protected hair cells in established EAHL. The hASCs decreased the proliferation of antigen specific Th1/Th17 cells and induced the production of anti-inflammatory cytokine interleukin10 in splenocytes. They also induced the generation of antigen specific CD4(+)CD25(+)Foxp3(+)T-reg cells. The experiment showed the restoration is due to the paracrine activities of human stem cells, since there are newly regenerated mice spiral ganglion cells, not human mesenchymal stem cells derived tissue given by intraperitoneally. PMID:26235980

  2. Central mechanisms involved in pilocarpine-induced pressor response.

    PubMed

    Takakura, Ana C; Moreira, Thiago S; Borella, Thais L; Paulin, Renata F; Colombari, Débora S A; De Luca, Laurival A; Colombari, Eduardo; Menani, José V

    2011-10-28

    Pilocarpine (cholinergic muscarinic agonist) injected peripherally may act centrally to produce pressor responses; in the present study, using c-fos immunoreactive expression, we investigated the forebrain and brainstem areas activated by pressor doses of intravenous (i.v.) pilocarpine. In addition, the importance of vasopressin secretion and/or sympathetic activation and the effects of lesions in the anteroventral third ventricle (AV3V) region in awake rats were also investigated. In male Holtzman rats, pilocarpine (0.04 to 4μmol/kg b.w.) i.v. induced transitory hypotension followed by long lasting hypertension. Sympathetic blockade with prazosin (1mg/kg b.w.) i.v. or AV3V lesions (1 day) almost abolished the pressor response to i.v. pilocarpine (2μmol/kg b.w.), whereas the vasopressin antagonist (10μg/kg b.w.) i.v. reduced the response to pilocarpine. Pilocarpine (2 and 4μmol/kg b.w.) i.v. increased the number of c-fos immunoreactive cells in the subfornical organ, paraventricular and supraoptic nuclei of the hypothalamus, organ vasculosum of the lamina terminalis, median preoptic nucleus, nucleus of the solitary tract and caudal and rostral ventrolateral medulla. These data suggest that i.v. pilocarpine activates specific forebrain and brainstem mechanisms increasing sympathetic activity and vasopressin secretion to induce pressor response. PMID:21689994

  3. Inhibitors of Histone Deacetylases Attenuate Noise-Induced Hearing Loss.

    PubMed

    Chen, Jun; Hill, Kayla; Sha, Su-Hua

    2016-08-01

    Loss of auditory sensory hair cells is the major pathological feature of noise-induced hearing loss (NIHL). Currently, no established clinical therapies for prevention or amelioration of NIHL are available. The absence of treatments is due to our lack of a comprehensive understanding of the molecular mechanisms underlying noise-induced damage. Our previous study indicates that epigenetic modification of histones alters hair cell survival. In this study, we investigated the effect of noise exposure on histone H3 lysine 9 acetylation (H3K9ac) in the inner ear of adult CBA/J mice and determined if inhibition of histone deacetylases by systemic administration of suberoylanilide hydroxamic acid (SAHA) could attenuate NIHL. Our results showed that H3K9ac was decreased in the nuclei of outer hair cells (OHCs) and marginal cells of the stria vascularis in the basal region after exposure to a traumatic noise paradigm known to induce permanent threshold shifts (PTS). Consistent with these results, levels of histone deacetylases 1, 2, and 3 (HDAC1, HDAC2 and HDAC3) were increased predominately in the nuclei of cochlear cells. Silencing of HDAC1, HDAC2, or HDAC3 with siRNA reduced the expression of the target HDAC in OHCs, but did not attenuate noise-induced PTS, whereas treatment with the pan-HDAC inhibitor SAHA, also named vorinostat, reduced OHC loss, and attenuated PTS. These findings suggest that histone acetylation is involved in the pathogenesis of noise-induced OHC death and hearing loss. Pharmacological targeting of histone deacetylases may afford a strategy for protection against NIHL. PMID:27095478

  4. Neural pathways that mediate the effects of afferent stimuli on paraventricular nucleus multiunit activity in freely moving rats.

    PubMed

    Mor, G; Saphier, D; Feldman, S

    1987-01-01

    The direct involvement of the hypothalamic paraventricular nucleus (PVN) in the control of adrenocortical secretion is now generally accepted. In order to contribute to our understanding of the electrical activity of cells in this region during adrenocortical activation, we have recorded multiunit electrical activity (MUA) in response to acute neural stimuli in freely moving male rats and have examined the pathways involved. Photic, acoustic, olfactory, and sciatic nerve stimulation all increased PVN MUA by between 130% and 250%. These responses were selectively blocked, according to the stimulus modality tested, by radiofrequency lesions of central neural structures. Thus PVN responses to photic stimulation were blocked by lesions of the suprachiasmatic nuclei and reduced by mammillary peduncle lesions but were unaffected by lesions of the bed nuclei of the stria terminalis. Responses to acoustic stimulation were blocked by lesions of the mammillary peduncles but not by those placed in the suprachiasmatic nuclei, the septum, or the bed nuclei of the stria terminalis. Lesions of the septum blocked the response to sciatic nerve stimulation but did not affect the response to olfactory stimulation with amyl acetate fumes, which was blocked by lesions of the bed nuclei of the stria terminalis. The data confirm those obtained in endocrine studies concerning the neural pathways involved in the transmission of neural stimuli that produce adrenocortical activation. PMID:3625806

  5. Mitochondria toxin-induced acute cochlear cell death indicates cellular activity-correlated energy consumption.

    PubMed

    Zou, Jing; Zhang, Ya; Zhang, Weikai; Poe, Dennis; Zhai, Suoqiang; Yang, Shiming; Pyykkö, Ilmari

    2013-09-01

    The different cell types within the cochlea may have a specific contribution to the pathological changes during metabolism failure, which may provide clues for developing novel strategies for inner ear therapy. In order to evaluate activity-correlated cell death during metabolism failure in the cochlea, 3-nitropropionic acid was used to irreversibly inhibit the respiratory chain. Dose-response of the cochlear cells to 3-nitropropionic acid was analyzed in vitro. 3-Nitropropionic acid was administered onto the round window of guinea pigs. Cell death was identified by terminal transferase labeling the free 3'OH breaks in the DNA strands in vivo and propidium iodide nuclear permeation in vitro. As a result, 23.6 and 96.3 % cell death were induced by 10 and 100 mM 3-nitropropionic acid, respectively, in vitro. In the guinea pigs, 500 mM 3-nitropropionic acid induced vestibular dysfunction and severe to profound hearing losses. The cells that are the most sensitive to 3-nitropropionic acid treatment include the stria marginal and intermediate cells, epithelial cells of the Reissner's membrane, and spiral ligament fibrocytes (types II and V). Moderate sensitive cells were satellite fibrocytes of the spiral limbic central zone, osteocytes of the cochlear shell, hair cells, and spiral ganglion cells. Reduction of neurofilament in the soma and periphery processes of spiral ganglion cells occurred after the exposure. These results may be relevant to the mechanisms of injury in sudden onset sensorineural hearing loss and hazardous substance exposure-induced hearing loss. PMID:23179932

  6. Cadmium and naphthalene-induced hyperglycemia in the fiddler crab, Uca pugilator: Differential modes of action on the neutroendocrine system

    SciTech Connect

    Reddy, P.S.; Katyayani, R.V.; Fingerman, M.

    1996-03-01

    Hyperglycemia is a typical response of aquatic organisms to heavy metals. In crustaceans, the medulla terminalis X-organ-sinus gland neuroendocrine complex in the eyestalk is the source of the crustacean hyperglycemic hormone (CHH). The role of CHH in pollutant-induced b1ood glucose changes has only recently begun to be studied. Reddy provided evidence that CHH mediates cadmium-induced hyperglycemia in the red swamp crayfish, Procambarus clarkii. In a study of another hormonally-regulated function, color changes, cadmium exposure resulted in pigment in the melanophores of the fiddler crab, Uca pugilator, becoming less dispersed than in unexposed crabs. Earlier studies showed that, like cadmium, both a PCB, Aroclor 1242, and naphthalene induced black pigment aggregation in Uca poor. In general, when crabs are exposed to a pollutant, hydrocarbon or cadmium, they aggregate the pigment in their melanophores, but apparently by different mechanisms. Hydrocarbons appear to inhibit release of black pigment-dispersing hormone (BDPH), whereas cadmium appears to inhibit its synthesis. These apparent different modes of action of cadmium and naphthalene on the color change mechanism led us to compare the impact of these pollutants on the hormonal regulation of blood glucose in Uca pugilator. The present study was performed to determine (1) whether cadmium and naphthalene induce hyperglycemia in Uca pugilator, (2) whether CH has a role, if naphthalene and cadmium do induce hyperglycemia, and (3) the effects, if any, of cadmium and naphthalene on CHH activity in the eyestalk neuroendocrine complex.

  7. Experimental estrogen-induced hyperprolactinemia results in bone-related hearing loss in the guinea pig.

    PubMed

    Horner, Kathleen C; Cazals, Yves; Guieu, Régis; Lenoir, Marc; Sauze, Nicole

    2007-11-01

    Our group (Horner KC, Guieu R, Magnan J, Chays A, Cazals Y. Neuropsychopharmacology 26: 135-138, 2002) has earlier described hyperprolactinemia in some patients presenting inner ear dysfunction. However, in that study, it was not possible to determine whether hyperprolactinemia was a cause or an effect of the symptoms. To investigate the effect of hyperprolactinemia on inner ear function, we first developed a model of hyperprolactinemia in estrogen-primed Fischer 344 rats and then performed functional studies on pigmented guinea pigs. Hyperprolactinemia induced, after 2 mo, a hearing loss of approximately 30-40 dB across all frequencies, as indicated by the compound action potential audiogram. During the 3rd mo, the hearing loss continued to deteriorate. The threshold shifts were more substantial in males than in females. Observations under a dissection microscope revealed bone dysmorphology of the bulla and the cochlea. Light microscopy observations of cryostat sections confirmed bone-related pathology of the bony cochlear bulla and the cochlear wall and revealed morphopathology of the stria vascularis and spiral ligament. Scanning electron microscopy revealed loss of hair cells and stereocilia damage, in particular in the upper three cochlear turns and the two outermost hair cell rows. The data provide the first evidence of otic capsule and hair cell pathology associated with estrogen-induced prolonged hyperprolactinemia and suggest that conditions such as pregnancy, anti-psychotic drug treatment, aging, and/or stress might lead to similar ear dysfunctions. PMID:17711987

  8. JAK2/STAT3 Inhibition Attenuates Noise-Induced Hearing Loss

    PubMed Central

    Wilson, Teresa; Omelchenko, Irina; Foster, Sarah; Zhang, Yuan; Shi, Xiaorui; Nuttall, Alfred L.

    2014-01-01

    Signal transducers and activators of transcription 3 (STAT3) is a stress responsive transcription factor that plays a key role in oxidative stress-mediated tissue injury. As reactive oxygen species (ROS) are a known source of damage to tissues of the inner ear following loud sound exposure, we examined the role of the Janus kinase 2 (JAK2)/STAT3 signaling pathway in noise induce hearing loss using the pathway specific inhibitor, JSI-124. Mice were exposed to a moderately damaging level of loud sound revealing the phosphorylation of STAT3 tyrosine 705 residues and nuclear localization in many cell types in the inner ear including the marginal cells of the stria vascularis, type II, III, and IV fibrocytes, spiral ganglion cells, and in the inner hair cells. Treatment of the mice with the JAK2/STAT3 inhibitor before noise exposure reduced levels of phosphorylated STAT3 Y705. We performed auditory brain stem response and distortion product otoacoustic emission measurements and found increased recovery of hearing sensitivity at two weeks after noise exposure with JAK2/STAT3 inhibition. Performance of cytocochleograms revealed improved outer hair cell survival in JSI-124 treated mice relative to control. Finally, JAK2/STAT3 inhibition reduced levels of ROS detected in outer hair cells at two hours post noise exposure. Together, these findings demonstrate that inhibiting the JAK2/STAT3 signaling pathway is protective against noise-induced cochlear tissue damage and loss of hearing sensitivity. PMID:25275304

  9. Role of the copper transporter, CTR1, in platinum-induced ototoxicity.

    PubMed

    More, Swati S; Akil, Omar; Ianculescu, Alexandra G; Geier, Ethan G; Lustig, Lawrence R; Giacomini, Kathleen M

    2010-07-14

    The goal of this study was to determine the role of an influx copper transporter, CTR1, in the ototoxicity induced by cisplatin, a potent anticancer platinum analog used in the treatment of a variety of solid tumors. As determined through reverse transcriptase-PCR (RT-PCR), quantitative RT-PCR, Western blot, and immunohistochemistry, mouse CTR1 (Ctr1) was found to be abundantly expressed and highly localized at the primary sites of cisplatin toxicity in the inner ear, mainly outer hair cells (OHCs), inner hair cells, stria vascularis, spiral ganglia, and surrounding nerves in the mouse cochlea. A CTR1 substrate, copper sulfate, decreased the uptake and cytotoxicity of cisplatin in HEI-OC1, a cell line that expresses many molecular markers reminiscent of OHCs. Small interfering RNA-mediated knockdown of Ctr1 in this cell line caused a corresponding decrease in cisplatin uptake. In mice, intratympanic administration of copper sulfate 30 min before intraperitoneal administration of cisplatin was found to prevent hearing loss at click stimulus and 8, 16, and 32 kHz frequencies. To date, the utility of cisplatin remains severely limited because of its ototoxic effects. The studies described in this report suggest that cisplatin-induced ototoxicity and cochlear uptake can be modulated by administration of a CTR1 inhibitor, copper sulfate. The possibility of local administration of CTR1 inhibitors during cisplatin therapy as a means of otoprotection is thereby raised. PMID:20631178

  10. Ventral Subiculum Stimulation Promotes Persistent Hyperactivity of Dopamine Neurons and Facilitates Behavioral Effects of Cocaine.

    PubMed

    Glangetas, Christelle; Fois, Giulia R; Jalabert, Marion; Lecca, Salvatore; Valentinova, Kristina; Meye, Frank J; Diana, Marco; Faure, Philippe; Mameli, Manuel; Caille, Stéphanie; Georges, François

    2015-12-15

    The ventral subiculum (vSUB) plays a key role in addiction, and identifying the neuronal circuits and synaptic mechanisms by which vSUB alters the excitability of dopamine neurons is a necessary step to understand the motor changes induced by cocaine. Here, we report that high-frequency stimulation of the vSUB (HFSvSUB) over-activates ventral tegmental area (VTA) dopamine neurons in vivo and triggers long-lasting modifications of synaptic transmission measured ex vivo. This potentiation is caused by NMDA-dependent plastic changes occurring in the bed nucleus of the stria terminalis (BNST). Finally, we report that the modification of the BNST-VTA neural circuits induced by HFSvSUB potentiates locomotor activity induced by a sub-threshold dose of cocaine. Our findings unravel a neuronal circuit encoding behavioral effects of cocaine in rats and highlight the importance of adaptive modifications in the BNST, a structure that influences motivated behavior as well as maladaptive behaviors associated with addiction. PMID:26628379

  11. Functional and topographic concordance of right atrial neural structures inducing sinus tachycardia.

    PubMed

    Eickholt, Christian; Mischke, Karl; Schimpf, Thomas; Knackstedt, Christian; Scherer, Kira; Pauza, Danius; Marx, Nikolaus; Shin, Dong-In; Kelm, Malte; Meyer, Christian

    2013-01-01

    Cardiorespiratory autonomic control is in tight interaction with an intracardiac neural network modulating sinus node function. To gain novel mechanistical insights and to investigate possible novel targets concerning the treatment of inadequate sinus tachycardia, we aimed to characterize functionally and topographically the right atrial neural network modulating sinus node function. In 16 sheep 3-dimensional electro-anatomical mapping of the right atrium was performed. In five animals additionally magnetically steered remote navigation was used. Selective stimulation of nerve fibers was conducted by applying high frequency (200 Hz) electrical impulses within the atrial refractory period. Histological analysis of whole heart preparations by acetylcholinesterase staining was performed and compared to the acquired neuroanatomical mapping.We found that neural stimulation in the cranial part of the right atrium, within a perimeter around the sinus node area, elicited predominantly shortening of the sinus cycle length of -20.3 ± 10.1 % (n = 80, P < 0.05). Along the course of the crista terminalis atrial premature beats (n = 117) and atrial fibrillation (n = 123) could be induced. Catheter stability was excellent during remote catheter navigation. Histological work-up (n = 4) was in accord with the distribution of neurostimulation sites. Ganglions were mainly innervated by the dorsal right-atrial subplexus, with substantial additional input from the ventral right atrial subplexus. In conclusion, our findings suggest a functional and topographic concordance of right atrial neural structures inducing sinus tachycardia. This might open up new avenues in the treatment of heart rate related disorders. PMID:23835988

  12. Regional expression of c-fos antigen in the basal forebrain following intraventricular infusions of angiotensin and its modulation by drinking either water or saline.

    PubMed

    Herbert, J; Forsling, M L; Howes, S R; Stacey, P M; Shiers, H M

    1992-12-01

    The expression of c-fos protein was examined in the basal forebrains of male rats 60 min following intracerebroventricular infusions of 250 pmol angiotensin II. Levels of corticosterone and vasopressin were also measured at the same time point. In animals not allowed access to water after infusion, angiotensin II induced intense c-fos expression in a band of neurons extending throughout the anterior region of the third ventricle region, including the organum vasculosum of the lamina terminalis, the median preoptic nucleus (nucleus medianus) and the subfornical organ. There were also high levels of expression in the hypothalamic supraoptic nucleus and the paraventricular nucleus, particularly its lateral (magnocellular) region, though other, parvicellular areas were also affected. No other area of the hypothalamus was altered. There was increased c-fos expression in the central nucleus of the amygdala and the bed nucleus of the stria terminalis. Allowing rats to drink during the 60-min survival period modified this pattern of response. c-fos was markedly reduced in the supraoptic nucleus and the paraventricular nucleus but not in the other areas examined, including the anterior region of the third ventricle and the amygdala. When water was withheld for 15 min, but then allowed, rats drank the same total volume but c-fos expression was no longer inhibited in either the supraoptic nucleus or paraventricular nucleus. When rats were given 0.9% saline to drink, they ingested about three times as much as water, but angiotensin II-induced c-fos expression was similar to that in rats denied access to water. The pattern was similar following access to 1.8% saline, though levels in the organum vasculosum of the lamina terminalis were reduced. There was a marked correlation between the number of c-fos-positive neurons in the supraoptic nucleus or paraventricular nucleus and plasma levels of corticosterone 60 min after infusion, but not with arginine-vasopressin levels. These

  13. Mesolimbic neuropeptide W coordinates stress responses under novel environments.

    PubMed

    Motoike, Toshiyuki; Long, Jeffrey M; Tanaka, Hirokazu; Sinton, Christopher M; Skach, Amber; Williams, S Clay; Hammer, Robert E; Sakurai, Takeshi; Yanagisawa, Masashi

    2016-05-24

    Neuropeptide B (NPB) and neuropeptide W (NPW) are endogenous neuropeptide ligands for the G protein-coupled receptors NPBWR1 and NPBWR2. Here we report that the majority of NPW neurons in the mesolimbic region possess tyrosine hydroxylase immunoreactivity, indicating that a small subset of dopaminergic neurons coexpress NPW. These NPW-containing neurons densely and exclusively innervate two limbic system nuclei in adult mouse brain: the lateral bed nucleus of the stria terminalis and the lateral part of the central amygdala nucleus (CeAL). In the CeAL of wild-type mice, restraint stress resulted in an inhibition of cellular activity, but this stress-induced inhibition was attenuated in the CeAL neurons of NPW(-/-) mice. Moreover, the response of NPW(-/-) mice to either formalin-induced pain stimuli or a live rat (i.e., a potential predator) was abnormal only when they were placed in a novel environment: The mice failed to show the normal species-specific self-protective and aversive reactions. In contrast, the behavior of NPW(-/-) mice in a habituated environment was indistinguishable from that of wild-type mice. These results indicate that the NPW/NPBWR1 system could play a critical role in the gating of stressful stimuli during exposure to novel environments. PMID:27140610

  14. TMT predator odor activated neural circuit in C57BL/6J mice indicates TMT-stress as a suitable model for uncontrollable intense stress.

    PubMed

    Janitzky, K; D'Hanis, W; Kröber, A; Schwegler, H

    2015-03-01

    Intense stressful events can result in chronic disorders such as posttraumatic stress disorder (PTSD). In vulnerable individuals, a single aversive experience can be sufficient to cause long-lasting behavioral changes. Candidate brain regions implicated in stress-related psychopathology are the amygdala, the bed nucleus of the stria terminalis (BNST), and the hypothalamic pituitary adrenal (HPA) axis. In rodents exposure to 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), an ethologically relevant stressor, has been shown to induce intense stress and innate anxiety responses. To study dispositions for the development of maladaptive stress responses, mice models are required. Therefore C57BL/6J mice were exposed to TMT and Fos expression was studied in key brain regions implicated in stress responses and anxiety-like behavior. Our results show TMT-induced activation of a distinct neural circuit involving the BNST, the lateral septum (LS), the paraventricular nucleus of the hypothalamus (PVN), the periaqueductal gray (PAG) and the locus coeruleus (LC). Anatomical interconnection of the BNST with all these regions could point to an important modulatory role of this nucleus. Since, the BNST gets direct input from the olfactory bulbs and projects to the PVN and PAG and is therefore well positioned to modulate behavioral and endocrine stress responses to TMT. Hence, we suggest that TMT exposure is suitable to investigate uncontrollable stress responses in mice which exhibit similarities to maladaptive stress responses underlying PTSD in humans. PMID:25532494

  15. Subcortical BOLD responses during visual sexual stimulation vary as a function of implicit porn associations in women.

    PubMed

    Borg, Charmaine; de Jong, Peter J; Georgiadis, Janniko R

    2014-02-01

    Lifetime experiences shape people's attitudes toward sexual stimuli. Visual sexual stimulation (VSS), for instance, may be perceived as pleasurable by some, but as disgusting or ambiguous by others. VSS depicting explicit penile-vaginal penetration (PEN) is relevant in this respect, because the act of penetration is a core sexual activity. In this study, 20 women without sexual complaints participated. We used functional magnetic resonance imaging and a single-target implicit association task to investigate how brain responses to PEN were modulated by the initial associations in memory (PEN-'hot' vs PEN-disgust) with such hardcore pornographic stimuli. Many brain areas responded to PEN in the same way they responded to disgust stimuli, and PEN-induced brain activity was prone to modulation by subjective disgust ratings toward PEN stimuli. The relative implicit PEN-disgust (relative to PEN-'hot') associations exclusively modulated PEN-induced brain responses: comparatively negative (PEN-disgust) implicit associations with pornography predicted the strongest PEN-related responses in the basal forebrain (including nucleus accumbens and bed nucleus of stria terminalis), midbrain and amygdala. Since these areas are often implicated in visual sexual processing, the present findings should be taken as a warning: apparently their involvement may also indicate a negative or ambivalent attitude toward sexual stimuli. PMID:23051899

  16. Subcortical BOLD responses during visual sexual stimulation vary as a function of implicit porn associations in women

    PubMed Central

    de Jong, Peter J.; Georgiadis, Janniko R.

    2014-01-01

    Lifetime experiences shape people’s attitudes toward sexual stimuli. Visual sexual stimulation (VSS), for instance, may be perceived as pleasurable by some, but as disgusting or ambiguous by others. VSS depicting explicit penile–vaginal penetration (PEN) is relevant in this respect, because the act of penetration is a core sexual activity. In this study, 20 women without sexual complaints participated. We used functional magnetic resonance imaging and a single-target implicit association task to investigate how brain responses to PEN were modulated by the initial associations in memory (PEN-‘hot’ vs PEN-disgust) with such hardcore pornographic stimuli. Many brain areas responded to PEN in the same way they responded to disgust stimuli, and PEN-induced brain activity was prone to modulation by subjective disgust ratings toward PEN stimuli. The relative implicit PEN-disgust (relative to PEN-‘hot’) associations exclusively modulated PEN-induced brain responses: comparatively negative (PEN-disgust) implicit associations with pornography predicted the strongest PEN-related responses in the basal forebrain (including nucleus accumbens and bed nucleus of stria terminalis), midbrain and amygdala. Since these areas are often implicated in visual sexual processing, the present findings should be taken as a warning: apparently their involvement may also indicate a negative or ambivalent attitude toward sexual stimuli. PMID:23051899

  17. Water deprivation-induced sodium appetite: humoral and cardiovascular mediators and immediate early genes

    NASA Technical Reports Server (NTRS)

    De Luca, Laurival A Jr; Xu, Zhice; Schoorlemmer, Guus H M.; Thunhorst, Robert L.; Beltz, Terry G.; Menani, Jose V.; Johnson, Alan Kim

    2002-01-01

    Adult rats deprived of water for 24-30 h were allowed to rehydrate by ingesting only water for 1-2 h. Rats were then given access to both water and 1.8% NaCl. This procedure induced a sodium appetite defined by the operational criteria of a significant increase in 1.8% NaCl intake (3.8 +/- 0.8 ml/2 h; n = 6). Expression of Fos (as assessed by immunohistochemistry) was increased in the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus (MnPO), subfornical organ (SFO), and supraoptic nucleus (SON) after water deprivation. After rehydration with water but before consumption of 1.8% NaCl, Fos expression in the SON disappeared and was partially reduced in the OVLT and MnPO. However, Fos expression did not change in the SFO. Water deprivation also 1) increased plasma renin activity (PRA), osmolality, and plasma Na+; 2) decreased blood volume; and 3) reduced total body Na+; but 4) did not alter arterial blood pressure. Rehydration with water alone caused only plasma osmolality and plasma Na+ concentration to revert to euhydrated levels. The changes in Fos expression and PRA are consistent with a proposed role for ANG II in the control of the sodium appetite produced by water deprivation followed by rehydration with only water.

  18. Reward deficiency and anti-reward in pain chronification.

    PubMed

    Borsook, D; Linnman, C; Faria, V; Strassman, A M; Becerra, L; Elman, I

    2016-09-01

    Converging lines of evidence suggest that the pathophysiology of pain is mediated to a substantial degree via allostatic neuroadaptations in reward- and stress-related brain circuits. Thus, reward deficiency (RD) represents a within-system neuroadaptation to pain-induced protracted activation of the reward circuits that leads to depletion-like hypodopaminergia, clinically manifested anhedonia, and diminished motivation for natural reinforcers. Anti-reward (AR) conversely pertains to a between-systems neuroadaptation involving over-recruitment of key limbic structures (e.g., the central and basolateral amygdala nuclei, the bed nucleus of the stria terminalis, the lateral tegmental noradrenergic nuclei of the brain stem, the hippocampus and the habenula) responsible for massive outpouring of stressogenic neurochemicals (e.g., norepinephrine, corticotropin releasing factor, vasopressin, hypocretin, and substance P) giving rise to such negative affective states as anxiety, fear and depression. We propose here the Combined Reward deficiency and Anti-reward Model (CReAM), in which biopsychosocial variables modulating brain reward, motivation and stress functions can interact in a 'downward spiral' fashion to exacerbate the intensity, chronicity and comorbidities of chronic pain syndromes (i.e., pain chronification). PMID:27246519

  19. Rose odor can innately counteract predator odor.

    PubMed

    Matsukawa, Mutsumi; Imada, Masato; Murakami, Toyotaka; Aizawa, Shin; Sato, Takaaki

    2011-03-24

    When animals smell a predator odor such as 2,5-Dihydro-2,4,5-trimethylthiazoline (TMT), even if it is a novel substance, the hypothalamo-pituitary-adrenal (HPA) axis is activated, causing stress-like behaviors. Although the medial part of the bed nucleus of stria terminalis (mBST) is known to be involved in this process, the mechanism remains unclear. Moreover, it is unknown whether there is any odor that can counteract the predator odor, even when the odorants are novel substances for the animals. In this study, we assessed whether rose odor can counteract by counting the number of activated neurons in mice brain following the presentation of rose odor with or without TMT for 30 min. The number of activated cells in the mBST and in the ventrorostral part of the anterior piriform cortex (APC) was significantly reduced by a mixture of TMT and rose odor; however, no significant differences were noted in the dorsal part of the APC and in the olfactory bulb (OB) following TMT presentation with or without rose odor. The results suggest that rose odor may counteract the TMT-induced stress response in the OB and/or APC and suppress the neural circuit to the mBST. It also indicates that there are some odors that can innately counteract predator odor, even when they have not been experienced before. PMID:21266167

  20. Behavioral transition from attack to parenting in male mice: a crucial role of the vomeronasal system.

    PubMed

    Tachikawa, Kashiko S; Yoshihara, Yoshihiro; Kuroda, Kumi O

    2013-03-20

    Sexually naive male mice show robust aggressive behavior toward pups. However, the proportion of male mice exhibiting pup-directed aggression declines after cohabitation with a pregnant female for 2 weeks after mating. Subsequently, on becoming fathers, they show parental behavior toward pups, similar to maternal behavior by mothers. To elucidate the neural mechanisms underlying this behavioral transition, we examined brain regions differentially activated in sexually naive males and fathers after exposure to pups, using c-Fos expression as a neuronal activation marker. We found that, after pup exposure, subsets of neurons along the vomeronasal neural pathway-including the vomeronasal sensory neurons, the accessory olfactory bulb, the posterior medial amygdala, the medioposterior division of the bed nucleus of stria terminalis, and the anterior hypothalamic area-were more strongly activated in sexually naive males than in fathers. Notably, c-Fos induction was not observed in the vomeronasal sensory neurons of fathers after pup exposure. Surgical ablation of the vomeronasal organ in sexually naive males resulted in the abrogation of pup-directed aggression and simultaneous induction of parental behavior. These results suggest that chemical cues evoking pup-directed aggression are received by the vomeronasal sensory neurons and activate the vomeronasal neural pathway in sexually naive male mice but not in fathers. Thus, the downregulation of pup pheromone-induced activation of the vomeronasal system might be important for the behavioral transition from attack to parenting in male mice. PMID:23516278

  1. Revisiting the neural role of estrogen receptor beta in male sexual behavior by conditional mutagenesis.

    PubMed

    Naulé, Lydie; Marie-Luce, Clarisse; Parmentier, Caroline; Martini, Mariangela; Albac, Christelle; Trouillet, Anne-Charlotte; Keller, Matthieu; Hardin-Pouzet, Hélène; Mhaouty-Kodja, Sakina

    2016-04-01

    Estradiol derived from neural aromatization of gonadal testosterone plays a key role in the perinatal organization of the neural circuitry underlying male sexual behavior. The aim of this study was to investigate the contribution of neural estrogen receptor (ER) β in estradiol-induced effects without interfering with its peripheral functions. For this purpose, male mice lacking ERβ in the nervous system were generated. Analyses of males in two consecutive tests with a time interval of two weeks showed an effect of experience, but not of genotype, on the latencies to the first mount, intromission, pelvic thrusting and ejaculation. Similarly, there was an effect of experience, but not of genotype, on the number of thrusts and mating length. Neural ERβ deletion had no effect on the ability of males to adopt a lordosis posture in response to male mounts, after castration and priming with estradiol and progesterone. Indeed, only low percentages of both genotypes exhibited a low lordosis quotient. It also did not affect their olfactory preference. Quantification of tyrosine hydroxylase- and kisspeptin-immunoreactive neurons in the preoptic area showed unaffected sexual dimorphism of both populations in mutants. By contrast, the number of androgen receptor- and ERα-immunoreactive cells was significantly increased in the bed nucleus of stria terminalis of mutant males. These data show that neural ERβ does not play a crucial role in the organization and activation of the neural circuitry underlying male sexual behavior. These discrepancies with the phenotype of global ERβ knockout models are discussed. PMID:26836767

  2. Stress and Drug Dependence Differentially Modulate Norepinephrine Signaling in Animals with Varied HPA Axis Function

    PubMed Central

    Fox, Megan E; Studebaker, R Isaac; Swofford, Nathaniel J; Wightman, R Mark

    2015-01-01

    Previous work has demonstrated the importance of genetic factors and stress-sensitive circuits in the development of affective disorders. Anxiety and numerous psychological disorders are comorbid with substance abuse, and noradrenergic signaling in the bed nucleus of the stria terminalis (BNST) is thought to be a source of this convergence. Here, we examined the effects of different stressors on behavior and norepinephrine dynamics in the BNST of rat strains known to differ in their HPA-axis function. We compared the effects of acute morphine dependence and social isolation in non-anxious Sprague Dawley (SD) rats, and a depression model, Wistar-Kyoto (WKY) rats. We found a shared phenotype in drug-dependent and singly housed SD rats, characterized by slowed norepinephrine clearance, decreased autoreceptor function, and elevated anxiety. WKY rats exhibited changes in anxiety and autoreceptor function only following morphine dependence. To ascertain the influence of LC inhibition on this plasticity, we administered the LC-terminal-selective toxin DSP-4 to SD and WKY rats. DSP-4-treated SD rats demonstrated a dependence-like phenotype, whereas WKY rats were unchanged. Overall, our findings suggest that individuals with varying stress susceptibilities have different noradrenergic signaling changes in response to stress. These changes may establish conditions that favor stress-induced reinstatement and increase the risk for addiction. PMID:25601230

  3. Quantitative autoradiography of /sup 3/H-nomifensine binding sites in rat brain

    SciTech Connect

    Scatton, B.; Dubois, A.; Dubocovich, M.L.; Zahniser, N.R.; Fage, D.

    1985-03-04

    The distribution of /sup 3/H-nomifensine binding sites in the rat brain has been studied by quantitative autoradiography. The binding of /sup 3/H-nomifensine to caudate putamen sections was saturable, specific, of a highly affinity (Kd = 56 nM) and sodium-dependent. The dopamine uptake inhibitors benztropine, nomifensine, cocaine, bupropion and amfonelic acid were the most potent competitors of /sup 3/H-nomifensine binding to striatal sections. The highest levels of (benztropine-displaceable) /sup 3/H-nomifensine binding sites were found in the caudate-putamen, the olfactory tubercle and the nucleus accumbens. 6-Hydroxy-dopamine-induced lesion of the ascending dopaminergic bundle resulted in a marked decrease in the /sup 3/H-ligand binding in these areas. Moderately high concentrations of the /sup 3/H-ligand were observed in the bed nucleus of the stria terminalis, the anteroventral thalamic nucleus, the cingulate cortex, the lateral septum, the hippocampus, the amygdala, the zona incerta and some hypothalamic nuclei. There were low levels of binding sites in the habenula, the dorsolateral geniculate body, the substantia nigra, the ventral tegmental area and the periaqueductal gray matter. These autoradiographic data are consistent with the hypothesis that /sup 3/H-nomifensine binds primarily to the presynaptic uptake site for dopamine but also labels the norepinephrine uptake site. 33 references, 2 figures, 1 table.

  4. AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue.

    PubMed

    Steculorum, Sophie M; Ruud, Johan; Karakasilioti, Ismene; Backes, Heiko; Engström Ruud, Linda; Timper, Katharina; Hess, Martin E; Tsaousidou, Eva; Mauer, Jan; Vogt, Merly C; Paeger, Lars; Bremser, Stephan; Klein, Andreas C; Morgan, Donald A; Frommolt, Peter; Brinkkötter, Paul T; Hammerschmidt, Philipp; Benzing, Thomas; Rahmouni, Kamal; Wunderlich, F Thomas; Kloppenburg, Peter; Brüning, Jens C

    2016-03-24

    Activation of Agouti-related peptide (AgRP) neurons potently promotes feeding, and chronically altering their activity also affects peripheral glucose homeostasis. We demonstrate that acute activation of AgRP neurons causes insulin resistance through impairment of insulin-stimulated glucose uptake into brown adipose tissue (BAT). AgRP neuron activation acutely reprograms gene expression in BAT toward a myogenic signature, including increased expression of myostatin. Interference with myostatin activity improves insulin sensitivity that was impaired by AgRP neurons activation. Optogenetic circuitry mapping reveals that feeding and insulin sensitivity are controlled by both distinct and overlapping projections. Stimulation of AgRP → LHA projections impairs insulin sensitivity and promotes feeding while activation of AgRP → anterior bed nucleus of the stria terminalis (aBNST)vl projections, distinct from AgRP → aBNSTdm projections controlling feeding, mediate the effect of AgRP neuron activation on BAT-myostatin expression and insulin sensitivity. Collectively, our results suggest that AgRP neurons in mice induce not only eating, but also insulin resistance by stimulating expression of muscle-related genes in BAT, revealing a mechanism by which these neurons rapidly coordinate hunger states with glucose homeostasis. PMID:27015310

  5. Deep brain stimulation affects conditioned and unconditioned anxiety in different brain areas.

    PubMed

    van Dijk, A; Klanker, M; van Oorschot, N; Post, R; Hamelink, R; Feenstra, M G P; Denys, D

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has proven to be an effective treatment for therapy refractory obsessive-compulsive disorder. Clinical observations show that anxiety symptoms decrease rapidly following DBS. As in clinical studies different regions are targeted, it is of principal interest to understand which brain area is responsible for the anxiolytic effect and whether high-frequency stimulation of different areas differentially affect unconditioned (innate) and conditioned (learned) anxiety. In this study, we examined the effect of stimulation in five brain areas in rats (NAc core and shell, bed nucleus of the stria terminalis (BNST), internal capsule (IC) and the ventral medial caudate nucleus (CAU)). The elevated plus maze was used to test the effect of stimulation on unconditioned anxiety, the Vogel conflict test for conditioned anxiety, and an activity test for general locomotor behaviour. We found different anxiolytic effects of stimulation in the five target areas. Stimulation of the CAU decreased both conditioned and unconditioned anxiety, while stimulation of the IC uniquely reduced conditioned anxiety. Remarkably, neither the accumbens nor the BNST stimulation affected conditioned or unconditioned anxiety. Locomotor activity increased with NAc core stimulation but decreased with the BNST. These findings suggest that (1) DBS may have a differential effect on unconditioned and conditioned anxiety depending on the stimulation area, and that (2) stimulation of the IC exclusively reduces conditioned anxiety. This suggests that the anxiolytic effects of DBS seen in OCD patients may not be induced by stimulation of the NAc, but rather by the IC. PMID:23900312

  6. Pro-arrhythmogenic effects of atrial fibrillation-induced electrical remodelling: insights from the three-dimensional virtual human atria.

    PubMed

    Colman, Michael A; Aslanidi, Oleg V; Kharche, Sanjay; Boyett, Mark R; Garratt, Clifford; Hancox, Jules C; Zhang, Henggui

    2013-09-01

    Chronic atrial fibrillation (AF) is associated with structural and electrical remodelling in the atria, which are associated with a high recurrence of AF. Through biophysically detailed computer modelling, this study investigated mechanisms by which AF-induced electrical remodelling promotes and perpetuates AF. A family of Courtemanche-Ramirez-Nattel variant models of human atrial cell action potentials (APs), taking into account of intrinsic atrial electrophysiological properties, was modified to incorporate various experimental data sets on AF-induced changes of major ionic channel currents (ICaL, IKur, Ito, IK1, IKs, INaCa) and on intracellular Ca(2+) handling. The single cell models for control and AF-remodelled conditions were incorporated into multicellular three-dimensional (3D) atrial tissue models. Effects of the AF-induced electrical remodelling were quantified as the changes of AP profile, AP duration (APD) and its dispersion across the atria, and the vulnerability of atrial tissue to the initiation of re-entry. The dynamic behaviour of re-entrant excitation waves in the 3D models was characterised. In our simulations, AF-induced electrical remodelling abbreviated atrial APD non-uniformly across the atria; this resulted in relatively short APDs co-existing with marked regional differences in the APD at junctions of the crista terminalis/pectinate muscle, pulmonary veins/left atrium. As a result, the measured tissue vulnerability to re-entry initiation at these tissue junctions was increased. The AF-induced electrical remodelling also stabilized and accelerated re-entrant excitation waves, leading to rapid and sustained re-entry. Under the AF-remodelled condition, re-entrant scroll waves in the 3D model degenerated into persistent and erratic wavelets, leading to fibrillation. In conclusion, realistic 3D atrial tissue models indicate that AF-induced electrical remodelling produces regionally heterogeneous and shortened APD; these respectively facilitate

  7. Connectivity between the superior colliculus and the amygdala in humans and macaque monkeys: virtual dissection with probabilistic DTI tractography

    PubMed Central

    Koller, Kristin; Bultitude, Janet H.; Mullins, Paul; Ward, Robert; Mitchell, Anna S.; Bell, Andrew H.

    2015-01-01

    It has been suggested that some cortically blind patients can process the emotional valence of visual stimuli via a fast, subcortical pathway from the superior colliculus (SC) that reaches the amygdala via the pulvinar. We provide in vivo evidence for connectivity between the SC and the amygdala via the pulvinar in both humans and rhesus macaques. Probabilistic diffusion tensor imaging tractography revealed a streamlined path that passes dorsolaterally through the pulvinar before arcing rostrally to traverse above the temporal horn of the lateral ventricle and connect to the lateral amygdala. To obviate artifactual connectivity with crossing fibers of the stria terminalis, the stria was also dissected. The putative streamline between the SC and amygdala traverses above the temporal horn dorsal to the stria terminalis and is positioned medial to it in humans and lateral to it in monkeys. The topography of the streamline was examined in relation to lesion anatomy in five patients who had previously participated in behavioral experiments studying the processing of emotionally valenced visual stimuli. The pulvinar lesion interrupted the streamline in two patients who had exhibited contralesional processing deficits and spared the streamline in three patients who had no deficit. Although not definitive, this evidence supports the existence of a subcortical pathway linking the SC with the amygdala in primates. It also provides a necessary bridge between behavioral data obtained in future studies of neurological patients, and any forthcoming evidence from more invasive techniques, such as anatomical tracing studies and electrophysiological investigations only possible in nonhuman species. PMID:26224780

  8. Induced Abortion

    MedlinePlus

    ... Induced Abortion Patient Education FAQs Induced Abortion Patient Education Pamphlets - Spanish Induced Abortion FAQ043, May 2015 PDF Format Induced ... Your Practice Patient Safety & Quality Payment Reform (MACRA) Education & Events Annual ... Pamphlets Teen Health About ACOG About Us Leadership & ...

  9. Neuropeptide Y input to the rat basolateral amygdala complex and modulation by conditioned fear.

    PubMed

    Leitermann, Randy J; Rostkowski, Amanda B; Urban, Janice H

    2016-08-15

    Within the basolateral amygdaloid complex (BLA), neuropeptide Y (NPY) buffers against protracted anxiety and fear. Although the importance of NPY's actions in the BLA is well documented, little is known about the source(s) of NPY fibers to this region. The current studies identified sources of NPY projections to the BLA by using a combination of anatomical and neurochemical approaches. NPY innervation of the BLA was assessed in rats by examining the degree of NPY coexpression within interneurons or catecholaminergic fibers with somatostatin and tyrosine hydroxylase (TH) or dopamine β-hydroxylase (DβH), respectively. Numerous NPY(+) /somatostatin(+) and NPY(+) /somatostatin(-) fibers were observed, suggesting at least two populations of NPY fibers within the BLA. No colocalization was noted between NPY and TH or DβH immunoreactivities. Additionally, Fluorogold (FG) retrograde tracing with immunohistochemistry was used to identify the precise origin of NPY projections to the BLA. FG(+) /NPY(+) cells were identified within the amygdalostriatal transition area (AStr) and stria terminalis and scattered throughout the bed nucleus of the stria terminalis. The subpopulation of NPY neurons in the AStr also coexpressed somatostatin. Subjecting animals to a conditioned fear paradigm increased NPY gene expression within the AStr, whereas no changes were observed within the BLA or stria terminalis. Overall, these studies identified limbic regions associated with stress circuits providing NPY input to the BLA and demonstrated that a unique NPY projection from the AStr may participate in the regulation of conditioned fear. J. Comp. Neurol. 524:2418-2439, 2016. © 2016 Wiley Periodicals, Inc. PMID:26779765

  10. Genetic knockdown of estrogen receptor-alpha in the subfornical organ augments ANG II-induced hypertension in female mice.

    PubMed

    Xue, Baojian; Zhang, Zhongming; Beltz, Terry G; Guo, Fang; Hay, Meredith; Johnson, Alan Kim

    2015-03-15

    The present study tested the hypotheses that 1) ERα in the brain plays a key role in the estrogen-protective effects against ANG II-induced hypertension, and 2) that the subfornical organ (SFO) is a key site where ERα mediates these protective actions. In this study, a "floxed" ERα transgenic mouse line (ERα(flox)) was used to create models in which ERα was knocked down in the brain or just in the SFO. Female mice with ERα ablated in the nervous system (Nestin-ERα(-) mice) showed greater increases in blood pressure (BP) in response to ANG II. Furthermore, females with ERα knockdown specifically in the SFO [SFO adenovirus-Cre (Ad-Cre) injected ERα(flox) mice] also showed an enhanced pressor response to ANG II. Immunohistochemical (IHC), RT-PCR, and Western blot analyses revealed a marked reduction in the expression of ERα in nervous tissues and, in particular, in the SFO. These changes were not present in peripheral tissues in Nestin-ERα(-) mice or Ad-Cre-injected ERα(flox) mice. mRNA expression of components of the renin-angiotensin system in the lamina terminalis were upregulated in Nestin-ERα(-) mice. Moreover, ganglionic blockade on day 7 after ANG II infusions resulted in a greater reduction of BP in Nestin-ERα(-) mice or SFO Ad-Cre-injected mice, suggesting that knockdown of ERα in the nervous system or the SFO alone augments central ANG II-induced increase in sympathetic tone. The results indicate that interfering with the action of estrogen on SFO ERα is sufficient to abolish the protective effects of estrogen against ANG II-induced hypertension. PMID:25552661

  11. Extending the amygdala in theories of threat processing

    PubMed Central

    Fox, Andrew S.; Oler, Jonathan A.; Tromp, Do P.M.; Fudge, Julie L.; Kalin, Ned H.

    2015-01-01

    The central extended amygdala is an evolutionarily conserved set of interconnected brain regions that play an important role in threat processing to promote survival. Two core components of the central extended amygdala, the central nucleus of the amygdala (Ce) and the lateral bed nucleus of the stria terminalis (BST) are highly similar regions that serve complimentary roles by integrating fear- and anxiety-relevant information. Survival depends on the central extended amygdala's ability to rapidly integrate and respond to threats that vary in their immediacy, proximity, and characteristics. Future studies will benefit from understanding alterations in central extended amygdala function in relation to stress-related psychopathology. PMID:25851307

  12. Localization and characterization of (/sup 3/H)desmethylimipramine binding sites in rat brain by quantitative autoradiography

    SciTech Connect

    Biegon, A.; Rainbow, T.C.

    1983-05-01

    The high affinity binding sites for the antidepressant desmethlyimipramine (DMI) have been localized in rat brain by quantitative autoradiography. There are high concentrations of binding sites in the locus ceruleus, the anterior ventral thalamus, the ventral portion of the bed nucleus of the stria terminalis, the paraventricular and the dorsomedial nuclei of the hypothalamus. The distribution of DMI binding sites is in striking accord with the distribution of norepinephrine terminals. Pretreatment of rats with the neurotoxin 6-hydroxydopamine, which causes a selective degeneration of catecholamine terminals, results in 60 to 90% decrease in DMI binding. These data support the idea that high affinity binding sites for DMI are located on presynaptic noradrenergic terminals.

  13. Blockade of ENaCs by Amiloride Induces c-Fos Activation of the Area Postrema

    PubMed Central

    Miller, Rebecca L.; Denny, George O.; Knuepfer, Mark M.; Kleyman, Thomas R.; Jackson, Edwin K.; Salkoff, Lawrence B.; Loewy, Arthur D.

    2015-01-01

    Epithelial sodium channels (ENaCs) are strongly expressed in the circumventricular organs (CVOs), and these structures may play an important role in sensing plasma sodium levels. Here, the potent ENaC blocker amiloride was injected intraperitoneally in rats and 2 hours later, the c-Fos activation pattern in the CVOs was studied. Amiloride elicited dose-related activation in the area postrema (AP) but only ~10% of the rats showed c-Fos activity in the organum vasculosum of the lamina terminalis (OVLT) and subfornical organ (SFO). Tyrosine hydroxylase-immunoreactive (catecholamine) AP neurons were activated, but tryptophan hydroxylase-immunoreactive (serotonin) neurons were unaffected. The AP projects to FoxP2-expressing neurons in the dorsolateral pons which include the pre-locus coeruleus nucleus and external lateral part of the parabrachial nucleus; both cell groups were c-Fos activated following systemic injections of amiloride. In contrast, another AP projection target - the aldosterone-sensitive neurons of the nucleus tractus solitarius which express the enzyme 11-β-hydroxysteriod dehydrogenase type 2 (HSD2) were not activated. As shown here, plasma concentrations of amiloride used in these experiments were near or below the IC50 level for ENaCs. Amiloride did not induce changes in blood pressure, heart rate, or regional vascular resistance, so sensory feedback from the cardiovascular system was probably not a causal factor for the c-Fos activity seen in the CVOs. In summary, amiloride may have a dual effect on sodium homeostasis causing a loss of sodium via the kidney and inhibiting sodium appetite by activating the central satiety pathway arising from the AP. PMID:25557402

  14. Regional specificity of manganese accumulation and clearance in the mouse brain: implications for manganese-enhanced MRI.

    PubMed

    Grünecker, B; Kaltwasser, S F; Zappe, A C; Bedenk, B T; Bicker, Y; Spoormaker, V I; Wotjak, C T; Czisch, M

    2013-05-01

    Manganese-enhanced MRI has recently become a valuable tool for the assessment of in vivo functional cerebral activity in animal models. As a result of the toxicity of manganese at higher dosages, fractionated application schemes have been proposed to reduce the toxic side effects by using lower concentrations per injection. Here, we present data on regional-specific manganese accumulation during a fractionated application scheme over 8 days of 30 mg/kg MnCl2 , as well as on the clearance of manganese chloride over the course of several weeks after the termination of the whole application protocol supplying an accumulative dose of 240 mg/kg MnCl2 . Our data show most rapid accumulation in the superior and inferior colliculi, amygdala, bed nucleus of the stria terminalis, cornu ammonis of the hippocampus and globus pallidus. The data suggest that no ceiling effects occur in any region using the proposed application protocol. Therefore, a comparison of basal neuronal activity differences in different animal groups based on locally specific manganese accumulation is possible using fractionated application. Half-life times of manganese clearance varied between 5 and 7 days, and were longest in the periaqueductal gray, amygdala and entorhinal cortex. As the hippocampal formation shows one of the highest T1 -weighted signal intensities after manganese application, and manganese-induced memory impairment has been suggested, we assessed hippocampus-dependent learning as well as possible manganese-induced atrophy of the hippocampal volume. No interference of manganese application on learning was detected after 4 days of Mn(2+) application or 2 weeks after the application protocol. In addition, no volumetric changes induced by manganese application were found for the hippocampus at any of the measured time points. For longitudinal measurements (i.e. repeated manganese applications), a minimum of at least 8 weeks should be considered using the proposed protocol to allow for

  15. Stressor and glucocorticoid-dependent induction of the immediate early gene kruppel-like factor 9: implications for neural development and plasticity.

    PubMed

    Bonett, Ronald M; Hu, Fang; Bagamasbad, Pia; Denver, Robert J

    2009-04-01

    Krüppel-like factor 9 (KLF9) is a thyroid hormone-induced, immediate early gene implicated in neural development in vertebrates. We analyzed stressor and glucocorticoid (GC)-dependent regulation of KLF9 expression in the brain of the frog Xenopus laevis, and investigated a possible role for KLF9 in neuronal differentiation. Exposure to shaking/confinement stressor increased plasma corticosterone (CORT) concentration, and KLF9 immunoreactivity in several brain regions, which included the medial amygdala and bed nucleus of the stria terminalis, anterior preoptic area (homologous to the mammalian paraventricular nucleus), and optic tectum (homologous to the mammalian superior colliculus). The stressor-induced KLF9 mRNA expression in the brain was blocked by pretreatment with the GC receptor antagonist RU486, or mimicked by injection of CORT. Treatment with CORT also caused a rapid and dose-dependent increase in KLF9 mRNA in X. laevis XTC-2 cells that was resistant to inhibition of protein synthesis. The action of CORT on KLF9 expression in XTC-2 cells was blocked by RU486, but not by the mineralocorticoid receptor antagonist spironolactone. To test for functional consequences of up-regulation of KLF9, we introduced a KLF9 expression plasmid into living tadpole brain by electroporation-mediated gene transfer. Forced expression of KLF9 in tadpole brain caused an increase in Golgi-stained cells, reflective of neuronal differentiation/maturation. Our results support that KLF9 is a direct, GC receptor target gene that is induced by stress, and functions as an intermediary in the actions of GCs on brain gene expression and neuronal structure. PMID:19036875

  16. Immunohistochemical evidence for the involvement of gonadotropin releasing hormone in neuroleptic and cataleptic effects of haloperidol in mice.

    PubMed

    Fegade, Harshal A; Umathe, Sudhir N

    2016-04-01

    Blockade of dopamine D2 receptor by haloperidol is attributed for neuroleptic and cataleptic effects; and also for the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH agonist is reported to exhibit similar behavioural effects as that of haloperidol, and pre-treatment with GnRH antagonist is shown to attenuate the effects of haloperidol, suggesting a possibility that GnRH might mediate the effects of haloperidol. To substantiate such possibility, the influence of haloperidol on GnRH immunoreactivity (GnRH-ir) in the brain was studied in vehicle/antide pre-treated mice by peroxidase-antiperoxidase method. Initially, an earlier reported antide-haloperidol interaction in rat was confirmed in mice, wherein haloperidol (250μg/kg, i.p.) exhibited suppression of conditioned avoidance response (CAR) on two-way shuttle box, and induced catalepsy in bar test; and pre-treatment with antide (50μg/kg, s.c., GnRH antagonist) attenuated both effects of haloperidol. Immunohistochemical study was carried out to identify GnRH-ir in the brain, isolated 1h after haloperidol treatment to mice pre-treated with vehicle/antide. The morphometric analysis of microphotographs of brain sections revealed that haloperidol treatment increased integrated density units of GnRH-ir in various regions of the limbic system. Considering basal GnRH-ir in vehicle treated group as 100%, the increase in GnRH-ir after haloperidol treatment was by 100.98% in the medial septum; 54.26% in the bed nucleus of the stria terminalis; 1152.85% in the anteroventral periventricular nucleus; 120.79% in the preoptic area-organum vasculosum of the lamina terminalis and 138.82% in the arcuate nucleus. Antide did not influence basal and haloperidol induced increase in GnRH-ir in any of the regions. As significant increase in GnRH-ir after haloperidol treatment was observed in such regions of the brain which are reported to directly or indirectly communicate with the hippocampus and basal

  17. Neuroanatomical Circuitry Mediating the Sensory Impact of Nicotine in the Central Nervous System

    PubMed Central

    Dehkordi, Ozra; Rose, Jed E.; Asadi, Sadegh; Manaye, Kebreten F.; Millis, Richard M.; Jayam-Trouth, Annapurni

    2014-01-01

    Direct actions of nicotine in the CNS appear to be essential for its reinforcing properties. However, activation of nicotinic acetylcholine receptors (nAChRs) on afferent sensory nerve fibers are important components of addiction to, and withdrawal from, cigarette smoking. The present study was to identify the neuroanatomical substrates activated by the peripheral actions of nicotine and to determine whether these sites overlap brain structures stimulated by direct actions of nicotine. Mouse brains were examined by immunohistochemistry for c-Fos protein after intraperitoneal injection of either nicotine (NIC, 30 and 40 µg/kg) and/or nicotine pyrrolidine methiodide (NIC-PM, 20 and 30 µg/kg). NIC-PM induced c-Fos immunoreactivity (IR) at multiple brain sites. In the brainstem, c-Fos IR was detected in locus coeruleus, laterodorsal tegmental nucleus and pedunculotegmental nucleus. In the midbrain, c-Fos IR was observed in areas overlapping the ventral tegmental area (VTA) which includes paranigral nucleus, parainterfascicular nucleus, parabrachial pigmental area and rostral VTA. Other structures of the nicotine brain-reward circuitry activated by NIC-PM included hypothalamus, paraventricular thalamic nucleus, lateral habenular nucleus, hippocampus, amygdala, accumbens nucleus, piriform cortex, angular insular cortex, anterior olfactory nucleus, lateral septal nucleus, bed nucleus of stria terminalis, cingulate and medial prefrontal cortex, olfactory tubercle, medial and lateral orbital cortex. Nicotine, acting through central and peripheral nAChRs, produced c-Fos IR in areas that overlapped NIC-PM induced c-Fos expressing sites. These neuroanatomical data are the first to demonstrate that the CNS structures which are the direct targets of nicotine are also anatomical substrates for the peripheral sensory impact of nicotine. PMID:25223294

  18. Induction of FosB/DeltaFosB in the brain stress system-related structures during morphine dependence and withdrawal.

    PubMed

    Núñez, Cristina; Martín, Fátima; Földes, Anna; Luisa Laorden, M; Kovács, Krisztina J; Victoria Milanés, M

    2010-07-01

    The transcription factor DeltaFosB is induced in the nucleus accumbens (NAc) by drugs of abuse. This study was designed to evaluate the possible modifications in FosB/DeltaFosB expression in both hypothalamic and extrahypothalamic brain stress system during morphine dependence and withdrawal. Rats were made dependent on morphine and, on day 8, were injected with saline or naloxone. Using immunohistochemistry and western blot, the expression of FosB/DeltaFosB, tyrosine hydroxylase (TH), corticotropin-releasing factor (CRF) and pro-dynorphin (DYN) was measured in different nuclei from the brain stress system in morphine-dependent rats and after morphine withdrawal. Additionally, we studied the expression of FosB/DeltaFosB in CRF-, TH- and DYN-positive neurons. FosB/DeltaFosB was induced after chronic morphine administration in the parvocellular part of the hypothalamic paraventricular nucleus (PVN), NAc-shell, bed nucleus of the stria terminalis, central amygdala and A(2) noradrenergic part of the nucleus tractus solitarius (NTS-A(2)). Morphine dependence and withdrawal evoked an increase in FosB/DeltaFosB-TH and FosB/DeltaFosB-CRF double labelling in NTS-A(2) and PVN, respectively, besides an increase in TH levels in NTS-A(2) and CRF expression in PVN. These data indicate that neuroadaptation to addictive substances, observed as accumulation of FosB/DeltaFosB, is not limited to the reward circuits but may also manifest in other brain regions, such as the brain stress system, which have been proposed to be directly related to addiction. PMID:20438612

  19. Cocaine treatment alters oxytocin receptor binding but not mRNA production in postpartum rat dams.

    PubMed

    Jarrett, T M; McMurray, M S; Walker, C H; Johns, J M

    2006-06-01

    Gestational cocaine treatment in rat dams results in decreased oxytocin (OT) levels, up-regulated oxytocin receptor (OTR) binding density and decreased receptor affinity in the whole amygdala, all concomitant with a significant increase in maternal aggression on postpartum day six. Rat dams with no gestational drug treatment that received an infusion of an OT antagonist directly into the central nucleus of the amygdala (CeA) exhibited similarly high levels of maternal aggression towards intruders. Additionally, studies indicate that decreased OT release from the hypothalamic division of the paraventricular nucleus (PVN) is coincident with heightened maternal aggression in rats. Thus, it appears that cocaine-induced alterations in OT system dynamics (levels, receptors, production, and/or release) may mediate heightened maternal aggression following cocaine treatment, but the exact mechanisms through which cocaine impacts the OT system have not yet been determined. Based on previous studies, we hypothesized that two likely mechanisms of cocaine's action would be, increased OTR binding specifically in the CeA, and decreased OT mRNA production in the PVN. Autoradiography and in situ hybridization assays were performed on targeted nuclei in brain regions of rat dams on postpartum day six, following gestational treatment twice daily with cocaine (15 mg/kg) or normal saline (1 ml/kg). We now report cocaine-induced reductions in OTR binding density in the ventromedial hypothalamus (VMH) and bed nucleus of the stria terminalis (BNST), but not the CeA. There was no significant change in OT mRNA production in the PVN following cocaine treatment. PMID:16677710

  20. Phasic and sustained fear in humans elicits distinct patterns of brain activity

    PubMed Central

    Alvarez, Ruben P.; Chen, Gang; Bodurka, Jerzy; Kaplan, Raphael; Grillon, Christian

    2011-01-01

    Aversive events are typically more debilitating when they occur unpredictably than predictably. Studies in humans and animals indicate that predictable and unpredictable aversive events can induce phasic and sustained fear, respectively. Research in rodents suggests that anatomically related but distinct neural circuits may mediate phasic and sustained fear. We explored this issue in humans by examining threat predictability in three virtual reality contexts, one in which electric shocks were predictably signaled by a cue, a second in which shocks occurred unpredictably but never paired with a cue, and a third in which no shocks were delivered. Evidence of threat-induced phasic and sustained fear was presented using fear ratings and skin conductance. Utilizing recent advances in functional magnetic resonance imaging (fMRI), we were able to conduct whole-brain fMRI at relatively high spatial resolution and still have enough sensitivity to detect transient and sustained signal changes in the basal forebrain. We found that both predictable and unpredictable threat evoked transient activity in the dorsal amygdala, but that only unpredictable threat produced sustained activity in a forebrain region corresponding to the bed nucleus of the stria terminalis complex. Consistent with animal models hypothesizing a role for the cortex in generating sustained fear, sustained signal increases to unpredictable threat were also found in anterior insula and a frontoparietal cortical network associated with hypervigilance. In addition, unpredictable threat led to transient activity in the ventral amygdala–hippocampal area and pregenual anterior cingulate cortex, as well as transient activation and subsequent deactivation of subgenual anterior cingulate cortex, limbic structures that have been implicated in the regulation of emotional behavior and stress responses. In line with basic findings in rodents, these results provide evidence that phasic and sustained fear in humans may

  1. Evidence for the involvement of neuropeptide Y in the antidepressant effect of imipramine in type 2 diabetes.

    PubMed

    Nakhate, Kartik T; Yedke, Sadanand U; Bharne, Ashish P; Subhedar, Nishikant K; Kokare, Dadasaheb M

    2016-09-01

    Depression is a major comorbidity factor of diabetes and the outcome of one disorder influences the other. Our aim is to scrutinize the link between the two, if any. Since neuropeptide Y (NPY) system plays an important role in regulating central glucose sensing mechanisms, and also depression-related behavior, we test the involvement of NPY in the modulation of depression in type 2 diabetic mice. The mice were fed on high-fat diet and administered with low dose of streptozotocin to induce type 2 diabetes. These animals showed augmented plasma glucose and increased immobility time in tail suspension test (TST) suggesting induction of diabetes and depression. Intracerebroventricular (icv) treatment with NPY or NPY Y1 receptor agonist [Leu(31), Pro(34)]-NPY and intraperitoneal treatment with imipramine decreased immobility time. However, opposite effect was produced by NPY Y1 receptor antagonist BIBP3226 (icv). Moreover, reduced immobility time by imipramine was potentiated by NPY and [Leu(31), Pro(34)]-NPY, but attenuated by BIBP3226. Immunohistochemical analysis of the different nuclei of the extended amygdala, the region primarily involved in affective disorders, was undertaken. A significant reduction in NPY immunoreactivity in the central nucleus of amygdala, nucleus accumbens shell and lateral division of bed nucleus of stria terminalis of the diabetic mice was noticed; the response was ameliorated in imipramine treated animals. The results suggest that decreased NPY expression in the extended amygdala might be causally linked with the depression induced following type 2 diabetes and that the antidepressant action of imipramine in diabetic mice might be mediated by NPY-NPY Y1 receptor system. PMID:27208493

  2. Neuroanatomical circuitry mediating the sensory impact of nicotine in the central nervous system.

    PubMed

    Dehkordi, Ozra; Rose, Jed E; Asadi, Sadegh; Manaye, Kebreten F; Millis, Richard M; Jayam-Trouth, Annapurni

    2015-02-01

    Direct actions of nicotine in the CNS appear to be essential for its reinforcing properties. However, activation of nicotinic acetylcholine receptors (nAChRs) on afferent sensory nerve fibers is an important component of addiction to, and withdrawal from, cigarette smoking. The aim of the present study was to identify the neuroanatomical substrates activated by the peripheral actions of nicotine and to determine whether these sites overlap brain structures stimulated by direct actions of nicotine. Mouse brains were examined by immunohistochemistry for c-Fos protein after intraperitoneal injection of either nicotine hydrogen tartrate salt (NIC; 30 and 40 μg/kg) or nicotine pyrrolidine methiodide (NIC-PM; 20 and 30 μg/kg). NIC-PM induced c-Fos immunoreactivity (IR) at multiple brain sites. In the brainstem, c-Fos IR was detected in the locus coeruleus, laterodorsal tegmental nucleus, and pedunculotegmental nucleus. In the midbrain, c-Fos IR was observed in areas overlapping the ventral tegmental area (VTA), which includes the paranigral nucleus, parainterfascicular nucleus, parabrachial pigmental area, and rostral VTA. Other structures of the nicotine brain-reward circuitry activated by NIC-PM included the hypothalamus, paraventricular thalamic nucleus, lateral habenular nucleus, hippocampus, amygdala, accumbens nucleus, piriform cortex, angular insular cortex, anterior olfactory nucleus, lateral septal nucleus, bed nucleus of stria terminalis, cingulate and medial prefrontal cortex, olfactory tubercle, and medial and lateral orbital cortex. NIC, acting through central and peripheral nAChRs, produced c-Fos IR in areas that overlapped NIC-PM-induced c-Fos-expressing sites. These neuroanatomical data are the first to demonstrate that the CNS structures that are the direct targets of nicotine are also anatomical substrates for the peripheral sensory impact of nicotine. PMID:25223294

  3. Corticotropin-releasing factor within the central nucleus of the amygdala and the nucleus accumbens shell mediates the negative affective state of nicotine withdrawal in rats

    PubMed Central

    Marcinkiewcz, Catherine A.; Prado, Melissa M.; Isaac, Shani K.; Marshall, Alex; Rylkova, Daria; Bruijnzeel, Adrie W.

    2008-01-01

    Tobacco addiction is a chronic disorder that is characterized by a negative affective state upon smoking cessation and relapse after periods of abstinence. Previous research has shown that an increased central release of corticotropin-releasing factor (CRF) at least partly mediates the deficit in brain reward function associated with nicotine withdrawal in rats. The aim of these studies was to investigate the role of CRF in the central nucleus of the amygdala (CeA), the lateral bed nucleus of the stria terminalis (BNST), and the nucleus accumbens shell (Nacc shell) in the deficit in brain reward function associated with precipitated nicotine withdrawal. The intracranial self-stimulation procedure was used to assess the negative affective aspects of nicotine withdrawal. Elevations in brain reward thresholds are indicative of a deficit in brain reward function. In all experiments, the nicotinic receptor antagonist mecamylamine (3 mg/kg) elevated the brain reward thresholds of the nicotine dependent rats (9 mg/kg/day of nicotine salt) and did not affect the brain reward thresholds of the saline-treated control rats. The administration of the nonspecific CRF1/2 receptor antagonist D-Phe CRF(12–41) into the CeA and the Nacc shell prevented the mecamylamine-induced elevations in brain reward thresholds in the nicotine dependent rats. Blockade of CRF1/2 receptors in the lateral BNST did not prevent the mecamylamine-induced elevations in brain reward thresholds in the nicotine dependent rats. These studies indicate that the negative emotional state associated with precipitated nicotine withdrawal is at least partly mediated by an increased release of CRF in the CeA and Nacc shell. PMID:19145226

  4. Anxiolytic Effects and Neuroanatomical Targets of Estrogen Receptor-β (ERβ) Activation by a Selective ERβ Agonist in Female Mice

    PubMed Central

    Oyola, Mario G.; Portillo, Wendy; Reyna, Andrea; Foradori, Chad D.; Kudwa, Andrea; Hinds, Laura; Handa, Robert J.

    2012-01-01

    The dichotomous anxiogenic and anxiolytic properties of estrogens have been reported to be mediated by two distinct neural estrogen receptors (ER), ERα and ERβ, respectively. Using a combination of pharmacological and genetic approaches, we confirmed that the anxiolytic actions of estradiol are mediated by ERβ and extended and these observations to demonstrate the neuroanatomical targets involved in ERβ activation in these behavioral responses. We examined the effects of the biologically active S-enantiomer of diarylpropionitrile (S-DPN) on anxiety-related behavioral measures, the corresponding stress hormonal response to hypothalamo-pituitary-adrenal axis reactivity, and potential sites of neuronal activation in mutant female mice carrying a null mutation for ERβ gene (βERKO). S-DPN administration significantly reduced anxiety-like behaviors in the open field, light-dark exploration, and the elevated plus maze (EPM) in ovariectomized wild-type (WT) mice, but not in their βERKO littermates. Stress-induced corticosterone (CORT) and ACTH were also attenuated by S-DPN in the WT mice but not in the βERKO mice. Using c-fos induction after elevated plus maze, as a marker of stress-induced neuronal activation, we identified the anterodorsal medial amygdala and bed nucleus of the stria terminalis as the neuronal targets of S-DPN action. Both areas showed elevated c-fos mRNA expression with S-DPN treatment in the WT but not βERKO females. These studies provide compelling evidence for anxiolytic effects mediated by ERβ, and its neuroanatomical targets, that send or receive projections to/from the paraventricular nucleus, providing potential indirect mode of action for the control of hypothalamo-pituitary-adrenal axis function and behaviors. PMID:22186418

  5. Anxiogenic effects of CGRP within the BNST may be mediated by CRF acting at BNST CRFR1 receptors

    PubMed Central

    Sink, KS; Chung, A; Ressler, KJ; Davis, M; Walker, DL

    2013-01-01

    Calcitonin gene-related peptide (CGRP) acting within the bed nucleus of the stria terminalis (BNST) increases anxiety as well as neural activation in anxiety-related structures, and mediates behavioral stress responses. Similar effects have been described following intra-ventricular as well as intra-BNST infusions of the stress-responsive neuropeptide, corticotropin releasing factor (CRF). Interestingly, CGRP-positive terminals within the lateral division of the BNST form perisomatic baskets around neurons that express CRF, suggesting that BNST CGRP could exert its anxiogenic effects by increasing release of CRF from these neurons. With this in mind, the present set of experiments was designed to examine the role of CRFR1 signaling in the anxiogenic effects of CGRP within the BNST and to determine whether CRF from BNST neurons contributes to these effects. Consistent with previous studies, we found that 400 ng CGRP infused bilaterally into the BNST increased the acoustic startle response and induced anxiety-like behavior in the elevated plus maze compared to vehicle. Both of these effects were attenuated by 10 mg/kg PO of the CRFR1 antagonist, GSK876008. GSK876008 alone did not affect startle. An intra-BNST infusion of the CRFR1 antagonist CP376395 (2 μg) also blocked increases in acoustic startle induced by intra-BNST infusion of CGRP, as did virally-mediated siRNA knockdown of CRF expression locally within the BNST. Together, these results suggest that the anxiogenic effects of intra-BNST CGRP may be mediated by CRF from BNST neurons acting at local CRFR1 receptors. PMID:23376701

  6. Investigation of the neuroanatomical substrates of reward seeking following protracted abstinence in mice

    PubMed Central

    Madsen, Heather B; Brown, Robyn M; Short, Jennifer L; Lawrence, Andrew J

    2012-01-01

    Persistent vulnerability to relapse represents a major challenge in the treatment of drug addiction. The brain circuitry that underlies relapse-like behaviour can be investigated using animal models of drug seeking. As yet there have been no comprehensive brain mapping studies that have specifically examined the neuroanatomical substrates of cue-induced opiate seeking following abstinence in a mouse operant paradigm. The aim of this study was to compare the brain regions involved in sucrose vs. morphine seeking following protracted abstinence in mice. Male CD1 mice were trained to respond for either sucrose (10% w/v) or intravenous morphine (0.1 mg kg−1 per infusion) in an operant paradigm in the presence of a discrete cue. Once stable responding was established, mice were subjected to abstinence in their home cages for 3 weeks and then perfused for tissue collection, or returned to the operant chambers to assess cue-induced reward seeking before being perfused for tissue collection. Brain tissue was processed for Fos immunohistochemistry and Fos expression was quantified in a range of brain nuclei. We identified unique patterns of neuronal activation for sucrose and morphine seeking mice as well as some overlap. Structures activated in both ‘relapse’ groups included the anterior cingulate and orbitofrontal cortex, nucleus accumbens shell, bed nucleus of the stria terminalis, substantia nigra pars compacta, ventral tegmental area, hippocampus, periaqueductal grey, locus coeruleus and lateral habenula. Structures that were more activated in morphine seeking mice included the nucleus accumbens core, basolateral amygdala, substantia nigra pars reticulata, and the central nucleus of the amygdala. The dorsal raphe was the only structure examined that was specifically activated in sucrose seeking mice. Overall our findings support a cortico-striatal limbic circuit driving opiate seeking, and we have identified some additional circuitry potentially relevant to

  7. Changes in Central Sodium and not Osmolarity or Lactate Induce Panic-Like Responses in a Model of Panic Disorder

    PubMed Central

    Molosh, Andre I; Johnson, Philip L; Fitz, Stephanie D; DiMicco, Joseph A; Herman, James P; Shekhar, Anantha

    2010-01-01

    Panic disorder is a severe anxiety disorder characterized by recurrent panic attacks that can be consistently provoked with intravenous (i.v.) infusions of hypertonic (0.5 M) sodium lactate (NaLac), yet the mechanism/CNS site by which this stimulus triggers panic attacks is unclear. Chronic inhibition of GABAergic synthesis in the dorsomedial hypothalamus/perifornical region (DMH/PeF) of rats induces a vulnerability to panic-like responses after i.v. infusion of 0.5 M NaLac, providing an animal model of panic disorder. Using this panic model, we previously showed that inhibiting the anterior third ventricle region (A3Vr; containing the organum vasculosum lamina terminalis, the median preoptic nucleus, and anteroventral periventricular nucleus) attenuates cardiorespiratory and behavioral responses elicited by i.v. infusions of NaLac. In this study, we show that i.v. infusions of 0.5 M NaLac or sodium chloride, but not iso-osmolar -mannitol, increased ‘anxiety' (decreased social interaction) behaviors, heart rate, and blood pressure responses. Using whole-cell patch-clamp preparations, we also show that bath applications of NaLac (positive control), but not lactic acid (lactate stimulus) or -mannitol (osmolar stimulus), increases the firing rates of neurons in the A3Vr, which are retrogradely labeled from the DMH/PeF and which are most likely glutamatergic based on a separate study using retrograde tracing from the DMH/PeF in combination with in situ hybridization for vesicular glutamate transporter 2. These data show that hypertonic sodium, but not hyper-osmolarity or changes in lactate, is the key stimulus that provokes panic attacks in panic disorder, and is consistent with human studies. PMID:20130534

  8. Distribution of vasotocin- and vasoactive intestinal peptide-like immunoreactivity in the brain of blue tit (Cyanistes coeruleus)

    PubMed Central

    Montagnese, Catherine M.; Székely, Tamás; Csillag, András; Zachar, Gergely

    2015-01-01

    Blue tits (Cyanistes coeruleus) are songbirds, used as model animals in numerous studies covering a wide field of research. Nevertheless, the distribution of neuropeptides in the brain of this avian species remains largely unknown. Here we present some of the first results on distribution of Vasotocine (AVT) and Vasoactive intestinal peptide (VIP) in the brain of males and females of this songbird species, using immunohistochemistry mapping. The bulk of AVT-like cells are found in the hypothalamic supraoptic, paraventricular and suprachiasmatic nuclei, bed nucleus of the stria terminalis, and along the lateral forebrain bundle. Most AVT-like fibers course toward the median eminence, some reaching the arcopallium, and lateral septum. Further terminal fields occur in the dorsal thalamus, ventral tegmental area and pretectal area. Most VIP-like cells are in the lateral septal organ and arcuate nucleus. VIP-like fibers are distributed extensively in the hypothalamus, preoptic area, lateral septum, diagonal band of Broca. They are also found in the bed nucleus of the stria terminalis, amygdaloid nucleus of taenia, robust nucleus of the arcopallium, caudo-ventral hyperpallium, nucleus accumbens and the brainstem. Taken together, these results suggest that both AVT and VIP immunoreactive structures show similar distribution to other avian species, emphasizing evolutionary conservatism in the history of vertebrates. The current study may enable future investigation into the localization of AVT and VIP, in relation to behavioral and ecological traits in the brain of tit species. PMID:26236200

  9. Effects of pelvic, pudendal, or hypogastric nerve cuts on Fos induction in the rat brain following vaginocervical stimulation.

    PubMed

    Pfaus, James G; Manitt, Colleen; Coopersmith, Carol B

    2006-12-30

    In the female rat, genitosensory input is conveyed to the central nervous system predominantly through the pelvic, pudendal, and hypogastric nerves. The present study examined the relative contribution of those three nerves in the expression of Fos immunoreactivity within brain regions previously shown to be activated by vaginocervical stimulation (VCS). Bilateral transection of those nerves, or sham neurectomy, was conducted in separate groups of ovariectomized, sexually-experienced females. After recovery, females were primed with estrogen and progesterone and given either 50 manual VCSs with a lubricated glass rod over the course of 1 h. VCS increased the number of neurons expressing Fos immunoreactivity in the medial preoptic area, lateral septum, bed nucleus of the stria terminalis, ventromedial hypothalamus, and medial amygdala of sham neurectomized females. Transection of the pelvic nerve reduced Fos immunoreactivity in the medial preoptic area, bed nucleus of the stria terminalis, ventromedial hypothalamus, and medial amygdala, whereas transection of the pudendal nerve had no effect. In contrast, transection of the hypogastric nerve increased Fos immunoreactivity in the medial preoptic area and lateral septum, whereas transaction of the pelvic nerve increased Fos immunoreactivity in the lateral septum, following VCS. All females given VCS, except those with pelvic neurectomy, displayed a characteristic immobility during each application. These data confirm that the pelvic nerve is largely responsible for the neural and behavioral effects of VCS, and support a separate function for the hypogastric nerve. PMID:16959279

  10. Connections of the corticomedial amygdala in the golden hamster. II. Efferents of the ''olfactory amygdala''

    SciTech Connect

    Kevetter, G.A.; Winans, S.S.

    1981-03-20

    The anterior cortical (C1) and posterolateral cortical (C2) nuclei of the amygdala are designated the ''olfactory amygdala'' because they each receive direct projections from the main olfactory bulb. The efferents of these nuclei were traced after stereotaxic placement of 1-5 muCi tritiated proline in the corticomedial amygdala of the male golden hamsters. Following survival times of 12, 24, or 48 hours, 20 micron frozen sections of the brains were processed for light microscopic autoradiography. Efferents from C2 terminate in layers II and III of the olfactory tubercle and in layer Ib of pars ventralis and pars medialis of the anterior olfactory nucleus. Fibers from this nucleus also project to layers I and II of the infralimbic cortex and to the molecular layer of the agranular insular cortex. More posteriorly, fibers from C2 terminate in layer I of the dorsolateral entorhinal cortex, and in the endopiriform nucleus. From C1, efferent fibers travel in the stria terminalis and terminate in the precommissural bed nucleus of the stria terminalis and in the mediobasal hypothalamus. Efferents from C1 also innervate the molecular layer of C2, the amygdalo-hippocampal area, and the adjacent piriform cortex. Neurons in both C1 and C2 project to the molecular layer of the medial amygdaloid nucleus and the posteromedial cortical nucleus of the amygdala, the plexiform layer of the ventral subiculum, and the molecular layer of the lateral entorhinal cortex.

  11. Distribution of sup 125 I-neurotensin binding sites in human forebrain: Comparison with the localization of acetylcholinesterase

    SciTech Connect

    Szigethy, E.; Quirion, R.; Beaudet, A. )

    1990-07-22

    The distribution of 125I-neurotensin binding sites was compared with that of acetylcholinesterase reactivity in the human basal forebrain by using combined light microscopic radioautography/histochemistry. High 125I-neurotensin binding densities were observed in the bed nucleus of the stria terminalis, islands of Calleja, claustrum, olfactory tubercle, and central nucleus of the amygdala; lower levels were seen in the caudate, putamen, medial septum, diagonal band nucleus, and nucleus basalis of Meynert. Adjacent sections processed for cholinesterase histochemistry demonstrated a regional overlap between the distribution of labeled neurotensin binding sites and that of intense acetylcholinesterase staining in all of the above regions, except in the bed nucleus of the stria terminalis, claustrum, and central amygdaloid nucleus, where dense 125I-neurotensin labeling was detected over areas containing only weak to moderate cholinesterase staining. At higher magnification, 125I-neurotensin-labeled binding sites in the islands of Calleja, supraoptic nucleus of the hypothalamus, medial septum, diagonal band nucleus, and nucleus basalis of Meynert were selectively associated with neuronal perikarya found to be cholinesterase-positive in adjacent sections. Moderate 125I-neurotensin binding was also apparent over the cholinesterase-reactive neuropil of these latter three regions. These data suggest that neurotensin (NT) may directly influence the activity of magnocellular cholinergic neurons in the human basal forebrain, and may be involved in the physiopathology of dementing disorders such as Alzheimer's disease, in which these neurons have been shown to be affected.

  12. The vasopressinergic innervation of the brain in normal and castrated rats.

    PubMed

    DeVries, G J; Buijs, R M; Van Leeuwen, F W; Caffé, A R; Swaab, D F

    1985-03-01

    A detailed description is given of the distribution of vasopressin-immunoreactive structures in the brain of intact adult male rats. By application of a modified immunocytochemical procedure, vasopressin-immunoreactive fibers were detected in many new areas. In adult male rats which were castrated 15 weeks before death, vasopressin-immunoreactive cell bodies had disappeared from the bed nucleus of the stria terminalis and the medial amygdaloid nucleus. No obvious changes were found in vasopressin-immunoreactive cell bodies in other areas. Furthermore, a very strong reduction was seen in the density of vasopressin-immunoreactive fibers in the olfactory tubercle, nucleus of the diagonal band and its immediate surroundings, ventral pallidum, basal nucleus of Meynert, lateral septum, septofimbrial nucleus, ventral hippocampal formation, amygdaloid area, pre- and supramammillary nucleus, supramammillary decussation, (inter)dorsomedial, parafascicular, and ventral aspect of paraventricular thalamic nuclei, zona incerta, lateral habenular nucleus, ventral tegmental area, substantia nigra, periventricular gray, dorsal and median raphe nucleus, and locus coeruleus. No changes were observed in other areas containing vasopressin-immunoreactive fibers. These changes following gonadectomy were not observed in castrated rats which had been treated with testosterone. The results suggest that vasopressin projections from the bed nucleus of the stria terminalis and possibly from the medial amygdaloid nucleus require the presence of gonadal hormones for their normal appearance. This is in contrast to pathways arising from the hypothalamic vasopressin-producing nuclei, which fail to show obvious changes following castration. PMID:3882778

  13. Vasopressin-immunoreactive cells in the dorsomedial hypothalamic region, medial amygdaloid nucleus and locus coeruleus of the rat.

    PubMed

    Caffé, A R; van Leeuwen, F W

    1983-01-01

    Recently, the existence of a vasopressin-immunoreactive cell group was described in the bed nucleus of the stria terminalis (van Leeuwen and Caffé 1983). In the present investigation additional nuclei containing vasopressin-immunoreactive cells were found, after colchicine pretreatment, in the dorsomedial hypothalamus, medial amygdaloid nucleus and the locus coeruleus. Vasopressin-immunoreactive cells in the dorsomedial hypothalamus and medial amygdaloid nucleus are small (8--14 micrometers and 10--14 micrometers, respectively), while those in the locus coeruleus are medium-sized (20--25 micrometers). Incubation with anti-bovine neurophysin II and anti-rat neurophysin revealed staining of the same cell group in the above-mentioned areas. None of these cell groups show stained cells after incubation with anti-oxytocin and anti-bovine neurophysin I. When sections of the homozygous Brattleboro rat, which shows a deficiency in vasopressin synthesis, are incubated with anti-vasopressin, anti-bovine neurophysin II, or anti-rat neurophysin, no immunoreactivity can be observed in these brain regions. The above-mentioned cell groups may contribute to the vasopressinergic innervation of brain sites that have been reported to persist after lesioning of the suprachiasmatic, paraventricular and bed nuclei of the stria terminalis. PMID:6616564

  14. D1 Dopamine Receptor-Mediated LTP at GABA Synapses Encodes Motivation to Self-Administer Cocaine in Rats

    PubMed Central

    Krawczyk, Michal; Mason, Xenos; DeBacker, Julian; Sharma, Robyn; Normandeau, Catherine P.; Hawken, Emily R.; Di Prospero, Cynthia; Chiang, Cindy; Martinez, Audrey; Jones, Andrea A.; Doudnikoff, Évelyne; Caille, Stephanie; Bézard, Erwan; Georges, François; Dumont, Éric C.

    2014-01-01

    Enhanced motivation to take drugs is a central characteristic of addiction, yet the neural underpinning of this maladaptive behavior is still largely unknown. Here, we report a D1-like dopamine receptor (DRD1)-mediated long-term potentiation of GABAA-IPSCs (D1-LTPGABA) in the oval bed nucleus of the stria terminalis that was positively correlated with motivation to self-administer cocaine in rats. Likewise, in vivo intra-oval bed nucleus of the stria terminalis DRD1 pharmacological blockade reduced lever pressing for cocaine more effectively in rats showing enhanced motivation toward cocaine. D1-LTPGABA resulted from enhanced function and expression of G-protein-independent DRD1 coupled to c-Src tyrosine kinases and required local release of neurotensin. There was no D1-LTPGABA in rats that self-administered sucrose, in those with limited cocaine self-administration experience, or in those that received cocaine passively (yoked). Therefore, our study reveals a novel neurophysiological mechanism contributing to individual motivation to self-administer cocaine, a critical psychobiological element of compulsive drug use and addiction. PMID:23864683

  15. D1 dopamine receptor-mediated LTP at GABA synapses encodes motivation to self-administer cocaine in rats.

    PubMed

    Krawczyk, Michal; Mason, Xenos; DeBacker, Julian; Sharma, Robyn; Normandeau, Catherine P; Hawken, Emily R; Di Prospero, Cynthia; Chiang, Cindy; Martinez, Audrey; Jones, Andrea A; Doudnikoff, Évelyne; Caille, Stephanie; Bézard, Erwan; Georges, François; Dumont, Éric C

    2013-07-17

    Enhanced motivation to take drugs is a central characteristic of addiction, yet the neural underpinning of this maladaptive behavior is still largely unknown. Here, we report a D1-like dopamine receptor (DRD1)-mediated long-term potentiation of GABAA-IPSCs (D1-LTPGABA) in the oval bed nucleus of the stria terminalis that was positively correlated with motivation to self-administer cocaine in rats. Likewise, in vivo intra-oval bed nucleus of the stria terminalis DRD1 pharmacological blockade reduced lever pressing for cocaine more effectively in rats showing enhanced motivation toward cocaine. D1-LTPGABA resulted from enhanced function and expression of G-protein-independent DRD1 coupled to c-Src tyrosine kinases and required local release of neurotensin. There was no D1-LTPGABA in rats that self-administered sucrose, in those with limited cocaine self-administration experience, or in those that received cocaine passively (yoked). Therefore, our study reveals a novel neurophysiological mechanism contributing to individual motivation to self-administer cocaine, a critical psychobiological element of compulsive drug use and addiction. PMID:23864683

  16. Age-related axonal swellings precede other neuropathological hallmarks in a knock-in mouse model of Huntington's disease.

    PubMed

    Marangoni, Martina; Adalbert, Robert; Janeckova, Lucie; Patrick, Jane; Kohli, Jaskaren; Coleman, Michael P; Conforti, Laura

    2014-10-01

    Axon degeneration precedes cell body death in many age-related neurodegenerative disorders, often determining symptom onset and progression. A sensitive method for revealing axon pathology could indicate whether this is the case also in Huntington's disease (HD), a fatal, devastating neurodegenerative disorder causing progressive deterioration of both physical and mental abilities, and which brain region is affected first. We studied the spatio-temporal relationship between axon pathology, neuronal loss, and mutant Huntingtin aggregate formation in HD mouse models by crossing R6/2 transgenic and HdhQ140 knock-in mice with YFP-H mice expressing the yellow fluorescent protein in a subset of neurons. We found large axonal swellings developing age-dependently first in stria terminalis and then in corticostriatal axons of HdhQ140 mice, whereas alterations of other neuronal compartments could not be detected. Although mutant Huntingtin accumulated with age in several brain areas, inclusions in the soma did not correlate with swelling of the corresponding axons. Axon abnormalities were not a prominent feature of the rapid progressive pathology of R6/2 mice. Our findings in mice genetically similar to HD patients suggest that axon pathology is an early event in HD and indicate the importance of further studies of stria terminalis axons in man. PMID:24906892

  17. Relative role of neural substrates in the aggressive behavior of rats.

    PubMed

    Patil, Shrirang N; Brid, Shivaji V

    2010-01-01

    Early animal studies have shown an association between aggression and brain dysfunction. The goal of the present study was to compare the effects of lesions of different parts of brain on aggression in rats. Adult rats (n = 40, weighing 200-260 g) were randomly divided into four groups of ten animals each and subjected to lesions of the septum (Group I), medial preoptic area (Group II), medial accumbens (Group III), and bed nucleus of stria terminalis (Group IV), using stereotaxy apparatus. Aggression toward an unfamiliar male intruder was observed before and after the lesion. The aggression score of each animal was recorded three times before lesion and averaged for use in analysis. Analysis of variance (ANOVA) was applied for finding homogeneity of the groups. Postoperative scores were also similarly recorded and summarized as mean +/- standard deviation. Pre- and post-lesion scores were compared using the t test. The scores were significantly reduced in Group I, II, and III, but increased in Group IV. We can conclude that the septum, medial preoptic area, medial accumbens, and bed nucleus of stria terminalis, by virtue of their interconnections, influence aggressive behavior. PMID:21305851

  18. Lipopolysaccharide-Induced Middle Ear Inflammation Disrupts the cochlear Intra-Strial Fluid–Blood Barrier through Down-Regulation of Tight Junction Proteins

    PubMed Central

    Zhang, Jinhui; Chen, Songlin; Hou, Zhiqiang; Cai, Jing; Dong, Mingmin; Shi, Xiaorui

    2015-01-01

    Middle ear infection (or inflammation) is the most common pathological condition that causes fluid to accumulate in the middle ear, disrupting cochlear homeostasis. Lipopolysaccharide, a product of bacteriolysis, activates macrophages and causes release of inflammatory cytokines. Many studies have shown that lipopolysaccharides cause functional and structural changes in the inner ear similar to that of inflammation. However, it is specifically not known how lipopolysaccharides affect the blood-labyrinth barrier in the stria vascularis (intra-strial fluid–blood barrier), nor what the underlying mechanisms are. In this study, we used a cell culture-based in vitro model and animal-based in vivo model, combined with immunohistochemistry and a vascular leakage assay, to investigate lipopolysaccharide effects on the integrity of the mouse intra-strial fluid–blood barrier. Our results show lipopolysaccharide-induced local infection significantly affects intra-strial fluid–blood barrier component cells. Pericytes and perivascular-resident macrophage-like melanocytes are particularly affected, and the morphological and functional changes in these cells are accompanied by substantial changes in barrier integrity. Significant vascular leakage is found in the lipopolysaccharide treated-animals. Consistent with the findings from the in vivo animal model, the permeability of the endothelial cell monolayer to FITC-albumin was significantly higher in the lipopolysaccharide-treated monolayer than in an untreated endothelial cell monolayer. Further study has shown the lipopolysaccharide-induced inflammation to have a major effect on the expression of tight junctions in the blood barrier. Lipopolysaccharide was also shown to cause high frequency hearing loss, corroborated by previous reports from other laboratories. Our findings show lipopolysaccharide-evoked middle ear infection disrupts inner ear fluid balance, and its particular effects on the intra-strial fluid

  19. Expression of Fos during sham sucrose intake in rats with central gustatory lesions.

    PubMed

    Mungarndee, Suriyaphun S; Lundy, Robert F; Norgren, Ralph

    2008-09-01

    For humans and rodents, ingesting sucrose is rewarding. This experiment tested the prediction that the neural activity produced by sapid sucrose reaches reward systems via projections from the pons through the limbic system. Gastric cannulas drained ingested fluid before absorption. For 10 days, the rats alternated an hour of this sham ingestion between sucrose and water. On the final test day, half of them sham drank water and the other half 0.6 M sucrose. Thirty minutes later, the rats were killed and their brains immunohistochemically stained for Fos. The groups consisted of controls and rats with excitotoxic lesions in the gustatory thalamus (TTA), the medial (gustatory) parabrachial nucleus (PBN), or the lateral (visceral afferent) parabrachial nucleus. In controls, compared with water, sham ingesting sucrose produced significantly more Fos-positive neurons in the nucleus of the solitary tract, PBN, TTA, and gustatory cortex (GC). In the ventral forebrain, sucrose sham licking increased Fos in the bed nucleus of the stria terminalis, central nucleus of amygdala, and the shell of nucleus accumbens. Thalamic lesions blocked the sucrose effect in GC but not in the ventral forebrain. After lateral PBN lesions, the Fos distributions produced by distilled H(2)O or sucrose intake did not differ from controls. Bilateral medial PBN damage, however, eliminated the sucrose-induced Fos increase not only in the TTA and GC but also in the ventral forebrain. Thus ventral forebrain areas associated with affective responses appear to be activated directly by PBN gustatory neurons rather than via the thalamocortical taste system. PMID:18635449

  20. Diencephalic and septal structures containing the avian vasotocin receptor (V1aR) involved in the regulation of food intake in chickens, Gallus gallus.

    PubMed

    Nagarajan, Gurueswar; Jurkevich, Alexander; Kang, Seong W; Kuenzel, Wayne J

    2016-10-01

    Recently, it was found that the avian central vasotocin receptor (V1aR) is associated with the regulation of food intake. To identify V1aR-containing brain structures regulating food intake, a selective V1aR antagonist SR-49059 that induced food intake was administrated intracerebroventricularly in male chickens followed by detection of brain structures using FOS immunoreactivity. Particularly, the hypothalamic core region of the paraventricular nucleus, lateral hypothalamic area, dorsomedial hypothalamic nucleus, a subnucleus of the central extended amygdalar complex [dorsolateral bed nucleus of the stria terminalis], medial septal nucleus and caudal brainstem [nucleus of the solitary tract] showed significantly increased FOS-ir cells. On the other hand, the supraoptic nucleus of the preoptic area and the nucleus of the hippocampal commissure of the septum showed suppressed FOS immunoreactivity in the V1aR antagonist treatment group. Further investigation revealed that neuronal activity of arginine vasotocin (AVT-ir) magnocellular neurons in the supraoptic nucleus, preoptic periventricular nucleus, paraventricular nucleus and ventral periventricular hypothalamic nucleus and most likely corticotropin releasing hormone (CRH-ir) neurons in the nucleus of the hippocampal commissure were reduced following the antagonist treatment. Dual immunofluorescence labeling results showed that perikarya of AVT-ir magnocellular neurons in the preoptic area and hypothalamus were colabeled with V1aR. Within the nucleus of the hippocampal commissure, CRH-ir neurons were shown in close contact with V1aR-ir glial cells. Results of the present study suggest that the V1aR plays a role in the regulation of food intake by modulating neurons that synthesize and release anorectic neuropeptides in the avian brain. PMID:27317836

  1. Sex-Dependent Effects of Prenatal Stress on Social Memory in Rats: A Role for Differential Expression of Central Vasopressin-1a Receptors.

    PubMed

    Grundwald, N J; Benítez, D P; Brunton, P J

    2016-04-01

    Prenatal stress (PNS) affects a number of traits in the offspring, including stress axis regulation, emotionality and cognition; however, much less is known about the effects of PNS on social memory and the underlying central mechanisms. In the present study, we investigated social preference, social memory under basal and stress conditions and olfactory memory for social and nonsocial odours in the adult offspring of dams exposed to social stress during late pregnancy. Given the key roles that the central oxytocin and vasopressin systems play in facilitating social memory, we further investigated the effects of PNS on the central expression of mRNA for oxytocin (Oxtr) and vasopressin-1a (Avpr1a) receptors. PNS did not affect social preference in either sex; however, social memory was impaired under basal conditions in PNS females but not PNS males. Accordingly, Avpr1a mRNA expression in the lateral septum and bed nucleus of stria terminalis (BNST) was unaltered in males but was significantly lower in PNS females compared to controls. No differences in Oxtr mRNA expression were detected between control and PNS offspring in either sex in any of the brain regions examined. Social memory deficits in PNS females persisted when social odours were used; however, this does not appear to be a result of impaired olfaction because memory for nonsocial odours was similar in control and PNS females. Under acute stress conditions, deficits in social memory were observed in both male and female control offspring; however, PNS males were unaffected. Moreover, acute stress facilitated social memory in PNS females and this was associated with an up-regulation of Avpr1a mRNA in the lateral septum and BNST. Our data support a role for altered signalling via central Avpr1a in PNS-induced sex-dependent changes in social memory and may have implications for understanding the aetiology of neurodevelopmental disorders characterised by social behaviour deficits in humans. PMID:26613552

  2. Social novelty increases tyrosine hydroxylase immunoreactivity in the extended olfactory amygdala of female prairie voles

    PubMed Central

    Cavanaugh, Breyanna L.; Lonstein, Joseph S.

    2010-01-01

    The monogamous social behaviors of prairie voles (Microtus ochrogaster) require olfactory inputs, which are processed by the posterodorsal medial amygdala (MeApd) and principal bed nucleus of the stria terminalis (pBST). The male prairie vole MeApd and pBST contain hundreds of cells densely immunoreactive for tyrosine hydroxylase (TH-ir). Female prairie voles have relatively few of these cells, but we previously found that the number of these TH-ir cells is greatly increased in females by exogenous estradiol. We here hypothesized that the number of TH-ir cells in the MeApd and pBST would also increase during the natural hormone surges associated with females’ induced estrus. We found that the number of TH-ir cells in both sites did significantly increase after females cohabitated for two days with an unfamiliar male. However, this increase did not require the presence of ovaries and even tended to occur in the pBST of females cohabitating for two days with unfamiliar females. We then determined if the greater number of TH-ir cells after heterosexual pairing was transient by examining two groups of long-term pairbonded females (primiparous and multiparous), and found these females also had significantly more TH-ir cells in the pBST and/or MeApd compared to unmated controls. Thus, social novelty arising from cohabitation with unfamiliar conspecifics produces a reoccurring increase in the number of TH-ir cells in the female prairie vole extended olfactory amygdala. Ovarian hormones are not necessarily required. This increase in catecholaminergic cells may facilitate acquisition and retention of olfactory memories necessary for social recognition in this species. PMID:20381508

  3. Pup odor and ultrasonic vocalizations synergistically stimulate maternal attention in mice.

    PubMed

    Okabe, Shota; Nagasawa, Miho; Kihara, Takashi; Kato, Masahiro; Harada, Toshihiro; Koshida, Nobuyoshi; Mogi, Kazutaka; Kikusui, Takefumi

    2013-06-01

    Pup ultrasonic vocalizations (USVs), which are emitted by hypothermic pups, and pup odor are thought to be triggers of maternal behavior in mice. We investigated whether pup odor stimulated maternal responses to pup USVs in mother C57BL/6 mice. Two-choice tests were conducted by introducing mothers into a test cage in which a tube was attached on each long wall, and the duration spent in each tube was compared. Pup USVs were reproduced by an ultrasonic speaker at the tube end. In some cases, cotton with pup odor was also presented at the end of the tube. Compared to no stimuli, mothers did not specifically approach the sole presentation of either reproduced pup USVs or pup odor. However, compared to the sole presentation of pup odor, the simultaneous presentation of pup USVs and odor induced a specific approach response. These results suggested that pup USVs and odor synergistically stimulated maternal behavior. In addition, it was confirmed that mothers approached hypothermic pups emitting pup USVs for longer than anesthetized silent pups. To investigate the underlying neural mechanisms, we observed neural responses to various stimuli with the immunohistochemistry of c-fos expression. In the bed nucleus of the stria terminalis, the medial preoptic area, the central nucleus of the amygdala, and the basolateral amygdala, the numbers of c-fos-positive cells were significantly increased following the simultaneous presentation of pup USVs and odor compared to the presentation of each alone, suggesting that these nuclei were involved in multimodal processing related to maternal behavior. PMID:23544596

  4. Differential impact of polysialyltransferase ST8SiaII and ST8SiaIV knockout on social interaction and aggression.

    PubMed

    Calandreau, L; Márquez, C; Bisaz, R; Fantin, M; Sandi, C

    2010-11-01

    Previous studies using neuronal cell adhesion molecule (NCAM) -/- knockout (KO) mice provided evidence for a role of NCAMs in social behaviors. However, polysialic acid (PSA), the most important post-translational modification of NCAM, was also absent in these mice, which makes it difficult to distinguish between the specific involvement of either PSA or NCAM in social interactions. To address this issue, we assessed two lines of mice deficient for one of the two sialyltransferase enzymes required for the polysialylation of NCAM, sialyltransferase-X (St8SiaII or STX) and polysialyltransferase (ST8SiaIV or PST), in a series of tests for social behaviors. Results showed that PST KO mice display a decreased motivation in social interaction. This deficit can be partly explained by olfactory deficits and was associated with a clear decrease in PSA-NCAM expression in all brain regions analyzed (amygdala, septum, bed nucleus of the stria terminalis and frontal cortices). STX KO mice displayed both a decreased social motivation and an increased aggressive behavior that cannot be explained by olfactory deficits. This finding might be related to the reduced anxiety-like behavior, increased locomotion and stress-induced corticosterone secretion observed in these mice. Moreover, STX KO mice showed mild increase of PSA-NCAM expression in the lateral septum and the orbitofrontal cortex. Altogether, these findings support a role for PSA-NCAM in the regulation of social behaviors ranging from a lack of social motivation to aggression. They also underscore STX KO mice as an interesting animal model that combines a behavioral profile of violence and hyperactivity with reduced anxiety-like behavior. PMID:20659171

  5. The underestimated role of olfaction in avian reproduction ?

    PubMed Central

    Balthazart, Jacques; Taziaux, Mélanie

    2009-01-01

    Until the second half of the 20th century, it was broadly accepted that most birds are microsmatic if not anosmic and unable to detect and use olfactory information. Exceptions were eventually conceded for species like procellariiforms, vultures or kiwis that detect their food at least in part based on olfactory signals. During the past 20–30 years, many publications have appeared indicating that this view is definitely erroneous. We briefly review here anatomical, electrophysiological and behavioral data demonstrating that birds in general possess a functional olfactory system and are able to use olfactory information in a variety of ethological contexts, including reproduction. Recent work also indicates that brain activation induced by sexual interactions with a female is significantly affected by olfactory deprivation in Japanese quail. Brain activation was measured via immunocytochemical detection of the protein product of the immediate early gene c-fos. Changes observed concerned two brain areas that play a key role in the control of male sexual behavior, the medial preoptic nucleus and the bed nucleus of the stria terminalis therefore suggesting a potential role of olfaction in the control of reproduction. The widespread idea that birds are anosmic or microsmatic is thus not supported by the available experimental data and presumably originates in our anthropomorphic view that leads us to think that birds do not smell because they have a rigid beak and nostrils and do not obviously sniff. Experimental analysis of this phenomenon is thus warranted and should lead to a significant change in our understanding of avian biology. PMID:18804490

  6. Neuropeptide Y system in accumbens shell mediates ethanol self-administration in posterior ventral tegmental area.

    PubMed

    Borkar, Chandrashekhar D; Upadhya, Manoj A; Shelkar, Gajanan P; Subhedar, Nishikant K; Kokare, Dadasaheb M

    2016-07-01

    Although modulatory effects of neuropeptide Y (NPY) on ethanol consumption are well established, its role in ethanol reward, in the framework of mesolimbic dopaminergic system, has not been studied. We investigated the influence of nucleus accumbens shell (AcbSh) NPYergic system on ethanol self-administration in posterior ventral tegmental area (p-VTA) using intracranial self-administration paradigm. Rats were stereotaxically implanted with cannulae targeted unilaterally at the right p-VTA and trained to self-administer ethanol (200 mg%) in standard two-lever (active/inactive) operant chamber, an animal model with high predictive validity to test the rewarding mechanisms. Over a period of 7 days, these rats showed a significant increase in the number of lever presses for ethanol self-administration suggesting reinforcement. While intra-AcbSh NPY (1 or 2 ng/rat) or [Leu(31) , Pro(34) ]-NPY (0.5 or 1 ng/rat) dose-dependently increased ethanol self-administration, BIBP3226 (0.4 or 0.8 ng/rat) produced opposite effect. The rats conditioned to self-administer ethanol showed significant increase in the population of NPY-immunoreactive cells and fibres in the AcbSh, central nucleus of amygdala (CeA), hypothalamic arcuate nucleus (ARC) and lateral part of bed nucleus of stria terminalis as compared with that in the naïve rats. Neuronal tracing studies showed that NPY innervations in the AcbSh may derive from the neurons of ARC and CeA. As NPY and dopamine systems in reward areas are known to interact, we suggest that NPY inputs from ARC and CeA may play an important role in modulation of the dopaminergic system in the AcbSh and consequently influence the ethanol induced reward and addiction. PMID:25929272

  7. Effects of estrogens on sex differentiation in Japanese quail and chicken.

    PubMed

    Brunström, Björn; Axelsson, Jeanette; Mattsson, Anna; Halldin, Krister

    2009-09-01

    Estrogen production by the female avian embryo induces development of a female phenotype of the reproductive organs whereas the low estrogen concentration in the male embryo results in a male phenotype. Treatment of female embryos with exogenous estrogens disrupts Müllerian duct development resulting in malformations and impaired oviductal function. Exposure of male embryos to estrogens results in ovotestis formation and persisting Müllerian ducts in the embryos and testicular malformations, reduced semen production and partially developed oviducts in the adult bird. Furthermore, studies in Japanese quail show that the male copulatory behavior is impaired by embryonic estrogen treatment. Results from our experiments with selective agonists for ERalpha and ERbeta suggest that the effects of estrogens on the reproductive organs are mediated via activation of ERalpha. Abundant expression of ERalpha mRNA was shown in gonads and Müllerian ducts of early Japanese quail embryos. Both ERalpha and ERbeta transcripts were detected by real-time PCR in early embryo brains of Japanese quail indicating that both receptors may be involved in sex differentiation of the brain. However, in 9-day-old quail embryo brains in situ hybridization showed expression of ERbeta mRNA, but not of ERalpha mRNA, in the medial preoptic nucleus (POM) and the bed nucleus of the stria terminalis (BSTm), areas implicated in copulatory behavior of adult male quail. Furthermore, embryonic treatment with the selective ERalpha agonist propyl pyrazol triol (PPT) had no effect on the male copulatory behavior. These results suggest that ERbeta may be important for the effects of estrogens on brain differentiation. PMID:19523394

  8. Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats.

    PubMed

    Vendruscolo, Leandro F; Barbier, Estelle; Schlosburg, Joel E; Misra, Kaushik K; Whitfield, Timothy W; Logrip, Marian L; Rivier, Catherine; Repunte-Canonigo, Vez; Zorrilla, Eric P; Sanna, Pietro P; Heilig, Markus; Koob, George F

    2012-05-30

    Alcoholism is characterized by a compulsion to seek and ingest alcohol, loss of control over intake, and the emergence of a negative emotional state during abstinence. We hypothesized that sustained activation of neuroendocrine stress systems (e.g., corticosteroid release via the hypothalamic-pituitary-adrenal axis) by alcohol intoxication and withdrawal and consequent alterations in glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation drive compulsive alcohol drinking. Our results showed that rats exposed to alcohol vapor to the point of dependence displayed increased alcohol intake, compulsive drinking measured by progressive-ratio responding, and persistent alcohol consumption despite punishment, assessed by adding quinine to the alcohol solution, compared with control rats that were not exposed to alcohol vapor. No group differences were observed in the self-administration of saccharin-sweetened water. Acute alcohol withdrawal was accompanied by downregulated GR mRNA in various stress/reward-related brain regions [i.e., prefrontal cortex, nucleus accumbens (NAc), and bed nucleus of the stria terminalis (BNST)], whereas protracted alcohol abstinence was accompanied by upregulated GR mRNA in the NAc core, ventral BNST, and central nucleus of the amygdala. No significant alterations in MR mRNA levels were found. Chronic GR antagonism with mifepristone (RU38486) prevented the escalation of alcohol intake and compulsive responding induced by chronic, intermittent alcohol vapor exposure. Chronic treatment with mifepristone also blocked escalated alcohol drinking and compulsive responding during protracted abstinence. Thus, the GR system appears to be involved in the development of alcohol dependence and may represent a potential pharmacological target for the treatment of alcoholism. PMID:22649234

  9. Contrasting regional Fos expression in adolescent and young adult rats following acute administration of the antidepressant paroxetine.

    PubMed

    Karanges, Emily A; Ramos, Linnet; Dampney, Bruno; Suraev, Anastasia S; Li, Kong M; McGregor, Iain S; Hunt, Glenn E

    2016-03-01

    Adolescents and adults may respond differently to antidepressants, with poorer efficacy and greater probability of adverse effects in adolescents. The mechanisms underlying this differential response are largely unknown, but likely relate to an interaction between the neural effects of antidepressants and brain development. We used Fos immunohistochemistry to examine regional differences in adolescent (postnatal day (PND) 28) and young adult (PND 56) male, Wistar rats given a single injection of the selective serotonin reuptake inhibitor paroxetine (10mg/kg). Paroxetine induced widespread Fos expression in both adolescent and young adult rats. Commonly affected areas include the bed nucleus of the stria terminalis (dorsolateral), medial preoptic area, paraventricular hypothalamic and thalamic nuclei and central nucleus of the amygdala. Fos expression was generally lower in adolescents with significantly greater Fos expression observed in young adults in the prelimbic cortex, supraoptic nucleus, basolateral amygdala, lateral parabrachial and Kölliker-Fuse nuclei. However, a small subset of regions showed greater adolescent Fos expression including the nucleus accumbens shell, lateral habenula and dorsal raphe. Paroxetine increased plasma corticosterone concentrations in young adults, but not adolescents. Plasma paroxetine levels were not significantly different between the age groups. These results indicate a different c-Fos signature of acute paroxetine in adolescent rats, with greater activation in key mesolimbic and serotonergic regions, but a more subdued cortical, brainstem and hypothalamic response. This suggests that the atypical response of adolescents to paroxetine may be related to a blunted neuroendocrine response, combined with insufficient top-down regulation of limbic regions involved in reward and impulsivity. PMID:26876759

  10. Terminal field specificity of forebrain efferent axons to brainstem gustatory nuclei.

    PubMed

    Kang, Yi; Lundy, Robert F

    2009-01-12

    Rostral forebrain structures like the gustatory cortex (GC), bed nucleus of the stria terminalis (BNST), central nucleus of the amygdala (CeA), and lateral hypothalamus (LH) send projections to the nucleus of solitary tract (NST) and the parabrachial nucleus (PBN) that modulate taste-elicited responses. However, the proportion of forebrain-induced excitatory and inhibitory effects often differs when taste cell recording changes from the NST to the PBN. The present study investigated whether this descending influence originates from a shared or distinct population of forebrain neurons. Under electrophysiological guidance, the retrograde tracers fast blue (FB) and fluorogold (FG) or green (GFB) and red (RFB) fluorescent latex microbeads were injected iontophoretically or by pressure pulses (10 ms at 20 psi) into the taste-responsive regions of the NST and the ipsilateral PBN in six rats. Seven days later, the animals were euthanized and tissue sections containing the LH, CeA, BNST, and GC were processed for co-localization of FB and FG or GFB and RFB. The results showed that the CeA is the major source of input to the NST (82.3+/-7.6 cells/section) and the PBN (76.7+/-11.5), compared to the BNST (31.8+/-4.5; 37.0+/-4.8), the LH (35.0+/-5.4; 33.6+/-5.7), and the GC (27.5+/-4.0; 29.0+/-4.6). Of the total number of retrogradely labeled cells, the incidence of tracer co-localization was 17+/-3% in the GC, 17+/-2% in the CeA, 15+/-3% in the BNST and 16+/-1% in the LH. Thus, irrespective of forebrain source the majority of descending input to the gustatory NST and PBN originates from distinct neuronal populations. This arrangement provides an anatomical substrate for differential modulation of taste processing in the first and second central relays of the ascending gustatory system. PMID:19028464

  11. The effects of perinatal testosterone exposure on the DNA methylome of the mouse brain are late-emerging

    PubMed Central

    2014-01-01

    Background The biological basis for sex differences in brain function and disease susceptibility is poorly understood. Examining the role of gonadal hormones in brain sexual differentiation may provide important information about sex differences in neural health and development. Permanent masculinization of brain structure, function, and disease is induced by testosterone prenatally in males, but the possible mediation of these effects by long-term changes in the epigenome is poorly understood. Methods We investigated the organizational effects of testosterone on the DNA methylome and transcriptome in two sexually dimorphic forebrain regions—the bed nucleus of the stria terminalis/preoptic area and the striatum. To study the contribution of testosterone to both the establishment and persistence of sex differences in DNA methylation, we performed genome-wide surveys in male, female, and female mice given testosterone on the day of birth. Methylation was assessed during the perinatal window for testosterone's organizational effects and in adulthood. Results The short-term effect of testosterone exposure was relatively modest. However, in adult animals the number of genes whose methylation was altered had increased by 20-fold. Furthermore, we found that in adulthood, methylation at a substantial number of sexually dimorphic CpG sites was masculinized in response to neonatal testosterone exposure. Consistent with this, testosterone's effect on gene expression in the striatum was more apparent in adulthood. Conclusion Taken together, our data imply that the organizational effects of testosterone on the brain methylome and transcriptome are dramatic and late-emerging. Our findings offer important insights into the long-term molecular effects of early-life hormonal exposure. PMID:24976947

  12. Expression of Fos during sham sucrose intake in rats with central gustatory lesions

    PubMed Central

    Mungarndee, Suriyaphun S.; Lundy, Robert F.; Norgren, Ralph

    2008-01-01

    For humans and rodents, ingesting sucrose is rewarding. This experiment tested the prediction that the neural activity produced by sapid sucrose reaches reward systems via projections from the pons through the limbic system. Gastric cannulas drained ingested fluid before absorption. For 10 days, the rats alternated an hour of this sham ingestion between sucrose and water. On the final test day, half of them sham drank water and the other half 0.6 M sucrose. Thirty minutes later, the rats were killed and their brains immunohistochemically stained for Fos. The groups consisted of controls and rats with excitotoxic lesions in the gustatory thalamus (TTA), the medial (gustatory) parabrachial nucleus (PBN), or the lateral (visceral afferent) parabrachial nucleus. In controls, compared with water, sham ingesting sucrose produced significantly more Fos-positive neurons in the nucleus of the solitary tract, PBN, TTA, and gustatory cortex (GC). In the ventral forebrain, sucrose sham licking increased Fos in the bed nucleus of the stria terminalis, central nucleus of amygdala, and the shell of nucleus accumbens. Thalamic lesions blocked the sucrose effect in GC but not in the ventral forebrain. After lateral PBN lesions, the Fos distributions produced by distilled H2O or sucrose intake did not differ from controls. Bilateral medial PBN damage, however, eliminated the sucrose-induced Fos increase not only in the TTA and GC but also in the ventral forebrain. Thus ventral forebrain areas associated with affective responses appear to be activated directly by PBN gustatory neurons rather than via the thalamocortical taste system. PMID:18635449

  13. Brain activation by an olfactory stimulus paired with juvenile play in female rats.

    PubMed

    Paredes-Ramos, P; McCarthy, M M; Bowers, J M; Miquel, M; Manzo, J; Coria-Avila, G A

    2014-06-22

    We have previously shown that reward experienced during social play at juvenile age can be paired with artificial odors, and later in adulthood facilitate olfactory conditioned partner preferences (PP) in female rats. Herein, we examined the expression of FOS immunoreactivity (FOS-IR) following exposure to the odor paired with juvenile play (CS+). Starting at day P31 females received daily 30-min periods of social play with lemon-scented (paired group) or unscented females (unpaired group). At day P42, they were tested for play-PP with two juvenile males, one bearing the CS+ (lemon) and one bearing a novel odor (almond). Females were ovariectomized, hormone-primed and at day P55 tested for sexual-PP between two adult stud males scented with lemon or almond. In both tests, females from the paired group displayed conditioned PP (play or sexual) toward males bearing the CS+. In the present experiments females were exposed at day P59 to the CS+ during 60 min and their brains processed for FOS-IR. One group of female rats (Play+Sex) underwent play-PP and sexual-PP, whereas a second group of females (Play-only) underwent exclusively play-PP but not sexual-PP. Results showed that in the Play-only experiment exposure to the CS+ induced more FOS-IR in the medial prefrontal cortex, orbitofrontal cortex, dorsal striatum, and ventral tegmental area as compared to females from the unpaired group. In the Play+Sex experiment, more FOS-IR was observed in the piriform cortex, dorsal striatum, lateral septum, nucleus accumbens shell, bed nucleus of the stria terminalis and medial amygdala as compared to females from the unpaired group. Taken together, these results indicate mesocorticolimbic brain areas direct the expectation and/or choice of conditioned partners in female rats. In addition, transferring the meaning of play to sex preference requires different brain areas. PMID:24835545

  14. Sustained alterations in neuroimmune gene expression after daily, but not intermittent, alcohol exposure.

    PubMed

    Gano, Anny; Doremus-Fitzwater, Tamara L; Deak, Terrence

    2016-09-01

    Acute ethanol intoxication is associated with Rapid Alterations in Neuroimmune Gene Expression (RANGE), including increased Interleukin (IL)-6 and Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), and suppressed IL-1β and Tumor necrosis factor (TNF) α, yet little is known about adaptations in cytokines across the first few ethanol exposures. Thus, the present studies examined central cytokines during intoxication (3h post-ethanol) following 2, 4 or 6 intragastric ethanol challenges (4g/kg) delivered either daily or every-other-day (EOD). Subsequent analyses of blood ethanol concentrations (BECs) and corticosterone were performed to determine whether the schedule of ethanol delivery would alter the pharmacokinetics of, or general sensitivity to, subacute ethanol exposure. As expected, ethanol led to robust increases in IL-6 and IκBα gene expression in hippocampus, amygdala and bed nucleus of the stria terminalis (BNST), whereas IL-1β and TNFα were suppressed, thereby replicating our prior work. Ethanol-dependent increases in IL-6 and IκBα remained significant in all structures - even after 6 days of ethanol. When these doses were administered EOD, modest IL-6 increases in BNST were observed, with TNFα and IL-1β suppressed exclusively in the hippocampus. Analysis of BECs revealed a small but significant reduction in ethanol after 4 EOD exposures - an effect which was not observed when ethanol was delivered after 6 daily intubations. These findings suggest that ethanol-induced RANGE effects are not simply a function of ethanol load per se, and underscore the critical role that ethanol dosing interval plays in determining the neuroimmune consequences of alcohol. PMID:27208497

  15. Intracerebral sex differences in the vasotocin system in birds: possible implication in behavioral and autonomic functions.

    PubMed

    Jurkevich, A; Barth, S W; Aste, N; Panzica, G; Grossmann, R

    1996-12-01

    The brain vasotocinergic system demonstrates clear sexual dimorphism in birds investigated so far. This paper examines the evidence obtained in studies on gallinaceous (domestic fowl, Japanese quail) and passerine (canary, junco, zebra finch) birds. Vasotocin (VT)-immunoreactive parvocellular neurons are present in the nucleus of stria terminalis of males, but they are less abundant or absent in the corresponding structure of females. A similar difference has been observed in the dorsal paraventricular area of domestic fowl. Sex-related differences in VT-gene expression have been confirmed by in situ hybridization. Moreover, overall brain content of VT mRNA in cockerels is about twice that of hens, suggesting that VT synthesis may also be sexually dimorphic in other brain areas where morphological sex differences have not yet been revealed. The vasotocinergic system in birds is implicated in body fluid homeostasis, and during ontogeny it starts to respond to osmotic challenges in a sexually dimorphic way. Photoperiod, aging, or castration--all associated with changes in circulating testosterone levels--affect sexually dimorphic VT pathways and cell clusters. Sexually dimorphic vasotocinergic circuits are distributed in regions containing steroid-concentrating cells and are closely intermingled with aromatase-containing neurons that may mediate activational effects of gonadal steroids on this peptidergic system. However, it remains undetermined whether the observed neuroanatomical sex differences are related to sexually dimorphic autonomic and behavioral effects induced by VT. Most likely, VT in birds has a modulatory rather than a specific regulatory function in control of male sexual behavior and vocalization. PMID:9047289

  16. Subpallial and hypothalamic areas activated following sexual and agonistic encounters in male chickens.

    PubMed

    Xie, Jingjing; Kuenzel, Wayne J; Anthony, Nicholas B; Jurkevich, Alexander

    2010-10-01

    Male sexual and agonistic behaviors are controlled by the common social behavior network, involving subpallial and hypothalamic brain areas. In order to understand how this common network generates different behavioral outcomes, induction of FOS protein was used to examine the patterns of neuronal activation in adult male chickens following interaction with a female or a male. Males were subjected to one of the following treatments: handling control, non-contact interaction with a female, contact interaction with a live female, a taxidermy female model or another male. The number of FOS-immunoreactive (FOS-ir) cells, and the area and immunostaining density of individual cells were quantified in the medial preoptic nucleus (POM), medial extended amygdala (nucleus taeniae of the amygdala, TnA, and dorsolateral and ventromedial subdivisions of the medial portion of the bed nucleus of stria terminalis, BSTM1 and BSTM2, respectively), lateral septum (SL), hypothalamic paraventricular nucleus (PVN), bed nucleus of the pallial commissure (NCPa) and ventrolateral thalamic nucleus (VLT). An increase in FOS-ir cells following appetitive sexual behavior was found in BSTM2 and NCPa. Copulation augmented FOS-ir in POM, SL, VLT, and PVN. Intermale interactions increased FOS-ir in all examined brain regions except the TnA and BSTM. Within the SL, copulatory and agonistic behavior activated spatially segregated cell groups. In the PVN, different social behaviors induced significant changes in the distribution of FOS-ir cell sizes suggesting activation of heterogeneous subpopulations of cells. Collectively, behavioral outcomes of male-female and male-male interactions are associated with a combination of common and site-specific patterns of neural activation. PMID:20600197

  17. Olfactory systems and neural circuits that modulate predator odor fear

    PubMed Central

    Takahashi, Lorey K.

    2014-01-01

    When prey animals detect the odor of a predator a constellation of fear-related autonomic, endocrine, and behavioral responses rapidly occur to facilitate survival. How olfactory sensory systems process predator odor and channel that information to specific brain circuits is a fundamental issue that is not clearly understood. However, research in the last 15 years has begun to identify some of the essential features of the sensory detection systems and brain structures that underlie predator odor fear. For instance, the main (MOS) and accessory olfactory systems (AOS) detect predator odors and different types of predator odors are sensed by specific receptors located in either the MOS or AOS. However, complex predator chemosignals may be processed by both the MOS and AOS, which complicate our understanding of the specific neural circuits connected directly and indirectly from the MOS and AOS to activate the physiological and behavioral components of unconditioned and conditioned fear. Studies indicate that brain structures including the dorsal periaqueductal gray (DPAG), paraventricular nucleus (PVN) of the hypothalamus, and the medial amygdala (MeA) appear to be broadly involved in predator odor induced autonomic activity and hypothalamic-pituitary-adrenal (HPA) stress hormone secretion. The MeA also plays a key role in predator odor unconditioned fear behavior and retrieval of contextual fear memory associated with prior predator odor experiences. Other neural structures including the bed nucleus of the stria terminalis and the ventral hippocampus (VHC) appear prominently involved in predator odor fear behavior. The basolateral amygdala (BLA), medial hypothalamic nuclei, and medial prefrontal cortex (mPFC) are also activated by some but not all predator odors. Future research that characterizes how distinct predator odors are uniquely processed in olfactory systems and neural circuits will provide significant insights into the differences of how diverse predator

  18. Vasopressin indirectly excites dorsal raphe serotonin neurons through activation of the vasopressin1A receptor.

    PubMed

    Rood, B D; Beck, S G

    2014-02-28

    The neuropeptide vasopressin (AVP; arginine-vasopressin) is produced in a handful of brain nuclei located in the hypothalamus and extended amygdala and is released both peripherally as a hormone and within the central nervous system as a neurotransmitter. Central projections have been associated with a number of functions including regulation of physiological homeostasis, control of circadian rhythms, and modulation of social behavior. The AVP neurons located in the bed nucleus of the stria terminalis and medial amygdala (i.e., extended amygdala) in particular have been associated with affiliative social behavior in multiple species. It was recently demonstrated that in the mouse AVP projections emanating from extended amygdala neurons innervate a number of forebrain and midbrain brain regions including the dorsal raphe nucleus (DR), the site of origin of most forebrain-projecting serotonin neurons. Based on the presence of AVP fibers in the DR, we hypothesized that AVP would alter the physiology of serotonin neurons via AVP 1A receptor (V1AR) activation. Using whole-cell electrophysiology techniques, we found that AVP increased the frequency and amplitude of excitatory post-synaptic currents (EPSCs) in serotonin neurons of male mice. The indirect stimulation of serotonin neurons was AMPA/kainate receptor dependent and blocked by the sodium channel blocker tetrodotoxin, suggesting an effect of AVP on glutamate neurons. Further, the increase in EPSC frequency induced by AVP was blocked by selective V1AR antagonists. Our data suggest that AVP had an excitatory influence on serotonin neurons. This work highlights a new target (i.e., V1AR) for manipulating serotonin neuron excitability. In light of our data, we propose that some of the diverse effects of AVP on physiology and behavior, including social behavior, may be due to activation of the DR serotonin system. PMID:24345477

  19. Inducing labor

    MedlinePlus

    ... surrounds your baby in the womb. It contains membranes or layers of tissue. One method of inducing ... break the bag of waters" or rupture the membranes. Your health care provider will do a pelvic ...

  20. A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration

    PubMed Central

    Sun, Changling; Wang, Xueling; Zheng, Zhaozhu; Chen, Dongye; Wang, Xiaoqin; Shi, Fuxin; Yu, Dehong; Wu, Hao

    2015-01-01

    This study aimed to investigate the sustained drug release properties and hearing protection effect of polyethylene glycol-coated polylactic acid (PEG-PLA) stealth nanoparticles loaded with dexamethasone (DEX). DEX was fabricated into PEG-PLA nanoparticles using an emulsion and evaporation technique, as previously reported. The DEX-loaded PEG-PLA nanoparticles (DEX-NPs) had a hydrodynamic diameter of 130±4.78 nm, and a zeta potential of −26.13±3.28 mV. The in vitro release of DEX from DEX-NPs lasted 24 days in phosphate buffered saline (pH 7.4), 5 days in artificial perilymph (pH 7.4), and 1 day in rat plasma. Coumarin 6-labeled NPs placed onto the round window membrane (RWM) of guinea pigs penetrated RWM quickly and accumulated to the organs of Corti, stria vascularis, and spiral ganglion cells after 1 hour of administration. The DEX-NPs locally applied onto the RWM of guinea pigs by a single-dose administration continuously released DEX in 48 hours, which was significantly longer than the free DEX that was cleared out within 12 hours after administration at the same dose. Further functional studies showed that locally administrated single-dose DEX-NPs effectively preserved outer hair cells in guinea pigs after cisplatin insult and thus significantly attenuated hearing loss at 4 kHz and 8 kHz frequencies when compared to the control of free DEX formulation. Histological analyses indicated that the administration of DEX-NPs did not induce local inflammatory responses. Therefore, prolonged delivery of DEX by PEG-PLA nanoparticles through local RWM diffusion (administration) significantly protected the hair cells and auditory function in guinea pigs from cisplatin toxicity, as determined at both histological and functional levels, suggesting the potential therapeutic benefits in clinical applications. PMID:25999718

  1. (/sup 3/H)-dihydrotestosterone in catecholamine neurons of rat brain stem: combined localization by autoradiography and formaldehyde-induced fluorescence

    SciTech Connect

    Heritage, A.S.; Stumpf, W.E.; Sar, M.; Grant, L.D.

    1981-01-01

    A combined formaldehyde-induced fluorescence (FIF)-autoradiography procedure was used to determine how and where the androgen, dihydrotestosterone (DHT), is associated with catecholamine systems in the rat brain. With this dual localization method, (/sup 3/H)-DHT target sites can be visualized in relation to catecholamine perikarya and terminals. In the hindbrain, catecholamine neurons adjacent to the fourth ventricle (group A4), the nucleus (n.) olivaris superior (group A5), the n. parabranchialis medialis (group A7), and in the locus coeruleus (group A6) and subcoeruleal regions, as well as in the substantia grisea centralis, concentrate (/sup 3/H)-DHT in their nuclei. (/sup 3/H)-DHT target neurons appear to be innervated by numerous catecholamine terminals in the following hindbrain regions: n. motorius dorsalis nervi vagi, n. tractus solitarii, n. commissuralis, n. raphe pallidus, n. olivaris inferior, the ventrolateral portion of the substantia grisea centralis, n. cuneiformis, and the ventrolateral reticular formation in the caudal mesencephalon. In the forebrain, (/sup 3/H)-DHT concentrates in nuclei of catecholamine neurons located in the n. arcuatus and n. periventricularis (group A12). In addition, (/sup 3/H)-DHT target neurons appear to be innervated by numerous catecholamine terminals in the following forebrain regions: n. periventricularis rotundocellularis, n. paraventricularis, n. dorsomedialis, n. periventricularis, area retrochiasmatica, n. interstititalis striae terminalis (ventral portion), and n. amygdaloideus centralis. The disclosure of a morphologic association between (/sup 3/H)-DHT target sites and certain brain catecholamine systems suggests a close functional interdependence between androgens and catecholamines.

  2. The use of heat-induced hydrolysis in immunohistochemistry on angiotensin II (AT1) receptors enhances the immunoreactivity in paraformaldehyde-fixed brain tissue of normotensive Sprague-Dawley rats.

    PubMed

    Thomas, Martin Alexander; Lemmer, Björn

    2006-11-13

    The research on components of the renin-angiotensin system delivered a broad image of angiotensin II-binding sites. Especially, immunohistochemistry (IHC) provided an exact anatomical localization of the AT(1) receptor in the rat brain. Yet, controversial results between in vitro receptor autoradiography and IHC as well as between immunohistochemical studies using various antisera started a vehement discussion concerning specificity and cross-reactivity of these antisera. In particular the magnocellular subdivision of the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) provided controversial results on the localization of AT(1) receptors. Both areas are known for angiotensin II-induced release of vasopressin (VP) and oxytocin (OXT). To evaluate the significance of the appropriate method of antigen retrieval and its relevance for the detection of AT(1) receptors we performed IHC on AT(1) receptors in paraformaldehyde-fixed and paraffin-embedded brain tissue of Sprague-Dawley rats using either the detergent Triton X-100 or microwave oven heating. This study demonstrates that heat-induced hydrolysis enhances the quality and quantity of immunoreactivity (IR) in IHC on AT(1) receptors. In the organum vasculosum lamina terminalis and in the parvocellular subdivisions of the PVN we report a distribution of AT(1)-like-IR similar to that observed with other methods. However, in addition, we provide evidence that distinct AT(1)-like-IR is also localized in few magnocellular neurons of the PVN and in few parvocellular neurons of the dorsal SON but not in magnocellular neurons of the SON. Moreover, parallel IHC indicates that few magnocellular OXT- or VP-releasing neurons of the PVN as well as parvocellular OXT-releasing neurons of the SON do also contain AT(1) receptors. PMID:17010318

  3. Onyx embolization of an avulsed thalamoperforator following endoscopic colloid cyst and lamina terminalis fenestration

    PubMed Central

    Turner, Raymond D; Chaudry, Imran; Turk, Aquilla; Spiotta, Alejandro

    2014-01-01

    A patient presented with headaches and was found to have a colloid cyst in the third ventricle and ventriculomegaly. The patient underwent endoscopic colloid cyst resection and third ventriculostomy without incidence. Prior to emergence, a blown right pupil was acutely noted, and bright red blood emanated from the ventricular drain that was routinely placed in the endoscopy tract at the conclusion of the procedure. CTangiography demonstrated active extravasation from the pre-pontine cistern into the third ventricle and subarachnoid space. Emergency DSA confirmed active extravasation from an avulsed thalamoperforator arising from the proximal right P1 posterior cerebral artery, which was immediately embolized without incident. PMID:25053667

  4. Onyx embolization of an avulsed thalamoperforator following endoscopic colloid cyst and lamina terminalis fenestration.

    PubMed

    Turner, Raymond D; Chaudry, Imran; Turk, Aquilla; Spiotta, Alejandro

    2015-08-01

    A patient presented with headaches and was found to have a colloid cyst in the third ventricle and ventriculomegaly. The patient underwent endoscopic colloid cyst resection and third ventriculostomy without incidence. Prior to emergence, a blown right pupil was acutely noted, and bright red blood emanated from the ventricular drain that was routinely placed in the endoscopy tract at the conclusion of the procedure. CTangiography demonstrated active extravasation from the pre-pontine cistern into the third ventricle and subarachnoid space. Emergency DSA confirmed active extravasation from an avulsed thalamoperforator arising from the proximal right P1 posterior cerebral artery, which was immediately embolized without incident. PMID:25063695

  5. Exercise-Induced Bronchoconstriction

    MedlinePlus

    ... Conditions & Treatments ▸ Conditions Dictionary ▸ Exercise-Induced Bronchoconstriction Share | Exercise-Induced Bronchoconstriction (EIB) « Back to A to Z Listing Exercise-Induced Bronchoconstriction, (EIB), often known as exercise-induced ...

  6. Negative Energy Balance Blocks Neural and Behavioral Responses to Acute Stress by “Silencing” Central Glucagon-Like Peptide 1 Signaling in Rats

    PubMed Central

    Maniscalco, James W.; Zheng, Huiyuan; Gordon, Patrick J.

    2015-01-01

    Previous reports indicate that caloric restriction attenuates anxiety and other behavioral responses to acute stress, and blunts the ability of stress to increase anterior pituitary release of adrenocorticotropic hormone. Since hindbrain glucagon-like peptide-1 (GLP-1) neurons and noradrenergic prolactin-releasing peptide (PrRP) neurons participate in behavioral and endocrine stress responses, and are sensitive to the metabolic state, we examined whether overnight food deprivation blunts stress-induced recruitment of these neurons and their downstream hypothalamic and limbic forebrain targets. A single overnight fast reduced anxiety-like behavior assessed in the elevated-plus maze and acoustic startle test, including marked attenuation of light-enhanced startle. Acute stress [i.e., 30 min restraint (RES) or 5 min elevated platform exposure] robustly activated c-Fos in GLP-1 and PrRP neurons in fed rats, but not in fasted rats. Fasting also significantly blunted the ability of acute stress to activate c-Fos expression within the anterior ventrolateral bed nucleus of the stria terminalis (vlBST). Acute RES stress suppressed dark-onset food intake in rats that were fed ad libitum, whereas central infusion of a GLP-1 receptor antagonist blocked RES-induced hypophagia, and reduced the ability of RES to activate PrRP and anterior vlBST neurons in ad libitum-fed rats. Thus, an overnight fast “silences” GLP-1 and PrRP neurons, and reduces both anxiety-like and hypophagic responses to acute stress. The partial mimicking of these fasting-induced effects in ad libitum-fed rats after GLP-1 receptor antagonism suggests a potential mechanism by which short-term negative energy balance attenuates neuroendocrine and behavioral responses to acute stress. SIGNIFICANCE STATEMENT The results from this study reveal a potential central mechanism for the “metabolic tuning” of stress responsiveness. A single overnight fast, which markedly reduces anxiety-like behavior in rats

  7. The Bed Nucleus Is a Neuroanatomical Substrate for the Anorectic Effect of Corticotropin-Releasing Factor and for Its Reversal by Nociceptin/Orphanin FQ

    PubMed Central

    Ciccocioppo, Roberto; Fedeli, Amalia; Economidou, Daina; Policani, Federica; Weiss, Friedbert; Massi, Maurizio

    2011-01-01

    Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid N/OFQ receptor (NOP), possesses marked functional anti-stress and anti-corticotropin-releasing factor (CRF) actions. We have shown that intracerebroventricular injection of N/OFQ reverses the hypophagic effect induced by stress or by CRF given intracerebroventricularly. To shed new light on the mechanisms involved in the anti-CRF action of N/OFQ, we investigated the ability of N/OFQ to prevent CRF-induced anorexia after microinjection studies into brain areas of potential interest in the control of feeding behavior and coexpressing NOP and CRF receptors. These areas include the bed nucleus of the stria terminalis (BNST), the central amygdala (CeA), the locus ceruleus (LC), the ventromedial hypothalamus (VMH), the paraventricular nucleus (PVN), and the dorsal raphe (DR). The results demonstrated that the anorectic effect of 0.04 nmol of CRF per rat (200 ng per rat) given intracerebroventricularly is reversed by pretreatment with 0.01– 0.21 nmol of N/OFQ per rat (25–500 ng per rat) injected into the BNST but not into the CeA, LC, VMH, PVN, or DR. Microinjection of 0.01– 0.02 nmol of CRF per site (50 –100 ng per site) into the BNST but not into the CeA or the LC induced marked anorexia in food-deprived rats. Pretreatment with 0.01– 0.21 nmol of N/OFQ per site (25–500 ng per site) into the BNST also blocked the anorectic action of 0.02 nmol of CRF per site (100 ng per site) given in the same area. Finally, intra-BNST microinjection of 0.01– 0.21 nmol of N/OFQ per site (25–500 ng per site) did not modify food intake in either food-sated or food-deprived rats. These data demonstrate that the BNST is involved in the modulation of CRF-induced anorexia, which is prevented by activation of N/OFQ receptors. PMID:14561874

  8. Reduced response to chronic mild stress in PACAP mutant mice is associated with blunted FosB expression in limbic forebrain and brainstem centers.

    PubMed

    Kormos, Viktória; Gáspár, László; Kovács, László Á; Farkas, József; Gaszner, Tamás; Csernus, Valér; Balogh, András; Hashimoto, Hitoshi; Reglődi, Dóra; Helyes, Zsuzsanna; Gaszner, Balázs

    2016-08-25

    Pituitary adenylate cyclase-activating polypeptide (PACAP) has been implicated in stress adaptation with potential relevance in mood disorder management. PACAP deficient (KO) mice on CD1 background were shown to have depression-like phenotype. Here we aimed at investigating effects of chronic variable mild stress (CVMS) in non-injected, vehicle and imipramine-treated KO mice vs. wildtype (WT) counterparts. We hypothesized reduced FosB neuronal activity in stress-related centers, altered activity and peptide/neurotransmitter content of corticotropin-releasing factor (CRF) cells of the oval (ovBST) bed nucleus of stria terminalis (BST), urocortin 1 (Ucn1) neurons of centrally projecting Edinger-Westphal nucleus (cpEW) and serotonin (5HT) cells of dorsal raphe (DR) in PACAP deficiency. CVMS caused decreased body weight and increased adrenal size, corticosterone (CORT) titers and depression-like behavior in WT mice, in contrast to KO animals. CVMS increased FosB in the central (CeA) and medial amygdala, dorsomedial (dmBST), ventral (vBST), ovBST, CA1 area, dentate gyrus (DG), ventral lateral septum, parvo- (pPVN) and magnocellular paraventricular nucleus, lateral periaqueductal gray, cpEW and DR. Lack of PACAP blunted the CVMS-induced FosB rise in the CeA, ovBST, dmBST, vBST, CA1 area, pPVN and DR. The CVMS-induced FosB expression in ovBST-CRF and cpEW-Ucn1 neurons was abolished in KO mice. Although CVMS did not induce FosB in 5HT-DR neurons, PACAP KO mice had increased 5HT cell counts and 5HT content. We conclude that PACAP deficiency affects neuronal reactivity in a brain area-specific manner in stress centers, as well as in ovBST-CRF, cpEW-Ucn1 and 5HT-DR neurons leading to reduced CVMS response and altered depression level. PMID:27282087

  9. Role of Testosterone in Mediating Prenatal Ethanol Effects on Hypothalamic-Pituitary-Adrenal Activity in Male Rats

    PubMed Central

    Lan, Ni; Hellemans, Kim G. C.; Ellis, Linda; Viau, Victor; Weinberg, Joanne

    2009-01-01

    preoptic nucleus and the principal nucleus of posterior bed nucleus of the stria terminalis were lower in E and PF compared to C males under intact conditions. Together, these data support our previous work suggesting altered sensitivity to testosterone in E males. Furthermore, differential effects of testosterone on the complex balance between central CRH and central AVP pathways may play a role in the HPA alterations observed. That some findings were similar in E and PF males suggests that nutritional effects of diet may have played a role in mediating at least some of the changes seen in E animals. PMID:19410376

  10. Pituitary adenylate cyclase activating polypeptide in stress-related disorders: data convergence from animal and human studies

    PubMed Central

    May, Victor

    2014-01-01

    The maladaptive expression and function of several stress-associated hormones have been implicated in pathological stress- and anxiety-related disorders. Among these, recent evidence has suggested that pituitary adenylate cyclase activating polypeptide (PACAP) has critical roles in central neurocircuits mediating stress-related emotional behaviors. We describe the PACAPergic systems, the data implicating PACAP in stress biology and how altered PACAP expression and signaling may result in psychopathologies. We include our work implicating PACAP signaling within the bed nucleus of the stria terminalis (BNST) in mediating the consequences of stressor exposure and relatedly, describe more recent studies suggesting that PACAP in the central nucleus of the amygdala (CeA) may impact the emotional aspects of chronic pain states. In aggregate, these results are consistent with data suggesting that PACAP dysregulation is associated with post-traumatic stress disorder (PTSD) in humans. PMID:25636177

  11. Evidence for coordinated functional activity within the extended amygdala of non-human and human primates

    PubMed Central

    Oler, Jonathan A.; Birn, Rasmus M.; Patriat, Rémi; Fox, Andrew S.; Shelton, Steven E.; Burghy, Cory A.; Stodola, Diane E.; Essex, Marilyn J.; Davidson, Richard J.; Kalin, Ned H.

    2012-01-01

    Neuroanatomists posit that the central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST) comprise two major nodes of a macrostructural forebrain entity termed the extended amygdala. The extended amygdala is thought to play a critical role in adaptive motivational behavior and is implicated in the pathophysiology of maladaptive fear and anxiety. Resting functional connectivity of the Ce was examined in 107 young anesthetized rhesus monkeys and 105 young humans using standard resting-state functional magnetic resonance imaging (fMRI) methods to assess temporal correlations across the brain. The data expand the neuroanatomical concept of the extended amygdala by finding, in both species, highly significant functional coupling between the Ce and the BST. These results support the use of in vivo functional imaging methods in nonhuman and human primates to probe the functional anatomy of major brain networks such as the extended amygdala. PMID:22465841

  12. SEXUAL DIFFERENTIATION OF CENTRAL VASOPRESSIN AND VASOTOCIN SYSTEMS IN VERTEBRATES: DIFFERENT MECHANISMS, SIMILAR ENDPOINTS

    PubMed Central

    De VRIES, G. J.; PANZICA, G. C.

    2006-01-01

    Vasopressin neurons in the bed nucleus of the stria terminalis and amygdala and vasotocin neurons in homologous areas in non-mammalian vertebrates show some of the most consistently found neural sex differences, with males having more cells and denser projections than females. These projections have been implicated in social and reproductive behaviors but also in autonomic functions. The sex differences in these projections may cause as well as prevent sex differences in these functions. This paper discusses the anatomy, steroid dependency, and sexual differentiation of these neurons. Although the final steps in sexual differentiation of vasopressin/vasotocin expression may be similar across vertebrate species, what triggers differentiation may vary dramatically. For example, during development, estrogen masculinizes vasopressin expression in rats but feminizes its counterpart in Japanese quail. Apparently, nature consistently finds a way of maintaining sex differences in vasopressin and vasotocin pathways, suggesting that the function of these differences is important enough that it was conserved during evolution. PMID:16310321

  13. Autoradiographic visualization of CNS receptors for vasoactive intestinal peptide

    SciTech Connect

    Shaffer, M.M.; Moody, T.W.

    1986-03-01

    Receptors for VIP were characterized in the rat CNS. /sup 125/I-VIP bound with high affinity to rat brain slices. Binding was time dependent and specific. Pharmacology studies indicated that specific /sup 125/I-VIP binding was inhibited with high affinity by VIP and low affinity by secretin and PHI. Using in vitro autoradiographic techniques high grain densities were present in the dentate gyrus, pineal gland, supraoptic and suprachiasmatic nuclei, superficial gray layer of the superior colliculus and the area postrema. Moderate grain densities were present in the olfactory bulb and tubercle, cerebral cortex, nucleus accumbens, caudate putamen, interstitial nucleus of the stria terminalis, paraventricular thalamic nucleus, medial amygdaloid nucleus, subiculum and the medial geniculate nucleus. Grains were absent in the corpus callosum and controls treated with 1 microM unlabeled VIP. The discrete regional distribution of VIP receptors suggest that it may function as an important modulator of neural activity in the CNS.

  14. Greater Sustained Anxiety but Not Phasic Fear in Women Compared to Men

    PubMed Central

    Grillon, Christian

    2009-01-01

    Startle reflex studies in rodents indicate that female are more reactive than rats in experimental models of sustained anxiety but not in models of phasic fear (Toufexis, 2007). This study examined evidence for a similar effect in humans. Participants were exposed to three conditions, (1) predictable aversive shocks signaled by a cue, (2) unpredictable shocks, and (3) no shocks. Acoustic startle stimuli were delivered regularly across conditions. Phasic startle potential to the threat cue in the predictable condition was not affected by sex. In contrast, and consistent with basic research, the sustained increase in startle in the predictable and unpredictable conditions was greater in women compared to men. Animal studies suggest that such an effect may be mediated by the effects of sexual dimorphism in limbic structures, including the bed nucleus of the stria terminalis. However, psychosocial factors may also contribute to this effect. PMID:18540756

  15. Receptors for GRP/bombesin-like peptides in the rat forebrain

    SciTech Connect

    Wolf, S.S.; Moody, T.W.

    1985-01-01

    Binding sites in the rat forebrain were characterized using ( SVI-Tyr4)bombesin as a receptor probe. Pharmacology experiments indicate that gastrin releasing peptide (GRP) and the GRP fragments GRP as well as Ac-GRP inhibited radiolabeled (Tyr4)bombesin binding with high affinity. Biochemistry experiments indicated that heat, N-ethyl maleimide or trypsin greatly reduced radiolabeled (Tyr4)bombesin binding. Also, autoradiographic studies indicated that highest grain densities were present in the stria terminalis, periventricular and suprachiasmatic nucleus of the hypothalamus, dorsomedial and rhomboid thalamus, dentate gyrus, hippocampus and medial amygdaloid nucleus. The data suggest that CNS protein receptors, which are discretely distributed in the rat forebrain, may mediate the action of endogenous GRP/bombesin-like peptides.

  16. Vasotocin and reproductive functions of the domestic chicken.

    PubMed

    Jurkevich, A; Grossmann, R

    2003-07-01

    The neurohypophyseal hormone arginine vasotocin (AVT) combines both antidiuretic and reproductive activities. In the domestic chicken AVT produces assimetric effects on the reproductive functions of males and females. AVT synthesized in magnocellular diencephalic neurons is released into circulation in a highly coordinated manner contributing to the peripheral control of oviposition in hens. Conversely, parvocellular AVT cells located in the limbic system (bed nucleus of stria terminalis (BST)) are quite different in their properties and, possible, functions. In domestic chickens these cells express AVT in a sexually dimorphic manner and are found solely in males. This sexually dimorphic part of the AVT system is sensitive to gonadal steroids. Experimental data demonstrated that AVT modulates different aspects of reproductive behavior including courtship vocalization and copulation. Sexual differentiation of these limbic vasotocinergic cells show striking correlation with sexual differentiation of masculine behavior. Evidences coming from physiological, anatomical and ethological studies suggest strong implication of the vasotocinergic system in the control of reproductive functions. PMID:12963102

  17. Afferent connections of the parabrachial nucleus in C57BL/6J mice

    PubMed Central

    Tokita, Kenichi; Inoue, Tomio; Boughter, John D.

    2009-01-01

    Although the mouse is an experimental model with an increasing importance in various fields of Neuroscience, the characteristics of its central gustatory pathways have not yet been well documented. Recent electrophysiological studies using the rat and hamster have revealed that taste processing in the brainstem gustatory relays is under the strong influence of inputs from forebrain gustatory structures. In the present study, we investigated the organization of afferent projections to the mouse parabrachial nucleus (PbN), which is located at a key site between the brainstem and gustatory, viscerosensory and autonomic centers in the forebrain. We made injections of the retrograde tracer Fluorogold centered around the “waist” area of the PbN, whose neurons are known to be highly responsive to taste stimuli. Retrogradely labeled neurons were found in the infralimbic, dysgranular and agranular insular cortex as well as the claustrum; the bed nucleus of the stria terminalis and the substantia innominata; the central nucleus of the amygdala; the lateral and medial preoptic areas, the paraventricular, the dorsomedial, the ventromedial, the arcuate, and the lateral hypothalamic areas; the periaqueductal gray, the substantia nigra pars compacta, and the ventral tegmental area; the supratrigeminal nucleus, rostral and caudal nucleus of the solitary tract; the parvicellular intermediate and gigantocellular reticular nucleus; the caudal and interpolar divisions of the spinal trigeminal nucleus, dorsomedial spinal trigeminal nucleus, and the area postrema. Numbers of labeled neurons in the main components of the gustatory system including the insular cortex, bed nucleus of the stria terminalis, central nucleus of the amygdala, lateral hypothalamus, and rostral nucleus of the solitary tract were quantified. These results are basically consistent with those of the previous rat and hamster studies, but some species differences were found. Functional implications of these

  18. Early Life Manipulations of the Nonapeptide System Alter Pair Maintenance Behaviors and Neural Activity in Adult Male Zebra Finches

    PubMed Central

    Baran, Nicole M.; Tomaszycki, Michelle L.; Adkins-Regan, Elizabeth

    2016-01-01

    Adult zebra finches (T. guttata) form socially monogamous pair bonds characterized by proximity, vocal communication, and contact behaviors. In this experiment, we tested whether manipulations of the nonapeptide hormone arginine vasotocin (AVT, avian homolog of vasopressin) and the V1a receptor (V1aR) early in life altered species-typical pairing behavior in adult zebra finches of both sexes. Although there was no effect of treatment on the tendency to pair in either sex, males in different treatments exhibited profoundly different profiles of pair maintenance behavior. Following a brief separation, AVT-treated males were highly affiliative with their female partner but sang very little compared to Controls. In contrast, males treated with a V1aR antagonist sang significantly less than Controls, but did not differ in affiliation. These effects on behavior in males were also reflected in changes in the expression of V1aR and immediate early gene activity in three brain regions known to be involved in pairing behavior in birds: the medial amygdala, medial bed nucleus of the stria terminalis, and the lateral septum. AVT males had higher V1aR expression in the medial amygdala than both Control and antagonist-treated males and immediate early gene activity of V1aR neurons in the medial amygdala was positively correlated with affiliation. Antagonist treated males showed decreased activity in the medial amygdala. In addition, there was a negative correlation between the activity of V1aR cells in the medial bed nucleus of the stria terminalis and singing. Treatment also affected the expression of V1aR and activity in the lateral septum, but this was not correlated with any behaviors measured. These results provide evidence that AVT and V1aR play developmental roles in specific pair maintenance behaviors and the neural substrate underlying these behaviors in a bird. PMID:27065824

  19. Early Life Manipulations of the Nonapeptide System Alter Pair Maintenance Behaviors and Neural Activity in Adult Male Zebra Finches.

    PubMed

    Baran, Nicole M; Tomaszycki, Michelle L; Adkins-Regan, Elizabeth

    2016-01-01

    Adult zebra finches (T. guttata) form socially monogamous pair bonds characterized by proximity, vocal communication, and contact behaviors. In this experiment, we tested whether manipulations of the nonapeptide hormone arginine vasotocin (AVT, avian homolog of vasopressin) and the V1a receptor (V1aR) early in life altered species-typical pairing behavior in adult zebra finches of both sexes. Although there was no effect of treatment on the tendency to pair in either sex, males in different treatments exhibited profoundly different profiles of pair maintenance behavior. Following a brief separation, AVT-treated males were highly affiliative with their female partner but sang very little compared to Controls. In contrast, males treated with a V1aR antagonist sang significantly less than Controls, but did not differ in affiliation. These effects on behavior in males were also reflected in changes in the expression of V1aR and immediate early gene activity in three brain regions known to be involved in pairing behavior in birds: the medial amygdala, medial bed nucleus of the stria terminalis, and the lateral septum. AVT males had higher V1aR expression in the medial amygdala than both Control and antagonist-treated males and immediate early gene activity of V1aR neurons in the medial amygdala was positively correlated with affiliation. Antagonist treated males showed decreased activity in the medial amygdala. In addition, there was a negative correlation between the activity of V1aR cells in the medial bed nucleus of the stria terminalis and singing. Treatment also affected the expression of V1aR and activity in the lateral septum, but this was not correlated with any behaviors measured. These results provide evidence that AVT and V1aR play developmental roles in specific pair maintenance behaviors and the neural substrate underlying these behaviors in a bird. PMID:27065824

  20. Distribution of secretagogin-containing neurons in the basal forebrain of mice, with special reference to the cholinergic corticopetal system

    PubMed Central

    Gyengesi, Erika; Andrews, Zane B.; Paxinos, George; Zaborszky, Laszlo

    2013-01-01

    Cholinergic and GABAergic corticopetal neurons in the basal forebrain play important roles in cortical activation, sensory processing, and attention. Cholinergic neurons are intermingled with peptidergic, and various calcium binding protein-containing cells, however, the functional role of these neurons is not well understood. In this study we examined the expression pattern of secretagogin (Scgn), a newly described calcium-binding protein, in neurons of the basal forebrain. We also assessed some of the corticopetal projections of Scgn neurons and their co-localization with choline acetyltransferase (ChAT), neuropeptide-Y, and other calcium-binding proteins (i.e., calbindin, calretinin, and parvalbumin). Scgn is expressed in cell bodies of the medial and lateral septum, vertical and horizontal diagonal band nuclei, and of the extension of the amygdala but it is almost absent in the ventral pallidum. Scgn is co-localized with ChAT in neurons of the bed nucleus of the stria terminalis, extension of the amygdala, and interstitial nucleus of the posterior limb of the anterior commissure. Scgn was co-localized with calretinin in the accumbens nucleus, medial division of the bed nucleus of stria terminalis, the extension of the amygdala, and interstitial nucleus of the posterior limb of the anterior commissure. We have not found co-expression of Scgn with parvalbumin, calbindin, or neuropeptide-Y. Retrograde tracing studies using Fluoro Gold in combination with Scgn-specific immunohistochemistry revealed that Scgn neurons situated in the nucleus of the horizontal limb of the diagonal band project to retrosplenial and cingulate cortical areas. PMID:23376788

  1. Species differences in paternal behavior and aggression in peromyscus and their associations with vasopressin immunoreactivity and receptors.

    PubMed

    Bester-Meredith, J K; Young, L J; Marler, C A

    1999-08-01

    Previous comparative studies have suggested that the distribution of arginine vasopressin (AVP) pathways within the brain is associated with species-typical patterns of social behavior. In the current study, male parental behavior and aggression were compared in two species of Peromyscus. As predicted based on other studies, male mice from a monogamous species, the California mouse Peromyscus californicus, spent more time providing parental care to offspring than males from a polygamous species, the white-footed mouse Peromyscus leucopus. Sexually naive male California mice also attacked opponents more rapidly than white-footed mice during resident-intruder and neutral aggression tests. Since AVP has been shown to modulate these behaviors, we compared the distribution of vasopressinergic neurons and receptors. We predicted that greater AVP-immunoreactive (AVP-ir) staining in the bed nucleus of the stria terminalis and AVP receptor density in the lateral septum would occur in the species with low levels of paternal care because this pattern was found in similar comparisons with sexually naive monogamous and polygamous voles. In contrast, in our study, monogamous male mice showed more AVP-ir staining in the bed nucleus of the stria terminalis than the polygamous species, as well as more AVP receptors in the lateral septum. Parental behavior therefore does not appear to predict differences in patterns of AVP-ir staining and receptor distribution across species or vice versa. We propose the hypothesis that aggression may be better correlated with species patterns of AVP-ir staining density and receptor distribution. PMID:10433884

  2. Oxytocin--a neuropeptide for affiliation: evidence from behavioral, receptor autoradiographic, and comparative studies.

    PubMed

    Insel, T R

    1992-01-01

    Oxytocin (OT) is a nine amino acid peptide synthesized in hypothalamic cells which project either to the neurohypophysis or to sites within the central nervous system. Although neurohypophyseal OT release has long been associated with uterine contraction and milk ejection, the function of intracerebral OT remains unclear. On the basis of behavioral, cellular, and comparative studies, this review suggests that brain OT influences the formation of social bonds. The first part of this review examines evidence linking central OT to several forms of affiliation. Central administration of OT induces maternal and reproductive behaviors in rats primed with gonadal steroids. OT antagonists and hypothalamic lesions block the initiation of maternal and reproductive behaviors but have no effects on these behaviors once established. Our new studies in rat pups demonstrate that central OT selectively decreases the separation response, an effect which mimics social contact. These studies of parental, reproductive, and attachment behaviors suggest that exogenous OT has "prosocial" effects and that endogenous OT may be essential for initiating social interaction. In a second series of experiments, we investigated the cellular mechanisms for OT's effects on social behavior by means of autoradiographic receptor binding. In the rat forebrain, OT receptors are expressed in several limbic regions believed to be involved in the integration of sensory processing. The regulation of these receptors is surprisingly resistant to either ablation of OT cells or repeated central administration of OT. However, receptors in two regions, the bed nucleus of the stria terminalis (BNST) and the ventromedial nucleus of the hypothalamus (VMN), appear selectively induced by exogenous or endogenous increases in gonadal steroids. At parturition, binding to OT receptors increases 84% in the BNST, and at estrus, binding increases 35% in the VMN. These results demonstrate that physiologic changes in gonadal

  3. Neonatal manipulation of oxytocin influences the partner preference in mandarin voles (Microtus mandarinus).

    PubMed

    Jia, Rui; Tai, Fadao; An, Shucheng; Broders, Hugh; Sun, Ruyong

    2008-01-01

    Neonatal manipulation of oxytocin (OT) has long-term effects on behavior and physiology. The objective of this research was to determine if neonatal exposure to OT can affect partner preferences and to characterize the mechanisms underlying social behavior such as neural activities of relevant brain regions in socially monogamous mandarin voles (Microtus mandarinus). After receiving a subcutaneous injection of isotonic saline (SAL) or OT within 24h of birth, mandarin vole at 60 days of age was paired with an unfamiliar opposite sex for 24h, followed immediately by an examination of their partner preference and 30 days later by the second examination of their partner preference and Fos expression in some brain regions. The results indicated that (1) while 24h cohabitation was insufficient for both female and male SAL-treated mandarin voles to form partner preference, neonatal exposure to OT significantly facilitate female, but not male mandarin voles to form partner preference within 24h of cohabitation; (2) the maintenance of partner preference in females was suppressed by neonatal OT treatment, while neonatal OT-treated males showed significant partner preference as neonatal SAL-treated males and females; in addition, the tendency of aggression to the strangers was impaired in both females and males, and neonatal OT-treated males showed significantly higher mounting behavior to the partner; (3) in comparison with saline-treated females, OT-treated females showed a significant decrease in Fos expression in all brain regions examined in response to partner preference. Relative to saline treatment, neonatal OT treatment induced to males a significant decrease of Fos expression in the bed nucleus of the stria terminalis (BNST), the hypothalamic paraventricular nucleus (PVN) and the mediodorsal thalamic nucleus (MD) as well as a significant increase in the medial preoptic area (MPOA), the dorsal part of the lateral septal nucleus (LSD) and the central amygdaloid

  4. Overexpression of Forebrain CRH During Early Life Increases Trauma Susceptibility in Adulthood.

    PubMed

    Toth, Mate; Flandreau, Elizabeth I; Deslauriers, Jessica; Geyer, Mark A; Mansuy, Isabelle M; Merlo Pich, Emilio; Risbrough, Victoria B

    2016-05-01

    Although early-life stress is a significant risk factor for developing anxiety disorders, including posttraumatic stress disorder (PTSD), the underlying mechanisms are unclear. Corticotropin releasing hormone (CRH) is disrupted in individuals with PTSD and early-life stress and hence may mediate the effects of early-life stress on PTSD risk. We hypothesized that CRH hyper-signaling in the forebrain during early development is sufficient to increase response to trauma in adulthood. To test this hypothesis, we induced transient, forebrain-specific, CRH overexpression during early-life (pre-puberty, CRHOEdev) in double-mutant mice (Camk2a-rtta2 × tetO-Crh) and tested their behavioral and gene expression responses to the predator stress model of PTSD in adulthood. In one cohort of CRHOEdev exposed and unexposed mice, avoidance and arousal behaviors were examined 7-15 days after exposure to predator stress. In another cohort, gene expression changes in Crhr1, Crhr2, and Fkbp51 in forebrain of CRHOEdev exposed and unexposed mice were examined 7 days after predator stress. CRHOEdev induced robust increases in startle reactivity and reductions in startle inhibition independently of predator stress in both male and female mice. Avoidance behaviors after predator stress were highly dependent on sex and CRHOEdev exposure. Whereas stressed females exhibited robust avoidance responses that were not altered by CRHOEdev, males developed significant avoidance only when exposed to both CRHOEdev and stress. Quantitative real-time-PCR analysis indicated that CRHOEdev unexposed males exhibit significant changes in Crhr2 expression in the amygdala and bed nucleus stria terminalis in response to stress, whereas males exposed to CRHOEdev did not. Similar to CRHOEdev males, females exhibited no significant Crhr2 gene expression changes in response to stress. Cortical Fkbp51 expression was also significantly reduced by stress and CRHOEdev exposure in males, but not in females. These

  5. Drug-induced hypoglycemia

    MedlinePlus

    ... medlineplus.gov/ency/article/000310.htm Drug-induced hypoglycemia To use the sharing features on this page, please enable JavaScript. Drug-induced hypoglycemia is low blood sugar that results from medication. ...

  6. The extended amygdala and salt appetite

    NASA Technical Reports Server (NTRS)

    Johnson, A. K.; de Olmos, J.; Pastuskovas, C. V.; Zardetto-Smith, A. M.; Vivas, L.

    1999-01-01

    Both chemo- and mechanosensitive receptors are involved in detecting changes in the signals that reflect the status of body fluids and of blood pressure. These receptors are located in the systemic circulatory system and in the sensory circumventricular organs of the brain. Under conditions of body fluid deficit or of marked changes in fluid distribution, multiple inputs derived from these humoral and neural receptors converge on key areas of the brain where the information is integrated. The result of this central processing is the mobilization of homeostatic behaviors (thirst and salt appetite), hormone release, autonomic changes, and cardiovascular adjustments. This review discusses the current understanding of the nature and role of the central and systemic receptors involved in the facilitation and inhibition of thirst and salt appetite and on particular components of the central neural network that receive and process input derived from fluid- and cardiovascular-related sensory systems. Special attention is paid to the structures of the lamina terminalis, the area postrema, the lateral parabrachial nucleus, and their association with the central nucleus of the amygdala and the bed nucleus of the stria terminalis in controlling the behaviors that participate in maintaining body fluid and cardiovascular homeostasis.

  7. Nr4a1-eGFP Is a Marker of Striosome-Matrix Architecture, Development and Activity in the Extended Striatum

    PubMed Central

    Davis, Margaret I.; Puhl, Henry L.

    2011-01-01

    Transgenic mice expressing eGFP under population specific promoters are widely used in neuroscience to identify specific subsets of neurons in situ and as sensors of neuronal activity in vivo. Mice expressing eGFP from a bacterial artificial chromosome under the Nr4a1 promoter have high expression within the basal ganglia, particularly within the striosome compartments and striatal-like regions of the extended amygdala (bed nucleus of the stria terminalis, striatal fundus, central amygdaloid nucleus and intercalated cells). Grossly, eGFP expression is inverse to the matrix marker calbindin 28K and overlaps with mu-opioid receptor immunoreactivity in the striatum. This pattern of expression is similar to Drd1, but not Drd2, dopamine receptor driven eGFP expression in structures targeted by medium spiny neuron afferents. Striosomal expression is strong developmentally where Nr4a1-eGFP expression overlaps with Drd1, TrkB, tyrosine hydroxylase and phospho-ERK, but not phospho-CREB, immunoreactivity in “dopamine islands”. Exposure of adolescent mice to methylphenidate resulted in an increase in eGFP in both compartments in the dorsolateral striatum but eGFP expression remained brighter in the striosomes. To address the role of activity in Nr4a1-eGFP expression, primary striatal cultures were prepared from neonatal mice and treated with forskolin, BDNF, SKF-83822 or high extracellular potassium and eGFP was measured fluorometrically in lysates. eGFP was induced in both neurons and contaminating glia in response to forskolin but SKF-83822, brain derived neurotrophic factor and depolarization increased eGFP in neuronal-like cells selectively. High levels of eGFP were primarily associated with Drd1+ neurons in vitro detected by immunofluorescence; however ∼15% of the brightly expressing cells contained punctate met-enkephalin immunoreactivity. The Nr4a1-GFP mouse strain will be a useful model for examining the connectivity, physiology, activity and development of the

  8. Effects of treadmill running on brain activation and the corticotropin-releasing hormone system.

    PubMed

    Timofeeva, Elena; Huang, Qingling; Richard, Denis

    2003-06-01

    The present study was conducted to investigate the effects of treadmill running on the corticotropin-releasing hormone (CRH), CRH receptor type 1 (CRH-R1) and CRH-binding protein (CRH-BP) in the brain of rats that were killed either at rest, immediately after 60 min of treadmill running, or 180 min following a 60-min session of intensive exercise. The expression of the neuronal activity marker c-FOS was also determined in the three conditions of this study. The levels of c-FOS mRNA immediately following running were high in the cortex, caudate-putamen, lateral septum, bed nucleus of the stria terminalis, dorsal and medial thalamus, hypothalamus, pontine nuclei, locus coeruleus and hypoglossal nucleus. In most brain regions investigated, excluding the locus coeruleus and the cingulate cortex, c-FOS mRNA expression returned to control levels after 2 h of recovery. The highest concentration of cells co-expressing the protein Fos and CRH mRNA neurons was found in the parvocellular part of the paraventricular nucleus, which also expressed CRH heteronuclear RNA and CRH-R1 mRNA. The medial preoptic area (MPOA), the medial mammillary nucleus and the posterior hypothalamic as well as the somatosensory cortex, the medial geniculate nucleus, the reticulotegmental nucleus, and Barrington's nucleus also co-expressed Fos and CRH mRNA. The expression of CRH-BP gene was induced in the MPOA following running. In summary, the present study demonstrates that treadmill running leads to a strong expression of c-FOS mRNA that is widely distributed throughout the brain. c-FOS mRNA was found in structures of the somatosensory and somatomotor systems, indicating that these regions were activated during exercise. The pattern of distribution of c-FOS mRNA showed similarities with that triggered by neurogenic and systemic stresses. The present results also indicate that treadmill running can strongly activate the hypophysiotropic CRH system, which suggests, in agreement with the pattern of c

  9. Flow-induced vibration

    SciTech Connect

    Blevins, R.D.

    1990-01-01

    This book reports on dimensional analysis; ideal fluid models; vortex-induced vibration; galloping and flutter; instability of tube and cylinder arrays; vibrations induced by oscillating flow; vibration induced by turbulence and sound; damping of structures; sound induced by vortex shedding; vibrations of a pipe containing a fluid flow; indices. It covers the analysis of the vibrations of structures exposed to fluid flows; explores applications for offshore platforms and piping; wind-induced vibration of buildings, bridges, and towers; and acoustic and mechanical vibration of heat exchangers, power lines, and process ducting.

  10. Cavitation-resistant inducer

    DOEpatents

    Dunn, Charlton; Subbaraman, Maria R.

    1989-01-01

    An improvement in an inducer for a pump wherein the inducer includes a hub, a plurality of radially extending substantially helical blades and a wall member extending about and encompassing an outer periphery of the blades. The improvement comprises forming adjacent pairs of blades and the hub to provide a substantially rectangular cross-sectional flow area which cross-sectional flow area decreases from the inlet end of the inducer to a discharge end of the inducer, resulting in increased inducer efficiency improved suction performance, reduced susceptibility to cavitation, reduced susceptibility to hub separation and reduced fabrication costs.

  11. Cavitation-resistant inducer

    DOEpatents

    Dunn, C.; Subbaraman, M.R.

    1989-06-13

    An improvement in an inducer for a pump is disclosed wherein the inducer includes a hub, a plurality of radially extending substantially helical blades and a wall member extending about and encompassing an outer periphery of the blades. The improvement comprises forming adjacent pairs of blades and the hub to provide a substantially rectangular cross-sectional flow area which cross-sectional flow area decreases from the inlet end of the inducer to a discharge end of the inducer, resulting in increased inducer efficiency improved suction performance, reduced susceptibility to cavitation, reduced susceptibility to hub separation and reduced fabrication costs. 11 figs.

  12. Fos Expression in Rat Brain During Depletion-Induced Thirst and Salt Appetite

    NASA Technical Reports Server (NTRS)

    Thunhorst, R. L.; Xu, Z.; Cicha, M. Z.; Zardetto-Smith, A. M.; Johnson, A. K.

    1998-01-01

    The expression of Fos protein (Fos immunoreactivity, Fos-ir) was mapped in the brain of rats subjected to an angiotensin-dependent model of thirst and salt appetite. The physiological state associated with water and sodium ingestion was produced by the concurrent subcutaneous administration of the diuretic furosemide (10 mg/kg) and a low dose of the angiotensin-converting enzyme (ACE) inhibitor captopril (5 mg/kg; Furo/Cap treatment). The animals were killed 2 h posttreatment, and the brains were processed for Fos-ir to assess neural activation. Furo/Cap treatment significantly increased Fos-ir density above baseline levels both in structures of the lamina terminalis and hypothalamus known to mediate the actions of ANG 2 and in hindbrain regions associated with blood volume and pressure regulation. Furo/Cap treatment also typically increased Fos-ir density in these structures above levels observed after administration of furosemide or captopril separately. Fos-ir was reduced to a greater extent in forebrain than in hindbrain areas by a dose of captopril (100 mg/kg sc) known to block the actions of ACE in the brain. The present work provides further evidence that areas of lamina terminalis subserve angiotensin-dependent thirst and salt appetite.

  13. Induced pluripotency with endogenous and inducible genes

    SciTech Connect

    Duinsbergen, Dirk; Eriksson, Malin; Hoen, Peter A.C. 't; Frisen, Jonas; Mikkers, Harald

    2008-10-15

    The recent discovery that two partly overlapping sets of four genes induce nuclear reprogramming of mouse and even human cells has opened up new possibilities for cell replacement therapies. Although the combination of genes that induce pluripotency differs to some extent, Oct4 and Sox2 appear to be a prerequisite. The introduction of four genes, several of which been linked with cancer, using retroviral approaches is however unlikely to be suitable for future clinical applications. Towards developing a safer reprogramming protocol, we investigated whether cell types that express one of the most critical reprogramming genes endogenously are predisposed to reprogramming. We show here that three of the original four pluripotency transcription factors (Oct4, Klf4 and c-Myc or MYCER{sup TAM}) induced reprogramming of mouse neural stem (NS) cells exploiting endogenous SoxB1 protein levels in these cells. The reprogrammed neural stem cells differentiated into cells of each germ layer in vitro and in vivo, and contributed to mouse development in vivo. Thus a combinatorial approach taking advantage of endogenously expressed genes and inducible transgenes may contribute to the development of improved reprogramming protocols.

  14. Space Station Induced Monitoring

    NASA Technical Reports Server (NTRS)

    Spann, James F. (Editor); Torr, Marsha R. (Editor)

    1988-01-01

    This report contains the results of a conference convened May 10-11, 1988, to review plans for monitoring the Space Station induced environment, to recommend primary components of an induced environment monitoring package, and to make recommendations pertaining to suggested modifications of the Space Station External Contamination Control Requirements Document JSC 30426. The contents of this report are divided as Follows: Monitoring Induced Environment - Space Station Work Packages Requirements, Neutral Environment, Photon Emission Environment, Particulate Environment, Surface Deposition/Contamination; and Contamination Control Requirements.

  15. Mania Induced by Opipramol

    PubMed Central

    Firoz, Kazhungil; Khaleel, Asfia; Rajmohan, V; Kumar, Manoj; Raghuram, TM

    2015-01-01

    Antidepressants have propensity to induce manic switch in patients with bipolar disorder. Opipramol is an atypical anxiolytic and antidepressant drug which predominantly acts on sigma receptors. Although structurally resembles tricyclic antidepressant imipramine it does not have inhibitory action on the reuptake of norepinephrine/serotonin and hence it is not presumed to cause manic switch in bipolar depression. Here, we describe a case of mania induced by opipramol, in a patient with bipolar affective disorder who was treated for moderate depressive episode with lithium and opipramol and we discuss neurochemical hypothesis of opipramol-induced mania. PMID:25722522

  16. Mania induced by opipramol.

    PubMed

    Firoz, Kazhungil; Khaleel, Asfia; Rajmohan, V; Kumar, Manoj; Raghuram, Tm

    2015-01-01

    Antidepressants have propensity to induce manic switch in patients with bipolar disorder. Opipramol is an atypical anxiolytic and antidepressant drug which predominantly acts on sigma receptors. Although structurally resembles tricyclic antidepressant imipramine it does not have inhibitory action on the reuptake of norepinephrine/serotonin and hence it is not presumed to cause manic switch in bipolar depression. Here, we describe a case of mania induced by opipramol, in a patient with bipolar affective disorder who was treated for moderate depressive episode with lithium and opipramol and we discuss neurochemical hypothesis of opipramol-induced mania. PMID:25722522

  17. Noise-Induced Hearing Loss

    MedlinePlus

    ... Info » Hearing, Ear Infections, and Deafness Noise-Induced Hearing Loss On this page: What is noise-induced hearing ... additional information about NIHL? What is noise-induced hearing loss? Every day, we experience sound in our environment, ...

  18. Vitiligo, drug induced (image)

    MedlinePlus

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat (macular) and depigmented, but maintains ...

  19. Drug-induced hepatitis

    MedlinePlus

    ... induced hepatitis. Painkillers and fever reducers that contain acetaminophen are a common cause of liver inflammation. These ... problem. However, if you took high doses of acetaminophen , treatment should be started as soon as possible ...

  20. Gasoline-induced mucositis

    SciTech Connect

    Hoffman, D.L.; Swanson, B.Z. Jr.; Lutins, N.D.

    1980-02-01

    Gasoline-induced mucositis may become more common because of fuel shortages or increased fuel cost. Dentists should, therefore, consider this oral irritant in the differential diagnosis of oral lesions.

  1. Thrombocytopenia - drug induced

    MedlinePlus

    ... and a seizure medicine called valproic acid may lead to this problem. Other medicines that cause drug-induced thrombocytopenia include: Furosemide Gold, used to treat arthritis Nonsteroidal anti-inflammatory drugs ( ...

  2. Drug-induced hepatitis

    MedlinePlus

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  3. Exercise-induced asthma

    MedlinePlus

    Wheezing - exercise-induced; Reactive airway disease - exercise ... Having asthma symptoms when you exercise does not mean you cannot or should not exercise. But be aware of your EIA triggers. Cold or dry air may ...

  4. Vitiligo, drug induced (image)

    MedlinePlus

    ... drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally occurs as a result of medications, as is the case with this individual. The typical vitiligo lesion is flat (macular) and depigmented, but maintains the normal skin texture.

  5. Drug-induced nightmares.

    PubMed

    2000-12-01

    (1) A wide variety of drugs have been implicated in nightmares, often on inadequate evidence. (2) Recurrent nightmares can be induced by many drugs, and not only agents with psychotropic or neurological effects. PMID:11475499

  6. Ethionamide-induced Pellagra.

    PubMed

    Gupta, Yashashree; Shah, Ira

    2015-08-01

    Pellagra is a disorder characterized by dermatitis, diarrhea, dementia and eventually death, resulting from a deficiency of niacin or its precursor tryptophan. Ethionamide (a second-line antituberculosis agent)-induced pellagra is rarely encountered in clinical practice. Prompt diagnosis and treatment with nicotinamide can prevent life-threatening complications. To date, only three cases have been reported. We report a 13-year-old girl presenting with ethionamide-induced pellagra that resolved after the administration of niacin. PMID:25828829

  7. Isoniazid-induced alopecia

    PubMed Central

    Gupta, K. B.; Kumar, V.; Vishvkarma, S.; Shandily, R.

    2011-01-01

    Isoniazid is a safe and very effective antituberculosis drug. Antimitotic agents routinely cause alopecia. Drug-induced alopecia is usually reversible upon withdrawal of the drug. Isoniazid, thiacetazone and ethionamide are the antituberculosis drugs which have been associated with alopecia. Isoniazid-induced alopecia was observed in one case and confirmed by the finding that hair growth resumed when drug removed from the regimen. PMID:21654989

  8. Induced polarization response of microbial induced sulfideprecipitation

    SciTech Connect

    Ntarlagiannis, Dimitrios; Williams, Kenneth Hurst; Slater, Lee; Hubbard, Susan

    2004-06-04

    A laboratory scale experiment was conducted to examine the use of induced polarization and electrical conductivity to monitor microbial induced sulfide precipitation under anaerobic conditions in sand filled columns. Three columns were fabricated; one for electrical measurements, one for geochemical sampling and a third non-inoculated column was used as a control. A continual upward flow of nutrients and metals in solution was established in each column. Desulfovibrio vulgaris microbes were injected into the middle of the geochemical and electrical columns. Iron and zinc sulfides precipitated along a microbial action front as a result of sulfate reduction due by Desulfovibrio vulgaris. The precipitation front initially developed near the microbial injection location, and subsequently migrated towards the nutrient inlet, as a result of chemotaxis by Desulfovibrio vulgaris. Sampling during and subsequent to the experiment revealed spatiotemporal changes in the biogeochemical measurements associated with microbial sulfate reduction. Conductivity measurements were insensitive to all biogeochemical changes occurred within the column. Changes in the IP response (of up to 14 mrad)were observed to coincide in place and in time with the active microbe respiration/sulfide precipitation front as determined from geochemical sampling. The IP response is correlated with the lactate concentration gradient, an indirect measurement of microbial metabolism, suggesting the potential of IP as a method for monitoring microbial respiration/activity. Post experimental destructive sample analysis and SEM imaging verified the geochemical results and supported our hypothesis that microbe induced sulfide precipitation is directly detectable using electrical methods. Although the processes not fully understood, the IP response appears to be sensitive to this anaerobic microbial precipitation, suggesting a possible novel application for the IP method.

  9. Drug-induced panniculitides.

    PubMed

    Borroni, G; Torti, S; D'Ospina, R M; Pezzini, C

    2014-04-01

    A substantial number of all panniculitides fails to recognize a specific etiology, and that is true also for a relatively frequent type of panniculitis, such as erythema nodosum (EN). Between the recognized causative factors of panniculitides, infectious, physical agents, autoimmune mechanisms and neoplastic disorders are well known. On the contrary, the role of drugs as inducers of panniculitides is marginally considered, and their report limited to anecdotal observations, often without due histopathological support. Since the clinical and histopathological features of drug-induced panniculitides are indistinguishable from those caused by other agents, the causative relationship may be demonstrated by the history of previous drug intake and by clinical improvement after drug discontinuation. We reviewed the currently reported descriptions of drug-induced panniculitis, including a few exemplificative original observations. EN results as the most frequently reported drug-induced panniculitis. Among the causative drugs of EN a variety of medications, with disparate, or even opposite, mechanisms of action are reported, thus limiting the understanding of the pathogenesis. Common causative drugs include oral contraceptives, nonsteroidal anti-inflammatory drugs, antiobiotics and leukotriene-modifying agents. Unfortunately, in several cases, the diagnosis of drug-induced EN is done on clinical findings alone. In those cases, the lack of histopathological support does not allow to define a precise clinicopathological correlation on etiologic grounds. Drug-induced lobular and mixed panniculitides, including eosinophilic panniculitis, are even more rarely described. Reported causative agents are glatiramer acetate, interferon beta and heparin (at sites of injections), and systemic steroids, tyrosine kinase inhibitors and BRAF with subcutaneous fat involvement at distance. In view of the recent introduction of new classes of drugs, attention should be paid to disclose their

  10. Crystalglobulin-Induced Nephropathy

    PubMed Central

    Gupta, Vinay; El Ters, Mireille; Kashani, Kianoush; Leung, Nelson

    2015-01-01

    Crystalline nephropathy refers to renal parenchymal deposition of crystals leading to kidney damage. The most common forms of crystalline nephropathy encountered in renal pathology are nephrocalcinosis and oxalate nephropathy. Less frequent types include urate nephropathy, cystinosis, dihydroxyadeninuria, and drug-induced crystalline nephropathy (e.g., caused by indinavir or triamterene). Monoclonal proteins can also deposit in the kidney as crystals and cause tissue damage. This occurs in conditions such as light chain proximal tubulopathy, crystal-storing histiocytosis, and crystalglobulinemia. The latter is a rare complication of multiple myeloma that results from crystallization of monoclonal proteins in the systemic vasculature, leading to vascular injury, thrombosis, and occlusion. In this report, we describe a case of crystalglobulin-induced nephropathy and discuss its pathophysiology and the differential diagnosis of paraprotein-induced crystalline nephropathy. PMID:25190731