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Sample records for accumbens lateral septum

  1. Dissociated Roles for the Lateral and Medial Septum in Elemental and Contextual Fear Conditioning

    ERIC Educational Resources Information Center

    Calandreau, Ludovic; Jaffard, Robert; Desmedt, Aline

    2007-01-01

    Extensive evidence indicates that the septum plays a predominant role in fear learning, yet the direction of this control is still a matter of debate. Increasing data suggest that the medial (MS) and lateral septum (LS) would be differentially required in fear conditioning depending on whether a discrete conditional stimulus (CS) predicts, or not,…

  2. Theta oscillations regulate the speed of locomotion via a hippocampus to lateral septum pathway

    PubMed Central

    Bender, Franziska; Gorbati, Maria; Cadavieco, Marta Carus; Denisova, Natalia; Gao, Xiaojie; Holman, Constance; Korotkova, Tatiana; Ponomarenko, Alexey

    2015-01-01

    Hippocampal theta oscillations support encoding of an animal's position during spatial navigation, yet longstanding questions about their impact on locomotion remain unanswered. Combining optogenetic control of hippocampal theta oscillations with electrophysiological recordings in mice, we show that hippocampal theta oscillations regulate locomotion. In particular, we demonstrate that their regularity underlies more stable and slower running speeds during exploration. More regular theta oscillations are accompanied by more regular theta-rhythmic spiking output of pyramidal cells. Theta oscillations are coordinated between the hippocampus and its main subcortical output, the lateral septum (LS). Chemo- or optogenetic inhibition of this pathway reveals its necessity for the hippocampal regulation of running speed. Moreover, theta-rhythmic stimulation of LS projections to the lateral hypothalamus replicates the reduction of running speed induced by more regular hippocampal theta oscillations. These results suggest that changes in hippocampal theta synchronization are translated into rapid adjustment of running speed via the LS. PMID:26455912

  3. Theta oscillations regulate the speed of locomotion via a hippocampus to lateral septum pathway.

    PubMed

    Bender, Franziska; Gorbati, Maria; Cadavieco, Marta Carus; Denisova, Natalia; Gao, Xiaojie; Holman, Constance; Korotkova, Tatiana; Ponomarenko, Alexey

    2015-01-01

    Hippocampal theta oscillations support encoding of an animal's position during spatial navigation, yet longstanding questions about their impact on locomotion remain unanswered. Combining optogenetic control of hippocampal theta oscillations with electrophysiological recordings in mice, we show that hippocampal theta oscillations regulate locomotion. In particular, we demonstrate that their regularity underlies more stable and slower running speeds during exploration. More regular theta oscillations are accompanied by more regular theta-rhythmic spiking output of pyramidal cells. Theta oscillations are coordinated between the hippocampus and its main subcortical output, the lateral septum (LS). Chemo- or optogenetic inhibition of this pathway reveals its necessity for the hippocampal regulation of running speed. Moreover, theta-rhythmic stimulation of LS projections to the lateral hypothalamus replicates the reduction of running speed induced by more regular hippocampal theta oscillations. These results suggest that changes in hippocampal theta synchronization are translated into rapid adjustment of running speed via the LS. PMID:26455912

  4. An excitatory ventral hippocampus to lateral septum circuit that suppresses feeding.

    PubMed

    Sweeney, Patrick; Yang, Yunlei

    2015-01-01

    Previous research has focused on feeding circuits residing in the hindbrain and midbrain that govern homeostatic or hedonic control of food intake. However, the feeding circuits controlling emotional or cognitive aspects of food intake are largely unknown. Here we use chemical genetics and optogenetic techniques to dissect appetite control circuits originating from ventral hippocampus (vHPC), a brain region implicated in emotion and cognition. We find that the vHPC projects functional glutamatergic synaptic inputs to the lateral septum (LS) and optogenetic activation of vHPC projections in LS reduces food intake. Consistently, food intake is suppressed by chemogenetic activation of glutamatergic neurons in the vHPC that project to the LS and inactivation of LS neurons blunts vHPC-induced suppression of feeding. Collectively, our results identify an anorexigenic neural circuit originating from vHPC to LS in the brain, revealing a potential therapeutic target for the treatment of anorexia or other appetite disorders. PMID:26666960

  5. On Lateral Septum-Like Characteristics of Outputs From the Accumbal Hedonic “Hotspot” of Peciña and Berridge With Commentary on the Transitional Nature of Basal Forebrain “Boundaries”

    PubMed Central

    Zahm, Daniel S.; Parsley, Kenneth P.; Schwartz, Zachary M.; Cheng, Anita Y.

    2014-01-01

    Peciña and Berridge (2005; J Neurosci 25:11777–11786) observed that an injection of the μ-opioid receptor agonist DAMGO (D-ala2-N-Me-Phe4-Glycol5-enkephalin) into the rostrodorsal part of the accumbens shell (rdAcbSh) enhances expression of hedonic “liking” responses to the taste of an appetitive sucrose solution. Insofar as the connections of this hedonic “hotspot” were not singled out for special attention in the earlier neuroanatomical literature, we undertook to examine them. We observed that the patterns of inputs and outputs of the rdAcbSh are not qualitatively different from those of the rest of the Acb, except that outputs from the rdAcbSh to the lateral preoptic area and anterior and lateral hypothalamic areas are anomalously robust and overlap extensively with those of the lateral septum. We also detected reciprocal interconnections between the rdAcbSh and lateral septum. Whether and how these connections subserve hedonic impact remains to be learned, but these observations lead us to hypothesize that the rdAcbSh represents a basal forebrain transition area, in the sense that it is invaded by neurons of the lateral septum, or possibly transitional neuronal forms sharing properties of both structures. We note that the proposed transition zone between lateral septum and rdAcbSh would be but one of many in the basal forebrain and conclude by reiterating the longstanding argument that the transitional nature of such boundary areas has functional importance, of which the precise nature will remain elusive until the neurophysiological and neuropharmacological implications of such zones of transition are more generally acknowledged and better addressed. PMID:22628122

  6. Role of lateral septum glucagon-like peptide 1 receptors in food intake.

    PubMed

    Terrill, Sarah J; Jackson, Christine M; Greene, Hayden E; Lilly, Nicole; Maske, Calyn B; Vallejo, Samantha; Williams, Diana L

    2016-07-01

    Hindbrain glucagon-like peptide 1 (GLP-1) neurons project to numerous forebrain areas, including the lateral septum (LS). Using a fluorescently labeled GLP-1 receptor (GLP-1R) agonist, Exendin 4 (Ex4), we demonstrated GLP-1 receptor binding throughout the rat LS. We examined the feeding effects of Ex4 and the GLP-1R antagonist Exendin (9-39) (Ex9) at doses subthreshold for effect when delivered to the lateral ventricle. Intra-LS Ex4 suppressed overnight chow and high-fat diet (HFD) intake, and Ex9 increased chow and HFD intake relative to vehicle. During 2-h tests, intra-LS Ex9 significantly increased 0.25 M sucrose and 4% corn oil. Ex4 can cause nausea, but intra-LS administration of Ex4 did not induce pica. Furthermore, intra-LS Ex4 had no effect on anxiety-like behavior in the elevated plus maze. We investigated the role of LS GLP-1R in motivation for food by examining operant responding for sucrose on a progressive ratio (PR) schedule, with and without a nutrient preload to maximize GLP-1 neuron activation. The preload strongly suppressed PR responding, but blockade of GLP-1R in the intermediate subdivision of the LS did not affect motivation for sucrose under either load condition. The ability of the nutrient load to suppress subsequent chow intake was significantly attenuated by intermediate LS Ex9 treatment. By contrast, blockade of GLP-1R in the dorsal subdivision of the LS increased both PR responding and overnight chow intake. Together, these studies suggest that endogenous activity of GLP-1R in the LS influence feeding, and dLS GLP-1Rs, in particular, play a role in motivation. PMID:27194565

  7. Neuroanatomy and sex differences of the lordosis-inhibiting system in the lateral septum

    PubMed Central

    Tsukahara, Shinji; Kanaya, Moeko; Yamanouchi, Korehito

    2014-01-01

    Female sexual behavior in rodents, termed lordosis, is controlled by facilitatory and inhibitory systems in the brain. It has been well demonstrated that a neural pathway from the ventromedial hypothalamic nucleus (VMN) to the midbrain central gray (MCG) is essential for facilitatory regulation of lordosis. The neural pathway from the arcuate nucleus to the VMN, via the medial preoptic nucleus, in female rats mediates transient suppression of lordosis, until female sexual receptivity is induced. In addition to this pathway, other regions are involved in inhibitory regulation of lordosis in female rats. The lordosis-inhibiting systems exist not only in the female brain but also in the male brain. The systems contribute to suppression of heterotypical sexual behavior in male rats, although they have the potential ability to display lordosis. The lateral septum (LS) exerts an inhibitory influence on lordosis in both female and male rats. This review focuses on the neuroanatomy and sex differences of the lordosis-inhibiting system in the LS. The LS functionally and anatomically links to the MCG to exert suppression of lordosis. Neurons of the intermediate part of the LS (LSi) serve as lordosis-inhibiting neurons and project axons to the MCG. The LSi-MCG neural connection is sexually dimorphic, and formation of the male-like LSi-MCG neural connection is affected by aromatized testosterone originating from the testes in the postnatal period. The sexually dimorphic LSi-MCG neural connection may reflect the morphological basis of sex differences in the inhibitory regulation of lordosis in rats. PMID:25278832

  8. Maternal defense is modulated by beta adrenergic receptors in lateral septum in mice.

    PubMed

    Scotti, Melissa-Ann L; Lee, Grace; Gammie, Stephen C

    2011-06-01

    Maternal defense (offspring protection) is a critical and highly conserved component of maternal care in mammalian systems that involves dramatic shifts in a female's behavioral response to social cues. Numerous changes occur in neuronal signaling and connectivity in the postpartum female, including decreases in norepinephrine (NE) signaling in subregions of the CNS. In this study using a strain of mice selected for maternal defense, we examined whether possible changes in NE signaling in the lateral septum (LS) could facilitate expression of maternal aggression. In separate studies that utilized a repeated measures design, mice were tested for maternal defense following intra-LS injections of either the β-adrenergic receptor agonist isoproterenol (10 μg or 30 μg) or vehicle (Experiment 1), the β-adrenergic receptor antagonist propranolol (2 μg) or vehicle (Experiment 2), or the β1-receptor antagonist, atenolol (Experiment 3). Mice were also evaluated for light-dark performance and pup retrieval. Thirty micrograms of the agonist isoproterenol significantly decreased number of attacks and time aggressive relative to vehicle without affecting pup retrieval or light-dark box performance. In contrast, the antagonist propranolol significantly increased maternal aggression (lowered latency to attack and increased total attack time) without altering light-dark box test. The β1-specific antagonist, atenolol, significantly decreased latency to attack (1 μg vs. vehicle) without altering other measures. Although the findings were identified in a unique strain of mice, the results of these studies support the hypothesis that changes in NE signaling in LS during the postpartum period contribute to the expression of offspring protection. PMID:21480688

  9. The Modulatory Role of the Lateral Septum on Neuroendocrine and Behavioral Stress Responses

    PubMed Central

    Singewald, Georg M; Rjabokon, Alesja; Singewald, Nicolas; Ebner, Karl

    2011-01-01

    The lateral septum (LS) has been shown to have a key role in emotional processes and stress responses. However, the exact role of the LS on stress modulation is not clear, as previous lesion studies mostly used electrolytic lesions, thereby destroying the whole septal area, including medial components and/or fibers of passage. The aim of the present study was therefore, to investigate the effects of selective excitotoxic ablation of the LS on neuroendocrine and behavioral stress responses in rats. Bilateral ibotenic acid lesions of the LS increased hypothalamo–pituitary–adrenocortical (HPA) axis responses to forced swim stress indicated by enhanced plasma ACTH and corticosterone responses and higher stress-induced c-Fos-like immunoreactivity in the paraventricular hypothalamic nucleus. Moreover, LS-lesioned animals showed a more passive coping style in the forced swim test indicated by increased floating and reduced struggling/swimming behavior compared with sham-lesioned controls. Interestingly, intraseptal corticosteroid receptor blockade modulated behavioral stress coping but failed to change HPA axis stress responses. Further experiments aimed at elucidating underlying neurochemical mechanisms revealed that intraseptal administration of the selective 5-HT1A receptor antagonist WAY-100635 increased and prolonged stress-induced ACTH and corticosterone levels mimicking lesion effects, while the agonist 8-OH-DPAT suppressed HPA axis activity facilitating the inhibitory role of the LS. In addition, 8-OH-DPAT-injected animals showed increased active and decreased passive coping strategies during forced swimming suggesting antidepressant efficacy. Taken together, our data suggest that the LS promotes active stress coping behavior and is involved in a HPA-inhibitory mechanism that is at least in part mediated by septal 5-HT1A receptors and does not involve a glucocorticoid mediated feedback mechanism. PMID:21160468

  10. MicroRNA expression is altered in lateral septum across reproductive stages.

    PubMed

    Saul, M C; Zhao, C; Driessen, T M; Eisinger, B E; Gammie, S C

    2016-01-15

    MicroRNAs (miRNAs) inhibit RNA targets and may contribute to postpartum central nervous system (CNS) gene expression changes, although this has never been tested. In the present study, we directly evaluated miRNA levels using RNA sequencing during reproduction in female mice in the lateral septum (LS). We found the reliable and robust changes of miRNAs away from the virgin stage at the three other stages, namely pregnant, day 1 postpartum, and day 8 postpartum. For a given miRNA that was significantly different from the virgin condition in more than one group, the direction of change was always the same. Overall, we identified 32 upregulated miRNAs and 25 downregulated miRNAs that were consistently different from the virgin state. 'Arm switching' occurs for miR-433-3 and miR-7b. Unexpectedly, a third of upregulated miRNAs (relative to virgin) were highly localized within the 12qF1 region of chromosome 12 that includes the Dlk1-Dio3 gene cluster implicated in stem cell and neuronal differentiation. Over 1500 genes were targeted by multiple upregulated miRNAs with about 100 genes targeted by five or more miRNAs. Over 1000 genes were targeted by multiple downregulated miRNAs with about 50 genes targeted by five or more miRNAs. Half of the target genes were regulated by up and downregulated miRNAs, indicating homeostatic regulation. Transcriptional regulation was the most enriched pathway for genes linked to up or down regulated miRNAs. Other enriched pathways included protein kinase activity (e.g., MAP kinase), CNS development, axon guidance, neurotrophin signaling, neuron development/differentiation, and neurogenesis. Previously published postpartum LS gene expression changes were enrichment for LS miRNA targets, as expected. Surprisingly, postpartum gene expression changes from other regions were also enriched against LS miRNA targets, suggesting a core group of miRNAs may act across the CNS during reproduction. Together, we directly examine miRNAs and find

  11. Electrophysiological and autoradiographical evidence of V1 vasopressin receptors in the lateral septum of the rat brain

    SciTech Connect

    Raggenbass, M.; Tribollet, E.; Dreifuss, J.J.

    1987-11-01

    Extracellular recordings were obtained from single neurons located in the lateral septum, an area known to receive a vasopressinergic innervation in the rat brain. Approximately half of the neurons tested responded to 8-L-arginine vasopressin (AVP) by a marked increase in firing rate at concentrations greater than 1 nM. The effect of vasopressin was blocked by synthetic structural analogues possessing antagonistic properties on peripheral vasopressin and oxytocin receptors. Oxytocin was much less potent than vasopressin in firing septal neurons, and a selective oxytocic agonist was totally ineffective. The action of vasopressin on neuronal firing was mimicked by the vasopressor agonist (2-phenylalanine,8-ornithine)vasotocin but not by the selective antidiuretic agonist 1-deamino(8-D-arginine)vasopressin. In a parallel study, sites that bind (/sup 3/H)AVP at low concentration (1.5 nM) were found by in vitro autoradiography in the lateral septum. Adjacent sections were also incubated with 1.5 mM (/sup 3/H)AVP and, in addition, with 100 nM (2-phenylalanine,8-ornithine)vasotocin or 1-deamino(8-D-arginine)vasopressin--i.e., the same compounds as those used for the electrophysiological study. Results showed that the vasopressor agonist, but not the antidiuretic agonist, displaced (/sup 3/H)AVP, thus indicating that the vasopressin binding sites detected by autoradiography in the septum were V1 (vasopressor type) rather than V2 (antidiuretic type) receptors. Based on the electrophysiological evidence, we conclude that these receptors, when occupied, lead to increased firing of lateral septal neurons.

  12. Electrophysiological and autoradiographical evidence of V1 vasopressin receptors in the lateral septum of the rat brain.

    PubMed Central

    Raggenbass, M; Tribollet, E; Dreifuss, J J

    1987-01-01

    Extracellular recordings were obtained from single neurons located in the lateral septum, an area known to receive a vasopressinergic innervation in the rat brain. Approximately half of the neurons tested responded to 8-L-arginine vasopressin (AVP) by a marked increase in firing rate at concentrations greater than 1 nM. The effect of vasopressin was blocked by synthetic structural analogues possessing antagonistic properties on peripheral vasopressin and oxytocin receptors. Oxytocin was much less potent than vasopressin in firing septal neurons, and a selective oxytocic agonist was totally ineffective. The action of vasopressin on neuronal firing was mimicked by the vasopressor agonist [2-phenylalanine,8-ornithine]vasotocin but not by the selective antidiuretic agonist 1-deamino[8-D-arginine]vasopressin. In a parallel study, sites that bind [3H]AVP at low concentration (1.5 nM) were found by in vitro autoradiography in the lateral septum. Adjacent sections were also incubated with 1.5 mM [3H]AVP and, in addition, with 100 nM [2-phenylalanine,8-ornithine]vasotocin or 1-deamino[8-D-arginine]vasopressin--i.e., the same compounds as those used for the electrophysiological study. Results showed that the vasopressor agonist, but not the antidiuretic agonist, displaced [3H]AVP, thus indicating that the vasopressin binding sites detected by autoradiography in the septum were V1 (vasopressor type) rather than V2 (antidiuretic type) receptors. Based on the electrophysiological evidence, we conclude that these receptors, when occupied, lead to increased firing of lateral septal neurons. Images PMID:2959962

  13. Vasopressin cells in the medial amygdala of the rat project to the lateral septum and ventral hippocampus.

    PubMed

    Caffé, A R; van Leeuwen, F W; Luiten, P G

    1987-07-01

    The rat brain contains a large number of vasopressin (VP) immunoreactive fibers, the sites of origin of which have not yet been established completely. For instance, the sources of VP fiber systems in the amygdala, ventral hippocampus (VH), mediodorsal thalamic nucleus, ventral tegmental area, and dorsal raphe yet remain obscure. These VP fibers may originate in any of the recently described extrahypothalamic VP cell groups, viz., medial amygdaloid nucleus (AME), dorsomedial hypothalamic nucleus, or locus coeruleus, since VP efferents from these cells still remain to be demonstrated. In search of AME VP efferents three approaches were followed: (1) the Phaseolus vulgaris anterograde tracing method, (2) immunocytochemistry after AME lesioning, and (3) retrograde transport of a fluorescent dye in combination with immunofluorescence. The results demonstrate that VP cells in the AME project to (1) the lateral septum (LS) by the ventral amygdalofugal pathway and (2) the VH via the amygdalohippocampal transition zone. In addition, the VP projection from the bed nucleus of the stria terminalis (BST) to the LS was confirmed. There was no indication that VP cells in the AME project through the amygdalotegmental pathway to the medulla oblongata and spinal cord. The results support the possibility that the BST and AME are an anatomical entity that may be part of the central loci controlling sexual processes in the rat. PMID:3305600

  14. GABAA Receptor Activation in the Lateral Septum Reduces the Expression of Conditioned Defeat and Increases Aggression in Syrian Hamsters

    PubMed Central

    McDonald, Mark M.; Markham, Chris M.; Norvelle, Alisa; Albers, H. Elliot; Huhman, Kim L.

    2012-01-01

    Exposure to social stressors can cause profound changes in an individual’s physiology and behavior. In Syrian hamsters, even a single social defeat results in conditioned defeat, which includes an abolishment of territorial aggression and the emergence of high levels of submissive behavior. The purpose of the current study was to determine whether the lateral septum (LS) is a component of the putative neural circuit underlying conditioned defeat. Experiment 1 explored the possibility that plasticity in the LS is necessary for the induction of conditioned defeat. Infusions of the protein synthesis inhibitor, anisomycin, prior to defeat training, however, failed to alter conditioned defeat during testing on the following day, suggesting that synaptic plasticity in the LS is not critical for defeat-induced suppression of aggression. Experiment 2 tested whether the LS is necessary for the expression of conditioned defeat. Infusions of the GABAA agonist muscimol into the LS prior to testing significantly increased aggression and decreased submission in previously defeated animals suggesting that the LS is an important component of the neural circuit mediating the expression of both aggression and submission in conditioned defeat. Experiment 3 examined whether the effects of muscimol on aggression were dependent on prior social defeat. Non-defeated animals receiving muscmol infusions prior to testing with a non-aggressive intruder displayed significantly more aggression than did hamsters receiving control injections. Thus, these data suggest that the activation of GABAA receptors in the LS increases aggression regardless of whether or not a hamster has previously experienced social defeat. PMID:22265703

  15. Deviated Septum

    MedlinePlus

    ... only when he or she also has a "cold" (an upper respiratory tract infection). In these individuals, ... problems related to the deviated septum. Once the "cold" resolves, and the nasal inflammation subsides, symptoms of ...

  16. 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

  17. Lateral hypothalamus, nucleus accumbens, and ventral pallidum roles in eating and hunger: interactions between homeostatic and reward circuitry

    PubMed Central

    Castro, Daniel C.; Cole, Shannon L.; Berridge, Kent C.

    2015-01-01

    The study of the neural bases of eating behavior, hunger, and reward has consistently implicated the lateral hypothalamus (LH) and its interactions with mesocorticolimbic circuitry, such as mesolimbic dopamine projections to nucleus accumbens (NAc) and ventral pallidum (VP), in controlling motivation to eat. The NAc and VP play special roles in mediating the hedonic impact (“liking”) and motivational incentive salience (“wanting”) of food rewards, and their interactions with LH help permit regulatory hunger/satiety modulation of food motivation and reward. Here, we review some progress that has been made regarding this circuitry and its functions: the identification of localized anatomical hedonic hotspots within NAc and VP for enhancing hedonic impact; interactions of NAc/VP hedonic hotspots with specific LH signals such as orexin; an anterior-posterior gradient of sites in NAc shell for producing intense appetitive eating vs. intense fearful reactions; and anatomically distributed appetitive functions of dopamine and mu opioid signals in NAc shell and related structures. Such findings help improve our understanding of NAc, VP, and LH interactions in mediating affective and motivation functions, including “liking” and “wanting” for food rewards. PMID:26124708

  18. MC4-R signaling within the nucleus accumbens shell, but not the lateral hypothalamus, modulates ethanol palatability in rats.

    PubMed

    Lerma-Cabrera, Jose M; Carvajal, Francisca; Chotro, Gabriela; Gaztañaga, Mirari; Navarro, Montserrat; Thiele, Todd E; Cubero, Inmaculada

    2013-02-15

    The Melanocortin (MC) system is one of the crucial neuropeptidergic systems that modulate energy balance. The roles of endogenous MC and MC-4 receptor (MC4-R) signaling within the hypothalamus in the control of homeostatic aspects of feeding are well established. Additional evidence points to a key role for the central MC system in ethanol consumption. Recently, we have shown that nucleus accumbens (NAc), but not lateral hypothalamic (LH), infusion of a selective MC4-R agonist decreases ethanol consumption. Given that MC signaling might contribute to non-homeostatic aspects of feeding within limbic circuits, we assessed here whether MC4-R signaling within the NAc and the lateral hypothalamus (LH) alters normal ingestive hedonic and/or aversive responses to ethanol in rats as measured by a taste reactivity test. Adult male Sprague-Dawley rats were given NAc- or LH- bilateral infusion of the selective MC4-R agonist cyclo (NH-CH(2)-CH(2)-CO-His-D-Phe-Arg-Trp-Glu)-NH(2) (0, 0.75 or 1.5μg/0.5μl/site) and following 30 min, the animals received 1 ml of ethanol solution (6% w/v) intraoral for 1 minute and aversive and hedonic behaviors were recorded. We found that NAc-, but not LH-administration, of a selective MC4-R agonist decreased total duration of hedonic reactions and significantly increased aversive reactions relative to saline-infused animals which support the hypothesis that MC signaling within the NAc may contribute to ethanol consumption by modulating non-homeostatic aspects (palatability) of intake. PMID:23146409

  19. Appetitive changes during salt deprivation are paralleled by widespread neuronal adaptations in nucleus accumbens, lateral hypothalamus, and central amygdala.

    PubMed

    Tandon, Shashank; Simon, Sidney A; Nicolelis, Miguel A L

    2012-08-01

    Salt appetite is a goal-directed behavior in which salt-deprived animals ingest high salt concentrations that they otherwise find aversive. Because forebrain areas such as the lateral hypothalamus (LH), central amygdala (CeA), and nucleus accumbens (NAc) are known to play an important role in this behavior, we recorded from these areas while water-deprived (WD) and salt-deprived (SD) rats performed a two-bottle choice test between 0.5 M salt (NaCl) and 0.4 M sucrose. In the SD state, the preference ratio for high molar salt markedly increased. Electrophysiological recordings analyzed with respect to the onset of licking clusters revealed the presence of both excitatory and inhibitory neuronal responses during salt and/or sucrose consumption. In the NAc, putative medium spiny neurons and tonically active neurons exhibited excitatory and inhibitory responses. In all areas, compared with those recorded during the WD state, neurons recorded during the SD state showed an increase in the percentage of salt-evoked excitatory responses and a decrease in the percentage of sucrose-evoked inhibitory responses, suggesting that a subset of the neuronal population in these areas codes for the increased motivational and/or hedonic value of the salt solution. In addition, in the SD state, the firing of excitatory neurons in LH and CeA became more synchronized, indicating a greater functional connectivity between salt-responsive neurons in these areas. We propose that plastic changes in the feeding-related neuronal populations of these forebrain areas arise when changes in metabolic state alter the hedonic and motivational value of a particular taste stimulus. PMID:22572944

  20. 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

  1. Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels.

    PubMed

    Reddy, I A; Pino, J A; Weikop, P; Osses, N; Sørensen, G; Bering, T; Valle, C; Bluett, R J; Erreger, K; Wortwein, G; Reyes, J G; Graham, D; Stanwood, G D; Hackett, T A; Patel, S; Fink-Jensen, A; Torres, G E; Galli, A

    2016-01-01

    Agonism of the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) has been effective at treating aspects of addictive behavior for a number of abused substances, including cocaine. However, the molecular mechanisms and brain circuits underlying the therapeutic effects of GLP-1R signaling on cocaine actions remain elusive. Recent evidence has revealed that endogenous signaling at the GLP-1R within the forebrain lateral septum (LS) acts to reduce cocaine-induced locomotion and cocaine conditioned place preference, both considered dopamine (DA)-associated behaviors. DA terminals project from the ventral tegmental area to the LS and express the DA transporter (DAT). Cocaine acts by altering DA bioavailability by targeting the DAT. Therefore, GLP-1R signaling might exert effects on DAT to account for its regulation of cocaine-induced behaviors. We show that the GLP-1R is highly expressed within the LS. GLP-1, in LS slices, significantly enhances DAT surface expression and DAT function. Exenatide (Ex-4), a long-lasting synthetic analog of GLP-1 abolished cocaine-induced elevation of DA. Interestingly, acute administration of Ex-4 reduces septal expression of the retrograde messenger 2-arachidonylglycerol (2-AG), as well as a product of its presynaptic degradation, arachidonic acid (AA). Notably, AA reduces septal DAT function pointing to AA as a novel regulator of central DA homeostasis. We further show that AA oxidation product γ-ketoaldehyde (γ-KA) forms adducts with the DAT and reduces DAT plasma membrane expression and function. These results support a mechanism in which postsynaptic septal GLP-1R activation regulates 2-AG levels to alter presynaptic DA homeostasis and cocaine actions through AA. PMID:27187231

  2. Role of dopamine D2-like receptors within the ventral tegmental area and nucleus accumbens in antinociception induced by lateral hypothalamus stimulation.

    PubMed

    Moradi, Marzieh; Yazdanian, Mohamadreza; Haghparast, Abbas

    2015-10-01

    Several lines of evidence have shown that stimulation of the lateral hypothalamus (LH) can induce antinociception. It has been indicated that hypothalamic orexinergic neurons send projections throughout the dopamine mesolimbic pathway. Functional interaction between the LH and the main area of the mesolimbic pathway such as the ventral tegmental area (VTA) and the nucleus accumbens (NAc) implicates in pain modulation. Thus, in this study, we investigated the role of D2-like dopamine receptors within the VTA and NAc in the LH stimulation-induced antinociception. Male Wistar rats weighing 230-280 g were unilaterally implanted with two separate cannulae into the LH and VTA or NAc. Animals received intra-VTA (0.25, 1 and 4 μg/0.3 μl DMSO) and intra-accumbal (0.125, 0.25, 1 and 4 μg/0.5 μl DMSO) infusions of sulpiride as a selective D2-like receptor antagonist, prior to intra-LH carbachol (125 nM/rat) administration. In the tail-flick test, the antinociceptive effects were measured using a tail-flick algesiometer and represented as maximal possible effect (%MPE) within 5, 15, 30, 45 and 60 min after injections. Our results showed that intra-VTA and intra-accumbal sulpiride dose-dependently attenuated the LH stimulation-induced antinociception. However, the blockade of D2-like receptors within the NAc was more significant than that of the VTA. These findings show that D2-like dopamine receptors in these regions play an important role in the LH-mediated modulation of nociceptive information in the acute model of pain in the rats. It seems that this pain modulating system is more relevant to D2-like receptors in the nucleus accumbens. PMID:26166189

  3. THE AGS ELECTROSTATIC SEPTUM.

    SciTech Connect

    HOCK,J.RUSSO,T.GLEN,J.BROWN,K.

    2003-05-12

    The previous slow beam extraction electro static septum in the AGS was designed in 1981. Research documented at the Fermi Laboratory was used as the base line for this design. The septum consisted of a ground plane of .002 inch diameter wire tungsten-rhenium alloy (75%W 25%Re) with a hollow welded titanium cathode assembly. The vacuum chamber is stationary and the septum is moved with a pair of high vacuum linear feed throughs. After years of beam time, the frequency of failures increased. The vacuum system design was poor by today's standards and resulted in long pump down times after repairs. The failures ranged from broken septum wires to a twisted cathode. In addition to the failures, the mechanical drive system had too much backlash, making the operating position difficult to repeat. The new septum needed to address all of these issues in order to become a more reliable septum.

  4. The lateral septum and anterior hypothalamus act in tandem to regulate burying in the shock-probe test but not open-arm avoidance in the elevated plus-maze.

    PubMed

    Lamontagne, Steven J; Olmstead, Mary C; Menard, Janet L

    2016-11-01

    Both the lateral septum (LS) and anterior hypothalamus (AHA) regulate behavioural defense. We tested whether those two interconnected structures act in serial in that regard. Infusions of the GABAA agonist muscimol into one side of the LS and the contralateral (but not ipsilateral) AHA suppressed rats' burying in the shock-probe test whereas none of our muscimol infusion approaches altered their open-arm avoidance in the elevated plus-maze. These results suggest that the LS-AHA circuit serves a specialized role in defensive responses towards discrete, localizable threat stimuli but not towards potential threats. PMID:27485402

  5. Enhanced Upregulation of CRH mRNA Expression in the Nucleus Accumbens of Male Rats after a Second Injection of Methamphetamine Given Thirty Days Later

    PubMed Central

    Cadet, Jean Lud; Brannock, Christie; Ladenheim, Bruce; McCoy, Michael T.; Krasnova, Irina N.; Lehrmann, Elin; Becker, Kevin G.; Jayanthi, Subramaniam

    2014-01-01

    Methamphetamine (METH) is a widely abused amphetamine analog. Few studies have investigated the molecular effects of METH exposure in adult animals. Herein, we determined the consequences of an injection of METH (10 mg/kg) on transcriptional effects of a second METH (2.5 mg/kg) injection given one month later. We thus measured gene expression by microarray analyses in the nucleus accumbens (NAc) of 4 groups of rats euthanized 2 hours after the second injection: saline-pretreated followed by saline-challenged (SS) or METH-challenged (SM); and METH-pretreated followed by saline-challenged (MS) or METH-challenged (MM). Microarray analyses revealed that METH (2.5 mg/kg) produced acute changes (1.8-fold; P<0.01) in the expression of 412 (352 upregulated, 60 down-regulated) transcripts including cocaine and amphetamine regulated transcript, corticotropin-releasing hormone (Crh), oxytocin (Oxt), and vasopressin (Avp) that were upregulated. Injection of METH (10 mg/kg) altered the expression of 503 (338 upregulated, 165 down-regulated) transcripts measured one month later (MS group). These genes also included Cart and Crh. The MM group showed altered expression of 766 (565 upregulated, 201 down-regulated) transcripts including Avp, Cart, and Crh. The METH-induced increased Crh expression was enhanced in the MM group in comparison to SM and MS groups. Quantitative PCR confirmed the METH-induced changes in mRNA levels. Therefore, a single injection of METH produced long-lasting changes in gene expression in the rodent NAc. The long-term increases in Crh, Cart, and Avp mRNA expression suggest that METH exposure produced prolonged activation of the endogenous stress system. The METH-induced changes in oxytocin expression also suggest the possibility that this neuropeptide might play a significant role in the neuroplastic and affiliative effects of this drug. PMID:24475032

  6. Deep brain stimulation reveals a dissociation of consummatory and motivated behaviour in the medial and lateral nucleus accumbens shell of the rat.

    PubMed

    van der Plasse, Geoffrey; Schrama, Regina; van Seters, Sebastiaan P; Vanderschuren, Louk J M J; Westenberg, Herman G M

    2012-01-01

    Following the successful application of deep brain stimulation (DBS) in the treatment of Parkinson's disease and promising results in clinical trials for obsessive compulsive disorder and major depression, DBS is currently being tested in small patient-populations with eating disorders and addiction. However, in spite of its potential use in a broad spectrum of disorders, the mechanisms of action of DBS remain largely unclear and optimal neural targets for stimulation in several disorders have yet to be established. Thus, there is a great need to examine site-specific effects of DBS on a behavioural level and to understand how DBS may modulate pathological behaviour. In view of the possible application of DBS in the treatment of disorders characterized by impaired processing of reward and motivation, like addiction and eating disorders, we examined the effect of DBS of the nucleus accumbens (NAcc) on food-directed behavior. Rats were implanted with bilateral stimulation electrodes in one of three anatomically and functionally distinct sub-areas of the NAcc: the core, lateral shell (lShell) and medial shell (mShell). Subsequently, we studied the effects of DBS on food consumption, and the motivational and appetitive properties of food. The data revealed a functional dissociation between the lShell and mShell. DBS of the lShell reduced motivation to respond for sucrose under a progressive ratio schedule of reinforcement, mShell DBS, however, profoundly and selectively increased the intake of chow. DBS of the NAcc core did not alter any form of food-directed behavior studied. DBS of neither structure affected sucrose preference. These data indicate that the intake of chow and the motivation to work for palatable food can independently be modulated by DBS of subregions of the NAcc shell. As such, these findings provide important leads for the possible future application of DBS as a treatment for eating disorders such as anorexia nervosa. PMID:22428054

  7. Role of orexin-2 receptors in the nucleus accumbens in antinociception induced by carbachol stimulation of the lateral hypothalamus in formalin test.

    PubMed

    Yazdi, Fatemeh; Jahangirvand, Mahboubeh; Ezzatpanah, Somayeh; Haghparast, Abbas

    2016-08-01

    Orexins, which are mainly produced by orexin-expressing neurons in the lateral hypothalamus (LH), play an important role in pain modulation. Previously, it has been established that the nucleus accumbens (NAc) is involved in the modulation of formalin-induced nociceptive responses, a model of tonic pain. In this study, the role of intra-accumbal orexin-2 receptors (OX2rs) in the mediation of formalin-induced pain was investigated. A volume of 0.5 μl of 10, 20, and 40 nmol/l solutions of TCS OX2 29, an OX2r antagonist, were unilaterally microinjected into the NAc 5 min before an intra-LH carbachol microinjection (0.5 μl of 250 nmol/l solution). After 5 min, animals received a subcutaneous injection of formalin 2.5% (50 μl) into the hind paw. Pain-related behaviors were assessed at 5 min intervals during a 60-min test period. The findings showed that TCS OX2 29 administration dose dependently blocked carbachol-induced antinociception during both phases of formalin-induced pain. The antianalgesic effect of TCS OX2 29 was greater during the late phase compared with the early phase. These observations suggest that the NAc, as a part of a descending pain-modulatory circuitry, partially mediates LH-induced analgesia in the formalin test through recruitment of OX2rs. This makes the orexinergic system a good potential therapeutic target in the control of persistent inflammatory pain. PMID:26871404

  8. A Relationship between Reduced Nucleus Accumbens Shell and Enhanced Lateral Hypothalamic Orexin Neuronal Activation in Long-Term Fructose Bingeing Behavior

    PubMed Central

    Rorabaugh, Jacki M.; Stratford, Jennifer M.; Zahniser, Nancy R.

    2014-01-01

    Fructose accounts for 10% of daily calories in the American diet. Fructose, but not glucose, given intracerebroventricularly stimulates homeostatic feeding mechanisms within the hypothalamus; however, little is known about how fructose affects hedonic feeding centers. Repeated ingestion of sucrose, a disaccharide of fructose and glucose, increases neuronal activity in hedonic centers, the nucleus accumbens (NAc) shell and core, but not the hypothalamus. Rats given glucose in the intermittent access model (IAM) display signatures of hedonic feeding including bingeing and altered DA receptor (R) numbers within the NAc. Here we examined whether substituting fructose for glucose in this IAM produces bingeing behavior, alters DA Rs and activates hedonic and homeostatic feeding centers. Following long-term (21-day) exposure to the IAM, rats given 8–12% fructose solutions displayed fructose bingeing but unaltered DA D1R or D2R number. Fructose bingeing rats, as compared to chow bingeing controls, exhibited reduced NAc shell neuron activation, as determined by c-Fos-immunoreactivity (Fos-IR). This activation was negatively correlated with orexin (Orx) neuron activation in the lateral hypothalamus/perifornical area (LH/PeF), a brain region linking homeostatic to hedonic feeding centers. Following short-term (2-day) access to the IAM, rats exhibited bingeing but unchanged Fos-IR, suggesting only long-term fructose bingeing increases Orx release. In long-term fructose bingeing rats, pretreatment with the Ox1R antagonist SB-334867 (30 mg/kg; i.p.) equally reduced fructose bingeing and chow intake, resulting in a 50% reduction in calories. Similarly, in control rats, SB-334867 reduced chow/caloric intake by 60%. Thus, in the IAM, Ox1Rs appear to regulate feeding based on caloric content rather than palatability. Overall, our results, in combination with the literature, suggest individual monosaccharides activate distinct neuronal circuits to promote feeding behavior

  9. Successful pregnancy outcome in an untreated case of concomitant transverse complete vaginal septum with unicornuate uterus

    PubMed Central

    Kumar, Naina; Tayade, Surekha

    2014-01-01

    Transverse vaginal septum is a result of faulty canalization of embryonic vagina. Septum may be complete but usually has laterally placed tiny hole giving an impression of vaginal vault without cervix. We described a case of untreated transverse vaginal septum with small central aperture diagnosed during labor and unicornuate uterus diagnosed intraoperatively, with successful pregnancy outcome. PMID:25624665

  10. Chemoarchitectonic Subdivisions of the Songbird Septum and a Comparative Overview of Septum Chemical Anatomy in Jawed Vertebrates

    PubMed Central

    Goodson, James L.; Evans, Andrew K.; Lindberg, Laura

    2008-01-01

    Available data demonstrate that the avian septal region shares a number of social behavior functions and neurochemical features in common with mammals. However, the structural and functional subdivisions of the avian septum remain largely unexplored. In order to delineate chemoarchitectural zones of the avian septum, we prepared a large dataset of double-, triple- and quadruple-labeled material in a variety of songbird species (finches and waxbills of the family Estrildidae and a limited number of emberizid sparrows) using antibodies against ten neuropeptides and enzymes. Ten septal zones were identified which are placed into lateral, medial, caudocentral and septohippocampal divisions, with the lateral and medial divisions each containing multiple zones. The distributions of numerous immunoreactive substances in the lateral septum closely match those of mammals (i.e., distributions of met-enkephalin, vasotocin, galanin, calcitonin gene-related peptide, tyrosine hydroxylase, vasoactive intestinal polypeptide, substance P, corticotropin-releasing factor, and neuropeptide Y), enabling detailed comparisons with numerous chemoarchitectonic zones of the mammalian lateral septum. Our septohippocampal and caudocentral divisions are topographically comparable to the mammalian septohippocampal and septofimbrial nuclei, respectively, although additional data will be required to establish homology. The present data also demonstrate the presence of a medial septal nucleus that is histochemically comparable to the medial septum of mammals. The avian medial septum is clearly defined by peptidergic markers and choline acetyltransferase immunoreactivity. These findings should provide a useful framework for functional and comparative studies, as they suggest that many features of the septum are highly conserved across vertebrate taxa. PMID:15116393

  11. Dyadic social interaction inhibits cocaine-conditioned place preference and the associated activation of the accumbens corridor

    PubMed Central

    Pinheiro, Barbara S.

    2015-01-01

    accumbens, but was observed in all regions medial to the anterior commissure (‘accumbens corridor’), including (from medial to lateral), the vertical limb of the diagonal band and the medial septum (VDB+MS), the major island of Calleja and the intermediate nucleus of the lateral septum (ICjM+LSI), the AcbShm, and the AcbCm. All effects were limited to GABAergic projection neurons (called ‘medium spiny neurons’, in the accumbens), encompassing both dopamine D1 receptor-expressing and D2 receptor-expressing medium spiny neuron subtypes. Our EGR1 expression findings were mirrored in multielectrode array recordings. Finally, we have validated our paradigm in C57BL/6 mice to make use of the plethora of transgenic models available in this genus. PMID:26221832

  12. Eosinophilic Angiocentric Fibrosis of the Nasal Septum

    PubMed Central

    Li, Yunchuan; Liu, Honggang; Zang, Hongrui; Wang, Tong; Hu, Bin

    2013-01-01

    Background. Eosinophilic angiocentric fibrosis (EAF) is a rare benign condition of unknown aetiology that causes stenosis of the upper respiratory tract. It is most commonly found at the nasal septum and sinus mucosa causing mucosal thickening and nasal obstructive symptoms. The diagnosis is mainly based on characteristic histologic findings. Case Report. A 27-year-old young woman presented with a slow growing mass at her anterior nasal septum for over eight years. She complained of persistent nasal obstruction, epistaxis, sometimes diffused facial pain, and chronic headache. 3 years ago, the tumor was partially resected for ventilation and a nasal septum perforation was left. Imaging findings indicated soft-tissue thickening of the anterior part of septum and adjacent lateral nasal walls. Pathological examination showed numerous inflammatory cells infiltrates containing eosinophils, fibroinflammatory lesion with a whorled appearance fibrosis which typically surrounded vessels. A diagnosis of eosinophilic angiocentric fibrosis was made. All laboratory tests were unremarkable. Skin prick test was positive. The tumor-like lesion was totally resected. Conclusions. EAF is a rare benign and progressive disorder causing destruction. Combined with radiological imaging of EAF historical findings contribute to the diagnosis. It is important to prevent tumor from recurrence by total resection of the lesion. PMID:23634315

  13. Fat in the ventricular septum

    PubMed Central

    Donaldson, Erin E.; Ko, Jong Mi; Kuiper, Johannes J.; Chamogeorgakis, Themistokles

    2014-01-01

    Described herein is a 68-year-old man who underwent cardiac transplantation for severe chronic heart failure resulting from ischemic cardiomyopathy. Examination of the excised heart showed not only extensive left ventricular scarring but also a huge collection of adipose tissue in the subepicardial region and surprisingly also in the ventricular septum. The finding of fat in the ventricular septum is extremely rare and prompted this report. PMID:24982572

  14. Surgery of the nasal septum.

    PubMed

    Mlynski, Gunter

    2006-11-01

    Long-term results after septoplasty are not satisfactory. Apart from a recurrence of deviation, there are various reasons for this: false preoperative analysis, complete straightening of the septum, and a disturbed nasal cycle. Preoperative functional diagnostics with a combination of rhinoresistometry, acoustic rhinometry, and long-term rhinoflowmetry are necessary for differentiating between "physiological" and "pathological" septal deviations and recognizing other causes for obstruction. The surgical procedure of septoplasty includes approach, mobilization, resection, reposition, and finally reconstruction of all three layers. The goal of the operation should not be complete straightening of the nasal septum. The space between the septum and turbinates is of utmost importance. It should not be enlarged as much as possible; rather, it must be shaped in such a way as to allow freely congestion and decongestion reciprocal on the two sides during the nasal cycle. PMID:17131264

  15. Intrapartum Diagnosis and Treatment of Longitudinal Vaginal Septum

    PubMed Central

    de França Neto, Antonio Henriques; Nóbrega, Bianca Virgolino; Clementino Filho, Jessé; do Ó, Tiago Cavalcanti; de Amorim, Melania Maria Ramos

    2014-01-01

    Longitudinal vaginal septum is a rare Müllerian malformation that may be associated with dyspareunia, dysmenorrhea, primary amenorrhea, and infertility. In this report, the authors present a case of longitudinal vaginal septum in a 15-year-old patient with a full-term pregnancy whose diagnosis was only made during labor following bidigital vaginal and speculum examination. Septoplasty was performed during the second stage of labor. Both mother and child progressed satisfactorily and were discharged from hospital in good health. Six months later, ultrasonography, hysterosalpingography, and hysteroscopy were carried out and no other associated abnormality was found. PMID:24891963

  16. Vaginoscopic resection of vaginal septum.

    PubMed

    Nassif, Joseph; Al Chami, Ali; Abu Musa, Antoine; Nassar, Anwar H; Kurdi, Ahmad; Ghulmiyyah, Labib

    2012-12-01

    We report the resection of a vaginal septum while preserving the virginity of a 12-year-old girl with Herlyn-Werner-Wunderlich Syndrome (HWWS) having a didelphys uterus, obstructed hemivagina, and an ipsilateral renal agenesis with follow-up at 18 months. Successful resection of the vaginal septum with conservation of the hymenal ring and complete drainage of both the hematocolpos and the hematometra were achieved. Cyclic dysmenorrhea and pelvic pain were completely resolved on follow-up visits at 4, 6, and 18 months. Office hysteroscopy performed during the last follow-up visit revealed a patent vaginal vault without evidence of adenosis or recurrence of the vaginal septum. Vaginoscopy is a safe, convenient, and efficient diagnostic and therapeutic modality that can be used in the management of patients with an obstructed hemivagina. It maintains the patient's virginity and it is useful in patients with a restrictive vaginal opening or narrow vaginal canal. Furthermore, the hysteroscopic excision of the vaginal septum offers minimal risk of recurrence of the septal defect. PMID:23315718

  17. Electrostatic septum for kilowatt heavy ion beams

    NASA Astrophysics Data System (ADS)

    Alfredson, S.; Marti, F.; Miller, P.; Poe, D.; Stork, G.

    2001-12-01

    A septum of improved design has replaced the standard tungsten septum with uniform thickness used in the deflector for the K1200 cyclotron at Michigan State University [1]. A V-notch in the leading edge enhanced radiation cooling, and an increased septum thickness away from the median plane enhanced conduction of heat to the water cooled housing. Previously observed degradation of beam transmission attributed to thermally induced deformation of the septum was greatly improved with the new septum. The demonstrated power dissipation with an Ar beam was 900 W.

  18. Imaging Septum Formation by Fluorescence Microscopy.

    PubMed

    Ribas, Juan Carlos; Cortés, Juan Carlos G

    2016-01-01

    Fungal cleavage furrow formation during cytokinesis relays in the coordinated contraction of an actomyosin-based ring and the centripetal synthesis of both new plasma membrane and a special wall structure named division septum. Through transmission electron microscopy, the septum exhibits a three-layered structure with a central primary septum, flanked at both sides by the secondary septum. In contrast to the chitinous primary septum present in most of fungi, the fission yeast Schizosaccharomyces pombe does not contain chitin, instead it divides through the formation of a linear β(1,3)glucan-rich primary septum, which has been shown to be specifically stained by the fluorochrome Calcofluor white. Recent findings in S. pombe have revealed the importance of septum synthesis for the steady contraction of the ring during cytokinesis. Therefore, to study the molecular mechanisms that connect the extracellular septum wall with the other components of the cytokinetic machinery located in the plasma membrane and cytoplasm, new experimental approaches are needed. Here we describe the methods developed to image the septum structure by fluorescence microscopy, with a special focus in the analysis of septum progression by the use of time-lapse microscopy. PMID:26519306

  19. Hemivaginal septum resection in a patient with a rare variant of Herlyn-Werner-Wunderlich syndrome.

    PubMed

    Pereira, Nigel; Anderson, Sharon H; Verrecchio, Elizabeth S; Brown, M Allyson; Glassner, Michael J

    2014-01-01

    Herlyn-Werner-Wunderlich syndrome is characterized by a triad of uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis. The syndrome should be suspected in any young woman with abdominal pain or cyclic dysmenorrhea, and radiologic evidence of müllerian duct and renal anomalies. Herein is presented the case of a 25-year-old woman with a rare variant of Herlyn-Werner-Wunderlich syndrome, characterized by an anomalous connection between the 2 endocervical canals, who underwent hemivaginal septum resection to relieve progressively worsening dysmenorrhea. The right hemivaginal septum was resected medially from the left cervix and laterally off the right vaginal wall. Hydrodissection between the hemivaginal septum and right cervix facilitated surgical resection. After resection of the hemivaginal septum there was complete resolution of dysmenorrhea and no recurrence of hematometra or hematocolpos. PMID:24858986

  20. Hysteroscopic Transcervical Resection of Uterine Septum

    PubMed Central

    Shi, Xiaoyan; Hua, Xiangdong; Gu, Xiaoyan; Yang, Dazhen

    2013-01-01

    Objective: To explore the method of diagnosis for uterine septum and the clinical effect of hysteroscopic transcervical resection of the septum. Methods: One-hundred ninety cases of patients with uterine septum who were diagnosed and treated at our hospital during 2007–2011 were selected, and their general information, perioperative status, postoperative recovery treatment, and postoperative pregnancy rates were statistically analyzed. Results: All 190 patients were cured with one surgery, with an average hysteroscopic operating time of 22.60 ± 10.67 minutes and intraoperative blood loss of 15.74 ± 9.64 mL. There were no complications such as uterine perforation, water intoxication, infection, or heavy bleeding. Among the 115 patients that we followed up, 86 became pregnant and delivered infants, 81 of which were born at term and 5 that were born premature. Conclusion: The combination of hysteroscopy and laparoscopy is still the most reliable method for the diagnosis of uterine septum. With a shorter operative time, less blood loss, a significantly increased postoperative pregnancy rate and live birth rate, and a significantly lower spontaneous abortion rate, transcervical resection of the septum was the preferred method for the treatment of uterine septum, and surgical instruments and skills were critical to the prognosis of uterine septum. PMID:24398191

  1. [The role of the nucleus accumbens in psychiatric disorders].

    PubMed

    Mavridis, I

    2015-01-01

    The nucleus accumbens is the most inferior part of the striatum and is mainly connected to the limbic system. It is neurochemically and immunohistochemically divided into a shell laterally and a core medially. As a functionally central structure between amygdala, basal ganglia, mesolimbic dopaminergic regions, mediodorsal thalamus and prefrontal cortex, the nucleus accumbens appears to play a modulative role in the flow of the information from the amygdaloid complex to these regions. Dopamine is a major neurotransmitter of the nucleus accumbens and this nucleus has a modulative function to the amygdala-basal ganglia-prefrontal cortex circuit. Together with the prefrontal cortex and amygdala, nucleus accumbens consists a part of the cerebral circuit which regulates functions associated with effort. It is anatomically located in a unique way to serve emotional and behavioral components of feelings. It is considered as a neural interface between motivation and action, having a key-role in food intake, sexual behavior, reward-motivated behavior, stress-related behavior and substance-dependence. It is involved in several cognitive, emotional and psychomotor functions, altered in some psychopathology. Moreover it is involved in some of the commonest and most severe psychiatric disorders, such as depression, schizophrenia, obsessive-compulsive disorder and other anxiety disorders, as well as in addiction, including drugs abuse, alcoholism and smoking. Nucleus accumbens has also a role in other psychiatric disorders such as bipolar disorder, attention deficit/ hyperactivity disorder and post-traumatic stress disorder. Because of its rich dopaminergic projections, this nucleus has been subject of many studies in animals as well as in humans, connecting its malfunction with the disturbed reward process observed in depression. Neuromodulation interventions targeting the nucleus accumbens are nowadays applied in strictly selected patients suffering from treatment

  2. Direct hypothalamic and indirect trans-pallidal, trans-thalamic, or trans-septal control of accumbens signaling and their roles in food intake

    PubMed Central

    Urstadt, Kevin R.; Stanley, B. Glenn

    2015-01-01

    Due in part to the increasing incidence of obesity in developed nations, recent research aims to elucidate neural circuits that motivate humans to overeat. Earlier research has described how the nucleus accumbens shell (AcbSh) motivates organisms to feed by activating neuronal populations in the lateral hypothalamus (LH). However, more recent research suggests that the LH may in turn communicate with the AcbSh, both directly and indirectly, to re-tune the motivation to consume foods with homeostatic and food-related sensory signals. Here, we discuss the functional and anatomical evidence for an LH to AcbSh connection and its role in eating behaviors. The LH appears to modulate Acb activity directly, using neurotransmitters such as hypocretin/orexin or melanin concentrating hormone (MCH). The LH also indirectly regulates AcbSh activity through certain subcortical “relay” regions, such as the lateral septum (LS), ventral pallidum (VP), and paraventricular thalamus, using a variety of neurotransmitters. This review aims to summarize studies on these topics and outline a model by which LH circuits processing energy balance can modulate AcbSh neural activity to regulate feeding behavior. PMID:25741246

  3. Congenital urethrovaginal fistula with transverse vaginal septum.

    PubMed

    Amer, Mohamed Ibrahim; Ahmed, Mortada El-Sayed; Ali, Ali Hagag

    2016-08-01

    Congenital urethrovaginal fistula is an extremely rare genitourinary anomaly. Literature search identified only five reported cases, all of which were associated with urogenital abnormalities. Transverse vaginal septum is another rare condition, resulting from abnormalities in the vertical fusion between the vaginal components of the Mullerian ducts and the urogenital sinus; and associated fistulous connection of the vagina with the urethra is even rarer. Herein we describe the case of a 35-year-old woman who presented with dyspareunia, and a 1-year history of infertility, who was found to have a urethrovaginal fistula with low transverse vaginal septum. The patient was successfully treated with excision of the septum and closure of the urethrovaginal fistula. PMID:27170419

  4. Surgery of the nasal septum and turbinates

    PubMed Central

    Matthias, Christoph

    2008-01-01

    The following article presents nasal septum and turbinate surgery. First an overview with special consideration of the anatomical and physiological background is given followed by indications for surgical procedures. Key steps of the gold standard procedure first described by Cottle and common variations are presented. Furthermore, some techniques dealing with special problems of the septumplasty are discussed followed by an overview on complications and long term results. However, it should be mentioned that studies on surgical procedures of the nasal septum are still not sufficient as higher evidence levels are very rare. Within a separated chapter techniques for closure of septum perforations are presented and indications particularly in the background of the standard procedure of bridge flaps forwarded by Schultz-Coulon are discussed. The second part focusses on turbinate surgery. Accordingly, anatomical and physiological basics are presented followed by indications for surgical procedures and the surgical steps of different procedures as well as postsurgical treatment and long term results. PMID:22073086

  5. Septal stapler use during septum surgery.

    PubMed

    Yildirim, Güven; Cingi, Cemal; Kaya, Ercan

    2013-03-01

    Although discussions regarding nasal packing are still ongoing, to eliminate any possible complications, surgeons have used nasal packing for many years. Septoplasty is one of the most frequently performed operations by head and neck surgeons. Any methods to diminish the surgical time or bring comfort to the surgeon will be well appreciated. In this study, we attempted to demonstrate the usefulness of the stapler method by comparing preoperative and postoperative results from the visual analog scale (VAS), nasal obstruction symptom evaluation (NOSE), rhinosinusitis quality of life questionnaire (RQLQ), and acoustic rhinomanometry values. In addition, we evaluated pain scores, postoperative complications, and breathing after nasal packing, stapling, and trans-septal suturing techniques. Patients were divided into three groups. In the first group, deviated cartilage was removed or repositioned and mucoperichondrial flaps were closed with a bioresorbable stapler after septoplasty. Four or five staples were placed on the septum. In the second group, the septum was sutured continuously with 4/0 Pegelak (Doğsan TR). In the third group, Merocel packs were used without any sutures and were kept for 48 h. Nasal packing leads to patient discomfort after septal surgery; however, there is no difference in patient comfort between closing the mucoperichondrial flaps by suturing the septum or using a stapler. After surgery, there were no differences between the groups in terms of successful breathing. This situation was assessed by endoscopic examination and acoustic rhinomanometry. Thus, there was no objective or subjective difference. Stapling increases the doctor's comfort level and surgical time is optimized. Although experienced surgeons can easily suture the septum, less experienced ones have some difficulty; therefore, stapling may provide more benefit to the latter. Further, four staples are sufficient to close the septum. PMID:22926990

  6. Relief memory consolidation requires protein synthesis within the nucleus accumbens.

    PubMed

    Bruning, Johann E A; Breitfeld, Tino; Kahl, Evelyn; Bergado-Acosta, Jorge R; Fendt, Markus

    2016-06-01

    Relief learning refers to the association of a stimulus with the relief from an aversive event. The thus-learned relief stimulus then can induce, e.g., an attenuation of the startle response or approach behavior, indicating positive valence. Previous studies revealed that the nucleus accumbens is essential for the acquisition and retrieval of relief memory. Here, we ask whether the nucleus accumbens is also the brain site for consolidation of relief memory into a long-term form. In rats, we blocked local protein synthesis within the nucleus accumbens by local infusions of anisomycin at different time points during a relief conditioning experiment. Accumbal anisomycin injections immediately after the relief conditioning session, but not 4 h later, prevented the consolidation into long-term relief memory. The retention of already consolidated relief memory was not affected by anisomycin injections. This identifies a time window and site for relief memory consolidation. These findings should complement our understanding of the full range of effects of adverse experiences, including cases of their distortion in humans such as post-traumatic stress disorder and/or phobias. PMID:26792192

  7. Pneumocephalus in Child Following Bilateral Otomastoiditis and Nasal Septum Infection.

    PubMed

    Soni, Jai Prakash; Choudhary, Sandeep; Makwana, Mohan; Tripathi, Nikita

    2016-07-01

    Pneumocephalus is collection of gas or air within the cranial cavity, commonly associated with trauma, cranial surgery, air embolism, open meningomyelocele; and rarely as a result of central nervous system infections. Asymptomatic pneumocephalus usually recovers spontaneously within few days. Untreated pneumocephalus can progress to tension pneumocephalus, manifesting as severe headache, dizziness, cranial nerve palsy, mental changes, seizure and disorientation. Herein, we report a rare case of pneumocephalus in a 9-month infant with subdural effusion following infection of nasal septum and otomastoiditis. There was no sign of meningitis but CThead showed communication of intracranial dura mater across widened foramen caecum with pre-nasal space, and bilateral otomastoiditis with erosion of anterior and lateral wall of right mastoid bone. The patient was treated successfully and discharged without sequelae. PMID:27504559

  8. Restrictive atrial septum after the Fontan procedure.

    PubMed

    Penford, Gemma; Quandt, Daniel; Stumper, Oliver

    2016-03-01

    In this study, three patients presenting with early or late postoperative Fontan complications were identified to suffer from restriction of the native atrial septum. This caused significant obstruction to pulmonary venous return and elevated systemic venous pressure. Dobutamine stress testing was used in one patient to identify this lesion. Transcatheter stenting was performed in the other two patients. Patients improved after relief of the obstruction. PMID:26175163

  9. Nucleus accumbens stimulation in pathological obesity.

    PubMed

    Harat, Marek; Rudaś, Marcin; Zieliński, Piotr; Birska, Julita; Sokal, Paweł

    2016-01-01

    One of the potential treatment methods of obesity is deep brain stimulation (DBS) of nucleus accumbens. We describe the case of 19 years old woman with hypothalamic obesity. She weighted 151.4 kg before DBS and the non-surgical methods proved to be inefficient. She was treated with implantation of DBS electrode to nucleus accumbens bilaterally. Results were measured with body mass index and neuropsychological tests. Follow-up was 14 months. Fourteen months after surgery weight was 138 kg, BMI was 48.3. Neuropsychological test results were intact. The presented case supports the thesis of treatment of obesity with nucleus accumbens stimulation. PMID:27154450

  10. Role of nucleus accumbens shell neuronal ensembles in context-induced reinstatement of cocaine-seeking.

    PubMed

    Cruz, Fabio C; Babin, Klil R; Leao, Rodrigo M; Goldart, Evan M; Bossert, Jennifer M; Shaham, Yavin; Hope, Bruce T

    2014-05-28

    Environmental contexts previously associated with drug use provoke relapse to drug use in humans and reinstatement of drug seeking in animal models of drug relapse. We examined whether context-induced reinstatement of cocaine seeking is mediated by activation of context-selected nucleus accumbens neurons. We trained rats to self-administer cocaine in Context A and extinguished their lever-pressing in a distinct Context B. On test day, reexposure to the cocaine-associated Context A reinstated cocaine seeking and increased expression of the neural activity marker Fos in 3.3% of accumbens shell and 1.6% of accumbens core neurons. To assess a causal role for these activated neurons, we used the Daun02 inactivation procedure to selectively inactivate these neurons. We trained c-fos-lacZ transgenic rats to self-administer cocaine in Context A and extinguished their lever-pressing in Context B. On induction day, we exposed rats to either Context A or a novel Context C for 30 min and injected Daun02 or vehicle into accumbens shell or core 60 min later. On test day, 3 d after induction day, the ability of Context A to reinstate cocaine seeking and increase neuronal activity in accumbens shell was attenuated when Daun02 was previously injected after exposure to Context A. Daun02 injections after exposure to the novel Context C had no effect on context-induced reinstatement of cocaine seeking despite much greater numbers of Fos-expressing neurons induced by Context C. Daun02 injections in accumbens core had no effect. Our data suggest that context-induced reinstatement of cocaine seeking is mediated by activation of context-selected accumbens shell but not core neuronal ensembles. PMID:24872549

  11. Social interaction and cocaine conditioning in mice increase spontaneous spike frequency in the nucleus accumbens or septal nuclei as revealed by multielectrode array recordings.

    PubMed

    Kummer, Kai K; El Rawas, Rana; Kress, Michaela; Saria, Alois; Zernig, Gerald

    2015-01-01

    Both cocaine and social interaction place preference conditioning lead to increased neuronal expression of the immediate early gene EGR1 in the nucleus accumbens, a central region of the reward pathway, suggesting that both drug and natural rewards may be processed in similar brain regions. In order to gain novel insights into the intrinsic in vitro electrical activity of the nucleus accumbens and adjacent brain regions and to explore the effects of reward conditioning on network activity, we performed multielectrode array recordings of spontaneous firing in acute brain slices of mice conditioned to either cocaine or social interaction place preference. Cocaine conditioning increased the spike frequency of neurons in the septal nuclei, whereas social interaction conditioning increased the spike frequency in the nucleus accumbens compared to saline control animals. In addition, social interaction conditioning decreased the amount of active neuron clusters in the nucleus accumbens. Our findings suggest that place preference conditioning for both drug and natural rewards may induce persistent changes in neuronal network activity in the nucleus accumbens and the septum that are still preserved in acute slice preparations. PMID:25592253

  12. Monitoring Chitin Deposition During Septum Assembly in Budding Yeast.

    PubMed

    Arcones, Irene; Roncero, Cesar

    2016-01-01

    The synthesis of the septum is a critical step during cytokinesis in the fungal cell. Moreover, in Saccharomyces cerevisiae septum assembly depends mostly on the proper synthesis and deposition of chitin and, accordingly, on the timely regulation of chitin synthases. In this chapter, we will see how to follow chitin synthesis by two complementary approaches: monitoring chitin deposition in vivo at the septum by calcofluor staining and fluorescence microscopy, and measuring the chitin synthase activities responsible for this synthesis. PMID:26519305

  13. Pediatric frontal mucocele secondary to a bifid frontal sinus septum.

    PubMed

    Plikaitis, Christina M; Purzycki, Adam R; Couture, Daniel; David, Lisa R

    2010-09-01

    A mucocele is a mucus-containing sac lined with epithelium that arises within a sinus when its drainage is compromised. The frontal sinus is the most common location, with frontal mucocele development occurring when the nasofrontal duct becomes obstructed because of polyps, bone tumors, prior surgery, sinusitis, trauma, or anatomic variation. We report an unusual case of a sterile pediatric frontal mucocele presenting as a slowly enlarging forehead mass due to a bifid frontal sinus septum. A 9-year-old girl presented to the craniofacial clinic for evaluation of a right frontal mass that had been slowly growing over the past year. She was otherwise healthy and had no history of previous trauma or sinus infections. Computed tomography (CT) scan results revealed a localized frontal fluid collection with protrusion and thinning of the anterior frontal bone between 2 midline bony septii. Surgical cranialization of the frontal sinus was performed. The anatomy of her lesion seen both on CT scan and intraoperatively likely explains this unusual case presentation. Instead of the usual inciting event of an intact frontal sinus drainage system becoming blocked, this patient seemed to have a primary developmental lack of any drainage system that led to her mucocele. During formation of her frontal sinus, she developed a bifid septum within the midline that excluded a portion of her frontal sinus from the lateral nasofrontal ducts. With mucus-producing epithelium trapped within these bony confines, pressure began to mount with expansion and thinning of the bone both anteriorly and posteriorly. The lack of any infectious symptoms and sterile culture results may support that this space developed primarily and was never in continuity with the external drainage system. Only 4 other patients have been reported with asymptomatic forehead swelling as the only presenting symptom, with the age ranging from 33 to 79 years. This patient represents the first clinical report of a congenital

  14. Dynamic risk control by human nucleus accumbens.

    PubMed

    Nachev, Parashkev; Lopez-Sosa, Fernando; Gonzalez-Rosa, Javier Jesus; Galarza, Ana; Avecillas, Josue; Pineda-Pardo, Jose Angel; Lopez-Ibor, Juan José; Reneses, Blanca; Barcia, Juan Antonio; Strange, Bryan

    2015-12-01

    Real-world decisions about reward often involve a complex counterbalance of risk and value. Although the nucleus accumbens has been implicated in the underlying neural substrate, its criticality to human behaviour remains an open question, best addressed with interventional methodology that probes the behavioural consequences of focal neural modulation. Combining a psychometric index of risky decision-making with transient electrical modulation of the nucleus accumbens, here we reveal profound, highly dynamic alteration of the relation between probability of reward and choice during therapeutic deep brain stimulation in four patients with treatment-resistant psychiatric disease. Short-lived phasic electrical stimulation of the region of the nucleus accumbens dynamically altered risk behaviour, transiently shifting the psychometric function towards more risky decisions only for the duration of stimulation. A critical, on-line role of human nucleus accumbens in dynamic risk control is thereby established. PMID:26428667

  15. DESIGN OF BEAM-EXTRACTION SEPTUM MAGNET FOR THE SNS.

    SciTech Connect

    TSOUPAS,N.; LEE,Y.Y.; RANK,J.; TUOZZOLO,J.

    2001-06-18

    The beam-extraction process from the SNS accumulator ring [1,2] requires a Lambertson septum magnet. In this paper we discuss the geometrical and magnetic field requirements of the magnet and present results obtained from two and three dimensional magnetic field calculations that shows the field quality in the regions of interest of the septum magnet.

  16. [A Rare Case of Subependymoma of the Septum Pellucidum as Intratumoral Hemorrhage].

    PubMed

    Kawahara, Ichiro; Fujimoto, Takashi; Hirose, Makoto; Toba, Tamotsu

    2015-12-01

    Subependymomas (SEs) are rare, benign, noninvasive, slow-growing tumors located anywhere along the ventricular walls. They arise most frequently in the fourth ventricle followed by the lateral ventricle, and less frequently in the septum pellucidum, third ventricle, and spinal cord. Most SEs are found incidentally at autopsy, but some may produce clinical symptoms. Tumor-related hemorrhage represents an extremely rare presentation sign. We describe a rare case of septum pellucidum SE as tumoral hemorrhage. The tumor was totally removed via an interhemispheric transcallosal approach. Histological examination found typical SE. Although the patient had transient memory impairment, he had a good postoperative course and was discharged on the twenty-first postoperative day. PMID:26646177

  17. Music and the nucleus accumbens.

    PubMed

    Mavridis, Ioannis N

    2015-03-01

    Music is a universal feature of human societies over time, mainly because it allows expression and regulation of strong emotions, thus influencing moods and evoking pleasure. The nucleus accumbens (NA), the most important pleasure center of the human brain (dominates the reward system), is the 'king of neurosciences' and dopamine (DA) can be rightfully considered as its 'crown' due to the fundamental role that this neurotransmitter plays in the brain's reward system. Purpose of this article was to review the existing literature regarding the relation between music and the NA. Studies have shown that reward value for music can be coded by activity levels in the NA, whose functional connectivity with auditory and frontal areas increases as a function of increasing musical reward. Listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the NA. The functional connectivity between brain regions mediating reward, autonomic and cognitive processing provides insight into understanding why listening to music is one of the most rewarding and pleasurable human experiences. Musical stimuli can significantly increase extracellular DA levels in the NA. NA DA and serotonin were found significantly higher in animals exposed to music. Finally, passive listening to unfamiliar although liked music showed activations in the NA. PMID:25102783

  18. Nucleus Accumbens Invulnerability to Methamphetamine Neurotoxicity

    PubMed Central

    Kuhn, Donald M.; Angoa-Pérez, Mariana; Thomas, David M.

    2016-01-01

    Methamphetamine (Meth) is a neurotoxic drug of abuse that damages neurons and nerve endings throughout the central nervous system. Emerging studies of human Meth addicts using both postmortem analyses of brain tissue and noninvasive imaging studies of intact brains have confirmed that Meth causes persistent structural abnormalities. Animal and human studies have also defined a number of significant functional problems and comorbid psychiatric disorders associated with long-term Meth abuse. This review summarizes the salient features of Meth-induced neurotoxicity with a focus on the dopamine (DA) neuronal system. DA nerve endings in the caudate-putamen (CPu) are damaged by Meth in a highly delimited manner. Even within the CPu, damage is remarkably heterogeneous, with ventral and lateral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared the damage that accompanies binge Meth intoxication, but relatively subtle changes in the disposition of DA in its nerve endings can lead to dramatic increases in Meth-induced toxicity in the CPu and overcome the normal resistance of the NAc to damage. In contrast to the CPu, where DA neuronal deficiencies are persistent, alterations in the NAc show a partial recovery. Animal models have been indispensable in studies of the causes and consequences of Meth neurotoxicity and in the development of new therapies. This research has shown that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of Meth to include brain structures not normally targeted for damage. The resistance of the NAc to Meth-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of Meth neurotoxicity by alterations in DA homeostasis is significant in light of the numerous important roles played by this brain structure. PMID:23382149

  19. Nonlinear excited waves on the interventricular septum

    NASA Astrophysics Data System (ADS)

    Bekki, Naoaki; Harada, Yoshifumi; Kanai, Hiroshi

    2012-11-01

    Using a novel ultrasonic noninvasive imaging method, we observe some phase singularities in propagating excited waves on a human cardiac interventricular septum (IVS) for a healthy young male. We present a possible physical model explaining one-dimensional dynamics of phase singularities in nonlinearly excited waves on the IVS. We show that at least one of the observed phase singularities in the excited waves on the IVS can be explained by the Bekki-Nozaki hole solution of the complex Ginzburg-Landau equation without any adjustable parameters. We conclude that the complex Ginzburg-Landau equation is such a suitable model for one-dimensional dynamics of cardiac phase singularities in nonlinearly excited waves on the IVS.

  20. Foetal therapy: what works? Closed interatrial septum.

    PubMed

    Herberg, Ulrike; Berg, Christoph; Geipel, Annegret; Gembruch, Ulrich; Breuer, Johannes

    2014-10-01

    Hypoplastic left-heart syndrome and critical aortic stenosis with severely restricted or intact foramen ovale are associated with high neonatal mortality and poor long-term outcome. Despite accurate foetal diagnosis and successful postnatal catheter-based and surgical intervention, the 1-month survival rate is about 33%. Changes in pulmonary vascular architecture resulting in pulmonary hypertension result in important long-term morbidity. Prenatal relief of left atrial and pulmonary hypertension may promote normal pulmonary vascular and parenchymal development and improve short- and long-term outcomes. Foetal atrial balloon septostomy, laser perforation, and stenting of the foetal interatrial septum are the current options for foetal therapy. This paper provides an overview of foetal diagnosis, selection of patients for foetal intervention, and interventional techniques, and also reviews the current status of foetal and postnatal outcomes after intrauterine intervention. PMID:25159557

  1. Medial septum regulates the hippocampal spatial representation

    PubMed Central

    Mamad, Omar; McNamara, Harold M.; Reilly, Richard B.; Tsanov, Marian

    2015-01-01

    The hippocampal circuitry undergoes attentional modulation by the cholinergic medial septum. However, it is unclear how septal activation regulates the spatial properties of hippocampal neurons. We investigated here what is the functional effect of selective-cholinergic and non-selective septal stimulation on septo-hippocampal system. We show for the first time selective activation of cholinergic cells and their differential network effect in medial septum of freely-behaving transgenic rats. Our data show that depolarization of cholinergic septal neurons evokes frequency-dependent response from the non-cholinergic septal neurons and hippocampal interneurons. Our findings provide vital evidence that cholinergic effect on septo-hippocampal axis is behavior-dependent. During the active behavioral state the activation of septal cholinergic projections is insufficient to evoke significant change in the spiking of the hippocampal neurons. The efficiency of septo-hippocampal processing during active exploration relates to the firing patterns of the non-cholinergic theta-bursting cells. Non-selective septal theta-burst stimulation resets the spiking of hippocampal theta cells, increases theta synchronization, entrains the spiking of hippocampal place cells, and tunes the spatial properties in a timing-dependent manner. The spatial properties are augmented only when the stimulation is applied in the periphery of the place field or 400–650 ms before the animals approached the center of the field. In summary, our data show that selective cholinergic activation triggers a robust network effect in the septo-hippocampal system during inactive behavioral state, whereas the non-cholinergic septal activation regulates hippocampal functional properties during explorative behavior. Together, our findings uncover fast septal modulation on hippocampal network and reveal how septal inputs up-regulate and down-regulate the encoding of spatial representation. PMID:26175674

  2. Dopamine in the nucleus accumbens modulates the memory of social defeat in Syrian hamsters (Mesocricetus auratus).

    PubMed

    Gray, C L; Norvelle, A; Larkin, T; Huhman, K L

    2015-06-01

    Conditioned defeat (CD) is a behavioral response that occurs in Syrian hamsters after they experience social defeat. Subsequently, defeated hamsters no longer produce territorial aggression but instead exhibit heightened levels of avoidance and submission, even when confronted with a smaller, non-aggressive intruder. Dopamine in the nucleus accumbens is hypothesized to act as a signal of salience for both rewarding and aversive stimuli to promote memory formation and appropriate behavioral responses to significant events. The purpose of the present study was to test the hypothesis that dopamine in the nucleus accumbens modulates the acquisition and expression of behavioral responses to social defeat. In Experiment 1, bilateral infusion of the non-specific D1/D2 receptor antagonist cis(z)flupenthixol (3.75 μg/150 nl saline) into the nucleus accumbens 5 min prior to defeat training significantly reduced submissive and defensive behavior expressed 24h later in response to a non-aggressive intruder. In Experiment 2, infusion of 3.75 μg cis-(Z)-flupenthixol 5 min before conditioned defeat testing with a non-aggressive intruder significantly increased aggressive behavior in drug-infused subjects. In Experiment 3, we found that the effect of cis-(Z)-flupenthixol on aggression was specific to defeated animals as infusion of drug into the nucleus accumbens of non-defeated animals did not significantly alter their behavior in response to a non-aggressive intruder. These data demonstrate that dopamine in the nucleus accumbens modulates both acquisition and expression of social stress-induced behavioral changes and suggest that the nucleus accumbens plays an important role in the suppression of aggression that is observed after social defeat. PMID:25721736

  3. Dopamine in the nucleus accumbens modulates the memory of social defeat in Syrian hamsters (Mesocricetus auratus)

    PubMed Central

    Gray, C.L.; Norvelle, A.; Larkin, T.; Huhman, K.L..

    2015-01-01

    Conditioned defeat (CD) is a behavioral response that occurs in Syrian hamsters after they experience social defeat. Subsequently, defeated hamsters no longer produce territorial aggression but instead exhibit heightened levels of avoidance and submission, even when confronted with a smaller, non-aggressive intruder. Dopamine in the nucleus accumbens is hypothesized to act as a signal of salience for both rewarding and aversive stimuli to promote memory formation and appropriate behavioral responses to significant events. The purpose of the present study was to test the hypothesis that dopamine in the nucleus accumbens modulates the acquisition and expression of behavioral responses to social defeat. In Exp. 1, bilateral infusion of the non-specific D1/D2 receptor antagonist cis(z)flupenthixol (3.75 μg/150 nl saline) into the nucleus accumbens 5 min prior to defeat training significantly reduced submissive and defensive behavior expressed 24 hr later in response to a non-aggressive intruder. In Exp. 2, infusion of 3.75 μg cis(z)flupenthixol 5 min before conditioned defeat testing with a non-aggressive intruder significantly increased aggressive behavior in drug-infused subjects. In Exp. 3, we found that the effect of cis(z)flupenthixol on aggression was specific to defeated animals as infusion of drug into the nucleus accumbens of non-defeated animals did not significantly alter their behavior in response to a non-aggressive intruder. These data demonstrate that dopamine in the nucleus accumbens modulates both acquisition and expression of social stress-induced behavioral changes and suggest that the nucleus accumbens plays an important role in the suppression of aggression that is observed after social defeat. PMID:25721736

  4. Laser valvotomy with balloon valvoplasty for pulmonary atresia with intact ventricular septum: five years' experience.

    PubMed Central

    Gibbs, J. L.; Blackburn, M. E.; Uzun, O.; Dickinson, D. F.; Parsons, J. M.; Chatrath, R. R.

    1997-01-01

    OBJECTIVE: To assess immediate and medium term results of transcatheter laser valvotomy with balloon valvoplasty in selected infants with pulmonary atresia and intact ventricular septum. DESIGN: Prospective study. SETTING: Tertiary cardiac unit. PATIENTS: All infants with pulmonary atresia and intact septum with no more than minor tricuspid valve hypoplasia referred between November 1990 and June 1995. Laser valvotomy was attempted in nine infants of median age 4-5 days and median weight 3.6 kg. INTERVENTION: The pulmonary valve was perforated using a 0.018 inch fibreoptic guidewire attached to a NdYag laser and introduced through a catheter positioned beneath the valve. After perforation the valve was dilated with progressively larger balloons. MAIN OUTCOME MEASURES: Successful laser valvotomy and balloon dilatation, complications, pulse oximetry, right ventricular outflow velocities, and need for surgical treatment. RESULTS: Valvotomy was successful in all but one case, the failure being due to laser breakdown. After perforation the valve was dilated to 6-8 mm diameter. Prostaglandin E was withdrawn immediately in six of the eight duct dependent infants, and 28 and 49 days later in two. No patient required an aortopulmonary shunt. Two patients had repeat valvoplasty at 20 days and three months of age, respectively; one required infundibular resection and closure of the atrial septum at age four and one is awaiting similar treatment. CONCLUSIONS: Laser valvotomy with balloon valvoplasty is safe and effective treatment for selected patients with pulmonary atresia and intact ventricular septum and should be considered as first line treatment in place of surgical valvotomy. Images PMID:9093038

  5. Spectrum of urorectal septum malformation sequence.

    PubMed

    Shah, Krupa; Nayak, Shalini S; Shukla, Anju; Girisha, Katta M

    2016-05-01

    Urorectal septum malformation sequence (URSMS) is a rare spectrum of malformations involving various organ systems. Here, we present eight cases of URSMS, noted in autopsy, with different degrees of complexity, seven being the complete type and one being the partial type. All cases had gastrointestinal tract malformation in the form of the imperforate anus and indeterminate genitalia. Other gastrointestinal tract anomalies were anal agenesis in two cases, anorectal agenesis in two cases, and malformed lower intestinal tract in four cases. The associated renal abnormality was noted in five cases, which were unilateral renal agenesis, dysplastic kidney, hydronephrosis, horseshoe kidney, and unilateral hypoplastic ectopic kidney. External genital malformation, present in both male and female fetuses, included a knob-like structure at perineum in female fetuses, genital fold hypoplasia and penile aplasia or hypoplasia in male fetuses. Skeletal abnormalities included two cases of sacral agenesis and one case of lumbosacral dysraphism. Other anomalies included a case with alobar holoprosencephaly, truncus arteriosus with hypoplastic lungs in one case, and three cases with abdominal wall defects. It is our attempt to delineate a spectrum of abnormalities associated with URSMS. PMID:26663027

  6. A Rare Case of Lipomatous Hypertrophy of the Interventricular Septum

    PubMed Central

    Matsiras, Sotirios; Vassilikos, Vassilios

    2016-01-01

    Asymmetrical left ventricular hypertrophy secondary to interventricular septum hypertrophy is usually considered a typical phenotype of hypertrophic cardiomyopathy. In rare cases other conditions such as tumors or lipomatous hypertrophy of the interventricular septum may have a similar presentation. We present a case of a male patient who presented for routine cardiology work up and was diagnosed of having ventricular septal hypertrophy secondary to localized lipomatous hypertrophy. PMID:27358712

  7. Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex

    PubMed Central

    Ikemoto, Satoshi

    2007-01-01

    Anatomical and functional refinements of the meso-limbic dopamine system of the rat are discussed. Present experiments suggest that dopaminergic neurons localized in the posteromedial ventral tegmental area (VTA) and central linear nucleus raphe selectively project to the ventromedial striatum (medial olfactory tubercle and medial nucleus accumbens shell), whereas the anteromedial VTA has few if any projections to the ventral striatum, and the lateral VTA largely projects to the ventrolateral striatum (accumbens core, lateral shell and lateral tubercle). These findings complement the recent behavioral findings that cocaine and amphetamine are more rewarding when administered into the ventromedial striatum than into the ventrolateral striatum. Drugs such as nicotine and opiates are more rewarding when administered into the posterior VTA or the central linear nucleus than into the anterior VTA. A review of the literature suggests that: (1) the midbrain has corresponding zones for the accumbens core and medial shell; (2) the striatal portion of the olfactory tubercle is a ventral extension of the nucleus accumbens shell; (3) a model of two dopamine projection systems from the ventral midbrain to the ventral striatum is useful for understanding reward function. The medial projection system is important in the regulation of arousal characterized by affect and drive, and plays a different role in goal-directed learning than the lateral projection system, as described in the variation-selection hypothesis of striatal functional organization. PMID:17574681

  8. Pulsed power supply for three APS septum magnets

    SciTech Connect

    McGhee, D.G.

    1991-03-24

    Three septum magnets will be operated at a repetition-rate of 2 Hz. Two of the septum magnets are identical and operate at the same values; these are the synchrotron extraction and the storage ring injection magnets. They are transformer septum magnets, with a primary inductance of 23 {mu}H and resistance of 6.3 m{Omega}, and must be pulsed at a 2 Hz rate to extract beam from the synchrotron and inject beam into the storage ring at 7.7 GeV. The third septum magnet is used to inject electrons into the synchrotron at 650 MeV or positrons at 450 MeV. It is also a transformer septum magnet, with a primary inductance of 21 {mu}H and resistance of 6.7 m{Omega}, and must be pulsed at a 2 Hz rate. A design study was performed of the power supply proposed in the APS Title I design. This supply produces a pulse that is approximately a half-sine-wave with a base width of approximately 1/3 ms; its peakcurrent is adjustable from 470 A to 4.7 kA and is repeatable within {plus_minus}0.05%. The septum steel is reset by a half-sine pulse of reverse polarity a few milliseconds after the forward current pulse. No beam is present during reset. The use of the transformer design minimizes the cost of the capacitors used for energy storage.

  9. Increased metabolic activity in the septum and habenula during stress is linked to subsequent expression of learned helplessness behavior

    PubMed Central

    Mirrione, Martine M.; Schulz, Daniela; Lapidus, Kyle A. B.; Zhang, Samuel; Goodman, Wayne; Henn, Fritz A.

    2013-01-01

    Uncontrollable stress can have a profound effect on an organism's ability to respond effectively to future stressful situations. Behavior subsequent to uncontrollable stress can vary greatly between individuals, falling on a spectrum between healthy resilience and maladaptive learned helplessness. It is unclear whether dysfunctional brain activity during uncontrollable stress is associated with vulnerability to learned helplessness; therefore, we measured metabolic activity during uncontrollable stress that correlated with ensuing inability to escape future stressors. We took advantage of small animal positron emission tomography (PET) and 2-deoxy-2[18F]fluoro-D-glucose (18FDG) to probe in vivo metabolic activity in wild type Sprague Dawley rats during uncontrollable, inescapable, unpredictable foot-shock stress, and subsequently tested the animals response to controllable, escapable, predictable foot-shock stress. When we correlated metabolic activity during the uncontrollable stress with consequent behavioral outcomes, we found that the degree to which animals failed to escape the foot-shock correlated with increased metabolic activity in the lateral septum and habenula. When used a seed region, metabolic activity in the habenula correlated with activity in the lateral septum, hypothalamus, medial thalamus, mammillary nuclei, ventral tegmental area, central gray, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and rostromedial tegmental nucleus, caudal linear raphe, and subiculum transition area. Furthermore, the lateral septum correlated with metabolic activity in the preoptic area, medial thalamus, habenula, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and caudal linear raphe. Together, our data suggest a group of brain regions involved in sensitivity to uncontrollable stress involving the lateral septum and habenula. PMID:24550809

  10. Septum Development in Neurospora crassa: The Septal Actomyosin Tangle

    PubMed Central

    Delgado-Álvarez, Diego Luis; Bartnicki-García, Salomón; Seiler, Stephan; Mouriño-Pérez, Rosa Reyna

    2014-01-01

    Septum formation in Neurospora crassa was studied by fluorescent tagging of actin, myosin, tropomyosin, formin, fimbrin, BUD-4, and CHS-1. In chronological order, we recognized three septum development stages: 1) septal actomyosin tangle (SAT) assembly, 2) contractile actomyosin ring (CAR) formation, 3) CAR constriction together with plasma membrane ingrowth and cell wall construction. Septation began with the assembly of a conspicuous tangle of cortical actin cables (SAT) in the septation site >5 min before plasma membrane ingrowth. Tropomyosin and myosin were detected as components of the SAT from the outset. The SAT gradually condensed to form a proto-CAR that preceded CAR formation. During septum development, the contractile actomyosin ring remained associated with the advancing edge of the septum. Formin and BUD-4 were recruited during the transition from SAT to CAR and CHS-1 appeared two min before CAR constriction. Actin patches containing fimbrin were observed surrounding the ingrowing septum, an indication of endocytic activity. Although the trigger of SAT assembly remains unclear, the regularity of septation both in space and time gives us reason to believe that the initiation of the septation process is integrated with the mechanisms that control both the cell cycle and the overall growth of hyphae, despite the asynchronous nature of mitosis in N. crassa. PMID:24800890

  11. Analysis of cardiac interventricular septum motion in different respiratory states

    NASA Astrophysics Data System (ADS)

    Tautz, Lennart; Feng, Li; Otazo, Ricardo; Hennemuth, Anja; Axel, Leon

    2016-03-01

    The interaction between the left and right heart ventricles (LV and RV) depends on load and pressure conditions that are affected by cardiac contraction and respiration cycles. A novel MRI sequence, XD-GRASP, allows the acquisition of multi-dimensional, respiration-sorted and cardiac-synchronized free-breathing image data. In these data, effects of the cardiac and respiratory cycles on the LV/RV interaction can be observed independently. To enable the analysis of such data, we developed a semi-automatic exploration workflow. After tracking a cross-sectional line positioned over the heart, over all motion states, the septum and heart wall border locations are detected by analyzing the grey-value profile under the lines. These data are used to quantify septum motion, both in absolute units and as a fraction of the heart size, to compare values for different subjects. In addition to conventional visualization techniques, we used color maps for intuitive exploration of the variable values for this multi-dimensional data set. We acquired short-axis image data of nine healthy volunteers, to analyze the position and the motion of the interventricular septum in different breathing states and different cardiac cycle phases. The results indicate a consistent range of normal septum motion values, and also suggest that respiratory phase-dependent septum motion is greatest near end-diastolic phases. These new methods are a promising tool to assess LV/RV ventricle interaction and the effects of respiration on this interaction.

  12. Upflow bioreactor with septum and pressure release mechanism

    DOEpatents

    Hansen, Conly L.; Hansen, Carl S.; Pack, Kevin; Milligan, John; Benefiel, Bradley C.; Tolman, C. Wayne; Tolman, Kenneth W.

    2010-04-20

    An upflow bioreactor includes a vessel having an inlet and an outlet configured for upflow operation. A septum is positioned within the vessel and defines a lower chamber and an upper chamber. The septum includes an aperture that provides fluid communication between the upper chamber and lower chamber. The bioreactor also includes means for releasing pressure buildup in the lower chamber. In one configuration, the septum includes a releasable portion having an open position and a closed position. The releasable portion is configured to move to the open position in response to pressure buildup in the lower chamber. In the open position fluid communication between the lower chamber and the upper chamber is increased. Alternatively the lower chamber can include a pressure release line that is selectively actuated by pressure buildup. The pressure release mechanism can prevent the bioreactor from plugging and/or prevent catastrophic damage to the bioreactor caused by high pressures.

  13. Nasal septum perforation in patient with pyoderma gangrenosum

    PubMed Central

    Maia, Camilla Bezerra da Cruz; Felix, Felippe; Paes, Vania; de Azevedo, Julia Alves; Grangeiro, Eliza Raquel Negrão; Riccio, Jonatah Lucas N.; Rito, Helen Cruz

    2012-01-01

    Summary Introduction: The cocaine is obtained from the leaves of the coca (Erythroxylon coca). It can be used in many ways, but the most common is the drug inhalation. The Cocaine also causes vasoconstriction at nasal mucous membrane and its chronic use can cause necrosis and nasal septum perforation. Pyoderma gangrenosum is an uncommon idiopathic disease characterized by ulcerations, usually observed on the legs. Its diagnosis is most common an exclusion of others diseases. So far, there is no specific treatment based on evidence by randomized controlled trials. Objective: Describe the rare association between Pyoderma gangrenosum and cocaine. Case Report: E. A., 27-year-old woman with destruction of nasal septum and palate who has been using a big amount of cocaine, been necessary note the difference from which disease cause de damage. Final Comments: Also there are only three cases of Pyoderma gangrenosum complicated with nasal septum perforation in cocaine users. PMID:25991946

  14. Cooperation between Paxillin-like Protein Pxl1 and Glucan Synthase Bgs1 Is Essential for Actomyosin Ring Stability and Septum Formation in Fission Yeast

    PubMed Central

    G. Cortés, Juan C.; Pujol, Nuria; Sato, Mamiko; Pinar, Mario; Ramos, Mariona; Moreno, Belén; Osumi, Masako; Ribas, Juan Carlos; Pérez, Pilar

    2015-01-01

    In fungal cells cytokinesis requires coordinated closure of a contractile actomyosin ring (CAR) and synthesis of a special cell wall structure known as the division septum. Many CAR proteins have been identified and characterized, but how these molecules interact with the septum synthesis enzymes to form the septum remains unclear. Our genetic study using fission yeast shows that cooperation between the paxillin homolog Pxl1, required for ring integrity, and Bgs1, the enzyme responsible for linear β(1,3)glucan synthesis and primary septum formation, is required for stable anchorage of the CAR to the plasma membrane before septation onset, and for cleavage furrow formation. Thus, lack of Pxl1 in combination with Bgs1 depletion, causes failure of ring contraction and lateral cell wall overgrowth towards the cell lumen without septum formation. We also describe here that Pxl1 concentration at the CAR increases during cytokinesis and that this increase depends on the SH3 domain of the F-BAR protein Cdc15. In consequence, Bgs1 depletion in cells carrying a cdc15ΔSH3 allele causes ring disassembly and septation blockage, as it does in cells lacking Pxl1. On the other hand, the absence of Pxl1 is lethal when Cdc15 function is affected, generating a large sliding of the CAR with deposition of septum wall material along the cell cortex, and suggesting additional functions for both Pxl1 and Cdc15 proteins. In conclusion, our findings indicate that CAR anchorage to the plasma membrane through Cdc15 and Pxl1, and concomitant Bgs1 activity, are necessary for CAR maintenance and septum formation in fission yeast. PMID:26132084

  15. Cooperation between Paxillin-like Protein Pxl1 and Glucan Synthase Bgs1 Is Essential for Actomyosin Ring Stability and Septum Formation in Fission Yeast.

    PubMed

    Cortés, Juan C G; Pujol, Nuria; Sato, Mamiko; Pinar, Mario; Ramos, Mariona; Moreno, Belén; Osumi, Masako; Ribas, Juan Carlos; Pérez, Pilar

    2015-07-01

    In fungal cells cytokinesis requires coordinated closure of a contractile actomyosin ring (CAR) and synthesis of a special cell wall structure known as the division septum. Many CAR proteins have been identified and characterized, but how these molecules interact with the septum synthesis enzymes to form the septum remains unclear. Our genetic study using fission yeast shows that cooperation between the paxillin homolog Pxl1, required for ring integrity, and Bgs1, the enzyme responsible for linear β(1,3)glucan synthesis and primary septum formation, is required for stable anchorage of the CAR to the plasma membrane before septation onset, and for cleavage furrow formation. Thus, lack of Pxl1 in combination with Bgs1 depletion, causes failure of ring contraction and lateral cell wall overgrowth towards the cell lumen without septum formation. We also describe here that Pxl1 concentration at the CAR increases during cytokinesis and that this increase depends on the SH3 domain of the F-BAR protein Cdc15. In consequence, Bgs1 depletion in cells carrying a cdc15ΔSH3 allele causes ring disassembly and septation blockage, as it does in cells lacking Pxl1. On the other hand, the absence of Pxl1 is lethal when Cdc15 function is affected, generating a large sliding of the CAR with deposition of septum wall material along the cell cortex, and suggesting additional functions for both Pxl1 and Cdc15 proteins. In conclusion, our findings indicate that CAR anchorage to the plasma membrane through Cdc15 and Pxl1, and concomitant Bgs1 activity, are necessary for CAR maintenance and septum formation in fission yeast. PMID:26132084

  16. Nail-patella-syndrome in a young patient followed up over 10 years: relevance of the sagittal trochlear septum for patellofemoral pathology

    PubMed Central

    Konrads, Christian; Reppenhagen, Stephan; Plumhoff, Piet; Rudert, Maximilian; Steinert, Andre; Barthel, Thomas

    2016-01-01

    Introduction: Nail-patella-syndrome (NPS) is a rare autosomal-dominant inherited disease with pathologies of nails, skeleton, kidneys, and eyes. Linkage to a mutated gene was found. It codes for the transcription-factor LMX1B. In most cases knees are symptomatic. Patients have hypoplastic patellae, which are laterally subluxated. In those individuals a sagittal trochlear fibrous septum was found, dividing the anterior knee-joint-space. In the literature the etiology and clinical significance of this anatomic abnormality is unclear. Based on clinical and intraoperative findings we developed a theory regarding knee pathology in nail-patella-syndrome. Successful treatment via early resection of the septum with sustained good outcome is presented. Methods: In a symptomatic six-year-old boy with nail-patella-syndrome we resected the fibrous sagittal septum adherent to the trochlea femoris and we balanced the patella via lateral release and medial plication in both knee joints. We analyzed the clinical outcome of this procedure prospectively over 10 years. Results: Postoperatively the hypoplastic patellae stayed centered and stable during further skeletal development. The patient was still pain free with normal range of motion of both operated knee joints after 10 years of follow-up. Discussion: In patients with nail-patella-syndrome and a subluxated or dislocated patella we recommend diagnostics with magnetic-resonance-imaging and early surgical treatment via resection of the trochlear septum and soft-tissue-balancing of the patella. When the septum displaces the patella and prevents physiological articulation of the patella with the trochlea femoris, early septum resection is likely to be important for a good functional outcome and proper development of the patellofemoral joint during growth. PMID:27247258

  17. An approach to the nasal septum in children.

    PubMed

    Healy, G B

    1986-11-01

    Surgery of the nasal septum has long been discouraged in the pediatric population. Concerns about growth and development of the nose have led surgeons to adopt an extremely cautious attitude toward the correction of nasal septal deformities in childhood. More recently, studies have shown that with proper preservation of septal cartilage, surgery can be safely undertaken in this area. Frequently, however, exposure to the nasal septum is limited in small children due to the size of the nasal vestibule. Sublabial septoplasty has been safely carried out now in ten patients ranging in age from 4 to 9 years. This approach allows for complete access to the nasal septum while avoiding any external cosmetic deformity. The nasal septum has been preserved in all cases through morsalization and repositioning. Growth and development of the nose has been followed for up to 60 months without evidence of deformity or alteration. Sublabial septoplasty would, therefore, appear to be a safe and cosmetically acceptable approach to the correction of severe nasal septal deformities of childhood. PMID:3773624

  18. A 77-118 GHz RESONANCE-FREE SEPTUM POLARIZER

    SciTech Connect

    Chen, Yen-Lin; Chiueh, Tzihong; Teng, Hsiao-Feng

    2014-03-01

    Measurements of polarized radiation often reveal specific physical properties of emission sources, such as the strengths and orientations of magnetic fields offered by synchrotron radiation and Zeeman line emission, and the electron density distribution caused by free-free emission. Polarization-capable, millimeter/sub-millimeter telescopes are normally equipped with either septum polarizers or ortho-mode transducers (OMT) to detect polarized radiation. Though the septum polarizer is limited to a significantly narrower bandwidth than the OMT, it possesses advantageous features unparalleled by the OMT when it comes to determining astronomical polarization measurements. We design an extremely wide-band circular waveguide septum polarizer, covering 42% bandwidth, from 77 GHz to 118 GHz, without any undesired resonance, challenging the conventional bandwidth limit. Stokes parameters, constructed from the measured data between 77 GHz and 115 GHz, show that the leakage from I to Q and U is below ±2%, and the Q – U mutual leakage is below ±1%. Such a performance is comparable to other modern polarizers, but the bandwidth of this polarizer can be at least twice as wide. This extremely wide-band design removes the major weakness of the septum polarizer and opens up a new window for future astronomical polarization measurements.

  19. A 77-118 GHz Resonance-free Septum Polarizer

    NASA Astrophysics Data System (ADS)

    Chen, Yen-Lin; Chiueh, Tzihong; Teng, Hsiao-Feng

    2014-03-01

    Measurements of polarized radiation often reveal specific physical properties of emission sources, such as the strengths and orientations of magnetic fields offered by synchrotron radiation and Zeeman line emission, and the electron density distribution caused by free-free emission. Polarization-capable, millimeter/sub-millimeter telescopes are normally equipped with either septum polarizers or ortho-mode transducers (OMT) to detect polarized radiation. Though the septum polarizer is limited to a significantly narrower bandwidth than the OMT, it possesses advantageous features unparalleled by the OMT when it comes to determining astronomical polarization measurements. We design an extremely wide-band circular waveguide septum polarizer, covering 42% bandwidth, from 77 GHz to 118 GHz, without any undesired resonance, challenging the conventional bandwidth limit. Stokes parameters, constructed from the measured data between 77 GHz and 115 GHz, show that the leakage from I to Q and U is below ±2%, and the Q - U mutual leakage is below ±1%. Such a performance is comparable to other modern polarizers, but the bandwidth of this polarizer can be at least twice as wide. This extremely wide-band design removes the major weakness of the septum polarizer and opens up a new window for future astronomical polarization measurements.

  20. Muscarinic antagonists attenuate the increase in accumbens and striatum dopamine metabolism produced by clozapine but not by haloperidol.

    PubMed Central

    Rivest, R.; Marsden, C. A.

    1991-01-01

    1. The effect of the muscarinic antagonists, scopolamine and atropine, were examined on the increase in extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens and the striatum induced by haloperidol and clozapine by use of in vivo differential pulse voltammetry with carbon fibre electrodes in anaesthetized rats. 2. Animals received saline (1 ml kg-1, s.c.), scopolamine (1 mg kg-1, o.p.) or atropine (20 micrograms, i.c.v.) followed 15 min later by saline (10 microliters, i.c.v.), haloperidol (1 mg kg-1, s.c.) or clozapine (30 mg kg-1, i.p.) and extracellular DOPAC was simultaneously recorded in the nucleus accumbens and the striatum every 5 min for 60 min after drug administration. 3. Scopolamine or atropine alone had no effect on the DOPAC peak height but attenuated the increase in extracellular DOPAC induced by clozapine in both brain regions. Neither scopolamine nor atropine altered the haloperidol-induced increase in accumbens or striatal extracellular DOPAC. 4. The present results demonstrate that muscarinic antagonists attenuate the increase in accumbens and striatal dopamine metabolism in vivo produced by the atypical neuroleptic clozapine but not the haloperidol-induced increase in dopamine metabolism. The results indicate that central muscarinic receptors are involved in the actions on dopaminergic function of clozapine but not haloperidol. PMID:1786513

  1. Nasal tip support: A finite element analysis of the role of the caudal septum during tip depression

    PubMed Central

    Manuel, Cyrus T.; Leary, Ryan; Protsenko, Dmitriy E.; Wong, Brian J.F.

    2014-01-01

    Objective/Hypothesis Although minor and major tip support mechanisms have been described in detail, no quantitative models exist to provide support for the relative contributions of the structural properties of the major alar cartilage, the fibrous attachments to surrounding structures, and the rigid support structures in an objective manner. Study Design The finite element method was used to compute the stress distribution in the nose during simple tip compression, and then identify the specific anatomic structures that resist deformation and thus contribute to “tip support”. Additionally, the impact of caudal septal resection on nasal tip support was examined. Method The computer models consisted of three tissue components with anatomically correct geometries for skin and bone derived from CT data. Septum, upper lateral cartilages, and major alar cartilages were fitted within the model using 3D CAD software. 5mm nasal tip compression was performed on the models with caudal septal resection (3mm and 5 mm) and without resection to simulate palpation, then the resulting spatial distribution of stress and displacement was calculated. Results The von Mises stress in the normal model was primarily concentrated along medial crural angle. As caudal septum length was reduced, stress was redistributed to adjacent soft tissue and bone, resulting in less force acting on the septum. In all models, displacement was greatest near the intermediate crura. Conclusions These models are the first step in the comprehensive mechanical analysis of nasal tip dynamics. Our model supports the concept of the caudal septum and major alar cartilage as providing the majority of critical load-bearing support. Level of Evidence N/A PMID:23878007

  2. Carcinoma of the recto-vaginal septum. Comprehensive literature review.

    PubMed

    Lopez, N; Grabowski, J P; De Santiago, J; Zapardiel, I

    2016-05-01

    Carcinoma of the recto-vaginal septum is an extremely rare entity. We performed a MEDLINE-based search on recto-vaginal septum carcinoma, focussing on its management, in order to clarify which are the best treatment options for this disease. In addition an unpublished case report has been added to the review. 34 case reports were included in our review. Surgery and adjuvant chemoradiation therapy seem to be the most common treatment option. However, since primary surgical treatment leads to mutilation by removing a large portion of the vagina and the anal sphincter with a permanent terminal colostomy, primary platinum-based chemoradiation therapy could be considered. In case of extragastrointestinal stromal tumours primary surgical treatment seems to be the best option. Due to the rarity of this entity only limited data is available. Therefore further investigation is necessary. PMID:26467428

  3. Complete bicornuate uterus with complete transverse vaginal septum

    PubMed Central

    Tehrani, Hatav Ghasemi; Hashemi, Leila; Ghasemi, Mojdeh

    2014-01-01

    Bicornuate uterus has two symmetric uterine cavities that are fused caudally and have some degree of communication between two cavities, usually at the uterine isthmus. A complete bicornuate uterus has a seperatory cleft of tissue that is extended to the internal OS. Lesser degree of septation of the two uterine horns has constitution, a partial bicornuate uterus. Bicornuate uterus is a class of four anomaly of American fertility society classification of mullerian anomalies. Here we report a case of a 19-year-old female patient with complaint of abdominal pain and spotting since 4 months ago. In sonography it revealed bicornuate uterus and hematocolpos. The patient underwent general anesthesia and examination that reveal the transverse vaginal septum. Septum removed by resectoscope was successful. PMID:25097613

  4. Echinococcal Cyst of the Interventricular Septum with Right Ventricular Protrusion

    PubMed Central

    Eren, E. Ergin; Aykut, Serap; Kayihan, Attila; Aydogan, Hakki; Dagsali, Sabri

    1989-01-01

    Although echinococcosis (echinococcal hydatidosis) is common in sheep-raising countries such as Turkey, cardiac involvement is rare; the presence of a hydatid cyst in the interventricular septum is rarer still. We report a case of hydatid cyst of the interventricular septum that was first revealed by 2-dimensional echocardiography and then confirmed by right ventricular angiography. The cyst was removed surgically under cardiopulmonary bypass. Within the context of the medical literature concerning this rare lesion, we discuss this case and 10 other cases of cardiac hydatidosis, previously unreported in the world literature, that we have treated from January 1967 through January 1987. (Texas Heart Institute Journal 1989;16:292-5) Images PMID:15227384

  5. Ameloblastoma of the Nasal Septum Origin: A Case Report

    PubMed Central

    Zatoński, Tomasz; Roszkowska, Anna; Kręcicki, Tomasz

    2013-01-01

    Background. Ameloblastoma is the most common odontogenic tumor. It represents about 1% of all tumors of the jaw. Extragnathic location of the ameloblastoma is typical and extremely rare. Case Report. We report a case of ameloblastoma of the nasal septum origin, causing nasal obstruction. According to our information, this is the first reported case of ameloblastoma coming from the nasal septum as a primary tumor without maxillary sinus involvement. Conclusions. Ameloblastoma can not only locate in the maxilla and mandible, but also in other regions of the craniofacial. Ameloblastoma should be considered in the differential diagnosis of tumors causing nasal obstruction. Nonspecific clinical features of sinonasal ameloblastoma make it extremely important to perform accurate diagnostic imaging and histopathological examination. PMID:24171127

  6. Early Stage Relapsing Polychondritis Diagnosed by Nasal Septum Biopsy

    PubMed Central

    Kobayashi, Takaaki; Moody, Sandra; Komori, Masafumi; Jibatake, Akira; Yaegashi, Makito

    2015-01-01

    Relapsing polychondritis is a rare inflammation of cartilaginous tissues, the diagnosis of which is usually delayed by a mean period of 2.9 years from symptom onset. We present the case of a 36-year-old man with nasal pain and fever. Physical examination of the nose was grossly unremarkable, but there was significant tenderness of the nasal bridge. Acute sinusitis was initially diagnosed due to thickened left frontal sinus mucosa on computed tomography (CT); however, there was no improvement after antibiotic intake. Repeat CT showed edematous inflammation of the nasal septum; biopsy of this site demonstrated erosion and infiltration of lymphocytes, plasma cells, eosinophils, and neutrophils in the hyaline cartilage. Relapsing polychondritis was confirmed by the modified McAdam's criteria and can be diagnosed at an early stage by nasal septum biopsy; it should be considered as a differential diagnosis in patients presenting with nasal symptoms alone or persistent sinus symptoms. PMID:26843866

  7. Urorectal septum malformation sequence in a newborn with VACTERL association.

    PubMed

    Patra, Soumya; Purkait, Radheshyam

    2012-02-01

    Urorectal septum malformation sequence (URSMS) is an extremely rare anomaly, consists of multiple system anomalies including ambiguous genitalia, absence of a perineal opening, an imperforate anus, and urological, colonic and lumbosacral defects. We describe a newborn with characteristic URSMS who also had features of congenital varus deformity of leg, polydactyly, tracheo-oesophageal fistula, cardiac defect, anal atresia and hydronephrosis in antenatal ultrasound characteristic of VACTERL association. PMID:22313652

  8. Partial tearing of the interventricular septum after blunt chest trauma.

    PubMed

    López-Ruiz, Nilson; Ramírez Gil, Lucas

    2015-01-01

    Cardiac trauma after blunt chest trauma is a rare complication of patients arriving alive to an emergency department. We here present the case of patient who had a partial rupture of the interventricular septum after having had a blunt chest trauma in a traffic accident. As there was no ventricular septal defect, conservative management was deemed appropriate. At 3-year follow-up, the patient was free of right heart failure symptoms suggestive of the septal defect progression. PMID:26031362

  9. Large Cardiac Hydatid Cyst in the Interventricular Septum

    PubMed Central

    Ipek, Gokhan; Omeroglu, Suat Nail; Goksedef, Deniz; Balkanay, Ozan Onur; Kanbur, Elmas; Engin, Ersoy; Baskurt, Murat; Kucukoglu, Serdar

    2011-01-01

    Cystic hydatid disease results from infection with the larval or adult form of the Echinococcus granulosus tapeworm. Cardiac involvement is seen in 0.5% to 2% of patients with hydatid disease, and involvement of the interventricular septum is even rarer. Herein, we report our surgical treatment of a large cardiac hydatid cyst in the interventricular septum. A 39-year-old woman presented with dyspnea. Transthoracic echocardiography revealed a large cyst in the apical part of the interventricular septum. Thoracic computed tomography showed a cystic lesion in that site, and magnetic resonance imaging confirmed the presence of a 50 × 55-mm mass. The patient was placed on cardiopulmonary bypass. Hypertonic saline solution-soaked sponges were distributed within the pericardial cavity to prevent local invasion of the parasite intraoperatively. Through an incision parallel to the left anterior descending coronary artery, and without opening adjacent cardiac chambers, we aspirated the entire contents of the cyst, removed its germinative membrane, and washed the cavity with 20% hypertonic saline solution. The patient recovered uneventfully. She had begun taking albendazole 5 days preoperatively, and this therapy was continued for 12 weeks postoperatively. In cases of an interventricular cardiac hydatid cyst, the combination of surgical resection, washout of the remaining cavity with hypertonic saline solution, and albendazole therapy typically yields excellent results. PMID:22199447

  10. Design of the PEP-II Interaction Region Septum Quadrupole

    NASA Astrophysics Data System (ADS)

    Osborn, J.; Tanabe, J.; Yee, D.; Younger, F.

    1997-05-01

    The PEP-II QF2 magnet is one of the final focus quadrupoles for the Low-Energy Ring (LER) and utilizes a septum aperture to accommodate the adjacent High-Energy Ring (HER) beamline. The LER lattice design specification calls for an extremely high field quality for this magnet. A conventional water-cooled copper coil and laminated steel core design was selected to allow adjustment in the excitation. The close proximity between the LER and HER beamlines and the required integrated quadrupole strength result in a moderately high current density septum design. The QF2 magnets are imbedded in a confined region at each end of the BaBar detector, thus requiring a small magnet core cross section. Pole face windings are included in the QF2 design to buck the skew octupole term induced by the solenoidal fringe field that leaks out of the detector. Back-leg windings are included to buck a small dipole component induced by the lack of perfect quadrupole symmetry in this septum design. 2D pole contour optimization and 3D end chamfers are used to minimize harmonic errors; a separate permanent-magnet Harmonic Corrector Ring compensates for remaining field errors. The design methods and approach, 2D and 3D analyses, and the resulting expected magnet performance are described in this paper.

  11. The Bivalent Side of the Nucleus Accumbens

    PubMed Central

    Levita, Liat; Hare, Todd A.; Voss, Henning U.; Glover, Gary; Ballon, Douglas J.; Casey, B.J.

    2009-01-01

    An increasing body of evidence suggests that the nucleus accumbens (NAcc) is engaged in both incentive reward processes and in adaptive responses to conditioned and unconditioned aversive stimuli. Yet, it has been argued that NAcc activation to aversive stimuli may be a consequence of the rewarding effects of their termination, i.e., relief. To address this question we used fMRI to delineate brain response to the onset and offset of unpleasant and pleasant auditory stimuli in the absence of learning or motor response. Increased NAcc activity was seen for the onset of both pleasant and unpleasant stimuli. Our results support the expanded bivalent view of NAcc function and call for expansion of current models of NAcc function that are solely focused on reward. PMID:18976715

  12. Advanced laparoscopic surgery for the removal of rectovaginal septum endometriotic or adenomyotic nodules.

    PubMed

    Donnez, J; Nisolle, M

    1995-12-01

    In the pelvis, three different forms of endometriosis (Donnez et al, 1992) must be considered: (1) peritoneal, (2) ovarian, (3) rectovaginal septum. By evaluation of the mitotic activity and the stromal vascularization, we have recently suggested (Nisolle et al, 1993) that peritoneal red lesions were the most aggressive form of the disease and progress to the so-called typical or black lesion, which must be considered as an enclosed implant surrounded by fibrosis. This type of infiltration must be clearly differentiated from the rectovaginal endometriotic nodule. Koninckx (1993) recently described three types of deep-infiltrating endometriosis: deep-infiltrating endometriosis of type I is a rather large lesion in the peritoneal cavity, infiltrating conically with the deeper parts becoming progressively smaller. It has been suggested that this type of endometriosis is caused by infiltration. In type II lesions, the main feature is that bowel is retracted over the lesion which thus becomes deeply situated in the rectovaginal septum although not actually infiltrating it. Type III lesions are the deepest and most severe. They are spherically shaped, situated deep in the rectovaginal septum, often only visible as a small typical lesion at laparoscopy or often not visible at all. This lesion is often more palpable than visible and is acutely tender if the patient is examined at the time of menstruation, and gives rise to severe dyspareunia. In our experience there are two different types of 'deep-infiltrating endometriosis': 1. True deep-infiltrating endometriosis caused by the invasion of a very active peritoneal lesion deep in the retroperitoneal space. In cases of lateral peritoneal invasion, uterosacral ligaments can be involved as well as the anterior wall of the rectosigmoid bowel junction resulting in a retraction, adhesions and secondary obliteration of the cul-de-sac. 2. Pseudo deep-infiltrating endometriosis or adenomyosis of the rectovaginal septum. This

  13. Rapid feedback processing in human nucleus accumbens and motor thalamus.

    PubMed

    Schüller, Thomas; Gruendler, Theo O J; Jocham, Gerhard; Klein, Tilmann A; Timmermann, Lars; Visser-Vandewalle, Veerle; Kuhn, Jens; Ullsperger, Markus

    2015-04-01

    The nucleus accumbens (NAcc) and thalamus are integral parts in models of feedback processing. Deep brain stimulation (DBS) has been successfully employed to alleviate symptoms of psychiatric conditions including obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). Common target structures are the NAcc and the ventral anterior and ventro-lateral nuclei (VA/VL) of the thalamus, for OCD and TS, respectively. The feedback related negativity (FRN) is an event-related potential associated with feedback processing reflecting posterior medial frontal cortex (pMFC) activity. Here we report on three cases where we recorded scalp EEG and local field potentials (LFP) from externalized electrodes located in the NAcc or thalamus (VA/VL) while patients engaged in a modified time estimation task, known to engage feedback processing and elicit the FRN. Additionally, scalp EEG were recorded from 29 healthy participants (HP) engaged in the same task. The signal in all structures (pMFC, NAcc, and thalamus) was differently modulated by positive and negative feedback. LFP activity in the NAcc showed a biphasic time course after positive feedback during the FRN time interval. Negative feedback elicited a much weaker and later response. In the thalamus a monophasic modulation was recorded during the FRN time interval. Again, this modulation was more pronounced after positive performance feedback compared to negative feedback. In channels outside the target area no modulation was observed. The surface-FRN was reliably elicited on a group level in HP and showed no significant difference following negative feedback between patients and HP. German Clinical Trial Register: Neurocognitive specification of dysfunctions within basal ganglia-cortex loops and their therapeutic modulation by deep brain stimulation in patients with obsessive compulsive disorder and Tourette syndrome, http://www.drks.de/DRKS00005316. PMID:25726897

  14. A thalamic input to the nucleus accumbens mediates opiate dependence.

    PubMed

    Zhu, Yingjie; Wienecke, Carl F R; Nachtrab, Gregory; Chen, Xiaoke

    2016-02-11

    Chronic opiate use induces opiate dependence, which is characterized by extremely unpleasant physical and emotional feelings after drug use is terminated. Both the rewarding effects of a drug and the desire to avoid withdrawal symptoms motivate continued drug use, and the nucleus accumbens is important for orchestrating both processes. While multiple inputs to the nucleus accumbens regulate reward, little is known about the nucleus accumbens circuitry underlying withdrawal. Here we identify the paraventricular nucleus of the thalamus as a prominent input to the nucleus accumbens mediating the expression of opiate-withdrawal-induced physical signs and aversive memory. Activity in the paraventricular nucleus of the thalamus to nucleus accumbens pathway is necessary and sufficient to mediate behavioural aversion. Selectively silencing this pathway abolishes aversive symptoms in two different mouse models of opiate withdrawal. Chronic morphine exposure selectively potentiates excitatory transmission between the paraventricular nucleus of the thalamus and D2-receptor-expressing medium spiny neurons via synaptic insertion of GluA2-lacking AMPA receptors. Notably, in vivo optogenetic depotentiation restores normal transmission at these synapses and robustly suppresses morphine withdrawal symptoms. This links morphine-evoked pathway- and cell-type-specific plasticity in the paraventricular nucleus of the thalamus to nucleus accumbens circuit to opiate dependence, and suggests that reprogramming this circuit holds promise for treating opiate addiction. PMID:26840481

  15. Control and readout of the extraction septum of AmPS

    NASA Astrophysics Data System (ADS)

    Vanes, J. T.; Luigjes, G.; Vantrigt, J. H.

    The electronics used for the septum translation-rotation control system and for the control of the 100 kV power supply of the electrostatic septum of the storage ring AmPS (Amsterdam Pulse Stretcher) are described. The translation and rotation of the septum are performed by stepping motors controlled by LVDT's (Linear Variable Differential Transformers), which are controlled by a bitbus module which also controls the high voltage power supply.

  16. Cavum Septum Pellucidum in Retired American Pro-Football Players.

    PubMed

    Gardner, Raquel C; Hess, Christopher P; Brus-Ramer, Marcel; Possin, Katherine L; Cohn-Sheehy, Brendan I; Kramer, Joel H; Berger, Mitchel S; Yaffe, Kristine; Miller, Bruce; Rabinovici, Gil D

    2016-01-01

    Previous studies report that cavum septum pellucidum (CSP) is frequent among athletes with a history of repeated traumatic brain injury (TBI), such as boxers. Few studies of CSP in athletes, however, have assessed detailed features of the septum pellucidum in a case-control fashion. This is important because prevalence of CSP in the general population varies widely (2% to 85%) between studies. Further, rates of CSP among American pro-football players have not been described previously. We sought to characterize MRI features of the septum pellucidum in a series of retired pro-football players with a history of repeated concussive/subconcussive head traumas compared with controls. We retrospectively assessed retired American pro-football players presenting to our memory clinic with cognitive/behavioral symptoms in whom structural MRI was available with slice thickness ≤2 mm (n=17). Each player was matched to a memory clinic control patient with no history of TBI. Scans were interpreted by raters blinded to clinical information and TBI/football history, who measured CSP grade (0-absent, 1-equivocal, 2-mild, 3-moderate, 4-severe) and length according to a standard protocol. Sixteen of 17 (94%) players had a CSP graded ≥2 compared with 3 of 17 (18%) controls. CSP was significantly higher grade (p<0.001) and longer in players than controls (mean length±standard deviation: 10.6 mm±5.4 vs. 1.1 mm±1.3, p<0.001). Among patients presenting to a memory clinic, long high-grade CSP was more frequent in retired pro-football players compared with patients without a history of TBI. PMID:25970145

  17. Management of the lateral walls in crooked nose.

    PubMed

    Seyhan, Ahmet

    2012-07-01

    In crooked noses, the lateral walls are different in shape and symmetry. Although the septum is very important to obtain a straight nose, identical and symmetrical lateral walls are needed for a straight looking nasal dorsum. As well as the septum, lateral walls also contribute in nasal skeletal support and stability. Thus, obtaining identical and symmetrical lateral walls is important. In order to obtain symmetrical and stable lateral walls, the requirements are to equalize the height, to set in a symmetric location and finally to stabilize the symmetry. These requirements must be taken into consideration while performing the steps of rhinoplasty, namely, hump resection, osteotomies and stabilization by spreader grafts or flaps. Here, we describe the management of the lateral walls in crooked nose in 7 cases. PMID:25734053

  18. Echocardiographic Discovery of Doubled Interatrial Septum: An Incidental Finding.

    PubMed

    Kumar, Priya A; Martinelli, Susan M; Kyle, Robert W; Arora, Harendra

    2016-09-01

    A double-walled interatrial septum is a rare congenital cardiac anomaly characterized by a distinct echolucent cavity between the atria formed by 2 separate interatrial septae. It may be a variant of other well-recognized cardiac anomalies such as persistent venous valve of the sinus venosus or cor triatriatum. Although uncommon, it may be associated with thromboembolic disease due to stagnant flow in the septal cavity. Awareness of this rare entity and its clinical significance along with a thorough echocardiographic examination to rule out similarly presenting or coexisting conditions are the key to an accurate diagnosis and appropriate management. PMID:25934559

  19. Glutamic acid decarboxylase isoform distribution in transgenic mouse septum: an anti-GFP immunofluorescence study.

    PubMed

    Verimli, Ural; Sehirli, Umit S

    2016-09-01

    The septum is a basal forebrain region located between the lateral ventricles in rodents. It consists of lateral and medial divisions. Medial septal projections regulate hippocampal theta rhythm whereas lateral septal projections are involved in processes such as affective functions, memory formation, and behavioral responses. Gamma-aminobutyric acidergic neurons of the septal region possess the 65 and 67 isoforms of the enzyme glutamic acid decarboxylase. Although data on the glutamic acid decarboxylase isoform distribution in the septal region generally appears to indicate glutamic acid decarboxylase 67 dominance, different studies have given inconsistent results in this regard. The aim of this study was therefore to obtain information on the distributions of both of these glutamic acid decarboxylase isoforms in the septal region in transgenic mice. Two animal groups of glutamic acid decarboxylase-green fluorescent protein knock-in transgenic mice were utilized in the experiment. Brain sections from the region were taken for anti-green fluorescent protein immunohistochemistry in order to obtain estimated quantitative data on the number of gamma-aminobutyric acidergic neurons. Following the immunohistochemical procedures, the mean numbers of labeled cells in the lateral and medial septal nuclei were obtained for the two isoform groups. Statistical analysis yielded significant results which indicated that the 65 isoform of glutamic acid decarboxylase predominates in both lateral and medial septal nuclei (unpaired two-tailed t-test p < 0.0001 for LS, p < 0.01 for MS). This study is the first to reveal the dominance of glutamic acid decarboxylase isoform 65 in the septal region in glutamic acid decarboxylase-green fluorescent protein transgenic mice. PMID:26643381

  20. Characterizing Septum Inhibition in Mycobacterium tuberculosis for Novel Drug Discovery

    SciTech Connect

    Respicio,L.; Nair, P.; Huang, Q.; Anil, B.; Tracz, S.; Truglio, J.; Kisker, C.; Raleigh, D.; Ojima, I.; et al

    2008-01-01

    A temperature sensitive mutation in the cell division protein FtsZ was used in combination with transcriptional analysis to identify biomarkers for inhibition of septum formation. Crystallography and modeling revealed that the glycine for aspartate substitution at amino acid 210 was located in helix 8 of the protein, adjacent to the T7 synergy loop. To verify the molecular behavior of FtsZD210G, the in vitro activity and structural stability were evaluated as a function of temperature. These analyses confirmed that the FtsZD210G mutant had reduced GTPase and polymerization activity compared to wild-type FtsZ, and CD spectroscopy demonstrated that both FtsZD210G and wild-type FtsZ had similar structure and stability. Significantly, the FtsZD210G merodiploid strain of M. tuberculosis had compromised growth at 37 C, substantiating the suitability of FtsZD210G as a molecular tool for global analysis in response to improper FtsZ polymerization and septum inhibition. Advanced model-based bioinformatics and transcriptional mapping were used to identify high-content multiple features that provide biomarkers for the development of a rational drug screening platform for discovering novel chemotherapeutics that target cell division.

  1. Nasal septum injury in preterm infants using nasal prongs 1

    PubMed Central

    Bonfim, Suely de Fátima Santos Freire; de Vasconcelos, Maria Gorete Lucena; de Sousa, Nayara Francisca Cabral; da Silva, Daiana Vieira Câmara; Leal, Luciana Pedrosa

    2014-01-01

    OBJECTIVE: to assess the incidence and risk factors associated with nasal septum injury in premature infants using reused and new nasal prongs. METHOD: the study was a cohort from an open therapeutic intervention. The sample included 70 infants with a gestational age inferior to 37 weeks, who used nasal prongs and were hospitalized at the neonatal service of a hospital in Recife-PE, in the Northeast of Brazil. The data were collected in patient files through the assessment of the application of the device and of the nasal septum. Multinomial Logistic Regression and Survival analyses were applied. RESULTS: the incidence of nasal injury corresponded to 62.9%. In the multiple analysis, only the length of the infant's treatment was a determinant factor for the occurrence and severity of the injuries. CONCLUSION: the type of nasal prong does not serve as a risk factor for the nasal injury. The high incidence of nasal injury indicates the need to adapt the nursing care with emphasis on prevention. PMID:25493679

  2. Acute Administration of Clozapine and Risperidone Altered Dopamine Metabolism More in Rat Caudate than in Nucleus Accumbens: A Dose-Response Relationship

    PubMed Central

    Batool, Farhat; Haleem, Muhammad A.; Haleem, Darakhshan J.

    2010-01-01

    The present study compares the extrapyramidal and neurochemical effects of clozapine and risperidone in rat caudate (corpus striatum) and nucleus accumbens (ventral striatum) dose-dependently. Animals injected with clozapine (2.5, 5.0 and 10.0 mg/kg IP) or risperidone (1.0, 2.5 and 5.0 mg/kg IP) in acute were sacrificed 1 h later to collect brain samples. Extrapyramidal side effects (EPS) in terms of locomotor activity and catalepsy were monitored in each animal after the drug or vehicle administration. Maximum cataleptic potentials were found only at high doses of clozapine (10.0 mg/kg; 60%) and risperidone (5.0 mg/kg; 100%). Neurochemical estimations were carried out by HPLC-EC. Both drugs at all doses significantly (p<0.01) increased the concentration of homovanillic acid (HVA), a metabolite of DA, in the caudate nucleus and decreased in nucleus accumbens. Levels of Dihydroxyphenylacetic acid (DOPAC) significantly (p<0.01) increased in the caudate by clozapine administration and decreased in the nucleus accumbens by the administration of both drugs in a dose-dependent manner. 5-Hydroxyindoleacetic acid (5-HIAA), the predominant metabolite of serotonin significantly decreased in the caudate and nucleus accumbens in a similar fashion. Levels of tryptophan (TRP) were remained insignificant in caudate and nucleus accumbens by the injections of two drugs. In caudate, clozapine and risperidone administrations significantly (p<0.01) decreased HVA/DA ratio and increased DOPAC/DA ratio in nucleus accumbens at all doses. The findings suggest the evidence for DA/5-HT receptor interaction as an important link in the lower incidence of EPS. The possible role of serotonin1A receptors in the pathophysiology of schizophrenia is also discussed. PMID:21179339

  3. Gene Expression Changes in the Septum: Possible Implications for MicroRNAs in Sculpting the Maternal Brain

    PubMed Central

    Zhao, Changjiu; Saul, Michael C.; Driessen, Terri; Gammie, Stephen C.

    2012-01-01

    The transition from the non-maternal to the maternal state is characterized by a variety of CNS alterations that support the care of offspring. The septum (including lateral and medial portions) is a brain region previously linked to various emotional and motivational processes, including maternal care. In this study, we used microarrays (PLIER algorithm) to examine gene expression changes in the septum of postpartum mice and employed gene set enrichment analysis (GSEA) to identify possible regulators of altered gene expression. Genes of interest identified as differentially regulated with microarray analysis were validated with quantitative real-time PCR. We found that fatty acid binding protein 7 (Fabp7) and galanin (Gal) were downregulated, whereas insulin-like growth factor binding protein 3 (Igfbp3) was upregulated in postpartum mice compared to virgin females. These genes were previously found to be differentially regulated in other brain regions during lactation. We also identified altered expression of novel genes not previously linked to maternal behavior, but that could play a role in postpartum processes, including glutamate-ammonia ligase (Glul) and somatostatin receptor 1 (Sstr1) (both upregulated in postpartum). Genes implicated in metabolism, cell differentiation, or proliferation also exhibited altered expression. Unexpectedly, enrichment analysis revealed a high number of microRNAs, transcription factors, or conserved binding sites (177 with corrected P-value <0.05) that were significantly linked to maternal upregulated genes, while none were linked to downregulated genes. MicroRNAs have been linked to placenta and mammary gland development, but this is the first indication they may also play a key role in sculpting the maternal brain. Together, this study provides new insights into genes (along with possible mechanisms for their regulation) that are involved in septum-mediated adaptations during the postpartum period. PMID:22701680

  4. Electromagnetic field analysis of septum magnet for APS positron accumulator ring

    SciTech Connect

    Yokoi, Toshiaki; Turner, L.R.

    1995-07-01

    This report consists of three parts. The first part describes a numerical analysis method for the electromagnetic field analysis of a septum magnet. A novel improvement to the treatment of exciting currents in the time-domain is proposed. The second part discusses numerical predictions of the electromagnetic characteristics of the APS PAR septum. The time variations of stray field and eddy currents are shown for three magnet designs. The last part explores how decreasing the septum material conductivity affects the stray field. The decrease of conductivity may be caused by an inadequate manufacturing of the septum material. The significance of a high quality septum, or flat interface between copper and iron, is emphasized from a point of view of stray field. An ideal method for joining two different metals without distortion, called HIP (Hot Isostatic Pressing), is introduced and recommended based on the authors` experience.

  5. Cavum Septum Pellucidum in Monozygotic Twins Discordant for Combat Exposure: Relationship to Posttraumatic Stress Disorder

    PubMed Central

    May, Flavia S.; Chen, Q. Cece; Gilbertson, Mark W.; Shenton, Martha E.; Pitman, Roger K.

    2009-01-01

    Background Abnormally large cavum septum pellucidum has been reported in posttraumatic stress disorder; however, the origin of this association is uncertain. Methods We utilized magnetic resonance imaging to measure cavum septum pellucidum in pairs of identical twins discordant for combat exposure in Vietnam. Results Presence of abnormal cavum septum pellucidum was significantly correlated between exposed and unexposed twins, indicating that it is partially determined by heredity and/or shared environment. There was a greater proportion of cavum septum pellucidum in combat-exposed twins with posttraumatic stress disorder and their noncombat-exposed co-twins. Conclusions The presence of abnormally large cavum septum pellucidum is a familial vulnerability factor for posttraumatic stress disorder. PMID:15013837

  6. The role of glutamatergic pathway between septum and hippocampus in the memory formation

    PubMed Central

    Khakpai, Fatemeh; Zarrindast, Mohammad Reza; Nasehi, Mohammad; Haeri-Rohani, Ali; Eidi, Akram

    2013-01-01

    The N-methyl-D-aspartate (NMDA) receptor is a subtype of glutamate receptor that is presented in highest density in the hippocampus and septum. NMDA receptors of the septum and the hippocampus are involved in cognitive performance, especially in learning and memory processes. The septum nucleus and hippocampal formation are two regions of the limbic system. The septum and the hippocampus are anatomically and functionally connected to each other. These areas made the septo-hippocampal and hippocampo-septal pathways, which are implicated in the cognitive processes. The activity of septal and hippocampal neurons is modulated by several neurotransmitters such as glutamate. Thus, changes in the glutamatergic transmission in the septum and hippocampus may influence learning and memory processes in these pathways.

  7. Hemangioma of the Interatrial Septum: CT and MRI Features

    SciTech Connect

    Hrabak-Paar, Maja; Huebner, Marisa; Stern-Padovan, Ranka; Lusic, Mario

    2011-02-15

    Hemangioma of the heart is a rare primary benign tumor mainly appearing as enhancing, homogenous, well-circumscribed mass. We report a case of a 61-year-old asymptomatic woman, whose echocardiography showed a cardiac mass, which was described as the atypical myxoma of the right atrium. For further imaging, contrast-enhanced computed tomography and cardiac magnetic resonance imaging were undertaken, which showed a tumor located in the interatrial septum with imaging characteristics of hemangioma. In the literature, cardiac hemangioma is usually described as an intensely enhancing mass. In our opinion, early peripheral puddling of contrast material with filling in on delayed images is a typical pattern of its enhancement. This characteristic, in addition to high signal intensity on T2-weighted images, allows differentiation of a hemangioma from other benign and malignant tumors.

  8. Ischaemic stroke with intact atrial septum--exclude arteriovenous malformations.

    PubMed

    Doering, Friederike; Eicken, Andreas; Hess, John

    2014-02-01

    A 44-year-old woman was referred to our centre for interventional cardiac catheterisation. The diagnostic work-up after a preceding ischaemic stroke led to the assumption of a patent foramen ovale due to a positive bubble study. Before the planned percutaneous closure of the patent foramen ovale, we performed a second bubble study, which showed an intact atrial septum. However, after two to three heart cycles bubbles could be detected in the left atrium, assuming a right-to-left shunt of an extracardiac origin most likely in the lung. We therefore performed cardiac catheterisation, yielding a pulmonary arteriovenous malformation in the lower lobe of the right lung. This was successfully closed interventionally by placing a Cook coil, as well as several plugs into the malformation and feeding vessels. PMID:23347820

  9. Design, tests and commissioning of the EMMA injection septum

    NASA Astrophysics Data System (ADS)

    Marinov, K.; Clarke, J. A.; Marks, N.; Tzenov, S.

    2013-02-01

    The paper describes the main steps taken during the design and commissioning stages of the EMMA injection and extraction septum magnets. A preliminary analysis of the problem is presented first followed by a discussion of the results obtained through finite element magnetic modeling and design optimization. The measures taken to suppress the stray field generated by the magnet are discussed in detail. Two sets of tests are performed on the magnet: magnetic field measurement resulting in a three-dimensional magnetic field map and measurement of the electron beam bending angle as a function of the magnet current. The values of the effective magnetic length resulting from the two sets of measurement are found to be in excellent agreement.

  10. Excessive disgust caused by brain lesions or temporary inactivations: Mapping hotspots of nucleus accumbens and ventral pallidum

    PubMed Central

    Ho, Chao-Yi; Berridge, Kent C.

    2014-01-01

    Disgust is a prototypical type of negative affect. In animal models of excessive disgust, only a few brain sites are known in which localized dysfunction (lesions or neural inactivations) can induce intense ‘disgust reactions’ (e.g., gapes) to a normally pleasant sensation such as sweetness. Here we aimed to map forebrain candidates more precisely to identify where either local neuronal damage (excitotoxin lesions) or local pharmacological inactivation (muscimol-baclofen microinjections) caused rats to emit excessive sensory disgust reactions to sucrose. Our study compared subregions of nucleus accumbens shell, ventral pallidum, lateral hypothalamus and adjacent extended amygdala. Results indicated the posterior half of ventral pallidum to be the only forebrain site where intense sensory disgust gapes to sucrose were induced by both lesions and temporary inactivations (this site was previously identified as a hedonic hotspot for enhancements of sweetness ‘liking’). By comparison, for the nucleus accumbens, temporary GABA inactivations in the caudal half of the medial shell also generated sensory disgust but lesions never did at any site. Further, even inactivations failed to induce disgust in the rostral half of accumbens shell (which also contains a hedonic hotspot). In other structures, neither lesions nor inactivations induced disgust as long as the posterior ventral pallidum remained spared. We conclude that the posterior ventral pallidum is an especially crucial hotspot for producing excessive sensory disgust by local pharmacological/lesion dysfunction. By comparison, the nucleus accumbens appears to segregate sites for pharmacological disgust induction and hedonic enhancement into separate posterior versus rostral halves of medial shell. PMID:25229197

  11. Real-Time Dopamine Efflux in the Nucleus Accumbens Core During Pavlovian Conditioning

    PubMed Central

    Sunsay, Ceyhun; Rebec, George V.

    2009-01-01

    To assess the role of dopamine input to the nucleus accumbens core in anticipatory learning, fast-scan cyclic voltammetry was combined with appetitive Pavlovian conditioning. One group of rats (Paired) received 16 tone-food pairings for at least four daily sessions while the control group (Unpaired) received the same number of unpaired tone and food presentations. Both groups showed transient dopamine responses during food presentation throughout training, confirming dopamine involvement in reward processing. Only the Paired Group, however, showed consistently timed dopamine transients during the 10-s tone presentation. Transients first appeared near the end of the tone period as each animal acquired the tone-food association and then occurred progressively sooner on subsequent sessions. Later sessions also revealed a consistently timed dopamine response soon after food delivery in Paired animals. Collectively, these results implicate phasic dopamine release in the acquisition of Pavlovian learning and also suggest an early dopamine response to the unconditioned stimulus as training continues. PMID:18410174

  12. Adhesio interthalamica and cavum septum pellucidum in mesial temporal lobe epilepsy.

    PubMed

    Trzesniak, Clarissa; Linares, Ila M; Coimbra, Érica R; Júnior, Alexandre Veriano; Velasco, Tonicarlo R; Santos, Antonio C; Hallak, Jaime E; Sakamoto, Americo C; Busatto, Geraldo F; Crippa, José A

    2016-09-01

    The absence of the adhesio interthalamica (AI; also called interthalamic adhesion or massa intermedia) and the presence of a large cavum septum pellucidum (CSP) later in life have been related to neurodevelopmental alterations and have not been systematically investigated in epilepsy to date. This study carried out a MRI evaluation of the AI and CSP in a large sample with mesial temporal lobe epilepsy (MTLE). A total of 179 patients, classified according to the side of the epileptogenic focus, and 156 age- and sex-balanced healthy controls were assessed. Between-group comparisons of the prevalence and length of both AI and CSP were conducted. Neuropsychological assessments were also performed in 160 MTLE patients. The patients exhibited reduction in the AI prevalence (P < 0.05; FDR-uncorrected) and length (P < 0.05; FDR-corrected) when compared to controls. Patients without AI showed lower scores in a proportion of neuropsychological tests than patients with AI. No CSP differences were found between MTLE patients and controls. These results support that AI anomalies have clinical significance in MTLE, as well as indicate that neurodevelopmental alterations may be implicated in this disorder. PMID:26497889

  13. The 80 kV electrostatic wire septum for AmPS

    NASA Astrophysics Data System (ADS)

    Vanderlinden, A.; Bijleveld, J. H. M.; Rookhuizen, H. Boer; Bruinsma, P. J. T.; Heine, E.; Lassing, P.; Prins, E.

    The characteristics of the wire septum for the Amsterdam Pulse Stretcher (AmPS) are summarized. In the extraction process of the AmPS the extracted beam is intercepted from the circulating beam by the 1 m long electrostatic wire septum. For a bending angle of 4.4 mrad, the maximum anode voltage is 80 kV. The system developed consists of a wire spacing of 0.65 mm between tungsten wires of 50 micrometers diameter. Stainless steel spring wires, bent in a half cylindrical carrier, stretch the septum wires two by two. Prototype tests were successful up to an anode voltage of 120 kV.

  14. Individual Differences in Ethanol Locomotor Sensitization Are Associated with Dopamine D1 Receptor Intra-Cellular Signaling of DARPP-32 in the Nucleus Accumbens

    PubMed Central

    Abrahao, Karina Possa; Oliveira Goeldner, Francine; Souza-Formigoni, Maria Lucia Oliveira

    2014-01-01

    In mice there are clear individual differences in the development of behavioral sensitization to ethanol, a progressive potentiation of its psychomotor stimulant effect. Variability in the behavioral responses to ethanol has been associated with alcohol preference. Here we investigated if the functional hyperresponsiveness of D1 receptors observed in ethanol sensitized mice leads to an increased activation of DARPP-32, a central regulatory protein in medium spiny neurons, in the nucleus accumbens - a brain region known to play a role in drug reinforcement. Swiss Webster mice received ethanol (2.2 g/kg/day) or saline i.p. administrations for 21 days and were weekly evaluated regarding their locomotor activity. From those treated with ethanol, the 33% with the highest levels of locomotor activity were classified as “sensitized” and the 33% with the lowest levels as "non-sensitized”. The latter presented similar locomotor levels to those of saline-treated mice. Different subgroups of mice received intra-accumbens administrations of saline and, 48 h later, SKF-38393, D1 receptor agonist 0.1 or 1 µg/side. Indeed, sensitized mice presented functional hyperresponsiveness of D1 receptors in the accumbens. Two weeks following the ethanol treatment, other subgroups received systemic saline or SKF 10 mg/kg, 20 min before the euthanasia. The nucleus accumbens were dissected for the Western Blot analyses of total DARPP-32 and phospho-Thr34-DARPP-32 expression. D1 receptor activation induced higher phospho-Thr34-DARPP-32 expression in sensitized mice than in non-sensitized or saline. The functionally hyperresponsiveness of D1 receptors in the nucleus accumbens is associated with an increased phospho-Thr34-DARPP-32 expression after D1 receptor activation. These data suggest that an enduring increase in the sensitivity of the dopamine D1 receptor intracellular pathway sensitivity represents a neurobiological correlate associated with the development of locomotor

  15. Hypoplastic left heart syndrome with intact atrial septum: case report

    PubMed Central

    Cester, Maddalena; Nanhorngue, Kimta; Pascoli, Irene; Garofano, Greta; Surico, Nicola; Paternoster, Delia Maria

    2007-01-01

    Summary Objectives Hypoplastic left heart syndrome (HLHS) with an intact atrial septum (IAS) is a rare finding, reported in only 1% of pathologic specimens with hypoplasia of the aortic tract complex. In newborns with left heart obstruction, the existence of an interatrial communication is very important for oxygenated blood to be distributed to the body and to prevent pulmonary congestion. The ability to predict prenatally restriction of the atrial defect may allow earlier surgery to be planned. Methods We report a case of prenatal diagnosis of HLHS with a complete premature closure of the foramen ovale that was not detected by prenatal echocardiography. Results and conclusion The management of neonates with HLHS in the first days of life is crucial to the results of the first stage of the Norwood procedure. We suggest that delivery of the mother close to surgical centre and avoiding neonatal transfer improve the results, but stabilisation with prostaglandins and balancing of the systemic and pulmonary resistances are also important. A restrictive or closed atrial septal defect may contribute to haemodynamic instability in the first days of life. The ability to predict this complication prenatally may help in the immediate postnatal management of the affected infant. PMID:22470823

  16. Deviated nasal septum hinders intranasal sprays: A computer simulation study

    PubMed Central

    Frank, Dennis O.; Kimbell, Julia S.; Cannon, Daniel; Pawar, Sachin S.; Rhee, John S.

    2013-01-01

    Background This study investigates how deviated nasal septum affects the quantity and distribution of spray particles, and examines the effects of inspiratory airflow and head position on particle transport. Methods Deposition of spray particles was analysed using a three-dimensional computational fluid dynamics model created from a computed tomography scan of a human nose with leftward septal deviation and a right inferior turbinate hypertrophy. Five simulations were conducted using Fluent™ software, with particle sizes ranging from 20-110μm, a spray speed of 3m/s, plume angle of 68°, and with steady state inspiratory airflow either present (15.7L/min) or absent at varying head positions. Results With inspiratory airflow present, posterior deposition on the obstructed side was approximately four times less than the contralateral side, regardless of head position, and was statistically significant (p<0.05). When airflow was absent, predicted deposition beyond the nasal valve on the left and right sides were between 16% and 69% lower and positively influenced by a dependent head position. Conclusions Simulations predicted that septal deviation significantly diminished drug delivery on the obstructed side. Furthermore, increased particle penetration was associated with presence of nasal airflow. Head position is an important factor in particle deposition patterns when inspiratory airflow is absent. PMID:22888490

  17. The case of a cyst hydatid localized within the interatrial septum.

    PubMed

    Karabay, Ozalp; Onen, Ahmet; Yildiz, Fidan; Yilmaz, Erkan; Erdal, Cenk A; Sanli, Aydin; Kilci, Göksel; Algin, Ibrahim; Itil, Oya; Açikel, Unal

    2004-07-01

    The ratio of cardiac involvement of Echinoccocus granulosus is 0.02-2% and although seen rarely, involvement of the interatrial septum has also been reported in the published literature. The present case was a 19-year-old male university student admitted to hospital with complaints of headache and dizziness. Computerized tomography of the cranium revealed a cystic mass located at the frontal region and enucleation of the cyst was performed during surgery. A cystic lesion 5 x 4 cm in size was detected within the interatrial septum on two-dimensional transthoracic echocardiography during the postoperative period and the patient was referred to our clinic. Open heart surgery was performed and a hydatid cyst that involved the interatrial septum was enucleated. The cyst wall was sutured to the interatrial septum. No complications developed during the postoperative period. The patient was discharged on the fifth day of hospitalization and medical therapy was started with albendazole. PMID:15353883

  18. Umbilical cyst due to patent urachus in a fetus with complete urorectal septum malformation sequence

    PubMed Central

    Kodandapani, Sreelakshmi; Shetty, Jyothi; Kumar, Pratap; Girisha, Katta M.

    2012-01-01

    Urorectal septum malformation sequence is a sporadic malformation due to failure of septation of primitive cloaca with no anal opening. Umbilical cyst can be associated with chromosomal aneuploidy such as trisomy 18 or trisomy 13. We report on a fetus with complete urorectal septum malformation sequence with an umbilical cyst resulting from a patent urachus and with meconium as its content. This report adds to the variety of the causes of umbilical cyst and the spectrum of consequences of urorectal septal defect.

  19. [Septum formation and cytomorphogenesis in Micrasterias denticulata after the action of ethanol].

    PubMed

    Kiermayer, O

    1966-12-01

    Cells of Micrasterias denticulata were treated with ethanol during the stage of septum formation. After this, cells were transferred into nutrient solutions and here the further development was studied. The following effects were observed: 1. A one-hour treatment of the cells with 10% ethanol lead to an irreversible inhibition of the septum growth. Because cell-elongation (bulbus-formation) remained uneffected, binuclear "double-cells" with a teratogenic "middle section" were formed. 2. The degree of differentiation of this "middle section" depends on the extent of septum formation. Thus a direct relationship between the degree of differentiation of the "middle section" and septum formation exists. 3. The experiments seem to indicate that the septum carries the prospective pattern of differentiation in a template-like manner. This fact is in good agreement with the hypothesis on a "septum-initial-pattern" in Micrasterias which we recently advanced. 4. It could be observed that in most cases the teratogenic "middle section" forms additional 3-dimensional lobes. A remarkable relationship exists between the differentiation of these lobes and the degree of lobe formation of the "middle section". PMID:24554105

  20. The contractile ring coordinates curvature-dependent septum assembly during fission yeast cytokinesis

    PubMed Central

    Zhou, Zhou; Munteanu, Emilia Laura; He, Jun; Ursell, Tristan; Bathe, Mark; Huang, Kerwyn Casey; Chang, Fred

    2015-01-01

    The functions of the actin-myosin–based contractile ring in cytokinesis remain to be elucidated. Recent findings show that in the fission yeast Schizosaccharomyces pombe, cleavage furrow ingression is driven by polymerization of cell wall fibers outside the plasma membrane, not by the contractile ring. Here we show that one function of the ring is to spatially coordinate septum cell wall assembly. We develop an improved method for live-cell imaging of the division apparatus by orienting the rod-shaped cells vertically using microfabricated wells. We observe that the septum hole and ring are circular and centered in wild-type cells and that in the absence of a functional ring, the septum continues to ingress but in a disorganized and asymmetric manner. By manipulating the cleavage furrow into different shapes, we show that the ring promotes local septum growth in a curvature-dependent manner, allowing even a misshapen septum to grow into a more regular shape. This curvature-dependent growth suggests a model in which contractile forces of the ring shape the septum cell wall by stimulating the cell wall machinery in a mechanosensitive manner. Mechanical regulation of the cell wall assembly may have general relevance to the morphogenesis of walled cells. PMID:25355954

  1. Successful Repair of Hypoplastic Left Heart Syndrome With Intact Atrial Septum, Congenital Diaphragm Hernia, and Anomalous Origin of Coronary Artery: Defying the Odds.

    PubMed

    Sathanandam, Shyam; Kumar, T K Susheel; Feliz, Alexander; Knott-Craig, Christopher J

    2016-07-01

    We report a case of an infant who was postnatally diagnosed with hypoplastic left heart syndrome and an intact atrial septum who underwent emergent atrial decompression followed by the Norwood operation. She was also found to have a congenital diaphragmatic hernia on the left side and a congenital eventration of the right diaphragm, both requiring surgical repair. She was later found to have an anomalous origin of the left circumflex coronary artery from the right pulmonary artery that was ligated at the time of the bilateral bidirectional Glenn operation. She is currently thriving at home, defying all odds. PMID:27343534

  2. Effects of systemic L-tyrosine on dopamine release from rat corpus striatum and nucleus accumbens

    NASA Technical Reports Server (NTRS)

    During, Matthew J.; Acworth, Ian N.; Wurtman, Richard J.

    1988-01-01

    Intracerebral dialysis was used to monitor extracellular fluid from rat striatum and nucleus accumbens following the intraperitoneal administration of tyrosine. Dopamine concentrations in dialysates from both the striatum and the nucleus accumbens increased significantly in response to the tyrosine. The magnitude of the tyrosine effect was greater in the nucleus accumbens than in the striatum. Hence, mesolimbic dopaminergic neurons may be especially responsive to precursor availability.

  3. Left nucleus accumbens atrophy in deficit schizophrenia: A preliminary study.

    PubMed

    De Rossi, Pietro; Dacquino, Claudia; Piras, Fabrizio; Caltagirone, Carlo; Spalletta, Gianfranco

    2016-08-30

    A question that remains to be answered is whether schizophrenia can be characterized by a single etiopathophysiology or whether separate sub-syndromes should be differentiated to define specific mechanisms for each sub-type. Individuals affected by the deficit subtype of schizophrenia (DSZ) display avolitional/amotivational features that respond poorly to conventional treatments. Characterizing DSZ from a neuroanatomical point of view may help clarify this issue and develop new treatment strategies. To determine if DSZ is associated with structural alterations in specific deep grey matter structures linked to its key clinical features, 22 DSZ patients, 22 non-deficit schizophrenia (NDSZ) patients and 22 healthy controls (HC) were recruited for a case-control cross-sectional study. High-resolution magnetic resonance imaging was performed in all subjects and volumes of deep grey matter structures were measured using FreeSurfer. DSZ patients displayed smaller left accumbens volumes compared to both NDSZ patients and HC. Moreover, age and duration of illness were significantly associated with lower volume of the left accumbens in DSZ but not in NDSZ. Findings indicate that DSZ is associated with lower volume of the nucleus accumbens in the dominant hemisphere. This is consistent with the psychopathological features and functional impairments present in DSZ and thus indicates a potential mechanism. PMID:27322868

  4. Recognition of Chewing Behavior from Electroencephalogram Recorded in the Rat's Nucleus Accumbens.

    PubMed

    Shao, Xiaozhuo; Zhang, Hengyi; Zheng, Xiaoxiang

    2005-01-01

    Nucleus accumbens is used to be considered as the interface to motor nerve system. In this paper, our object is to study the relationship between the electro-activity of neurons in nucleus accumbens and the rat-behavior. We recorded neurons action potentials with multichannel microelectrodes, which were chronically implanted in a rat's nucleus accumbens, during rats-chewing behavior. Through digital signal processing, we found significant features associated with the chewing activity and we could recognize the chewing behavior easily from the electroencephalogram with these features. This study suggests that neurons action potentials in a nucleus accumbens are activated by specific animal actions. PMID:17282644

  5. Variation in the Developmental and Morphological Interaction Between the Nasal Septum and Facial Skeleton.

    PubMed

    Foster, Austin; Holton, Nathan

    2016-06-01

    While the nasal septum exerts a morphogenetic influence on the facial skeleton, there is evidence that this relationship is highly variable. To better appreciate the precise role of the septum, it is important understand the variable interaction between the septum and surrounding skeleton during ontogeny. Here we analyzed nasal septal and facial skeletal postnatal phenotypic variation using cross-sectional samples of C3H/HeJ and C57BL/6J mice. Initial observations indicated between-strain variation in the magnitude of septal deviation, suggesting differences in septal and facial skeletal interaction. We examined whether variation in septal deviation is due to ontogenetic differences in septal size, or whether variation in facial skeletal growth imposes spatial constraints on the septum. Using microCT we quantified septal size and deviation, and collected coordinate landmark data, which we analyzed using geometric morphometrics. C3H/HeJ mice were significantly more deviated than C57BL/6J during development. We found no differences in septal size between the two strains. However, while both strains exhibited an ontogenetic increase in snout length, C3H/HeJ mice exhibited a non-allometric reduction in nasal bone length. This appears to be influenced by between-strain variation in the spatial relationship between the nasal septum and nasofrontal suture. Unlike C57BL/6J mice, the C3H/HeJ nasal septum is positioned anterior to the nasofrontal suture potentially limiting an early direct influence of septal growth (e.g., through interstitial expansion) on sutural growth. Ultimately, our results underscore that while the septum is a key facial growth center, its precise influence on facial growth varies even in narrow morphological and taxonomic ranges. Anat Rec, 299:730-740, 2016. © 2016 Wiley Periodicals, Inc. PMID:26940849

  6. Formation of the central canal and dorsal glial septum in the spinal cord of the domestic cat.

    PubMed Central

    Böhme, G

    1988-01-01

    Development of the neural tube results in a relative reduction of its lumen accompanied by an increasing thickness of its wall. The central canal measures only about one fifth of that of the former neural canal. This has been said to be the result of an obliteration or fusion of a part of the lumen. This transformation of the central canal takes place between fetal days 28 and 34 in the cat and is characterised by an elongation and shifting of the dorsal ependymal matrix cells and by an apposition of the lateral walls in the same region. It is suggested that the increase in size of the dorsal funiculi causes the elongation of the ependymal cells, the basal processes of which remain to form the dorsal glial septum. The proliferation of neurons and the resultant growth of the dorsal grey horns is believed to be responsible for the narrowing of the lumen. The lumen-contacting matrix cells are displaced from the former surface. These 'blast' cells develop into neurons or glial cells. Until two or three months after birth there is a small wedge-shaped area in the dorsal wall of the central canal which consists of fetal matrix cells with long tapering basal processes extending into the glial septum. After this date the matrix is exhausted and the ependyma forms the complete lining of the surface of the central canal. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 11 Fig. 12 PMID:3248971

  7. The cdc7 protein kinase is a dosage dependent regulator of septum formation in fission yeast.

    PubMed Central

    Fankhauser, C; Simanis, V

    1994-01-01

    Mutation of the Schizosaccharomyces pombe cdc7 gene prevents formation of the division septum and cytokinesis. We have cloned the cdc7 gene and show that it encodes a protein kinase which is essential for cell division. In the absence of cdc7 function, spore germination, DNA synthesis and mitosis are unaffected, but cells are unable to initiate formation of the division septum. Overexpression of p120cdc7 causes cell cycle arrest; cells complete mitosis and then undergo multiple rounds of septum formation without cell cleavage. This phenotype, which is similar to that resulting from inactivation of cdc16 protein, requires the kinase activity of p120cdc7. Mutations inactivating the early septation gene, cdc11, suppress the formation of multiple septa and allow cells to proliferate normally. If formation of the division septum is prevented by inactivation of either cdc14 or cdc15, p120cdc7 overproduction does not interfere with other events in the mitotic cell cycle. Septation is not induced by overexpression of p120cdc7 in G2 arrested cells, indicating that it does not bypass the normal dependency of septation upon initiation of mitosis. These findings indicate that the p120cdc7 protein kinase plays a key role in initiation of septum formation and cytokinesis in fission yeast and suggest that p120cdc7 interacts with the cdc11 protein in the control of septation. Images PMID:8039497

  8. Characterization of a folate-induced hypermotility response after bilateral injection into the rat nucleus accumbens

    SciTech Connect

    Stephens, R.L. Jr.

    1986-01-01

    The objective of these studies was to pharmacologically characterize the mechanism responsible for a folate-induced stimulation of locomotor activity in rats after bilateral injection into the nucleus accumbens region of the brain. Folic acid (FA) and 5-formyltetrahydrofolic acid (FTHF) produced this hypermotility response after intra-accumbens injection, while other reduced folic acid derivatives dihydrofolic acid, tetrahydrofolic acid, and 5-methyltetrahydrofolic acid were ineffective. Studies were designed to determine the role of catecholamines in the nucleus accumbens in the folate-induced hypermotility response. The findings suggest that the folate-induced response is dependent on intact neuronal dopamine stores, and is mediated by stimulation of dopamine receptors of the nucleus accumbens. However the folates do not appear to enhance dopaminergic neutransmission. Thus, FA and FTHF were inefficient at 1 mM concentrations in stimulating /sup 3/H-dopamine release from /sup 3/H-dopamine preloaded nucleus accumbens slices or dopamine from endogenous stores. Pteroic acid, the chemical precursor of folic acid which lacks the glutamate moiety, was ineffective in producing a stimulation of locomotor activity after intra-accumbens injection. Since glutamate is an excitatory amino acid (EAA), compounds characterized as EAA receptor antagonists were utilized to determine if the folate-induced hypermotility response is mediated by activation of EAA receptors in the nucleus accumbens. These results suggest that activation of quisqualate receptors of the nucleus accumbens may mediate the folate-induced hypermotility response.

  9. Giant cardiac hydatid cyst in the interventricular septum protruding to right ventricular epicardium☆

    PubMed Central

    Besir, Yuksel; Gucu, Arif; Surer, Suleyman; Rodoplu, Orhan; Melek, Mehmet; Tetik, Omer

    2013-01-01

    Cardiac hydatid cyst is a rare condition, and the location of a hydatid cyst in the interventricular septum is exceptional. A 54-year-old female was admitted to our hospital with complaints of chest pain, shortness of breath and malaise. Transthoracic echocardiography defined a cystic mass lesion of 50 × 59 mm originating from apex of the heart protruding into and compressing the interventricular septum. The cyst was excised surgically and the patient was discharged on the 8th postoperative day without symptoms. In our case, localization of the cystic mass was within interventricular septum which is an uncommon site. It limited both ventricular volumes significantly. In addition, this cyst was extensively protruding to the right ventricular epicardium. PMID:23438618

  10. DC septum magnets for the damping rings of the SLC SLAC Linear Collider

    SciTech Connect

    Bijleveld, J.; Peterson, J.M.; Jensen, D.

    1986-07-01

    The injection/extraction systems of the 1.21 GeV Stanford Linear Collider (SLC) damping rings uses four pairs of water cooled septum magnets. Each pair consists of a thin-septum, low-field (3 mm, 3 kilogauss) magnet plus a thick-septum, high-field (12 mm, 8 kilogauss) model. In the latest design cooling reliability was improved by using stainless-steel tubing imbedded in the copper. The operating current in each is 2600 amperes, at a density of up to 120 amperes per mmS. Plasma-sprayed alumina is used to provide electrical insulation. The magnet system is compatible with 10 Z torr ultra-high vacuum. The magnet design, fabrication, and measurements are described.

  11. Upflow bioreactor having a septum and an auger and drive assembly

    DOEpatents

    Hansen, Carl S.; Hansen, Conly L.

    2007-11-06

    An upflow bioreactor includes a vessel having an inlet and an outlet configured for upflow operation. A septum is positioned within the vessel and defines a lower chamber and an upper chamber. The septum includes an aperture that provides fluid communication between the upper chamber and lower chamber. The bioreactor also includes an auger positioned in the aperture of the septum. The vessel includes an opening in the top for receiving the auger. The auger extends from a drive housing, which is position over the opening and provides a seal around the opening. The drive housing is adjustable relative to the vessel. The position of the auger in the aperture can be adjusted by adjusting the drive housing relative to the vessel. The auger adjustment mechanism allows the auger to be accurately positioned within the aperture. The drive housing can also include a fluid to provide an additional seal around the shaft of the auger.

  12. Laser reshaping of nasal septum cartilage: clinical results for 40 patients

    NASA Astrophysics Data System (ADS)

    Sobol, Emil N.; Sviridov, Alexander P.; Bagratashvili, Victor N.; Omelchenko, Alexander I.; Ovchinnikov, Yuriy M.; Shekhter, Anatoliy B.; Svistushkin, Valeriy M.; Shinaev, Alexander N.

    2000-05-01

    Clinical results on sparing laser reshaping of nasal septum cartilage are reported for the first time. Forty patients have been treated with holmium laser to correct a deformed cartilage. The laser reshaping is a bloodless, painless procedure which takes few minutes to straighten nasal septum. The stability of the new shape and possible side effects have been examined during twelve months. The headache and other negative symptoms have disappeared, as a result of laser treatment for the most of patients. Rhinoscopic examination show an excellent long-term reshaping effects for nasal septum of 23 patients, and, also, good results for other 12 patients. For 5 patients only a little effect takes place. Our rhinomanometric examinations demonstrate a pronounced improvement of the breathing for 35 patients. No visible undesirable side effects were observed for all patients underwent to laser reshaping procedure.

  13. Performance improvement of an extraction Lambertson septum magnet in the SNS accumulator ring

    SciTech Connect

    Wang, Jian-Guang

    2009-04-01

    The SNS ring Extraction Lambertson Septum magnet contains a strong skew quadrupole term, which has been identified as the source of causing a beam profile distortion on the target. We have performed 3D computer simulations to study the magnetic field quality in the magnet. The skew quad term is computed with different methods in simulations and is compared to measurement data. The origin of the large skew quad term is thoroughly investigated. The remedy for minimizing the skew quad term by modifying the magnet is proposed. Particle tracking is performed to verify the beam profile evolution through the existing and modified septum. The magnetic interference to the septum performance from an adjacent quadrupole is also assessed.

  14. Characterization of Cognitive Deficits in Rats Overexpressing Human Alpha-Synuclein in the Ventral Tegmental Area and Medial Septum Using Recombinant Adeno-Associated Viral Vectors

    PubMed Central

    Hall, Hélène; Jewett, Michael; Landeck, Natalie; Nilsson, Nathalie; Schagerlöf, Ulrika; Leanza, Giampiero; Kirik, Deniz

    2013-01-01

    Intraneuronal inclusions containing alpha-synuclein (a-syn) constitute one of the pathological hallmarks of Parkinson's disease (PD) and are accompanied by severe neurodegeneration of A9 dopaminergic neurons located in the substantia nigra. Although to a lesser extent, A10 dopaminergic neurons are also affected. Neurodegeneration of other neuronal populations, such as the cholinergic, serotonergic and noradrenergic cell groups, has also been documented in PD patients. Studies in human post-mortem PD brains and in rodent models suggest that deficits in cholinergic and dopaminergic systems may be associated with the cognitive impairment seen in this disease. Here, we investigated the consequences of targeted overexpression of a-syn in the mesocorticolimbic dopaminergic and septohippocampal cholinergic pathways. Rats were injected with recombinant adeno-associated viral vectors encoding for either human wild-type a-syn or green fluorescent protein (GFP) in the ventral tegmental area and the medial septum/vertical limb of the diagonal band of Broca, two regions rich in dopaminergic and cholinergic neurons, respectively. Histopathological analysis showed widespread insoluble a-syn positive inclusions in all major projections areas of the targeted nuclei, including the hippocampus, neocortex, nucleus accumbens and anteromedial striatum. In addition, the rats overexpressing human a-syn displayed an abnormal locomotor response to apomorphine injection and exhibited spatial learning and memory deficits in the Morris water maze task, in the absence of obvious spontaneous locomotor impairment. As losses in dopaminergic and cholinergic immunoreactivity in both the GFP and a-syn expressing animals were mild-to-moderate and did not differ from each other, the behavioral impairments seen in the a-syn overexpressing animals appear to be determined by the long term persisting neuropathology in the surviving neurons rather than by neurodegeneration. PMID:23705016

  15. Top-down-directed synchrony from medial frontal cortex to nucleus accumbens during reward anticipation.

    PubMed

    Cohen, Michael X; Bour, Lo; Mantione, Mariska; Figee, Martijn; Vink, Matthijs; Tijssen, Marina A J; van Rootselaar, Anne-Fleur; van den Munckhof, Pepijn; Schuurman, P Richard; Denys, Damiaan

    2012-01-01

    The nucleus accumbens and medial frontal cortex (MFC) are part of a loop involved in modulating behavior according to anticipated rewards. However, the precise temporal landscape of their electrophysiological interactions in humans remains unknown because it is not possible to record neural activity from the nucleus accumbens using noninvasive techniques. We recorded electrophysiological activity simultaneously from the nucleus accumbens and cortex (via surface EEG) in humans who had electrodes implanted as part of deep-brain-stimulation treatment for obsessive-compulsive disorder. Patients performed a simple reward motivation task previously shown to activate the ventral striatum. Spectral Granger causality analyses were applied to dissociate "top-down" (cortex → nucleus accumbens)- from "bottom-up" (nucleus accumbens → cortex)-directed synchronization (functional connectivity). "Top-down"-directed synchrony from cortex to nucleus accumbens was maximal over medial frontal sites and was significantly stronger when rewards were anticipated. These findings provide direct electrophysiological evidence for a role of the MFC in modulating nucleus accumbens reward-related processing and may be relevant to understanding the mechanisms of deep-brain stimulation and its beneficial effects on psychiatric conditions. PMID:21547982

  16. Cortical drive of low-frequency oscillations in the human nucleus accumbens during action selection

    PubMed Central

    Litvak, Vladimir; Rutledge, Robb B.; Zaehle, Tino; Schmitt, Friedhelm C.; Voges, Jürgen; Heinze, Hans-Jochen; Dolan, Raymond J.

    2015-01-01

    The nucleus accumbens is thought to contribute to action selection by integrating behaviorally relevant information from multiple regions, including prefrontal cortex. Studies in rodents suggest that information flow to the nucleus accumbens may be regulated via task-dependent oscillatory coupling between regions. During instrumental behavior, local field potentials (LFP) in the rat nucleus accumbens and prefrontal cortex are coupled at delta frequencies (Gruber AJ, Hussain RJ, O'Donnell P. PLoS One 4: e5062, 2009), possibly mediating suppression of afferent input from other areas and thereby supporting cortical control (Calhoon GG, O'Donnell P. Neuron 78: 181–190, 2013). In this report, we demonstrate low-frequency cortico-accumbens coupling in humans, both at rest and during a decision-making task. We recorded LFP from the nucleus accumbens in six epilepsy patients who underwent implantation of deep brain stimulation electrodes. All patients showed significant coherence and phase-synchronization between LFP and surface EEG at delta and low theta frequencies. Although the direction of this coupling as indexed by Granger causality varied between subjects in the resting-state data, all patients showed a cortical drive of the nucleus accumbens during action selection in a decision-making task. In three patients this was accompanied by a significant coherence increase over baseline. Our results suggest that low-frequency cortico-accumbens coupling represents a highly conserved regulatory mechanism for action selection. PMID:25878159

  17. The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis.

    PubMed

    Scofield, M D; Heinsbroek, J A; Gipson, C D; Kupchik, Y M; Spencer, S; Smith, A C W; Roberts-Wolfe, D; Kalivas, P W

    2016-07-01

    The nucleus accumbens is a major input structure of the basal ganglia and integrates information from cortical and limbic structures to mediate goal-directed behaviors. Chronic exposure to several classes of drugs of abuse disrupts plasticity in this region, allowing drug-associated cues to engender a pathologic motivation for drug seeking. A number of alterations in glutamatergic transmission occur within the nucleus accumbens after withdrawal from chronic drug exposure. These drug-induced neuroadaptations serve as the molecular basis for relapse vulnerability. In this review, we focus on the role that glutamate signal transduction in the nucleus accumbens plays in addiction-related behaviors. First, we explore the nucleus accumbens, including the cell types and neuronal populations present as well as afferent and efferent connections. Next we discuss rodent models of addiction and assess the viability of these models for testing candidate pharmacotherapies for the prevention of relapse. Then we provide a review of the literature describing how synaptic plasticity in the accumbens is altered after exposure to drugs of abuse and withdrawal and also how pharmacological manipulation of glutamate systems in the accumbens can inhibit drug seeking in the laboratory setting. Finally, we examine results from clinical trials in which pharmacotherapies designed to manipulate glutamate systems have been effective in treating relapse in human patients. Further elucidation of how drugs of abuse alter glutamatergic plasticity within the accumbens will be necessary for the development of new therapeutics for the treatment of addiction across all classes of addictive substances. PMID:27363441

  18. Normal development of the muscular region of the interventricular septum. II. The importance of myocardial proliferation.

    PubMed

    Contreras-Ramos, A; Sánchez-Gómez, C; Fierro-Pastrana, R; González-Márquez, H; Acosta-Vazquez, F; Arellano-Galindo, J

    2009-06-01

    In a first paper, we concluded that the muscular region of the interventricular septum is developed by the trabecular branches and showed evidence that the developing interventricular septum elongates in a direction opposite to that of atria. Nevertheless, to date the literature is lacking precise information on the importance of myocardial proliferation not only in this process but also in the morphogenesis of the ventricular cavities. The aim of this study was to determine the spatial and temporal distribution of high-intensity foci of cycling myocytes in the ventricular region of the heart of chicken embryos during cardiac septation. Histological studies, detection of the proliferating cell nuclear antigen by light and confocal microscopy and flow cytometric analysis were carried out. The results corroborate that the developing interventricular septum grows in a direction opposite to that of atria. A remoulding mechanism that results in fenestrated trabecular sheets and trabecular branching is discussed. Our findings allowed us to summarize the normal morphogenesis of the muscular region of the interventricular septum in a way that is different from that suggested by other researchers. PMID:19469768

  19. Cavum septum pellucidum in a case of schizophrenia presenting with self-mutilating behavior

    PubMed Central

    Umesh, Shreekantiah; Bose, Swarnali; Khanra, Sourav; Das, Basudeb; Nizamie, S. Haque

    2015-01-01

    Cavum septum pellucidum (CSP) is a neurodevelopmental anomaly, which is commonly reported in schizophrenia patients. Various symptoms of schizophrenia, including thought disturbances have been associated with CSP. We present a rare case of undifferentiated schizophrenia with CSP who presented with self-mutilating behaviors. PMID:26257488

  20. Clinical and morphologic features of lipomatous hypertrophy ("massive fatty deposits") of the interatrial septum.

    PubMed

    Gay, J D; Guileyardo, J M; Townsend-Parchman, J K; Ross, K

    1996-03-01

    Lipomatous hypertrophy of the interatrial septum ("massive fatty deposits in the atrial septum") may represent an incidental autopsy finding or may be associated with atrial arrhythmias, obstructive symptoms, or sudden death. Antemortem diagnosis is becoming much more common. In a literature review and in a review of our 12 cases, this condition was found to occur more frequently in obese middle-aged or elderly subjects, who frequently demonstrated atherosclerotic coronary artery disease. The unencapsulated mass generally occurred anterior or superior to the fossa ovalis, and histologically was characterized by mature fat with varying quantities of fetal fat, inflammation and fibrosis, and entrapment of myocardial fibers with cytologic atypia. Cases were included that had a minimum atrial septal thickness of 1.0 cm. The septum ranged up to 7.0 cm in maximum thickness (2.6 cm average). In our cases, no deaths were directly attributed to this disorder. It is important that forensic pathologists become more generally aware of this condition. To further delineate the true pathological significance, the atrial septum should be routinely examined by palpation and sectioning to determine its thickness and fat content. PMID:8838469

  1. Compact fluorescent lamp using horizontal and vertical insulating septums and convective venting geometry

    DOEpatents

    Siminovitch, M.

    1998-02-10

    A novel design is described for a compact fluorescent lamp, including a lamp geometry which will increase light output and efficacy of the lamp in a base down operating position by providing horizontal and vertical insulating septums positioned in the ballast compartment of the lamp to provide a cooler coldspot. Selective convective venting provides additional cooling of the ballast compartment. 9 figs.

  2. Compact fluorescent lamp using horizontal and vertical insulating septums and convective venting geometry

    DOEpatents

    Siminovitch, Michael

    1998-01-01

    A novel design for a compact fluorescent lamp, including a lamp geometry which will increase light output and efficacy of the lamp in a base down operating position by providing horizontal and vertical insulating septums positioned in the ballast compartment of the lamp to provide a cooler coldspot. Selective convective venting provides additional cooling of the ballast compartment.

  3. LIFETIME MEASUREMENT WITH PSEUDO MOVEABLE SEPTUM IN NSLS X-RAY RING

    SciTech Connect

    Wang, G.M.; Choi; J.; Kramer; S.; Shaftan; T.; Heese; R.; Yang; X.

    2011-03-28

    The National Synchrotron Light Source II (NSLS-II) is a state of the art 3 GeV third generation light source currently under construction at Brookhaven National Laboratory and starts to commission in 2014. The beam injection works with two septa and four fast kicker magnets in an injection section. To improve the injection stability and reproducibility, we plan to implement a slow local bump on top of the fast bump so that the fast kicker strength is reduced. This bump works as a pseudo movable septum. We can also use this 'movable' septum to measure the storage ring beam partial lifetime resulting from the septum edge and possibly increasing the lifetime by moving the stored beam orbit away from the edge. We demonstrate the feasibility of this idea, by implementing DC bump in NSLS X-ray ring. We report the results of beam lifetime measurements as a function of the amplitude of this bumped orbit relative to the septum and the idea of a slow bump that could reduce the fast bump magnet strengths.

  4. In vitro evaluation of nasal mucociliary clearance using excised rat nasal septum.

    PubMed

    Inoue, Daisuke; Furubayashi, Tomoyuki; Ogawara, Ken-ichi; Kimura, Toshikiro; Higaki, Kazutaka; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira; Higashi, Yutaka

    2012-01-01

    Mucus on the nasal mucosa is translocated to the pharynx by ciliary beating, which is an important nonspecific defense mechanism called mucociliary clearance (MC). MC is one of the important factors determining the rate and extent of drug absorption after nasal application. The purpose of this study is to evaluate MC using rat nasal septum under physiological condition in an in vitro system. The nasal septum was excised from rats anesthetized with urethane and the movement of fluorescent microspheres (FMS) applied on the nasal septum was observed with a fluorescence microscope. FMS were transported at a constant velocity in the same direction for a few minutes, but addition of 4% mucin solution on the nasal septum maintained MC for at least 90 min after excision. With our evaluation system established by modifying the method of Saldiva, MC was determined to be around 1 mm/min. Furthermore, the ciliostatic effect of benzalkonium chloride was observed, and it was confirmed that β-adrenergic antagonists and a cholinergic antagonist decreased MC, and that β-adrenergic agonists and a cholinergic agonist tended to increase MC, indicating that our system is valid and useful for evaluating MC function and the effect of drugs and pharmaceutical additives for nasal application on MC. PMID:22687480

  5. Three-Dimensional Evaluation of Implant Positioning in the Maxillary Sinus Septum: A Retrospective Study

    PubMed Central

    Dragan, Eliza; Guillaume, Odri A.; Haba, Danisia; Olszewski, Raphael

    2015-01-01

    Background The aim of this study was to simulate implant placement in the maxillary sinus septum, as a potential alternative site to avoid sinus grafting. Material/Methods One hundred partially or completely edentulous patients, with their maxillary sinus septum present in the edentulous region, were selected from the database of the Department of Maxillofacial Surgery, Cliniques Universitaires Saint Luc, Bruxelles, Belgium. Three-dimensional (3D) reconstructions were created using 3D planning software. 3D reconstructions were performed for each maxillary sinus. Using the software implant library, the implants that presented the best fit with the maxillary sinus septum and that followed the established inclusion criteria were selected. Results All of the implants were inserted in premolar and molar regions. Most implants were inserted in the position of the second molar (21 of 55) or in the position of the first molar (17 of 55). In all sites the most frequently used implant was 4 mm in diameter and 7 mm in height. The mean coronal angle for the implant was 80.19±17.13 degrees and the mean sagittal angle was 94.83±9.94 degrees. The septal height represents 38.13% of the total available bone height (ABH). The mean percentage of the septum used to insert the implants was 47.33±2.47%. The septum increased the available bone height by a mean value of 2.18±1.47 mm. In 45 cases, the septa did not permit implant placement. Conclusions In completely edentulous patients, inserting implants in sinus septa does not exclude the need for sinus grafting, but in partially edentulous patients, this minimally invasive technique is an alternative to subantral augmentation. PMID:26363865

  6. Dopamine in nucleus accumbens: salience modulation in latent inhibition and overshadowing

    PubMed Central

    Nelson, AJD; Thur, KE; Marsden, CA; Cassaday, HJ

    2011-01-01

    Latent inhibition (LI) is demonstrated when non-reinforced pre-exposure to a to-be-conditioned stimulus retards later learning. Learning is similarly retarded in overshadowing, in this case using the relative intensity of competing cues to manipulate associability. Electrolytic/excitotoxic lesions to shell accumbens (NAc) and systemic amphetamine both reliably abolish LI. Here a conditioned emotional response procedure was used to demonstrate LI and overshadowing and to examine the role of dopamine (DA) within NAc. Experiment 1 showed that LI but not overshadowing was abolished by systemic amphetamine (1.0 mg/kg i.p.). In Experiment 2, 6-hydroxydopamine (6-OHDA) was used to lesion DA terminals within NAc: both shell- and core- (plus shell-)lesioned rats showed normal LI and overshadowing. Experiment 3 compared the effects of amphetamine microinjected at shell and core coordinates prior to conditioning: LI, but not overshadowing, was abolished by 10.0 but not 5.0 µg/side amphetamine injected in core but not shell NAc. These results suggest that the abolition of LI produced by NAc shell lesions is not readily reproduced by regionally restricted DA depletion within NAc; core rather than shell NAc mediates amphetamine-induced abolition of LI; overshadowing is modulated by different neural substrates. PMID:21262855

  7. Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens.

    PubMed

    Albaugh, Daniel L; Salzwedel, Andrew; Van Den Berge, Nathalie; Gao, Wei; Stuber, Garret D; Shih, Yen-Yu Ian

    2016-01-01

    Deep brain stimulation of the nucleus accumbens (NAc-DBS) is an emerging therapy for diverse, refractory neuropsychiatric diseases. Although DBS therapy is broadly hypothesized to work through large-scale neural modulation, little is known regarding the neural circuits and networks affected by NAc-DBS. Using a healthy, sedated rat model of NAc-DBS, we employed both evoked- and functional connectivity (fc) MRI to examine the functional circuit and network changes achieved by electrical NAc stimulation. Optogenetic-fMRI experiments were also undertaken to evaluate the circuit modulation profile achieved by selective stimulation of NAc neurons. NAc-DBS directly modulated neural activity within prefrontal cortex and a large number of subcortical limbic areas (e.g., amygdala, lateral hypothalamus), and influenced functional connectivity among sensorimotor, executive, and limbic networks. The pattern and extent of circuit modulation measured by evoked-fMRI was relatively insensitive to DBS frequency. Optogenetic stimulation of NAc cell bodies induced a positive fMRI signal in the NAc, but no other detectable downstream responses, indicating that therapeutic NAc-DBS might exert its effect through antidromic stimulation. Our study provides a comprehensive mapping of circuit and network-level neuromodulation by NAc-DBS, which should facilitate our developing understanding of its therapeutic mechanisms of action. PMID:27601003

  8. Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens

    PubMed Central

    Albaugh, Daniel L.; Salzwedel, Andrew; Van Den Berge, Nathalie; Gao, Wei; Stuber, Garret D.; Shih, Yen-Yu Ian

    2016-01-01

    Deep brain stimulation of the nucleus accumbens (NAc-DBS) is an emerging therapy for diverse, refractory neuropsychiatric diseases. Although DBS therapy is broadly hypothesized to work through large-scale neural modulation, little is known regarding the neural circuits and networks affected by NAc-DBS. Using a healthy, sedated rat model of NAc-DBS, we employed both evoked- and functional connectivity (fc) MRI to examine the functional circuit and network changes achieved by electrical NAc stimulation. Optogenetic-fMRI experiments were also undertaken to evaluate the circuit modulation profile achieved by selective stimulation of NAc neurons. NAc-DBS directly modulated neural activity within prefrontal cortex and a large number of subcortical limbic areas (e.g., amygdala, lateral hypothalamus), and influenced functional connectivity among sensorimotor, executive, and limbic networks. The pattern and extent of circuit modulation measured by evoked-fMRI was relatively insensitive to DBS frequency. Optogenetic stimulation of NAc cell bodies induced a positive fMRI signal in the NAc, but no other detectable downstream responses, indicating that therapeutic NAc-DBS might exert its effect through antidromic stimulation. Our study provides a comprehensive mapping of circuit and network-level neuromodulation by NAc-DBS, which should facilitate our developing understanding of its therapeutic mechanisms of action. PMID:27601003

  9. Nucleus accumbens core lesions enhance two-way active avoidance.

    PubMed

    Lichtenberg, N T; Kashtelyan, V; Burton, A C; Bissonette, G B; Roesch, M R

    2014-01-31

    The majority of work examining the nucleus accumbens core (NAc) has focused on functions pertaining to behaviors guided by appetitive outcomes. These studies have pointed to the NAc as being critical for motivating behavior toward desirable outcomes. For example, we have recently shown that lesions of the NAc impaired performance on a reward-guided decision-making task that required rats to choose between differently valued rewards. Unfortunately, much less is known about the role that the NAc plays in motivating behavior when aversive outcomes are predicted. To address this issue we asked if NAc lesions impact performance on a two-way active avoidance task in which rats must learn to shuttle back and forth in a behavioral training box in order to avoid a footshock predicted by an auditory tone. Although bilateral NAc lesions initially impaired reward-guided decision-making, we found that the same lesions improved acquisition and retention of two-way active avoidance. PMID:24275320

  10. Sensory Deviancy Detection Measured Directly Within the Human Nucleus Accumbens.

    PubMed

    Dürschmid, Stefan; Zaehle, Tino; Hinrichs, Hermann; Heinze, Hans-Jochen; Voges, Jürgen; Garrido, Marta I; Dolan, Raymond J; Knight, Robert T

    2016-03-01

    Rapid changes in the environment evoke a comparison between expectancy and actual outcome to inform optimal subsequent behavior. The nucleus accumbens (NAcc), a key interface between the hippocampus and neocortical regions, is a candidate region for mediating this comparison. Here, we report event-related potentials obtained from the NAcc using direct intracranial recordings in 5 human participants while they listened to trains of auditory stimuli differing in their degree of deviation from repetitive background stimuli. NAcc recordings revealed an early mismatch signal (50-220 ms) in response to all deviants. NAcc activity in this time window was also sensitive to the statistics of stimulus deviancy, with larger amplitudes as a function of the level of deviancy. Importantly, this NAcc mismatch signal also predicted generation of longer latency scalp potentials (300-400 ms). The results provide direct human evidence that the NAcc is a key component of a network engaged in encoding statistics of the sensory environmental. PMID:25576536

  11. Reward and reinforcement activity in the nucleus accumbens during learning

    PubMed Central

    Gale, John T.; Shields, Donald C.; Ishizawa, Yumiko; Eskandar, Emad N.

    2014-01-01

    The nucleus accumbens core (NAcc) has been implicated in learning associations between sensory cues and profitable motor responses. However, the precise mechanisms that underlie these functions remain unclear. We recorded single-neuron activity from the NAcc of primates trained to perform a visual-motor associative learning task. During learning, we found two distinct classes of NAcc neurons. The first class demonstrated progressive increases in firing rates at the go-cue, feedback/tone and reward epochs of the task, as novel associations were learned. This suggests that these neurons may play a role in the exploitation of rewarding behaviors. In contrast, the second class exhibited attenuated firing rates, but only at the reward epoch of the task. These findings suggest that some NAcc neurons play a role in reward-based reinforcement during learning. PMID:24765069

  12. Accumbens dopamine-acetylcholine balance in approach and avoidance.

    PubMed

    Hoebel, Bartley G; Avena, Nicole M; Rada, Pedro

    2007-12-01

    Understanding systems for approach and avoidance is basic for behavioral neuroscience. Research on the neural organization and functions of the dorsal striatum in movement disorders, such as Huntington's and Parkinson's Disease, can inform the study of the nucleus accumbens (NAc) in motivational disorders, such as addiction and depression. We propose opposing roles for dopamine (DA) and acetylcholine (ACh) in the NAc in the control of GABA output systems for approach and avoidance. Contrary to DA, which fosters approach, ACh release is a correlate or cause of meal satiation, conditioned taste aversion and aversive brain stimulation. ACh may also counteract excessive DA-mediated approach behavior as revealed during withdrawal from drugs of abuse or sugar when the animal enters an ACh-mediated state of anxiety and behavioral depression. This review summarizes evidence that ACh is important in the inhibition of behavior when extracellular DA is high and the generation of an anxious or depressed state when DA is relatively low. PMID:18023617

  13. Taste pathways that mediate accumbens dopamine release by sapid sucrose.

    PubMed

    Hajnal, Andras; Norgren, Ralph

    2005-03-16

    Although it has been associated with the release of dopamine in the forebrain, reward remains a conundrum in neuroscience. Sucrose is inherently rewarding and its sensory message reaches the brain via the gustatory system. In rodents, the central gustatory system bifurcates in the pontine parabrachial nuclei, one arm forming a standard thalamocortical axis, the other distributing widely in the limbic forebrain. We report here that lesions of the gustatory thalamus fail to affect dopamine overflow during sucrose licking (149+/-5% vs. 149+/-4% for controls). Similar damage to the parabrachial nuclei, which severs the limbic taste projection, substantially reduces dopamine release from the nucleus accumbens (121+/-4% vs. 168+/-9% for sham operated controls; p<0.02). This represents the first demonstration that the affective character of a sensory stimulus might separate from the thalamocortical system as early as the second central synapse. PMID:15763573

  14. Switching from Contextual to Tone Fear Conditioning and Vice Versa: The Key Role of the Glutamatergic Hippocampal-Lateral Septal Neurotransmission

    ERIC Educational Resources Information Center

    Calandreau, Ludovic; Desgranges, Bertrand; Jaffard, Robert; Desmedt, Aline

    2010-01-01

    The aim of the present experiment was to directly assess the role of the glutamatergic hippocampal-lateral septal (HPC-LS) neurotransmission in tone and contextual fear conditioning. We found that pretraining infusion of glutamatergic acid into the lateral septum promotes tone conditioning and concomitantly disrupts contextual conditioning.…

  15. [The application of the nanostructured bioplastic material for the plastic reconstruction of perforations in the nasal septum].

    PubMed

    Grigor'eva, M V; Akimov, A V; Bagautdinov, A A

    2014-01-01

    The objective of the present work was to estimate the effectiveness of the application of the nanostructured bioplastic material for the plastic reconstruction of perforations in the nasal septum. A total of 80 patients were recruited for the study. Half of them underwent plastic reconstruction of perforations in the nasal septum with the application of the nanostructured bioplastic material. Forty patients were treated using no biotransplants. The functional state of nasal cavity mucosa was evaluated before and after surgery. It is concluded that the nanostructured bioplastic material used in the present study ensures efficacious reconstruction of nasal septum integrity after plastic correction of septal perforations. PMID:25588475

  16. Neuroelectric signatures of reward learning and decision-making in the human nucleus accumbens.

    PubMed

    Cohen, Michael X; Axmacher, Nikolai; Lenartz, Doris; Elger, Christian E; Sturm, Volker; Schlaepfer, Thomas E

    2009-06-01

    Learning that certain actions lead to risky rewards is critical for biological, social, and economic survival, but the precise neural mechanisms of such reward-guided learning remain unclear. Here, we show that the human nucleus accumbens plays a key role in learning about risks by representing reward value. We recorded electrophysiological activity directly from the nucleus accumbens of five patients undergoing deep brain stimulation for treatment of refractory major depression. Patients engaged in a simple reward-learning task in which they first learned stimulus-outcome associations (learning task), and then were able to choose from among the learned stimuli (choosing task). During the learning task, nucleus accumbens activity reflected potential and received reward values both during the cue stimulus and during the feedback. During the choosing task, there was no nucleus accumbens activity during the cue stimulus, but feedback-related activity was pronounced and similar to that during the learning task. This pattern of results is inconsistent with a prediction error response. Finally, analyses of cross-correlations between the accumbens and simultaneous recordings of medial frontal cortex suggest a dynamic interaction between these structures. The high spatial and temporal resolution of these recordings provides novel insights into the timing of activity in the human nucleus accumbens, its functions during reward-guided learning and decision-making, and its interactions with medial frontal cortex. PMID:19092783

  17. Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users.

    PubMed

    Gilman, Jodi M; Kuster, John K; Lee, Sang; Lee, Myung Joo; Kim, Byoung Woo; Makris, Nikos; van der Kouwe, Andre; Blood, Anne J; Breiter, Hans C

    2014-04-16

    Marijuana is the most commonly used illicit drug in the United States, but little is known about its effects on the human brain, particularly on reward/aversion regions implicated in addiction, such as the nucleus accumbens and amygdala. Animal studies show structural changes in brain regions such as the nucleus accumbens after exposure to Δ9-tetrahydrocannabinol, but less is known about cannabis use and brain morphometry in these regions in humans. We collected high-resolution MRI scans on young adult recreational marijuana users and nonusing controls and conducted three independent analyses of morphometry in these structures: (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). Gray matter density analyses revealed greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only. Significant shape differences were detected in the left nucleus accumbens and right amygdala. The left nucleus accumbens showed salient exposure-dependent alterations across all three measures and an altered multimodal relationship across measures in the marijuana group. These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization. PMID:24741043

  18. Cannabis Use Is Quantitatively Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users

    PubMed Central

    Gilman, Jodi M.; Kuster, John K.; Lee, Sang; Lee, Myung Joo; Kim, Byoung Woo; Makris, Nikos; van der Kouwe, Andre; Blood, Anne J.

    2014-01-01

    Marijuana is the most commonly used illicit drug in the United States, but little is known about its effects on the human brain, particularly on reward/aversion regions implicated in addiction, such as the nucleus accumbens and amygdala. Animal studies show structural changes in brain regions such as the nucleus accumbens after exposure to Δ9-tetrahydrocannabinol, but less is known about cannabis use and brain morphometry in these regions in humans. We collected high-resolution MRI scans on young adult recreational marijuana users and nonusing controls and conducted three independent analyses of morphometry in these structures: (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). Gray matter density analyses revealed greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only. Significant shape differences were detected in the left nucleus accumbens and right amygdala. The left nucleus accumbens showed salient exposure-dependent alterations across all three measures and an altered multimodal relationship across measures in the marijuana group. These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization. PMID:24741043

  19. Solid Right Ventricular Compression by Intraventricular Septum-Hematoma Induced after Percutaneous Coronary Intervention

    PubMed Central

    El-Battrawy, Ibrahim; Akin, Ibrahim; Münz, Benedikt; Leistner, David Manuel; Behnes, Michael; Henzler, Thomas; Haubenreisser, Holger; Papavassiliu, Theano; Borggrefe, Martin; Lehmann, Ralf

    2016-01-01

    Intraventricular septum-hematoma is a rare complication following percutaneous coronary intervention (PCI). This complication may represent a challenge for accurate diagnosis and treatment. This case report is about a 60-year-old male patient being admitted with an acute coronary syndrome. Despite successful PCI with drug eluting stent implantation into the right coronary artery (RCA) the patient complained about recurrent angina pectoris according to Canadian Cardiovascular Society (CCS) class IV. Cardiac magnetic resonance imaging and transthoracic echocardiography revealed a massive 4.9 × 9.2 cm sized end-diastolic septum-hematoma, which compromised right ventricular cavity. Emergent recoronary angiography ruled out further contrast extravasation from the RCA. Conservative treatment was intended after discussion in the “heart-team.” The patient completely recovered with nearly complete resolution of the hematoma after 6 months. PMID:27119029

  20. Treatment of Virgin OHVIRA Syndrome with Haematometrocolpos by Complete Incision of Vaginal Septum without Hymenotomy

    PubMed Central

    Tug, Niyazi; Çelik, Ayhan; Alp, Turgut; Yenidede, Ilter

    2015-01-01

    Mullerian malformations result from defective fusion of the Mullerian ducts during development of the female reproductive system and have an incidence of 2-3%. The American Fertility Society classification of Mullerian anomalies is the most commonly utilized standardized classification. The least common form of these malformations is Herlyn-Werner-Wunderlich syndrome characterized by obstructed hemivagina and ipsilateral renal anomaly (OHVIRA). This syndrome has been described with case reports since 1922. Early diagnosis and surgery that include drainage of fluid and resection of the vaginal septum is necessary for OHVIRA to prevent late complications (i.e. pyocolpos, chronic cryptomenorrhea). Here in we report a case of Herlyn-Werner-Wunderlich syndrome that hymen has been preserved during the operation of non-fenestrated transverse vaginal septum resection with hysteroscopy. PMID:26676254

  1. Treatment of Virgin OHVIRA Syndrome with Haematometrocolpos by Complete Incision of Vaginal Septum without Hymenotomy.

    PubMed

    Tug, Niyazi; Sargin, Mehmet Akif; Çelik, Ayhan; Alp, Turgut; Yenidede, Ilter

    2015-11-01

    Mullerian malformations result from defective fusion of the Mullerian ducts during development of the female reproductive system and have an incidence of 2-3%. The American Fertility Society classification of Mullerian anomalies is the most commonly utilized standardized classification. The least common form of these malformations is Herlyn-Werner-Wunderlich syndrome characterized by obstructed hemivagina and ipsilateral renal anomaly (OHVIRA). This syndrome has been described with case reports since 1922. Early diagnosis and surgery that include drainage of fluid and resection of the vaginal septum is necessary for OHVIRA to prevent late complications (i.e. pyocolpos, chronic cryptomenorrhea). Here in we report a case of Herlyn-Werner-Wunderlich syndrome that hymen has been preserved during the operation of non-fenestrated transverse vaginal septum resection with hysteroscopy. PMID:26676254

  2. Will Septal Correction Surgery for Deviated Nasal Septum Improve the Sense of Smell? A Prospective Study

    PubMed Central

    Gupta, Neelima; Singh, P. P.; Bagla, Rahul Kumar

    2015-01-01

    Background and Objectives. Nasal obstruction due to deviated nasal septum is a common problem bringing a patient to an otorhinolaryngologist. Occasionally, these patients may also complain of olfactory impairment. We proposed to study the effect of septal deviation on the lateralised olfactory function and the change in olfaction after surgery of the septum (septoplasty). Methods. Forty-one patients with deviated nasal septum were evaluated for nasal airflow, olfactory score, and nasal symptomatology. Septoplasty was done under local anesthesia. Pre- and postoperative olfactory scores, airflow and olfactory scores, and nasal symptomatology and olfactory scores were compared and correlated. Results. The range of preoperative composite olfactory score (COS) on the side of septal deviation was 4–14 (mean 7.90 ± 2.234) and on the nonobstructed side was 9–18 (mean 14.49 ± 2.378). Severity of deviated nasal septum and preoperative COS of diseased side were correlated and the correlation was found to be significant (rho = −0.690, p = 0.000 (<0.001)). The preoperative mean COS (7.90 ± 2.234) was compared with the postoperative mean COS (12.39 ± 3.687) and the improvement was found to be statistically significant (p = 0.000 (<0.001)). Conclusion. We found improvement in olfactory function in 70.6% patients after surgery, no change in 20.1%, and reduced function in 7.6%. With the limitation of a small sample size and a potential repeat testing bias, we would conclude that correction of nasal septal deviation may lead to improvement in sense of smell. PMID:26491724

  3. Iron yoke eddy current induced losses with application to the ALS septum magnets

    SciTech Connect

    Schlueter, R.D.

    1991-08-16

    The theoretical development of relations governing the eddy current induced losses in iron electromagnet yokes is reviewed. A baseline laminated electromagnet design is analyzed and a parametric study illustrates the sensitivity of core losses to perturbations of various geometrical, material, and excitation parameters. Core losses and field gradients for the ALS septum magnets are calculated. Design modifications capable of eliminating transverse and longitudinal field gradients are discussed.

  4. Lupus vulgaris leading to perforation of nasal septum in a child.

    PubMed

    Singal, Archana; Arora, Rahul; Pandhi, Deepika

    2015-01-01

    Lupus vulgaris (LV) is a common form of cutaneous tuberculosis in India, mostly involving the lower half of the body. Facial involvement is uncommon. Untreated disease may lead to significant morbidity due to atrophic scarring, mutilation, and deformity. We report a case of multi-focal LV in a 10-year-old boy affecting the nose and cheek that resulted in perforation of the nasal septum, a rarely reported complication. PMID:26009716

  5. Beamstrahlung Photon Load on the TESLA Extraction Septum Blade(LCC-0104)

    SciTech Connect

    Seryi, A

    2003-10-02

    This note describes work performed in the framework of the International Linear Collider Technical Review Committee [1] to estimate the power load on the TESLA extraction septum blade due to beamstrahlung photons. It is shown, that under realistic conditions the photon load can be several orders of magnitude higher than what was estimated in the TESLA TDR [2] for the ideal Gaussian beams, potentially representing a serious limitation of the current design.

  6. Changes in benzodiazepine-GABA receptor coupling in an accumbens-habenula circuit after chronic diazepam treatment.

    PubMed Central

    Brett, R. R.; Pratt, J. A.

    1995-01-01

    1. The effects of subacute and of chronic diazepam treatment upon binding to the GABAA receptor have been examined by use of receptor autoradiography for determining flunitrazepam (FNZP) binding, GABA enhancement of FNZP binding. SR 95531 2-(3'-carboxy-2',propyl)-3-amino-6-p-methoxyphenylpyridazinium bromide) binding and GABA binding in parallel sections from rat brain. Prior to the autoradiographic procedures, a behavioural assessment of the rats was made in the elevated plus-maze test of anxiety. 2. Rats receiving diazepam either subacutely (3 days) or chronically (28 days) by both continuous release, from previously implanted subcutaneous silastic capsules, or by daily injection (5 mg kg-1) did not display changes in FNZP or GABA binding in any of the 47 brain structures analysed. Similarly, there were no significant effects of treatment upon mean total entries or on the open:total ratio for entries in the elevated plus-maze. 3. There were reductions in the GABA enhancement of FNZP binding in the nucleus accumbens and central grey after subacute diazepam treatment. This effect persisted in the nucleus accumbens after chronic treatment. Less marked effects occurred in the lateral habenula, dorsal raphe and substantia nigra pars compacta. In the dorsal tegmental nucleus, GABA enhancement of FNZP binding was enhanced after chronic treatment and this was accompanied by reductions in SR 95531 binding. Treatment did not otherwise affect SR 95531 binding, with the exception of the dorsal raphe where binding was decreased after subacute treatment. 4. In general, the patterns of binding produced by the two different treatment routes were very similar. However, SR 95531 binding was lower in certain hippocampal fields in the i.p. treated animals compared to the rats implanted with silastic capsules. 5. It is concluded that repeated administration of diazepam evokes changes in benzodiazepine and GABA receptor coupling, and to a lesser extent changes in low affinity GABA

  7. Comparative transcriptome analysis of atrial septal defect identifies dysregulated genes during heart septum morphogenesis.

    PubMed

    Wang, Wenju; Niu, Zhaoyi; Wang, Yi; Li, Yaxiong; Zou, Honglin; Yang, Li; Meng, Mingyao; Wei, Chuanyu; Li, Qinrui; Duan, Le; Xie, Yanhua; Zhang, Yayong; Cao, Yu; Han, Shen; Hou, Zongliu; Jiang, Lihong

    2016-01-10

    Congenital heart disease (CHD) is one of most common birth defects, causing fetal loss and death in newborn all over the world. Atrial and ventricular septal defects were the most common CHD subtypes in most districts. During the past decades, several genes were identified to control atrial septum formation, and mutations of these genes can cause cardiac septation defects. However, the pathogenic mechanism of ASD on transcriptional levels has not been well elucidated yet. Herein, we performed comparative transcriptome analysis between normal and atrial septal defect (ASD) patients by Illumina RNA sequencing (RNA-seq). Advanced bioinformatic analyses were employed to identify dysregulated genes in ASD. The results indicated that cardiac specific transcriptional factors (GATA4 and NKX2-5), extracellular signal molecules (VEGFA and BMP10) and cardiac sarcomeric proteins (MYL2, MYL3, MYH7, TNNT1 and TNNT3) were downregulated in ASD which may affect heart atrial septum formation, cardiomyocyte proliferation and cardiac muscle development. Importantly, cell cycle was dominant pathway among downregulated genes, and decreased expression of the proteins included in cell cycle may disturb cardiomyocyte growth and differentiation during atrial septum formation. Our study provided evidences of understanding pathogenic mechanism of ASD and resource for validation of CHD genomic studies. PMID:26375510

  8. Early life stress impairs social recognition due to a blunted response of vasopressin release within the septum of adult male rats.

    PubMed

    Lukas, Michael; Bredewold, Remco; Landgraf, Rainer; Neumann, Inga D; Veenema, Alexa H

    2011-07-01

    Early life stress poses a risk for the development of psychopathologies characterized by disturbed emotional, social, and cognitive performance. We used maternal separation (MS, 3h daily, postnatal days 1-14) to test whether early life stress impairs social recognition performance in juvenile (5-week-old) and adult (16-week-old) male Wistar rats. Social recognition was tested in the social discrimination test and defined by increased investigation by the experimental rat towards a novel rat compared with a previously encountered rat. Juvenile control and MS rats demonstrated successful social recognition at inter-exposure intervals of 30 and 60 min. However, unlike adult control rats, adult MS rats failed to discriminate between a previously encountered and a novel rat after 60 min. The social recognition impairment of adult MS rats was accompanied by a lack of a rise in arginine vasopressin (AVP) release within the lateral septum seen during social memory acquisition in adult control rats. This blunted response of septal AVP release was social stimulus-specific because forced swimming induced a rise in septal AVP release in both control and MS rats. Retrodialysis of AVP (1 μg/ml, 3.3 μl/min, 30 min) into the lateral septum during social memory acquisition restored social recognition in adult MS rats at the 60-min interval. These studies demonstrate that MS impairs social recognition performance in adult rats, which is likely caused by blunted septal AVP activation. Impaired social recognition may be linked to MS-induced changes in other social behaviors like aggression as shown previously. PMID:21185124

  9. Nucleus accumbens dopaminergic neurotransmission switches its modulatory action in chronification of inflammatory hyperalgesia.

    PubMed

    Dias, Elayne Vieira; Sartori, César Renato; Marião, Paula Ramos; Vieira, André Schwambach; Camargo, Lilian Calili; Athie, Maria Carolina Pedro; Pagliusi, Marco Oreste; Tambeli, Claudia Herrera; Parada, Carlos Amilcar

    2015-10-01

    Dopaminergic neurotransmission in the nucleus accumbens, a central component of the mesolimbic system, has been associated with acute pain modulation. As there is a transition from acute to chronic pain ('chronification'), modulatory structures may be involved in chronic pain development. Thus, this study aimed to elucidate the role of nucleus accumbens dopaminergic neurotransmission in chronification of pain. We used a rat model in which daily subcutaneous injection of prostaglandin E2 in the hindpaw for 14 days induces a long-lasting state of nociceptor sensitization that lasts for at least 30 days following the end of the treatment. Our findings demonstrated that the increase of dopamine in the nucleus accumbens by local administration of GBR12909 (0.5 nmol/0.25 μL), a dopamine reuptake inhibitor, blocked prostaglandin E2 -induced acute hyperalgesia. This blockade was prevented by a dopamine D2 receptor antagonist (raclopride, 10 nmol/0.25 μL) but not changed by a D1 receptor antagonist (SCH23390, 0.5, 3 or 10 nmol/0.25 μL), both co-administered with GBR12909 in the nucleus accumbens. In contrast, the induction of persistent hyperalgesia was facilitated by continuous infusion of GBR12909 in the nucleus accumbens (0.021 nmol/0.5 μL/h) over 7 days of prostaglandin E2 treatment. The development of persistent hyperalgesia was impaired by SCH23390 (0.125 nmol/0.5 μL/h) and raclopride (0.416 nmol/0.5 μL/h), both administered continuously in the nucleus accumbens over 7 days. Taken together, our data suggest that the chronification of pain involves the plasticity of dopaminergic neurotransmission in the nucleus accumbens, which switches its modulatory role from antinociceptive to pronociceptive. PMID:26173870

  10. The Nucleus Accumbens: A Switchboard for Goal-Directed Behaviors

    PubMed Central

    O'Donnell, Patricio

    2009-01-01

    Reward intake optimization requires a balance between exploiting known sources of rewards and exploring for new sources. The prefrontal cortex (PFC) and associated basal ganglia circuits are likely candidates as neural structures responsible for such balance, while the hippocampus may be responsible for spatial/contextual information. Although studies have assessed interactions between hippocampus and PFC, and between hippocampus and the nucleus accumbens (NA), it is not known whether 3-way interactions among these structures vary under different behavioral conditions. Here, we investigated these interactions with multichannel recordings while rats explored an operant chamber and while they performed a learned lever-pressing task for reward in the same chamber shortly afterward. Neural firing and local field potentials in the NA core synchronized with hippocampal activity during spatial exploration, but during lever pressing they instead synchronized more strongly with the PFC. The latter is likely due to transient drive of NA neurons by bursting prefrontal activation, as in vivo intracellular recordings in anesthetized rats revealed that NA up states can transiently synchronize with spontaneous PFC activity and PFC stimulation with a bursting pattern reliably evoked up states in NA neurons. Thus, the ability to switch synchronization in a task-dependent manner indicates that the NA core can dynamically select its inputs to suit environmental demands, thereby contributing to decision-making, a function that was thought to primarily depend on the PFC. PMID:19352511

  11. Accumbens dopamine-acetylcholine balance in approach and avoidance

    PubMed Central

    Hoebel, Bartley G.; Avena, Nicole M.; Rada, Pedro

    2008-01-01

    Summary Understanding systems for approach and avoidance is basic for behavioral neuroscience. Research on the neural organization and functions of the dorsal striatum in movement disorders, such as Huntington's and Parkinson's Disease, can inform the study of the nucleus accumbens (NAc) in motivational disorders, such as addiction and depression. We propose opposing roles for dopamine (DA) and acetylcholine (ACh) in the NAc in the control of GABA output systems for approach and avoidance. Contrary to DA, which fosters approach, ACh release is a correlate or cause of meal satiation, conditioned taste aversion and aversive brain stimulation. ACh may also counteract excessive DA-mediated approach behavior as revealed during withdrawal from drugs of abuse or sugar, when the animal enters an ACh-mediated state of anxiety and behavioral depression. This review summarizes evidence that ACh is important in the inhibition of behavior when extracellular DA is high and the generation of an anxious or depressed state when DA is relatively low. PMID:18023617

  12. 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

  13. Increases in cytoplasmic dopamine compromise the normal resistance of the nucleus accumbens to methamphetamine neurotoxicity

    PubMed Central

    Thomas, David M.; Francescutti-Verbeem, Dina M.; Kuhnt, Donald M.

    2016-01-01

    Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the caudate–putamen (CPu) where long-term DA depletion and microglial activation are most evident. Even damage within the CPu is remarkably heterogenous with lateral and ventral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared of the damage that accompanies binge METH intoxication. Increases in cytoplasmic DA produced by reserpine, L-DOPA or clorgyline prior to METH uncover damage in the NAc as evidenced by microglial activation and depletion of DA, tyrosine hydroxylase (TH), and the DA transporter. These effects do not occur in the NAc after treatment with METH alone. In contrast to the CPu where DA, TH, and DA transporter levels remain depleted chronically, DA nerve ending alterations in the NAc show a partial recovery over time. None of the treatments that enhance METH toxicity in the NAc and CPu lead to losses of TH protein or DA cell bodies in the substantia nigra or the ventral tegmentum. These data show that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of METH to include brain structures not normally targeted for damage by METH alone. The resistance of the NAc to METH-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of METH neurotoxicity by alterations in DA homeostasis is significant in light of the important roles played by this brain structure. PMID:19457119

  14. Drug-Paired Contextual Stimuli Increase Dendritic Spine Dynamics in Select Nucleus Accumbens Neurons.

    PubMed

    Singer, Bryan F; Bubula, Nancy; Li, Dongdong; Przybycien-Szymanska, Magdalena M; Bindokas, Vytautas P; Vezina, Paul

    2016-07-01

    Repeated exposure to amphetamine leads to both associative conditioning and nonassociative sensitization. Here we assessed the contribution of neuronal ensembles in the nucleus accumbens (NAcc) to these behaviors. Animals exposed to amphetamine IP or in the ventral tegmental area (VTA) showed a sensitized locomotor response when challenged with amphetamine weeks later. Both exposure routes also increased ΔFosB levels in the NAcc. Further characterization of these ΔFosB+ neurons, however, revealed that amphetamine had no effect on dendritic spine density or size, indicating that these neurons do not undergo changes in dendritic spine morphology that accompany the expression of nonassociative sensitization. Additional experiments determined how neurons in the NAcc contribute to the expression of associative conditioning. A discrimination learning procedure was used to expose rats to IP or VTA amphetamine either Paired or Unpaired with an open field. As expected, compared with Controls, Paired rats administered IP amphetamine subsequently showed a conditioned locomotor response when challenged with saline in the open field, an effect accompanied by an increase in c-Fos+ neurons in the medial NAcc. Further characterization of these c-Fos+ cells revealed that Paired rats showed an increase in the density of dendritic spines and the frequency of medium-sized spines in the NAcc. In contrast, Paired rats previously exposed to VTA amphetamine showed neither conditioned locomotion nor conditioned c-Fos+ expression. Together, these results suggest a role for c-Fos+ neurons in the medial NAcc and rapid changes in the morphology of their dendritic spines in the expression of conditioning evoked by amphetamine-paired contextual stimuli. PMID:26979294

  15. Relationship of Dopamine of the Nucleus Accumbens with Intra-infralimbic Apomorphine Microinjection

    PubMed Central

    Alimoradian, Abbas; Sajedianfard, Javad; Baha-aldini Beigy, Faegheh; Panjehshahin, Mohammad Reza; Owji, Ali Akbar

    2013-01-01

    Objective(s): The dopamine level of the nucleus accumbens changes during some stereotyped behaviors. To study dopamine level of the nucleus accumbens in intra infralimbic apomorphine-induced climbing, microdialysis probes were implanted into the nucleus accumbens shell of male Sprague Dawley rats weighting 275–400 g. Materials and Methods: The rats were divided into two groups (apomorphine and control) of least eleven rats in each group. Apomorphine at dose of 5 μg/0.5 μl or its vehicle was microinjected into the infralimbic in apomorphine and control groups respectively. Then, changes in dopamine levels in the nucleus accumbens shell were monitored. The concentration of dopamine was measured by High-Performance Liquid Chromatography-Electochemical (HPLC-ECD). Finally, the stereotyped behaviors were recorded. Results: The mean of dopamine levels for all of after microinjection period in control and drug groups were 450% and 150% respectively compared to those of before microinjection period. However, there was no significant difference between groups of apomorphine and control. In addition, the return of dopamine level to the baseline was faster in apomorphine group than the control group. Conclusion: The intra infralimbic apomorphine -induced climbing at dose of 5 μg/0.5 μl was not modulated via the increase of dopamine level in the nucleus accumbens area. PMID:23997899

  16. Optogenetically-induced tonic dopamine release from VTA-nucleus accumbens projections inhibits reward consummatory behaviors.

    PubMed

    Mikhailova, Maria A; Bass, Caroline E; Grinevich, Valentina P; Chappell, Ann M; Deal, Alex L; Bonin, Keith D; Weiner, Jeff L; Gainetdinov, Raul R; Budygin, Evgeny A

    2016-10-01

    Recent optogenetic studies demonstrated that phasic dopamine release in the nucleus accumbens may play a causal role in multiple aspects of natural and drug reward-related behaviors. The role of tonic dopamine release in reward consummatory behavior remains unclear. The current study used a combinatorial viral-mediated gene delivery approach to express ChR2 on mesolimbic dopamine neurons in rats. We used optical activation of this dopamine circuit to mimic tonic dopamine release in the nucleus accumbens and to explore the causal relationship between this form of dopamine signaling within the ventral tegmental area (VTA)-nucleus accumbens projection and consumption of a natural reward. Using a two bottle choice paradigm (sucrose vs. water), the experiments revealed that tonic optogenetic stimulation of mesolimbic dopamine transmission significantly decreased reward consummatory behaviors. Specifically, there was a significant decrease in the number of bouts, licks and amount of sucrose obtained during the drinking session. Notably, activation of VTA dopamine cell bodies or dopamine terminals in the nucleus accumbens resulted in identical behavioral consequences. No changes in water intake were evident under the same experimental conditions. Collectively, these data demonstrate that tonic optogenetic stimulation of VTA-nucleus accumbens dopamine release is sufficient to inhibit reward consummatory behavior, possibly by preventing this circuit from engaging in phasic activity that is thought to be essential for reward-based behaviors. PMID:27421228

  17. The involvement of nucleus accumbens dopamine in appetitive and aversive motivation.

    PubMed

    Salamone, J D

    1994-04-18

    In recent years, considerable emphasis has been placed upon the putative role of nucleus accumbens dopamine systems in appetitive motivation and positive reinforcement. However, considerable evidence indicates that brain dopamine in general, and nucleus accumbens dopamine in particular, is involved in aspects of aversive motivation. Administration of dopamine antagonists or localized interference with nucleus accumbens dopamine systems has been shown to disrupt active avoidance behavior. In addition, accumbens dopamine release and metabolism is activated by a wide variety of stressful conditions. A review of the literature indicates that there are substantial similarities between the characteristics of dopaminergic involvement in appetitive and aversive motivation. There is conflicting evidence about the role of dopamine in emotion, and little evidence to suggest that the profound and consistent changes in instrumental behavior produced by interference with DA systems are due to direct dopaminergic mediation of positive affective responses such as hedonia. It is suggested that nucleus accumbens dopamine is involved in aspects of sensorimotor functions that are involved in both appetitive and aversive motivation. PMID:8037860

  18. A randomized comparison of fluoroscopic techniques for implanting pacemaker lead on the right ventricular outflow tract septum.

    PubMed

    Chen, Dongli; Wei, Huiqiang; Tang, Jiaojiao; Liu, Lie; Wu, Shulin; Lin, Chunying; Zhang, Qianhuan; Liang, Yuanhong; Chen, Silin

    2016-05-01

    Right ventricular outflow tract (RVOT) septal pacing is commonly performed under the standard fluoroscopic positions during procedure. The aim of the prospective, randomized study was to evaluate the accuracy of the combination of standard fluoroscopic and left lateral (LL) fluoroscopic views for determination of RVOT septal position compared with standard fluoroscopic views alone. We prospectively enrolled patients who had indications for implantation of a permanent pacemaker. Patients were randomly assigned into two groups based on intraoperative fluoroscopic views as follows: LL group (three standard fluoroscopic views + LL fluoroscopic view) or standard group (three standard fluoroscopic views). Transthoracic echocardiography (TTE) determination of pacing sites was applied in all patients 3 days after pacemaker implantation. The implantation success rate of RVOT septal pacing was compared between groups. A total of 143 patients (59 males, mean age 57.6 ± 16.3 years) with symptomatic bradyarrhythmia were studied, of whom, 72 patients were randomized to LL group and 71 to standard group. TTE determination of pacing sites was compared with two groups. In the LL group, 60 patients (83 %) were achieved in RVOT septal position. In the standard group, however, the position of RVOT septum was only observed in 48 patients (68 %). The success rate of RVOT septal position in LL group was significantly higher than standard group (p = 0.029). Comparing to traditional views, combining LL view in the procedure will approve the accuracy of RVOT septal pacing site. PMID:26797500

  19. Behavioral Flexibility Is Increased by Optogenetic Inhibition of Neurons in the Nucleus Accumbens Shell during Specific Time Segments

    ERIC Educational Resources Information Center

    Aquili, Luca; Liu, Andrew W.; Shindou, Mayumi; Shindou, Tomomi; Wickens, Jeffery R.

    2014-01-01

    Behavioral flexibility is vital for survival in an environment of changing contingencies. The nucleus accumbens may play an important role in behavioral flexibility, representing learned stimulus-reward associations in neural activity during response selection and learning from results. To investigate the role of nucleus accumbens neural activity…

  20. A case of musical preference for Johnny Cash following deep brain stimulation of the nucleus accumbens.

    PubMed

    Mantione, Mariska; Figee, Martijn; Denys, Damiaan

    2014-01-01

    Music is among all cultures an important part of the live of most people. Music has psychological benefits and may generate strong emotional and physiological responses. Recently, neuroscientists have discovered that music influences the reward circuit of the nucleus accumbens (NAcc), even when no explicit reward is present. In this clinical case study, we describe a 60-year old patient who developed a sudden and distinct musical preference for Johnny Cash following deep brain stimulation (DBS) targeted at the NAcc. This case report substantiates the assumption that the NAcc is involved in musical preference, based on the observation of direct stimulation of the accumbens with DBS. It also shows that accumbens DBS can change musical preference without habituation of its rewarding properties. PMID:24834035

  1. A case of musical preference for Johnny Cash following deep brain stimulation of the nucleus accumbens

    PubMed Central

    Mantione, Mariska; Figee, Martijn; Denys, Damiaan

    2014-01-01

    Music is among all cultures an important part of the live of most people. Music has psychological benefits and may generate strong emotional and physiological responses. Recently, neuroscientists have discovered that music influences the reward circuit of the nucleus accumbens (NAcc), even when no explicit reward is present. In this clinical case study, we describe a 60-year old patient who developed a sudden and distinct musical preference for Johnny Cash following deep brain stimulation (DBS) targeted at the NAcc. This case report substantiates the assumption that the NAcc is involved in musical preference, based on the observation of direct stimulation of the accumbens with DBS. It also shows that accumbens DBS can change musical preference without habituation of its rewarding properties. PMID:24834035

  2. Neurons in the Nucleus Accumbens Promote Selection Bias for Nearer Objects

    PubMed Central

    Morrison, Sara E.

    2014-01-01

    Both animals and humans often prefer rewarding options that are nearby over those that are distant, but the neural mechanisms underlying this bias are unclear. Here we present evidence that a proximity signal encoded by neurons in the nucleus accumbens drives proximate reward bias by promoting impulsive approach to nearby reward-associated objects. On a novel decision-making task, rats chose the nearer option even when it resulted in greater effort expenditure and delay to reward; therefore, proximate reward bias was unlikely to be caused by effort or delay discounting. The activity of individual neurons in the nucleus accumbens did not consistently encode the reward or effort associated with specific alternatives, suggesting that it does not participate in weighing the values of options. In contrast, proximity encoding was consistent and did not depend on the subsequent choice, implying that accumbens activity drives approach to the nearest rewarding option regardless of its specific associated reward size or effort level. PMID:25319709

  3. Neurons in the nucleus accumbens promote selection bias for nearer objects.

    PubMed

    Morrison, Sara E; Nicola, Saleem M

    2014-10-15

    Both animals and humans often prefer rewarding options that are nearby over those that are distant, but the neural mechanisms underlying this bias are unclear. Here we present evidence that a proximity signal encoded by neurons in the nucleus accumbens drives proximate reward bias by promoting impulsive approach to nearby reward-associated objects. On a novel decision-making task, rats chose the nearer option even when it resulted in greater effort expenditure and delay to reward; therefore, proximate reward bias was unlikely to be caused by effort or delay discounting. The activity of individual neurons in the nucleus accumbens did not consistently encode the reward or effort associated with specific alternatives, suggesting that it does not participate in weighing the values of options. In contrast, proximity encoding was consistent and did not depend on the subsequent choice, implying that accumbens activity drives approach to the nearest rewarding option regardless of its specific associated reward size or effort level. PMID:25319709

  4. Histone arginine methylation in cocaine action in the nucleus accumbens.

    PubMed

    Damez-Werno, Diane M; Sun, HaoSheng; Scobie, Kimberly N; Shao, Ningyi; Rabkin, Jaclyn; Dias, Caroline; Calipari, Erin S; Maze, Ian; Pena, Catherine J; Walker, Deena M; Cahill, Michael E; Chandra, Ramesh; Gancarz, Amy; Mouzon, Ezekiell; Landry, Joseph A; Cates, Hannah; Lobo, Mary-Kay; Dietz, David; Allis, C David; Guccione, Ernesto; Turecki, Gustavo; Defilippi, Paola; Neve, Rachael L; Hurd, Yasmin L; Shen, Li; Nestler, Eric J

    2016-08-23

    Repeated cocaine exposure regulates transcriptional regulation within the nucleus accumbens (NAc), and epigenetic mechanisms-such as histone acetylation and methylation on Lys residues-have been linked to these lasting actions of cocaine. In contrast to Lys methylation, the role of histone Arg (R) methylation remains underexplored in addiction models. Here we show that protein-R-methyltransferase-6 (PRMT6) and its associated histone mark, asymmetric dimethylation of R2 on histone H3 (H3R2me2a), are decreased in the NAc of mice and rats after repeated cocaine exposure, including self-administration, and in the NAc of cocaine-addicted humans. Such PRMT6 down-regulation occurs selectively in NAc medium spiny neurons (MSNs) expressing dopamine D2 receptors (D2-MSNs), with opposite regulation occurring in D1-MSNs, and serves to protect against cocaine-induced addictive-like behavioral abnormalities. Using ChIP-seq, we identified Src kinase signaling inhibitor 1 (Srcin1; also referred to as p140Cap) as a key gene target for reduced H3R2me2a binding, and found that consequent Srcin1 induction in the NAc decreases Src signaling, cocaine reward, and the motivation to self-administer cocaine. Taken together, these findings suggest that suppression of Src signaling in NAc D2-MSNs, via PRMT6 and H3R2me2a down-regulation, functions as a homeostatic brake to restrain cocaine action, and provide novel candidates for the development of treatments for cocaine addiction. PMID:27506785

  5. Nucleus accumbens GLP-1 receptors influence meal size and palatability.

    PubMed

    Dossat, Amanda M; Diaz, Ryan; Gallo, Lindsay; Panagos, Alyssa; Kay, Kristen; Williams, Diana L

    2013-06-15

    Recent evidence suggests that the glucagon-like peptide-1 (GLP-1) neuronal projection to the nucleus accumbens core (NAcC) contributes to food intake control. To investigate the role of endogenous stimulation of GLP-1 receptors (GLP-1R) in NAcC, we examined the effects of the GLP-1R antagonist exendin-(9-39) (Ex9) on meal pattern and microstructure of ingestive behavior in rats. Intra-NAcC Ex9 treatment selectively increased meal size relative to vehicle in rats consuming 0.25 M sucrose solution or sweetened condensed milk. Microstructural analysis revealed effects of NAcC Ex9 on initial lick rate and the size and duration of licking bursts in rats consuming 0.1 or 0.25 M sucrose, suggesting that blockade of NAcC GLP-1R increases palatability. Because NAcC Ex9 did not affect licking for nonnutritive saccharin (0.1%), we suggest that the presence of nutrients in the gut may be required for endogenous stimulation of NAcC GLP-1R. Consistent with this, we also found that the meal size-suppressive effects of intragastric nutrient infusion were attenuated by NAcC delivery of Ex9 at a dose that had no effect when delivered alone. Analysis of licking patterns revealed that NAcC Ex9 did not reverse intragastric nutrient-induced suppression of burst number but rather blunted the effect of nutrient infusion on meal size primarily by increasing the size and duration of licking bursts. Together, our results suggest that NAcC Ex9 influences taste evaluation. We conclude that GLP-1 released in NAcC in response to gastrointestinal nutrients reduces the hedonic value of food. PMID:23612998

  6. Nucleus accumbens GLP-1 receptors influence meal size and palatability

    PubMed Central

    Dossat, Amanda M.; Diaz, Ryan; Gallo, Lindsay; Panagos, Alyssa; Kay, Kristen

    2013-01-01

    Recent evidence suggests that the glucagon-like peptide-1 (GLP-1) neuronal projection to the nucleus accumbens core (NAcC) contributes to food intake control. To investigate the role of endogenous stimulation of GLP-1 receptors (GLP-1R) in NAcC, we examined the effects of the GLP-1R antagonist exendin-(9–39) (Ex9) on meal pattern and microstructure of ingestive behavior in rats. Intra-NAcC Ex9 treatment selectively increased meal size relative to vehicle in rats consuming 0.25 M sucrose solution or sweetened condensed milk. Microstructural analysis revealed effects of NAcC Ex9 on initial lick rate and the size and duration of licking bursts in rats consuming 0.1 or 0.25 M sucrose, suggesting that blockade of NAcC GLP-1R increases palatability. Because NAcC Ex9 did not affect licking for nonnutritive saccharin (0.1%), we suggest that the presence of nutrients in the gut may be required for endogenous stimulation of NAcC GLP-1R. Consistent with this, we also found that the meal size-suppressive effects of intragastric nutrient infusion were attenuated by NAcC delivery of Ex9 at a dose that had no effect when delivered alone. Analysis of licking patterns revealed that NAcC Ex9 did not reverse intragastric nutrient-induced suppression of burst number but rather blunted the effect of nutrient infusion on meal size primarily by increasing the size and duration of licking bursts. Together, our results suggest that NAcC Ex9 influences taste evaluation. We conclude that GLP-1 released in NAcC in response to gastrointestinal nutrients reduces the hedonic value of food. PMID:23612998

  7. Cannabinoid receptor 1-expressing neurons in the nucleus accumbens.

    PubMed

    Winters, Bradley D; Krüger, Juliane M; Huang, Xiaojie; Gallaher, Zachary R; Ishikawa, Masago; Czaja, Krzysztof; Krueger, James M; Huang, Yanhua H; Schlüter, Oliver M; Dong, Yan

    2012-10-01

    Endocannabinoid signaling critically regulates emotional and motivational states via activation of cannabinoid receptor 1 (CB1) in the brain. The nucleus accumbens (NAc) functions to gate emotional and motivational responses. Although expression of CB1 in the NAc is low, manipulation of CB1 signaling within the NAc triggers robust emotional/motivational alterations related to drug addiction and other psychiatric disorders, and these effects cannot be exclusively attributed to CB1 located at afferents to the NAc. Rather, CB1-expressing neurons in the NAc, although sparse, appear to be critical for emotional and motivational responses. However, the cellular properties of these neurons remain largely unknown. Here, we generated a knock-in mouse line in which CB1-expressing neurons expressed the fluorescent protein td-Tomato (tdT). Using these mice, we demonstrated that tdT-positive neurons within the NAc were exclusively fast-spiking interneurons (FSIs). These FSIs were electrically coupled with each other, and thus may help synchronize populations/ensembles of NAc neurons. CB1-expressing FSIs also form GABAergic synapses on adjacent medium spiny neurons (MSNs), providing feed-forward inhibition of NAc output. Furthermore, the membrane excitability of tdT-positive FSIs in the NAc was up-regulated after withdrawal from cocaine exposure, an effect that might increase FSI-to-MSN inhibition. Taken together with our previous findings that the membrane excitability of NAc MSNs is decreased during cocaine withdrawal, the present findings suggest that the basal functional output of the NAc is inhibited during cocaine withdrawal by multiple mechanisms. As such, CB1-expressing FSIs are targeted by cocaine exposure to influence the overall functional output of the NAc. PMID:23012412

  8. Expression of c-Fos protein in medial septum/diagonal band of Broca and CA3 region, associated with the temporary inactivation of the supramammillary area.

    PubMed

    Aranda, Lourdes

    2016-07-01

    The supramammillary (SuM) area is part of the diencephalic nuclei comprising the mammillary bodies, and is a key structure in the memory and spatial learning processes. It is a critical region in the modulation/generation of hippocampal theta rhythm. In addition, many papers have recently shown a clear involvement of this structure in the processes of spatial learning and memory in animal models, although it is still not known how it modulates spatial navigation and response emotional. The aim of the present research was to study the effect of the temporary inactivation of the SuM area on synaptic plasticity of crucial structures in the formation of spatial memory and emotional response. Sprague-Dawley rats were asigned in three groups: a control group where the animals were not subjected to any treatment, and two groups where the rats received microinjections of tetrodotoxin (TTX) in the SuM area (5ng diluted in 0.5μl of saline) or saline (0.5μl). The microinjections were administered 90min before the perfusion. Later, cellular activity in medial septum/diagonal band of Broca (MS/DBB) and CA3 region of the dorsal hippocampus was assessed, by measuring the immediate early gene c-fos. The results show a clear hiperactivity cellular in medial septum/diagonal band of Broca and a clear hypoactivity cellular in the CA3 region of the hippocampus when there was a functional inactivation of the SuM area. It suggests that the SuM area seems to be part of the connection and information input pathways to CA3 region of the hippocampal formation, key for proper functioning in spatial memory and emotional response. PMID:26802745

  9. Bekki--Nozaki Hole in Traveling Excited Waves on Human Cardiac Interventricular Septum

    NASA Astrophysics Data System (ADS)

    Bekki, Naoaki; Harada, Yoshifumi; Kanai, Hiroshi

    2012-07-01

    We observe some phase singularities in traveling excited waves noninvasively measured by a novel ultrasonic method, on a human cardiac interventricular septum (IVS) for a healthy young male. We present a possible physical model explaining a part of one-dimensional cardiac dynamics of the observed phase defects on the IVS. We show that at least one of the observed phase singularities in the excited waves on the IVS can be explained by the Bekki--Nozaki hole solution in the complex Ginzburg--Landau equation, although the creation and annihilation of phase singularities on the IVS give birth to a variety of complex patterns.

  10. Pulmonary atresia with intact ventricular septum and hypoplastic right ventricle in an Arabian foal.

    PubMed

    Krüger, M U; Wünschmann, A; Ward, C; Stauthammer, C D

    2016-09-01

    Pulmonary atresia with intact ventricular septum, rudimentary tricuspid valve, hypoplastic right ventricle, and right-to-left atrial shunting were identified in a four-day-old, male Arabian foal with clinical signs of cyanotic heart disease. Pulmonary blood flow was apparently derived from a ductus arteriosus. Echocardiographic evaluation revealed the majority of cardiac abnormalities and also findings compatible with right-sided congestive heart failure. Congenital cardiac defects have a high incidence in this breed, and this is the first description of this combination of congenital cardiac defects. PMID:27283083

  11. Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats.

    PubMed

    Salti, Ahmad; Kummer, Kai K; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

    2015-12-01

    We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. PMID:26300300

  12. Phosphorylation of Bni4 by MAP kinases contributes to septum assembly during yeast cytokinesis.

    PubMed

    Pérez, Jacqueline; Arcones, Irene; Gómez, Alberto; Casquero, Verónica; Roncero, César

    2016-09-01

    Previous work has shown that the synthetic lethality of the slt2Δrim101Δ mutant results from a combination of factors, including improper functioning of the septum assembly machinery. Here, we identify new multicopy suppressors of this lethality including Kss1, Pcl1 and Sph1, none of which seems to be linked to the upregulation of chitin synthesis. Characterization of the suppression mediated by Kss1 showed that it is independent of the transcriptional response of the CWI signaling response, but efficiently restores the Bni4 localization defects produced by the absence of Slt2. Accordingly, Bni4 interacts physically with both kinases, and its levels of phosphorylation are reduced in the slt2Δ mutant but increased after Kss1 overexpression. Using an assay based on hypersensitive cells of the cdc10-11 mutant, we have pinpointed several MAP kinase phosphorylatable residues required for Bni4 function. Our results, together with a genetic correlation analysis, strongly support a functional model linking Slt2 MAP kinase and Pcl1, a Pho85 cyclin-dependent kinase, in septum assembly through Bni4. This model, based on the coordinated phosphorylation of Bni4 by both kinases, would be able to integrate cellular signals rapidly to maintain cell integrity during cytokinesis. PMID:27400980

  13. Enhanced chondrogenesis of human nasal septum derived progenitors on nanofibrous scaffolds.

    PubMed

    Shafiee, Abbas; Seyedjafari, Ehsan; Sadat Taherzadeh, Elham; Dinarvand, Peyman; Soleimani, Masoud; Ai, Jafar

    2014-07-01

    Topographical cues can be exploited to regulate stem cell attachment, proliferation, differentiation and function in vitro and in vivo. In this study, we aimed to investigate the influence of different nanofibrous topographies on the chondrogenic differentiation potential of nasal septum derived progenitors (NSP) in vitro. Aligned and randomly oriented Ploy (l-lactide) (PLLA)/Polycaprolactone (PCL) hybrid scaffolds were fabricated via electrospinning. First, scaffolds were fully characterized, and then NSP were seeded on them to study their capacity to support stem cell attachment, proliferation and chondrogenic differentiation. Compared to randomly oriented nanofibers, aligned scaffolds showed a high degree of nanofiber alignment with much better tensile strength properties. Both scaffolds supported NSP adhesion, proliferation and chondrogenic differentiation. Despite the higher rate of cell proliferation on random scaffolds, a better chondrogenic differentiation was observed on aligned nanofibers as deduced from higher expression of chondrogenic markers such as collagen type II and aggrecan on aligned scaffolds. These findings demonstrate that electrospun constructs maintain NSP proliferation and differentiation, and that the aligned nanofibrous scaffolds can significantly enhance chondrogenic differentiation of nasal septum derived progenitors. PMID:24857513

  14. [Rupture of the interventricular septum after the blunt trauma of thorax].

    PubMed

    Smejkal, K; Parízková, R; Harrer, J; Lukes, A; Koudelka, J; Zvák, I

    2008-02-01

    Authors present the case of little patient with the dissection, pseudoaneurysm and finally a rupture of the interventricular septum after the blunt thracic injury. The patient was smitten as a pedestrian by a car and during the whole period of her stay in the hospital she was showing signs of circulatory instability. Due to the current intraabdominal injuries this circulatory decompensation was first assigned to hemoperitoneum, for which the girl was operated on about 3 hours after admission. Nevertheless, even after the abdminal cavity check, after the treatment of supreficial liver lacerations and intensive volume resuscitation the patient showed signs of insufficiency. Diagnosis was finally determined on the base of the transthoracic echocardiography (TTE), which proved the traumatic rupture of interventricular septum. The operation followed correcting the defect, which was performed with a good result according to the TTE postoperatively. Nevertheless, 27 hours after the admission the patient died due to the electromechanical dissociation. In the discussion the authors then evoke a number of papers concerning the same topic. PMID:18380159

  15. Pacing the right ventricular outflow tract septum: time to embrace the future.

    PubMed

    Hillock, Richard J; Mond, Harry G

    2012-01-01

    Transvenous pacing has revolutionized the management of patients with potentially life-threatening bradycardias and at its most basic level ensures rate support to maintain cardiac output. However, we have known for at least a decade that pacing from the right ventricle (RV) apex can induce left ventricle (LV) dysfunction, atrial fibrillation, heart failure, and maybe an increased mortality. Although pacemaker manufacturers have developed successful pacing algorithms designed to minimize unnecessary ventricular pacing, it cannot be avoided in a substantial proportion of pacemaker-dependent patients. Just as there is undoubted evidence that RV apical pacing is injurious, there is emerging evidence that pacing from the RV septum is associated with a shorter duration of activation, improved haemodynamics, and less LV remodelling. The move from traditional RV apical pacing to RV septal pacing requires a change in mindset for many practitioners. The anatomical landmarks and electrocardiograph features of RV septal pacing are well described and easily recognized. While active fixation is required to place the lead on the septum, shaped stylets are now available to assist the implanter. In addition, concerns about the stability and longevity of steroid-eluting active fixation leads have proven to be unfounded. We therefore encourage all implanters to adopt RV septal pacing to minimize the potential of harm to their patients. PMID:21846639

  16. CyDiv, a Conserved and Novel Filamentous Cyanobacterial Cell Division Protein Involved in Septum Localization

    PubMed Central

    Mandakovic, Dinka; Trigo, Carla; Andrade, Derly; Riquelme, Brenda; Gómez-Lillo, Gabriela; Soto-Liebe, Katia; Díez, Beatriz; Vásquez, Mónica

    2016-01-01

    Cell division in bacteria has been studied mostly in Escherichia coli and Bacillus subtilis, model organisms for Gram-negative and Gram-positive bacteria, respectively. However, cell division in filamentous cyanobacteria is poorly understood. Here, we identified a novel protein, named CyDiv (Cyanobacterial Division), encoded by the all2320 gene in Anabaena sp. PCC 7120. We show that CyDiv plays a key role during cell division. CyDiv has been previously described only as an exclusive and conserved hypothetical protein in filamentous cyanobacteria. Using polyclonal antibodies against CyDiv, we showed that it localizes at different positions depending on cell division timing: poles, septum, in both daughter cells, but also in only one of the daughter cells. The partial deletion of CyDiv gene generates partial defects in cell division, including severe membrane instability and anomalous septum localization during late division. The inability to complete knock out CyDiv strains suggests that it is an essential gene. In silico structural protein analyses and our experimental results suggest that CyDiv is an FtsB/DivIC-like protein, and could therefore, be part of an essential late divisome complex in Anabaena sp. PCC 7120. PMID:26903973

  17. Regulation of septum formation by the Bud3-Rho4 GTPase module in Aspergillus nidulans.

    PubMed

    Si, Haoyu; Justa-Schuch, Daniela; Seiler, Stephan; Harris, Steven D

    2010-05-01

    The ability of fungi to generate polarized cells with a variety of shapes likely reflects precise temporal and spatial control over the formation of polarity axes. The bud site selection system of Saccharomyces cerevisiae represents the best-understood example of such a morphogenetic regulatory system. However, the extent to which this system is conserved in the highly polarized filamentous fungi remains unknown. Here, we describe the functional characterization and localization of the Aspergillus nidulans homolog of the axial bud site marker Bud3. Our results show that AnBud3 is not required for polarized hyphal growth per se, but is involved in septum formation. In particular, our genetic and biochemical evidence implicates AnBud3 as a guanine nucleotide exchange factor for the GTPase Rho4. Additional results suggest that the AnBud3-Rho4 module acts downstream of the septation initiation network to mediate recruitment of the formin SepA to the site of contractile actin ring assembly. Our observations provide new insight into the signaling pathways that regulate septum formation in filamentous fungi. PMID:20176976

  18. Nasal septum changes in adolescent patients treated with rapid maxillary expansion

    PubMed Central

    Aziz, Tehnia; Wheatley, Francis Carter; Ansari, Kal; Lagravere, Manuel; Major, Michael; Flores-Mir, Carlos

    2016-01-01

    Objective: To analyze cone-beam computed tomography (CBCT) scans to measure changes in nasal septal deviation (NSD) after rapid maxillary expansion (RME) treatment in adolescent patients. Methods: This retrospective study involved 33 patients presenting with moderate to severe nasal septum deviation as an incidental finding. Out of these 33 patients, 26 were treated for transverse maxillary constriction with RME and seven, who did not undergo RME treatment, were included in the study as control group. CBCT scans were taken before appliance insertion and after appliance removal. These images were analyzed to measure changes in nasal septum deviation (NSD). Analysis of variance for repeated measures (ANOVA) was used. Results: No significant changes were identified in NSD regardless of the application or not of RME treatment and irrespective of the baseline deviation degree. Conclusion: This study did not provide strong evidence to suggest that RME treatment has any effect on NSD in adolescent patients; however, the results should be interpreted with caution, due to the small sample size and large variation amongst individual patient characteristics. PMID:27007761

  19. Interaction of a vasopressin antagonist with vasopressin receptors in the septum of the rat brain

    SciTech Connect

    Dorsa, D.M.; Brot, M.D.; Shewey, L.M.; Meyers, K.M.; Szot, P.; Miller, M.A.

    1988-01-01

    The ability of d(CH2)5-Tyr(Me)-arginine-8-vasopressin, an antagonist of peripheral pressoric (V1-type) vasopressin receptors, to label vasopressin binding sites in the septum of the rat brain was evaluated. Using crude membrane preparations from the septum, /sup 3/H-arginine-8-vasopressin (AVP) specifically labels a single class of binding sites with a Kd of 2.9 nM and maximum binding site concentration of 19.8 fmole/mg protein. /sup 3/H-Antag also labels a single class of membrane sites but with higher affinity (Kd = 0.47 nM) and lower capacity (10.1 fmole/mg protein) than /sup 3/H-AVP. The rank order of potency of various competitor peptides for /sup 3/H-AVP and /sup 3/H-Antag binding was similar. Oxytocin was 100-1,000 fold less potent than AVP in competing for binding with both ligands. /sup 3/H-AVP and /sup 3/H-Antag showed similar labeling patterns when incubated with septal tissue slices. Unlabeled Antag also effectively antagonized vasopressin-stimulated phosphatidylinositol hydrolysis in septal tissue slices.

  20. Beneficial effect of cibenzoline on left ventricular pressure gradient with sigmoid septum.

    PubMed

    Konishi, Chika; Shiraishi, Jun; Muraguchi, Naoko; Ohtsuki, Katsuichi; Inoue, Miho; Tatsumi, Tetsuya; Azuma, Akihiro; Matsubara, Hiroaki

    2004-10-01

    An 83-year-old woman with hypertension was admitted to hospital with episodes of dyspnea on effort after having breakfast. Physical examination revealed a systolic murmur at the left sternal border in the third to fourth intercostal space. Cross-sectional echocardiography showed a sigmoid-shaped interventricular septum markedly protruding into the left ventricle, concentric left ventricular hypertrophy, systolic anterior motion of the mitral valve, and a resultant left ventricular outflow tract obstruction with a pressure gradient of 121.8 mmHg. She began daily treatment with 60 mg metoprolol. However, the chest symptoms were not relieved and the left ventricular outflow tract obstruction was still visible on echocardiography. She was then given 200 mg daily of cibenzoline, in addition to 40 mg metoprolol, and the left ventricular pressure gradient significantly decreased and she was free of symptoms without any complications. This case shows that cibenzoline may be useful in the treatment of left ventricular outflow tract obstruction caused by sigmoid septum. PMID:15459474

  1. Low-Velocity Nail-Gun Injuries to the Interventricular Septum: Report of Two Cases, One in a Child

    PubMed Central

    Michalsen, Kara L.; Iguidbashian, John P.; Kyser, James P.

    2015-01-01

    Nail-gun injury to the heart is rare. Nail-gun injury to the interventricular septum is rarer: we could find only 5 reported cases, and none involving a child. We report 2 additional cases, in which nails penetrated the interventricular septum without causing acute pericardial tamponade, heart block, or shunt across the septum. Transesophageal echocardiography provides a dynamic way to evaluate the patient preoperatively, intraoperatively, and postoperatively. In the cases reported here, both the adult with multiple interventricular nails and the child with a single nail underwent foreign-object removal via median sternotomy. The child needed cardiopulmonary bypass for removal of the nail. There were no short-term or long-term sequelae from these interventricular septal injuries. PMID:26413027

  2. Nucleus accumbens μ-opioid receptors mediate social reward.

    PubMed

    Trezza, Viviana; Damsteegt, Ruth; Achterberg, E J Marijke; Vanderschuren, Louk J M J

    2011-04-27

    Positive social interactions are essential for emotional well-being and proper behavioral development of young individuals. Here, we studied the neural underpinnings of social reward by investigating the involvement of opioid neurotransmission in the nucleus accumbens (NAc) in social play behavior, a highly rewarding social interaction in adolescent rats. Intra-NAc infusion of morphine (0.05-0.1 μg) increased pinning and pouncing, characteristic elements of social play behavior in rats, and blockade of NAc opioid receptors with naloxone (0.5 μg) prevented the play-enhancing effects of systemic morphine (1 mg/kg, s.c.) administration. Thus, stimulation of opioid receptors in the NAc was necessary and sufficient for morphine to increase social play. Intra-NAc treatment with the selective μ-opioid receptor agonist [D-Ala(2),N-MePhe(4),Gly(5)-ol]enkephalin (DAMGO) (0.1-10 ng) and the μ-opioid receptor antagonist Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP) (0.3-3 μg) increased and decreased social play, respectively. The δ-opioid receptor agonist DPDPE ([D-Pen(2),D-Pen(5)]-enkephalin) (0.3-3 μg) had no effects, whereas the κ-opioid receptor agonist U69593 (N-methyl-2-phenyl-N-[(5R,7S,8S)-7-(pyrrolidin-1-yl)-1-oxaspiro[4.5]dec-8-yl]acetamide) (0.01-1 μg) decreased social play. Intra-NAc treatment with β-endorphin (0.01-1 μg) increased social play, but met-enkephalin (0.1-5 μg) and the enkephalinase inhibitor thiorphan (0.1-1 μg) were ineffective. DAMGO (0.1-10 ng) increased social play after infusion into both the shell and core subregions of the NAc. Last, intra-NAc infusion of CTAP (3 μg) prevented the development of social play-induced conditioned place preference. These findings identify NAc μ-opioid receptor stimulation as an important neural mechanism for the attribution of positive value to social interactions in adolescent rats. Altered NAc μ-opioid receptor function may underlie social impairments in psychiatric disorders such as autism

  3. Swallowing-Induced Atrial Tachyarrhythmias Successfully Ablated at the Left Posterior Interatrial Septum in Patient with Wolff-Parkinson-White Syndrome

    PubMed Central

    Ban, Ji-Eun; Lee, Hyun-Soo; Choi, Jong-Il; Kim, Young-Hoon

    2015-01-01

    We reported a case of a 55-year-old patient who presented with palpitation after swallowing. Initial surface electrocardiogram revealed ventricular preexcitation utilizing a left lateral bypass tract. The orthodromic atrioventricular reentrant tachycardia (AVRT) was induced during electrophysiologic studies. After successful ablation of the AVRT utilizing a left lateral free wall bypass tract, 2 different atrial tachycardias (ATs) were induced under isoproterenol infusion. When the patient swallowed saliva or drank water, 2 consecutive beats of atrial premature complexes (APCs) preceded another non-sustained AT repeatedly, which was coincident with the patient's symptom. The preceding APC couplet had the same activation sequence with one induced AT, and the subsequent non-sustained AT had the same activation sequence with the other induced AT, respectively. We first targeted the preceding 2 consecutive APCs at the left posterior interatrial septum. The following non-sustained AT was also eliminated following ablation of the APCs. After ablation, the patient remained free from the swallowing-induced atrial tachyarrhythmias during the one year follow-up. PMID:26023316

  4. Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens

    PubMed Central

    Hadar, R; Vengeliene, V; Barroeta Hlusicke, E; Canals, S; Noori, H R; Wieske, F; Rummel, J; Harnack, D; Heinz, A; Spanagel, R; Winter, C

    2016-01-01

    Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse. PMID:27327255

  5. Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens.

    PubMed

    Hadar, R; Vengeliene, V; Barroeta Hlusicke, E; Canals, S; Noori, H R; Wieske, F; Rummel, J; Harnack, D; Heinz, A; Spanagel, R; Winter, C

    2016-01-01

    Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse. PMID:27327255

  6. Invigoration of reward-seeking by cue and proximity encoding in the nucleus accumbens

    PubMed Central

    McGinty, Vincent B.; Lardeux, Sylvie; Taha, Sharif A.; Kim, James J.; Nicola, Saleem M.

    2014-01-01

    Summary A key function of the nucleus accumbens is to promote vigorous reward-seeking, but the corresponding neural mechanism has not been identified despite many years of research. Here we study cued flexible approach behavior, a form of reward-seeking that strongly depends on the accumbens, and we describe a robust, single-cell neural correlate of behavioral vigor in the excitatory response of accumbens neurons to reward-predictive cues. Well before locomotion begins, this cue-evoked excitation predicts both the movement initiation latency and speed of subsequent flexible approach responses, but not of stereotyped, inflexible responses. Moreover, the excitation simultaneously signals the subject’s proximity to the approach target, a signal that appears to mediate greater response vigor on trials that begin with the subject closer to the target. These results demonstrate a neural mechanism for response invigoration whereby accumbens neuronal encoding of reward availability and target proximity together drive the onset and speed of reward-seeking locomotion. PMID:23764290

  7. Good Vibrations: Cross-Frequency Coupling in the Human Nucleus Accumbens during Reward Processing

    ERIC Educational Resources Information Center

    Cohen, Michael X.; Axmacher, Nikolai; Lenartz, Doris; Elger, Christian E.; Sturm, Volker; Schlaepfer, Thomas E.

    2009-01-01

    The nucleus accumbens is critical for reward-guided learning and decision-making. It is thought to "gate" the flow of a diverse range of information (e.g., rewarding, aversive, and novel events) from limbic afferents to basal ganglia outputs. Gating and information encoding may be achieved via cross-frequency coupling, in which bursts of…

  8. The Role of the Nucleus Accumbens in Knowing when to Respond

    ERIC Educational Resources Information Center

    Singh, Teghpal; McDannald, Michael A.; Takahashi, Yuji K.; Haney, Richard Z.; Cooch, Nisha K.; Lucantonio, Federica; Schoenbaum, Geoffrey

    2011-01-01

    While knowing what to expect is important, it is equally important to know when to expect it and to respond accordingly. This is apparent even in simple Pavlovian training situations in which animals learn to respond more strongly closer to reward delivery. Here we report that the nucleus accumbens core, an area well-positioned to represent…

  9. Atypical nucleus accumbens morphology in psychopathy: another limbic piece in the puzzle.

    PubMed

    Boccardi, Marina; Bocchetta, Martina; Aronen, Hannu J; Repo-Tiihonen, Eila; Vaurio, Olli; Thompson, Paul M; Tiihonen, Jari; Frisoni, Giovanni B

    2013-01-01

    Psychopathy has been associated with increased putamen and striatum volumes. The nucleus accumbens - a key structure in reversal learning, less effective in psychopathy - has not yet received specific attention. Moreover, basal ganglia morphology has never been explored. We examined the morphology of the caudate, putamen and accumbens, manually segmented from magnetic resonance images of 26 offenders (age: 32.5 ± 8.4) with medium-high psychopathy (mean PCL-R=30 ± 5) and 25 healthy controls (age: 34.6 ± 10.8). Local differences were statistically modeled using a surface-based radial distance mapping method (p<0.05; multiple comparisons correction through permutation tests). In psychopathy, the caudate and putamen had normal global volume, but different morphology, significant after correction for multiple comparisons, for the right dorsal putamen (permutation test: p=0.02). The volume of the nucleus accumbens was 13% smaller in psychopathy (p corrected for multiple comparisons <0.006). The atypical morphology consisted of predominant anterior hypotrophy bilaterally (10-30%). Caudate and putamen local morphology displayed negative correlation with the lifestyle factor of the PCL-R (permutation test: p=0.05 and 0.03). From these data, psychopathy appears to be associated with an atypical striatal morphology, with highly significant global and local differences of the accumbens. This is consistent with the clinical syndrome and with theories of limbic involvement. PMID:23399314

  10. Accumbens Shell AMPA Receptors Mediate Expression of Extinguished Reward Seeking through Interactions with Basolateral Amygdala

    ERIC Educational Resources Information Center

    Millan, E. Zayra; McNally, Gavan P.

    2011-01-01

    Extinction is the reduction in drug seeking when the contingency between drug seeking behavior and the delivery of drug reward is broken. Here, we investigated a role for the nucleus accumbens shell (AcbSh). Rats were trained to respond for 4% (v/v) alcoholic beer in one context (Context A) followed by extinction in a second context (Context B).…

  11. Activity in the nucleus accumbens and amygdala underlies individual differences in prosocial and individualistic economic choices.

    PubMed

    Haruno, Masahiko; Kimura, Minoru; Frith, Christopher D

    2014-08-01

    Much decision-making requires balancing benefits to the self with benefits to the group. There are marked individual differences in this balance such that individualists tend to favor themselves whereas prosocials tend to favor the group. Understanding the mechanisms underlying this difference has important implications for society and its institutions. Using behavioral and fMRI data collected during the performance of the ultimatum game, we show that individual differences in social preferences for resource allocation, so-called "social value orientation," is linked with activity in the nucleus accumbens and amygdala elicited by inequity, rather than activity in insula, ACC, and dorsolateral pFC. Importantly, the presence of cognitive load made prosocials behave more prosocially and individualists more individualistically, suggesting that social value orientation is driven more by intuition than reflection. In parallel, activity in the nucleus accumbens and amygdala, in response to inequity, tracked this behavioral pattern of prosocials and individualists. In addition, we conducted an impunity game experiment with different participants where they could not punish unfair behavior and found that the inequity-correlated activity seen in prosocials during the ultimatum game disappeared. This result suggests that the accumbens and amygdala activity of prosocials encodes "outcome-oriented emotion" designed to change situations (i.e., achieve equity or punish). Together, our results suggest a pivotal contribution of the nucleus accumbens and amygdala to individual differences in sociality. PMID:24564471

  12. Harmine augments electrically evoked dopamine efflux in the nucleus accumbens shell.

    PubMed

    Brierley, Daniel I; Davidson, Colin

    2013-01-01

    Harmine is a β-carboline alkaloid and major component of ayahuasca, a traditional South American psychoactive tea with anecdotal efficacy for treatment of cocaine dependence. Harmine is an inhibitor of monoamine oxidase A (MAO-A) and interacts in vitro with several pharmacological targets which modulate dopamine (DA) neurotransmission. In vivo studies have demonstrated dopaminergic effects of harmine, attributed to monoamine oxidase inhibitor (MAOI) activity, however none have directly demonstrated a pharmacological mechanism. This study investigated the acute effects, and pharmacological mechanism(s), of harmine on electrically evoked DA efflux parameters in the nucleus accumbens both in the absence and presence of cocaine. Fast cyclic voltammetry in rat brain slices was used to measure electrically evoked DA efflux in accumbens core and shell. Harmine (300 nM) significantly augmented DA efflux (148±8% of baseline) in the accumbens shell. Cocaine augmented efflux in shell additive to harmine (260±35%). Harmine had no effect on efflux in the accumbens core or on reuptake in either sub-region. The effect of harmine in the shell was attenuated by the 5-HT(2A/2C) antagonist ketanserin. The MAOI moclobemide (10 µM) had no effect on DA efflux. These data suggest that harmine augments DA efflux via a novel, shell-specific, presynaptic 5-HT(2A) receptor-dependent mechanism, independent of MAOI activity. A DA-releasing 'agonist therapy' mechanism may thus contribute to the putative therapeutic efficacy of ayahuasca for cocaine dependence. PMID:23076833

  13. Excitant amino acid projections from rat amygdala and thalamus to nucleus accumbens

    SciTech Connect

    Robinson, T.G.; Beart, P.M.

    1988-04-01

    High affinity uptake of D-(/sup 3/H)aspartate, (/sup 3/H)choline and (/sup 3/H)GABA was examined in synaptosomal-containing preparations of rat nucleus accumbens septi 7 to 10 days after unilateral or bilateral N-methyl-D-aspartate lesions confined to the parataenial nucleus of the thalamus or the basolateral nucleus of the amygdala. Uptake of both D-(/sup 3/H)aspartate and (/sup 3/H)choline was significantly reduced (11% and 14% less than control, respectively) by unilateral lesion of the thalamus, whereas (/sup 3/H)GABA uptake was unaffected. Bilateral thalamic lesions significantly reduced D-(/sup 3/H)aspartate uptake (11% less than control) into homogenates of the nucleus accumbens, whilst (/sup 3/H)GABA uptake was unaltered. D-(/sup 3/H)aspartate uptake was significantly reduced (26% less than control) following unilateral lesion of the amygdala, whereas both (/sup 3/H)GABA and (/sup 3/H)choline uptake were unaffected. Bilateral amygdaloid lesions significantly increased D-(/sup 3/H)aspartate uptake (39% greater than control), whilst uptake of (/sup 3/H)GABA was not affected. The results implicate glutamate and/or aspartate as putative neurotransmitters in afferent projections from the basolateral amygdala and the parataenial thalamus to the nucleus accumbens. Thalamic afferents to the nucleus accumbens may also utilize acetylcholine as their transmitter.

  14. Hedonic and Nucleus Accumbens Neural Responses to a Natural Reward Are Regulated by Aversive Conditioning

    ERIC Educational Resources Information Center

    Roitman, Mitchell F.; Wheeler, Robert A.; Tiesinga, Paul H. E.; Roitman, Jamie D.; Carelli, Regina M.

    2010-01-01

    The nucleus accumbens (NAc) plays a role in hedonic reactivity to taste stimuli. Learning can alter the hedonic valence of a given stimulus, and it remains unclear how the NAc encodes this shift. The present study examined whether the population response of NAc neurons to a taste stimulus is plastic using a conditioned taste aversion (CTA)…

  15. Individual Differences in Dopamine Efflux in Nucleus Accumbens Shell and Core during Instrumental Learning

    ERIC Educational Resources Information Center

    Cheng, Jingjun; Feenstra, Matthijs G. P.

    2006-01-01

    Combined activation of dopamine D1- and NMDA-glutamate receptors in the nucleus accumbens has been strongly implicated in instrumental learning, the process in which an individual learns that a specific action has a wanted outcome. To assess dopaminergic activity, we presented rats with two sessions (30 trials each) of a one-lever appetitive…

  16. Functional and structural deficits at accumbens synapses in a mouse model of Fragile X

    PubMed Central

    Neuhofer, Daniela; Henstridge, Christopher M.; Dudok, Barna; Sepers, Marja; Lassalle, Olivier; Katona, István; Manzoni, Olivier J.

    2015-01-01

    Fragile X is the most common cause of inherited intellectual disability and a leading cause of autism. The disease is caused by mutation of a single X-linked gene called fmr1 that codes for the Fragile X mental retardation protein (FMRP), a 71 kDa protein, which acts mainly as a translation inhibitor. Fragile X patients suffer from cognitive and emotional deficits that coincide with abnormalities in dendritic spines. Changes in spine morphology are often associated with altered excitatory transmission and long-term plasticity, the most prominent deficit in fmr1-/y mice. The nucleus accumbens, a central part of the mesocortico-limbic reward pathway, is now considered as a core structure in the control of social behaviors. Although the socio-affective impairments observed in Fragile X suggest dysfunctions in the accumbens, the impact of the lack of FMRP on accumbal synapses has scarcely been studied. Here we report for the first time a new spike timing-dependent plasticity paradigm that reliably triggers NMDAR-dependent long-term potentiation (LTP) of excitatory afferent inputs of medium spiny neurons (MSN) in the nucleus accumbens core region. Notably, we discovered that this LTP was completely absent in fmr1-/y mice. In the fmr1-/y accumbens intrinsic membrane properties of MSNs and basal excitatory neurotransmission remained intact in the fmr1-/y accumbens but the deficit in LTP was accompanied by an increase in evoked AMPA/NMDA ratio and a concomitant reduction of spontaneous NMDAR-mediated currents. In agreement with these physiological findings, we found significantly more filopodial spines in fmr1-/y mice by using an ultrastructural electron microscopic analysis of accumbens core medium spiny neuron spines. Surprisingly, spine elongation was specifically due to the longer longitudinal axis and larger area of spine necks, whereas spine head morphology and postsynaptic density size on spine heads remained unaffected in the fmr1-/y accumbens. These findings

  17. Functional and structural deficits at accumbens synapses in a mouse model of Fragile X.

    PubMed

    Neuhofer, Daniela; Henstridge, Christopher M; Dudok, Barna; Sepers, Marja; Lassalle, Olivier; Katona, István; Manzoni, Olivier J

    2015-01-01

    Fragile X is the most common cause of inherited intellectual disability and a leading cause of autism. The disease is caused by mutation of a single X-linked gene called fmr1 that codes for the Fragile X mental retardation protein (FMRP), a 71 kDa protein, which acts mainly as a translation inhibitor. Fragile X patients suffer from cognitive and emotional deficits that coincide with abnormalities in dendritic spines. Changes in spine morphology are often associated with altered excitatory transmission and long-term plasticity, the most prominent deficit in fmr1-/y mice. The nucleus accumbens, a central part of the mesocortico-limbic reward pathway, is now considered as a core structure in the control of social behaviors. Although the socio-affective impairments observed in Fragile X suggest dysfunctions in the accumbens, the impact of the lack of FMRP on accumbal synapses has scarcely been studied. Here we report for the first time a new spike timing-dependent plasticity paradigm that reliably triggers NMDAR-dependent long-term potentiation (LTP) of excitatory afferent inputs of medium spiny neurons (MSN) in the nucleus accumbens core region. Notably, we discovered that this LTP was completely absent in fmr1-/y mice. In the fmr1-/y accumbens intrinsic membrane properties of MSNs and basal excitatory neurotransmission remained intact in the fmr1-/y accumbens but the deficit in LTP was accompanied by an increase in evoked AMPA/NMDA ratio and a concomitant reduction of spontaneous NMDAR-mediated currents. In agreement with these physiological findings, we found significantly more filopodial spines in fmr1-/y mice by using an ultrastructural electron microscopic analysis of accumbens core medium spiny neuron spines. Surprisingly, spine elongation was specifically due to the longer longitudinal axis and larger area of spine necks, whereas spine head morphology and postsynaptic density size on spine heads remained unaffected in the fmr1-/y accumbens. These findings

  18. Aortopulmonary window: a rare mechanism of inter-circulatory mixing and prepared left ventricle in transposition of the great arteries with intact ventricular septum.

    PubMed

    Gopalan Nair, Rajesh; Kalathingathodika, Sajeer; Bastian, Cicy

    2014-08-01

    Transposition of the great arteries with intact ventricular septum and aortopulmonary window is an extremely rare anatomic combination associated with high morbidity and mortality. We report a case of a 3-month-old baby with d-transposition of the great arteries with intact ventricular septum and a large aortopulmonary window as a mechanism of inter-circulatory mixing. PMID:24020981

  19. Violence as a source of pleasure or displeasure is associated with specific functional connectivity with the nucleus accumbens

    PubMed Central

    Porges, Eric C.; Decety, Jean

    2013-01-01

    The appraisal of violent stimuli is dependent on the social context and the perceiver's individual characteristics. To identify the specific neural circuits involved in the perception of violent videos, forty-nine male participants were scanned with functional MRI while watching video-clips depicting Mixed Martial Arts (MMA) and Capoeira as a baseline. Prior to scanning, a self-report measure of pleasure or displeasure when watching MMA was collected. Watching MMA was associated with activation of the anterior insula (AI), brainstem, ventral tegmental area (VTA), striatum, medial, and lateral prefrontal cortex, orbitofrontal cortex, somatosensory cortex, and supramarginal gyrus. While this pattern of brain activation was not related to participants' reported experience of pleasure or displeasure, pleasurable ratings of MMA predicted increased functional connectivity (FC) seeded in the nucleus accumbens (NAcc) (a structure known to be responsive to anticipating both positive and negative outcomes) with the subgenual anterior cingulate cortex (ACC) and anterior insular cortex (AIC) (regions involved in positive feelings and visceral somatic representations). Displeasure ratings of MMA were related to increased FC with regions of the prefrontal cortex and superior parietal lobule, structures implicated in cognitive control and executive attention. These data suggest that functional connectivity is an effective approach to investigate the relationship between subjective feelings of pleasure and pain of neural structures known to respond to both the anticipation of positive and negative outcomes. PMID:23964226

  20. Sex differences in interactions between nucleus accumbens and visual cortex by explicit visual erotic stimuli: an fMRI study.

    PubMed

    Lee, S W; Jeong, B S; Choi, J; Kim, J-W

    2015-01-01

    Men tend to have greater positive responses than women to explicit visual erotic stimuli (EVES). However, it remains unclear, which brain network makes men more sensitive to EVES and which factors contribute to the brain network activity. In this study, we aimed to assess the effect of sex difference on brain connectivity patterns by EVES. We also investigated the association of testosterone with brain connection that showed the effects of sex difference. During functional magnetic resonance imaging scans, 14 males and 14 females were asked to see alternating blocks of pictures that were either erotic or non-erotic. Psychophysiological interaction analysis was performed to investigate the functional connectivity of the nucleus accumbens (NA) as it related to EVES. Men showed significantly greater EVES-specific functional connection between the right NA and the right lateral occipital cortex (LOC). In addition, the right NA and the right LOC network activity was positively correlated with the plasma testosterone level in men. Our results suggest that the reason men are sensitive to EVES is the increased interaction in the visual reward networks, which is modulated by their plasma testosterone level. PMID:25971857

  1. Differential Involvement of the Basolateral Amygdala, Orbitofrontal Cortex, and Nucleus Accumbens Core in the Acquisition and Use of Reward Expectancies

    PubMed Central

    Ramirez, Donna R.; Savage, Lisa M.

    2008-01-01

    In this study, the authors tested the hypothesis that the basolateral amygdala (BLA), orbitofrontal cortex (OFC), nucleus accumbens core (NA-core), and the extended hippocampus mediate different aspects of the development–maintenance of unique reward expectancies produced by the differential outcomes procedure (DOP). Rats were trained with either DOP or a nondifferential outcomes procedure (NOP) on a simple discrimination task. Fornix lesions did not affect either version of the task, demonstrating that the extended hippocampal system has no role in stimulus–outcome (S-O) associations. In contrast, in the DOP condition, BLA lesions impaired performance throughout training, OFC lesions impaired choice accuracy only in the later maintenance phase, and NA-core lesions resulted in enhanced learning. These results suggest that BLA and OFC are important for establishment (BLA) and behavioral maintenance (OFC) of S-O associations, whereas the NA-core is not needed and can in fact impede using multiple S-O associations. No impairments were observed in the NOP condition, demonstrating that these structures are not critical to stimulus–response learning. PMID:17907822

  2. Extensive Chondrosarcoma of the Nasal Septum: Endoscopic Resection and Long-Term Follow-Up.

    PubMed

    Alqudah, Mohammad; Odat, Haitham; Issa, Ibrahim; Al-Qudah, Mohannad

    2016-06-01

    Chondrosarcoma of the nasal septum is extremely rare slow growing malignant tumor of nonepithelial origin. Preoperative differentiation between low-grade chondrosarcoma and benign cartilaginous tumors such as chondroma may be difficult. Surgical excision is the treatment of choice. Radiotherapy is reserved for residual or recurrent patients. Recent advance in endoscopic sinus surgery has allowed successful, noninvasive excision of many sinonasal tumors with low morbidity.The authors herein report, what we believe, the most extensive case of posterior nasal septal chondrosarcoma with the longest follow-up period that was completely excised endoscopically with no evidence of local or systemic recurrence after 5 years. The authors also discuss its relevant clinical presentation, diagnosis, and management. PMID:27192653

  3. Cardiac lipoma and lipomatous hypertrophy of the interatrial septum: cardiac magnetic resonance imaging findings.

    PubMed

    Salanitri, John C; Pereles, F Scott

    2004-01-01

    Cardiac lipomas are uncommon, usually asymptomatic benign primary tumors of the heart that may incidentally be discovered during computed tomography (CT) or magnetic resonance imaging (MRI). Although the finding of a low-attenuation mass with density similar to fat on CT is pathognomonic, the MRI appearances of fatty cardiac masses are variable depending on the sequences employed. The MRI findings of 4 patients with cardiac lipomas or lipomatous hypertrophy of the interatrial septum are presented. All patients had lesions with characteristic low-signal-intensity margins and high central signal intensity on "bright-blood" balanced gradient-echo cardiac MRI sequences with very low repetition and echo times. It is proposed that this appearance results from intravoxel phase cancellation effects occurring at the fat/tissue interface and is sufficiently characteristic to obviate the need for confirmatory CT. PMID:15538164

  4. Partial urorectal septum malformation sequence in a kitten with disorder of sexual development.

    PubMed

    Reynolds, Brice S; Pain, Amélie; Meynaud-Collard, Patricia; Nowacka-Woszuk, Joanna; Szczerbal, Izabela; Switonski, Marek; Chastant-Maillard, Sylvie

    2014-12-01

    A 2-month-old kitten exhibited simultaneously an imperforate anus, hypospadias, rectourethral fistula and genital dysgenesis (penis restricted to the glans, absence of prepuce and bifid scrotum). Surgical correction consisted of separation of the urinary and digestive tracts, perineal urethrostomy and connection of the rectum to the newly made anal opening. Pathological examination of the testes, conventionally removed at 9 months of age, showed no mature spermatozoa and underdevelopment of germ and Leydig cells. In humans, the absence of an anal opening in association with abnormal sexual development defines the urorectal septum malformation sequence. Here, we describe the first case of this syndrome in a kitten with a normal male karyotype (38,XY) and a normal coding sequence for the SRY gene. Both the rectourethral fistula and observed genital abnormalities might have been induced by a disturbance in the hedgehog signalling pathway. However, although four polymorphic sites were identified by DHH gene sequencing, none cosegregated with the malformation. PMID:24718294

  5. Lipomatous hypertrophy of the interatrial septum and fibrosing mediastinal lymphadenopathy causing superior vena cava obstruction

    PubMed Central

    Baikoussis, Nikolaos G.; Argiriou, Orestis; Kratimenos, Theodoros; Dedeilias, Panagiotis; Argiriou, Michalis

    2015-01-01

    Lipomatous hypertrophy of the interatrial septum (LHIS) is an uncommon cause of superior vena cava syndrome (SVCS). Fibrosing mediastinal lymphadenopathy is another cause of SVCS. We present a 65-year-old female patient with a history of tuberculosis (TB) and the coexistence of LHIS and fibrosing mediastinitis due to TB of the lung. Fibrosing or sclerosing mediastinitis is a rare entity with few cases published in the western literature. She presented with mild symptomatology of SVCS and she underwent on transthoracic and transesophageal echocardiography, computed tomography scan, magnetic resonance imaging, and venography. Due to the development of an abundant collateral venous system seen on venography and her negation for any treatment, she did not undergo yet on any intervention. To our knowledge, this is the first case reported in the international bibliography in which LHIS and sclerosing lymphadenopathy are simultaneously diagnosed in the same patient. PMID:26440257

  6. Division genes in Escherichia coli are expressed coordinately to cell septum requirements by gearbox promoters.

    PubMed

    Aldea, M; Garrido, T; Pla, J; Vicente, M

    1990-11-01

    The cell division ftsQAZ cluster and the ftsZ-dependent bolA morphogene of Escherichia coli are found to be driven by gearboxes, a distinct class of promoters characterized by showing an activity that is inversely dependent on growth rate. These promoters contain specific sequences upstream from the mRNA start point, and their -10 region is essential for the inverse growth rate dependence. Gearbox promoters are essential for driving ftsQAZ and bolA gene expression so that the encoded products are synthesized at constant amounts per cell independently of cell size. This mode of regulation would be expected for the expression of proteins that either play a regulatory role in cell division or form a stoichiometric component of the septum, a structure that, independently of cell size and growth rate, is produced once per cell cycle. PMID:1698623

  7. ‘Saddle nose’ deformity caused by advanced squamous cell carcinoma of the nasal septum

    PubMed Central

    Graham, Hamish Edward; Connolly, Cara; Pahal, Gurjinderpal S; Stafford, Francis W

    2014-01-01

    Hidden behind their common garden symptoms, malignant tumours of the nasal cavity are typically advanced when detected. Squamous cell carcinoma (SCC) is the most common histological type of these rare tumours which may simply present with epistaxis or a blocked nose. A 79-year-old woman attended our clinic with a 2-year history of progressive nasal collapse resulting in a ‘saddle nose deformity’. Imaging showed a soft tissue mass with absolute destruction of the nasal septum and bones with hard palate and maxillary involvement. Histology confirmed a poorly differentiated SCC. Following discussion at the local head and neck multidisciplinary team meeting, the patient was offered radiotherapy alone due to her advanced presentation. She has had a good response to treatment with no further disease progression. Nasal septal SCC is far more successfully treated in the early stages. A suspicious clinician is the patients best ally. PMID:25096649

  8. Role of nucleus accumbens glutamatergic plasticity in drug addiction

    PubMed Central

    Quintero, Gabriel C

    2013-01-01

    Substance dependence is characterized by a group of symptoms, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR). These symptoms include tolerance, withdrawal, drug consumption for alleviating withdrawal, exaggerated consumption beyond original intention, failure to reduce drug consumption, expending a considerable amount of time obtaining or recovering from the substance’s effects, disregard of basic aspects of life (for example, family), and maintenance of drug consumption, despite facing adverse consequences. The nucleus accumbens (NAc) is a brain structure located in the basal forebrain of vertebrates, and it has been the target of addictive drugs. Different neurotransmitter systems at the level of the NAc circuitry have been linked to the different problems of drug addiction, like compulsive use and relapse. The glutamate system has been linked mainly to relapse after drug-seeking extinction. The dopamine system has been linked mainly to compulsive drug use. The glutamate homeostasis hypothesis centers around the dynamics of synaptic and extrasynaptic levels of glutamate, and their impact on circuitry from the prefrontal cortex (PFC) to the NAc. After repetitive drug use, deregulation of this homeostasis increases the release of glutamate from the PFC to the NAc during drug relapse. Glial cells also play a fundamental role in this hypothesis; glial cells shape the interactions between the PFC and the NAc by means of altering glutamate levels in synaptic and extrasynaptic spaces. On the other hand, cocaine self-administration and withdrawal increases the surface expression of subunit glutamate receptor 1 (GluA1) of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors at the level of the NAc. Also, cocaine self-administration and withdrawal induce the formation of subunit glutamate receptor 2 (GluA2), lacking the Ca2+-permeable AMPA receptors (CP-AMPARs) at the level of the NAc

  9. Role of nucleus accumbens glutamatergic plasticity in drug addiction.

    PubMed

    Quintero, Gabriel C

    2013-01-01

    Substance dependence is characterized by a group of symptoms, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR). These symptoms include tolerance, withdrawal, drug consumption for alleviating withdrawal, exaggerated consumption beyond original intention, failure to reduce drug consumption, expending a considerable amount of time obtaining or recovering from the substance's effects, disregard of basic aspects of life (for example, family), and maintenance of drug consumption, despite facing adverse consequences. The nucleus accumbens (NAc) is a brain structure located in the basal forebrain of vertebrates, and it has been the target of addictive drugs. Different neurotransmitter systems at the level of the NAc circuitry have been linked to the different problems of drug addiction, like compulsive use and relapse. The glutamate system has been linked mainly to relapse after drug-seeking extinction. The dopamine system has been linked mainly to compulsive drug use. The glutamate homeostasis hypothesis centers around the dynamics of synaptic and extrasynaptic levels of glutamate, and their impact on circuitry from the prefrontal cortex (PFC) to the NAc. After repetitive drug use, deregulation of this homeostasis increases the release of glutamate from the PFC to the NAc during drug relapse. Glial cells also play a fundamental role in this hypothesis; glial cells shape the interactions between the PFC and the NAc by means of altering glutamate levels in synaptic and extrasynaptic spaces. On the other hand, cocaine self-administration and withdrawal increases the surface expression of subunit glutamate receptor 1 (GluA1) of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors at the level of the NAc. Also, cocaine self-administration and withdrawal induce the formation of subunit glutamate receptor 2 (GluA2), lacking the Ca(2+)-permeable AMPA receptors (CP-AMPARs) at the level of the NAc

  10. A simple and fast technique for radiofrequency-assisted perforation of the atrial septum in congenital heart disease

    PubMed Central

    Sandoval, Juan Pablo; Chaturvedi, Rajiv R

    2016-01-01

    Radiofrequency (RF) assisted perforation of the atrial septum was performed successfully in three infants using a 0.035” RF wire deployed through a Williams right posterior catheter. Balloon atrial septoplasty was performed over the 0.035” RF wire in two of them, shortening the procedural time. PMID:27011690

  11. A simple and fast technique for radiofrequency-assisted perforation of the atrial septum in congenital heart disease.

    PubMed

    Sandoval, Juan Pablo; Chaturvedi, Rajiv R

    2016-01-01

    Radiofrequency (RF) assisted perforation of the atrial septum was performed successfully in three infants using a 0.035" RF wire deployed through a Williams right posterior catheter. Balloon atrial septoplasty was performed over the 0.035" RF wire in two of them, shortening the procedural time. PMID:27011690

  12. LocZ Is a New Cell Division Protein Involved in Proper Septum Placement in Streptococcus pneumoniae

    PubMed Central

    Holečková, Nela; Molle, Virginie; Buriánková, Karolína; Benada, Oldřich; Kofroňová, Olga; Ulrych, Aleš; Branny, Pavel

    2014-01-01

    ABSTRACT How bacteria control proper septum placement at midcell, to guarantee the generation of identical daughter cells, is still largely unknown. Although different systems involved in the selection of the division site have been described in selected species, these do not appear to be widely conserved. Here, we report that LocZ (Spr0334), a newly identified cell division protein, is involved in proper septum placement in Streptococcus pneumoniae. We show that locZ is not essential but that its deletion results in cell division defects and shape deformation, causing cells to divide asymmetrically and generate unequally sized, occasionally anucleated, daughter cells. LocZ has a unique localization profile. It arrives early at midcell, before FtsZ and FtsA, and leaves the septum early, apparently moving along with the equatorial rings that mark the future division sites. Consistently, cells lacking LocZ also show misplacement of the Z-ring, suggesting that it could act as a positive regulator to determine septum placement. LocZ was identified as a substrate of the Ser/Thr protein kinase StkP, which regulates cell division in S. pneumoniae. Interestingly, homologues of LocZ are found only in streptococci, lactococci, and enterococci, indicating that this close phylogenetically related group of bacteria evolved a specific solution to spatially regulate cell division. PMID:25550321

  13. Ectopic Acromegaly Arising from a Pituitary Adenoma within the Bony Intersphenoid Septum of a Patient with Empty Sella Syndrome

    PubMed Central

    Arzamendi, Audrey E.; Shahlaie, Kiarash; Latchaw, Richard E.; Lechpammer, Mirna; Arzumanyan, Hasmik

    2016-01-01

    Objective  To describe the work-up and treatment of rare ectopic acromegaly caused by a biopsy-proven somatotroph pituitary adenoma located within the bony intersphenoid septum of a patient with empty sella syndrome (ESS). Methods  We report the presentation, clinical course, diagnostic work-up, and lesion localization and treatment challenges encountered in a 55-year-old patient, with a brief review of relevant literature. Results  A 55-year-old African-American man presented with acromegaly and ESS. Attempts to definitively localize the causative tumor were unsuccessful, though petrosal sinus sampling supported central growth hormone production and imaging suggested bone-enclosed subsellar pituitary tissue. Endoscopic endonasal transphenoidal exploration was undertaken with resection of a somatotroph pituitary microadenoma, and subsequent clinical improvement and biochemical remission. Retrospective review revealed the patient's pituitary to have been located ectopically within a unique bony intersphenoid septum. Conclusion  This report describes the first known case of an ectopic pituitary adenoma located within the midline bony intersphenoid septum, which we postulate to have resulted from anomalous embryological pituitary migration. Intra-intersphenoid septal tumors should be considered in cases of apparent central acromegaly with ESS or absence of tumor tissue within the paranasal sinuses or other peripheral locations. Indexing  Acromegaly, ESS, pituitary adenoma, sphenoid sinus septum. PMID:27468406

  14. The Relationship between Large Cavum Septum Pellucidum and Antisocial Behavior, Callous-Unemotional Traits and Psychopathy in Adolescents

    ERIC Educational Resources Information Center

    White, Stuart F.; Brislin, Sarah; Sinclair, Stephen; Fowler, Katherine A.; Pope, Kayla; Blair, R. James R.

    2013-01-01

    Background: The presence of a large cavum septum pellucidum (CSP) has been previously associated with antisocial behavior/psychopathic traits in an adult community sample. Aims: The current study investigated the relationship between a large CSP and symptom severity in disruptive behavior disorders (DBD; conduct disorder and oppositional defiant…

  15. The presence of pacemaker HCN channels identifies theta rhythmic GABAergic neurons in the medial septum

    PubMed Central

    Varga, Viktor; Hangya, Balázs; Kránitz, Kinga; Ludányi, Anikó; Zemankovics, Rita; Katona, István; Shigemoto, Ryuichi; Freund, Tamás F; Borhegyi, Zsolt

    2008-01-01

    The medial septum (MS) is an indispensable component of the subcortical network which synchronizes the hippocampus at theta frequency during specific stages of information processing. GABAergic neurons exhibiting highly regular firing coupled to the hippocampal theta rhythm are thought to form the core of the MS rhythm-generating network. In recent studies the hyperpolarization-activated, cyclic nucleotide-gated non-selective cation (HCN) channel was shown to participate in theta synchronization of the medial septum. Here, we tested the hypothesis that HCN channel expression correlates with theta modulated firing behaviour of MS neurons by a combined anatomical and electrophysiological approach. HCN-expressing neurons represented a subpopulation of GABAergic cells in the MS partly overlapping with parvalbumin (PV)-containing neurons. Rhythmic firing in the theta frequency range was characteristic of all HCN-expressing neurons. In contrast, only a minority of HCN-negative cells displayed theta related activity. All HCN cells had tight phase coupling to hippocampal theta waves. As a group, PV-expressing HCN neurons had a marked bimodal phase distribution, whereas PV-immunonegative HCN neurons did not show group-level phase preference despite significant individual phase coupling. Microiontophoretic blockade of HCN channels resulted in the reduction of discharge frequency, but theta rhythmic firing was perturbed only in a few cases. Our data imply that HCN-expressing GABAergic neurons provide rhythmic drive in all phases of the hippocampal theta activity. In most MS theta cells rhythm genesis is apparently determined by interactions at the level of the network rather than by the pacemaking property of HCN channels alone. PMID:18565991

  16. Differential sensitivity of the caudal and rostral nucleus accumbens to the rewarding effects of a H1-histaminergic receptor blocker as measured with place-preference and self-stimulation behavior.

    PubMed

    Zimmermann, P; Privou, C; Huston, J P

    1999-01-01

    A recent series of studies in rats has demonstrated positively reinforcing and memory enhancing effects following lesions of the nucleus tuberomammillaris, which is the only known source of neuronal histamine. The aim of the present experiments was to assess whether inhibition of histaminergic neurotransmission in the ventral striatum has positively reinforcing effects. In Experiment 1 rats with chronically-implanted cannulae were injected with the H1 receptor blocker d-( + )-chlorpheniramine at doses of 0.1, 1.0 and 10.0 microg into the rostral or caudal parts of the nucleus accumbens, a brain region known to be involved in reward-related processes. Immediately after the treatment the animals were placed into one of four restricted quadrants of a circular open field (closed corral) for a single conditioning trial. During the drug-free test for conditioned place preference, when a choice among the four quadrants was provided, those rats injected with 10.0 microg chlorpheniramine in the caudal nucleus accumbens spent more time in the treatment corral, indicative of a positively rewarding drug action. In Experiment 2 the question was posed whether injection of chlorpheniramine into the nucleus accumbens influences electrical self-stimulation of the lateral hypothalamus. For this purpose rats were chronically implanted with two bipolar electrodes aimed at the lateral-hypothalami and with two additional guide cannulae aimed either at the rostral or caudal nucleus accumbens. After having established reliable self-stimulation behavior at one of the two electrode sites the animals were allowed to self-stimulate for one hour (baseline). Then they were unilaterally injected with 10.0 microg chlorpheniramine or vehicle and allowed to self-stimulate for another hour (test). On the next day the same procedure took place, except for the difference that the animals received an injection aimed at the hemisphere not treated so far. Animals treated with chlorpheniramine in the

  17. Reproductive outcome after IVF following hysteroscopic division of incomplete uterine septum/arcuate uterine anomaly in women with primary infertility

    PubMed Central

    Abuzeid, M.; Ghourab, G.; Abuzeid, O.; Mitwally, M.; Ashraf, M.; Diamond, M.

    2014-01-01

    Objective: To determine reproductive outcome after in-vitro fertilization/embryo transfer (IVF-ET) in women with primary infertility following hysteroscopic septoplasty of incomplete uterine septum or arcuate uterine anomaly. Methods: This is a historical cohort study. The study group consisted of 156 consecutive patients who underwent a total of 221 cycles of IVF/ET following hysteroscopic septoplasty of an incomplete uterine septum or arcuate anomaly (Group 1). The control group included 196 consecutive patients with normal endometrial cavity on hysteroscopy who underwent a total of 369 cycles of IVF/ET (Group 2). The reproductive outcome after the first cycle of IVF-ET and the best reproductive outcome of all the cycles the patient underwent were calculated. In addition, we compared the reproductive outcome in the study group based on the type of the anomalies (septum versus arcuate). Results: In the first fresh cycle, following septoplasty, there were significantly higher clinical pregnancy and delivery rates in Group 1 (60.3% and 51.3% respectively) compared to Group 2 (38.8% and 33.2% respectively). However, there was no significant difference between the two groups in the clinical pregnancy (74.4% vs. 67.3%) or in the delivery (65.4% vs. 60.2%) rates per patient, respectively. There was no significant difference in the reproductive outcome after IVF-ET between patients who previously had arcuate uterine anomaly versus incomplete uterine septum. Conclusion: Reproductive outcome of IVF-ET after hysteroscopic correction of incomplete uterine septum/arcuate uterine anomaly in women with primary infertility is no different from women with normal uterine cavity. PMID:25593694

  18. Nucleus accumbens injections of the mGluR2/3 agonist LY379268 increase cue-induced sucrose seeking following adult, but not adolescent sucrose self-administration.

    PubMed

    Myal, S; O'Donnell, P; Counotte, D S

    2015-10-01

    Adolescence is often portrayed as a period of enhanced sensitivity to reward, with long-lasting neurobiological changes upon reward exposure. However, we previously found that time-dependent increases in cue-induced sucrose seeking were more pronounced in rats trained to self-administer sucrose as adults than as adolescents. In addition, adult, but not adolescent sucrose self-administration led to a decreased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-Methyl-D-aspartate (AMPA/NMDA) ratio in the nucleus accumbens core, suggesting that long-lasting changes in glutamatergic transmission may affect adult processing of natural rewards. Here we tested whether altering glutamatergic transmission in the nucleus accumbens core via local injection of an mGluR2/3 agonist and antagonist affects cue-induced sucrose seeking following abstinence and whether this is different in the two age groups. Rats began oral sucrose self-administration training (10 days) on postnatal day (P) 35 (adolescents) or P70 (adults). Following 21 days of abstinence, rats received microinjections of the mGluR2/3 agonist LY379268 (0.3 or 1.0 μg/side) or vehicle into the nucleus accumbens core, and 15 min later cue-induced sucrose seeking was assessed. An additional group of rats trained as adults received nucleus accumbens core microinjections of the mGluR2/3 antagonist (RS)-α-Methyl-4-phosphonophenylglycine (MPPG) (0.12 or 0.5 μg/side). Confirming our previous results, adult rats earned more sucrose reinforcers, while sucrose intake per body weight was similar across ages. On abstinence day 22, local injection of the mGluR2/3 agonist LY379268 increased cue-induced sucrose seeking only in adult rats, and had no effect in adolescents. Local injections of the mGluR2/3 antagonist MPPG had no effect on sucrose seeking in adult rats. These data suggest an important developmental difference in the neural substrates of natural reward, specifically a difference in glutamatergic transmission in

  19. Nicotine Withdrawal Increases Stress-Associated Genes in the Nucleus Accumbens of Female Rats in a Hormone-Dependent Manner

    PubMed Central

    Torres, Oscar V.; Pipkin, Joseph A.; Ferree, Patrick; Carcoba, Luis M.

    2015-01-01

    Introduction: Previous work led to our hypothesis that sex differences produced by nicotine withdrawal are modulated by stress and dopamine systems in the nucleus accumbens (NAcc). We investigated our hypothesis by studying intact females to determine whether the mechanisms that promote withdrawal are ovarian-hormone mediated. Methods: Female rats were ovariectomized (OVX) or received sham surgery (intact) on postnatal day (PND 45–46). On PND 60, they received sham surgery (controls) or were prepared with nicotine pumps. Fourteen days later, half of the rats had their pumps removed (nicotine withdrawal) and the other half received sham surgery (nicotine exposure). Twenty-four hours later, the rats were tested for anxiety-like behavior using the elevated plus maze and light/dark transfer procedures. The NAcc was then dissected for analysis of several genes related to stress (CRF, UCN, CRF-R1, CRF-R2, CRF-BP, and Arrb2) or receptors for dopamine (Drd1 and Drd2) and estradiol (Esr2). Results: During withdrawal, intact females displayed an increase in anxiety-like behavior in both tests and CRF, UCN, and Drd1 gene expression. During nicotine exposure, intact females displayed a decrease in CRF-R1, CRF-R2, Drd3, and Esr2 gene expression and an increase in CRF-BP. This pattern of results was absent in OVX females. Conclusions: Nicotine withdrawal produced an increase in anxiety-like behavior and stress-associated genes in intact females that is distinct from changes produced by nicotine exposure. The latter effects were absent in OVX females, suggesting that stress produced by withdrawal is ovarian-hormone mediated. These findings have important implications towards understanding tobacco use liability among females. PMID:25762751

  20. Subcellular and subsynaptic localization of group I metabotropic glutamate receptors in the nucleus accumbens of cocaine-treated rats

    PubMed Central

    Mitrano, D.A.; Arnold, C.; Smith, Y.

    2008-01-01

    There is significant pharmacological and behavioral evidence that group I metabotropic glutamate receptors (mGluR1a and mGluR5) in the nucleus accumbens play an important role in the neurochemical and pathophysiological mechanisms that underlie addiction to psychostimulants. To further address this issue, we undertook a detailed ultrastructural analysis to characterize changes in the subcellular and subsynaptic localization of mGluR1a and mGluR5 in the core and shell of nucleus accumbens following acute or chronic cocaine administration in rats. After a single cocaine injection (30mg/kg) and 45 minutes withdrawal, there was a significant decrease in the proportion of plasma membrane-bound mGluR1a in accumbens shell dendrites. Similarly, the proportion of plasma membrane-bound mGluR1a was decreased in large dendrites of accumbens core neurons following chronic cocaine exposure (i.e. 1 week treatment followed by three weeks withdrawal). However, neither acute nor chronic cocaine treatments induced significant change in the localization of mGluR5 in accumbens core and shell, which is in contrast with the significant reduction of plasma membrane-bound mGluR1a and mGluR5 induced by local intra-accumbens administration of the group I mGluR agonist, DHPG. In conclusion, these findings demonstrate that cocaine-induced glutamate imbalance (Smith et al., 1995; Pierce et al., 1996; Reid et al., 1997) has modest effects on the trafficking of group I mGluRs in the nucleus accumbens. These results provide valuable information on the neuroadaptive mechanisms of accumbens group I mGluRs in response to cocaine administration. PMID:18479833

  1. Directed Communication between Nucleus Accumbens and Neocortex in Humans Is Differentially Supported by Synchronization in the Theta and Alpha Band

    PubMed Central

    Horschig, Jörn M.; Smolders, Ruud; Bonnefond, Mathilde; Schoffelen, Jan-Mathijs; van den Munckhof, Pepijn; Schuurman, P. Richard; Cools, Roshan; Denys, Damiaan; Jensen, Ole

    2015-01-01

    Here, we report evidence for oscillatory bi-directional interactions between the nucleus accumbens and the neocortex in humans. Six patients performed a demanding covert visual attention task while we simultaneously recorded brain activity from deep-brain electrodes implanted in the nucleus accumbens and the surface electroencephalogram (EEG). Both theta and alpha oscillations were strongly coherent with the frontal and parietal EEG during the task. Theta-band coherence increased during processing of the visual stimuli. Granger causality analysis revealed that the nucleus accumbens was communicating with the neocortex primarily in the theta-band, while the cortex was communicating the nucleus accumbens in the alpha-band. These data are consistent with a model, in which theta- and alpha-band oscillations serve dissociable roles: Prior to stimulus processing, the cortex might suppress ongoing processing in the nucleus accumbens by modulating alpha-band activity. Subsequently, upon stimulus presentation, theta oscillations might facilitate the active exchange of stimulus information from the nucleus accumbens to the cortex. PMID:26394404

  2. Behavioral flexibility is increased by optogenetic inhibition of neurons in the nucleus accumbens shell during specific time segments

    PubMed Central

    Aquili, Luca; Liu, Andrew W.; Shindou, Mayumi; Shindou, Tomomi; Wickens, Jeffery R.

    2014-01-01

    Behavioral flexibility is vital for survival in an environment of changing contingencies. The nucleus accumbens may play an important role in behavioral flexibility, representing learned stimulus–reward associations in neural activity during response selection and learning from results. To investigate the role of nucleus accumbens neural activity in behavioral flexibility, we used light-activated halorhodopsin to inhibit nucleus accumbens shell neurons during specific time segments of a bar-pressing task requiring a win–stay/lose–shift strategy. We found that optogenetic inhibition during action selection in the time segment preceding a lever press had no effect on performance. However, inhibition occurring in the time segment during feedback of results—whether rewards or nonrewards—reduced the errors that occurred after a change in contingency. Our results demonstrate critical time segments during which nucleus accumbens shell neurons integrate feedback into subsequent responses. Inhibiting nucleus accumbens shell neurons in these time segments, during reinforced performance or after a change in contingencies, increases lose–shift behavior. We propose that the activity of nucleus shell accumbens shell neurons in these time segments plays a key role in integrating knowledge of results into subsequent behavior, as well as in modulating lose–shift behavior when contingencies change. PMID:24639489

  3. Lateral orientation (image)

    MedlinePlus

    A lateral orientation is a position away from the midline of the body. For instance, the arms are lateral to the ... ears are lateral to the head. A medial orientation is a position toward the midline of the ...

  4. Cell-Type Specific Increases in Female Hamster Nucleus Accumbens Spine Density following Female Sexual Experience

    PubMed Central

    Staffend, Nancy A.; Hedges, Valerie L.; Chemel, Benjamin R.; Watts, Val J.; Meisel, Robert L.

    2013-01-01

    Female sexual behavior is an established model of a naturally motivated behavior which is regulated by activity within the mesolimbic dopamine system. Repeated activation of the mesolimbic circuit by female sexual behavior elevates dopamine release and produces persistent postsynaptic alterations to dopamine D1 receptor signaling within the nucleus accumbens. Here we demonstrate that sexual experience in female Syrian hamsters significantly increases spine density and alters morphology selectively in D1 receptor expressing medium spiny neurons within the nucleus accumbens core, with no corresponding change in dopamine receptor binding or protein expression. Our findings demonstrate that previous life experience with a naturally motivated behavior has the capacity to induce persistent structural alterations to the mesolimbic circuit that can increase reproductive success and are analogous to the persistent structural changes following repeated exposure to many drugs of abuse. PMID:23934655

  5. Sensitivity of the Nucleus Accumbens to Violations in Expectation of Reward

    PubMed Central

    Spicer, Julie; Galvan, Adriana; Hare, Todd A; Voss, Henning; Glover, Gary; Casey, BJ

    2007-01-01

    This study examined whether ventral frontostriatal regions differentially code expected and unexpected reward outcomes. We parametrically manipulated the probability of reward and examined the neural response to reward and nonreward for each probability condition in the ventral striatum and the orbitofrontal cortex (OFC). By late trials of the experiment, subjects showed slower behavioral responses for the condition with the lowest probability of reward, relative to the condition with the highest probability of reward. At the neural level, both the nucleus accumbens (NAcc) and OFC showed greater activation to rewarded relative to nonrewarded trials, but the accumbens appeared to be most sensitive to violations in expected reward outcomes. These data suggest distinct roles for frontostriatal circuitry in reward prediction and in responding to violations in expectations. PMID:17049884

  6. Endocannabinoid-Mediated Plasticity in Nucleus Accumbens Controls Vulnerability to Anxiety after Social Defeat Stress.

    PubMed

    Bosch-Bouju, Clémentine; Larrieu, Thomas; Linders, Louisa; Manzoni, Olivier J; Layé, Sophie

    2016-08-01

    Chronic social defeat stress (CSDS) is a clinically relevant model of mood disorders. The relationship between the CSDS model and a physiologically pertinent paradigm of synaptic plasticity is not known. Here, we found that cluster analysis of the emotional behavior states of mice exposed to CSDS allowed their segregation into anxious and non-anxious groups. Endocannabinoid-mediated spike-timing dependent plasticity (STDP) in the nucleus accumbens was attenuated in non-anxious mice and abolished in anxious mice. Anxiety-like behavior in stressed animals was specifically correlated with their ability to produce STDP. Pharmacological enhancement of 2-arachidonoyl glycerol (2-AG) signaling in the nucleus accumbens normalized the anxious phenotype and STDP in anxious mice. These data reveal that endocannabinoid modulation of synaptic efficacy in response to a naturalistic activity pattern is both a molecular correlate of behavioral adaptability and a crucial factor in the adaptive response to chronic stress. PMID:27452462

  7. Targeted disruption of cocaine-activated accumbens neurons prevents context-specific sensitization

    PubMed Central

    Koya, Eisuke; Golden, Sam A.; Harvey, Brandon K.; Guez, Danielle H.; Berkow, Alexander; Simmons, Danielle E.; Bossert, Jennifer M.; Nair, Sunila G.; Uejima, Jamie L.; Marin, Marcelo T.; Mitchell, Timothy; Farquhar, David; Ghosh, Sukhen; Mattson, Brandi J.; Hope, Bruce T.

    2009-01-01

    Learned associations between effects of abused drugs and the drug administration environment play important roles in drug addiction. Histochemical and electrophysiological studies suggest that these associations are encoded in sparsely distributed nucleus accumbens neurons that are selectively activated by drugs and drug-associated cues. Although correlations between accumbens neuronal activity and responsivity to drugs and drug cues have been observed, no technique exists for selectively manipulating these activated neurons and establishing their causal role in behavioral effects of drugs and drug cues. Here we describe a novel method, termed ‘Daun02-inactivation method’, that selectively inactivates a minority of neurons activated by cocaine in an environment repeatedly paired with cocaine to demonstrate a causal role for these activated neurons in context-specific cocaine-induced psychomotor sensitization in rats. This method provides a new tool to study causal roles of selectively activated neurons in behavioral effects of drugs and drug cues and in other learned behaviors. PMID:19620976

  8. Subcortical nuclei volumes in suicidal behavior: nucleus accumbens may modulate the lethality of acts.

    PubMed

    Gifuni, Anthony J; Ding, Yang; Olié, Emilie; Lawrence, Natalia; Cyprien, Fabienne; Le Bars, Emmanuelle; Bonafé, Alain; Phillips, Mary L; Courtet, Philippe; Jollant, Fabrice

    2016-03-01

    Previously, studies have demonstrated cortical impairments in those who complete or attempt suicide. Subcortical nuclei have less often been implicated in the suicidal vulnerability. In the present study, we investigated, with a specific design in a large population, variations in the volume of subcortical structures in patients with mood disorders who have attempted suicide. We recruited 253 participants: 73 suicide attempters with a past history of both mood disorders and suicidal act, 89 patient controls with a past history of mood disorders but no history of suicidal act, and 91 healthy controls. We collected 1.5 T magnetic resonance imaging data from the caudate, pallidum, putamen, nucleus accumbens, hippocampus, amygdala, ventral diencephalon, and thalamus. Surface-based morphometry (Freesurfer) analysis was used to comprehensively evaluate gray matter volumes. In comparison to controls, suicide attempters showed no difference in subcortical volumes when controlled for intracranial volume. However, within attempters negative correlations between the left (r = -0.35, p = 0.002), and right (r = -0.41, p < 0.0005) nucleus accumbens volumes and the lethality of the last suicidal act were found. Our study found no differences in the volume of eight subcortical nuclei between suicide attempters and controls, suggesting a lack of association between these regions and suicidal behavior in general. However, individual variations in nucleus accumbens structure and functioning may modulate the lethality of suicidal acts during a suicidal crisis. The known role of nucleus accumbens in action selection toward goals determined by the prefrontal cortex, decision-making or mental pain processing are hypothesized to be potential explanations. PMID:25759286

  9. α2δ-1 Signaling in Nucleus Accumbens Is Necessary for Cocaine-Induced Relapse

    PubMed Central

    Brown, Robyn M.; Quintero, Gabriel C.; Kupchik, Yonatan M.; Thomas, Charles A.; Reissner, Kathryn J.; Kalivas, Peter W.

    2014-01-01

    Relapse to cocaine seeking is associated with potentiated excitatory synapses in nucleus accumbens. α2δ-1 is an auxiliary subunit of voltage-gated calcium channels that affects calcium-channel trafficking and kinetics, initiates extracellular signaling cascades, and promotes excitatory synaptogenesis. Previous data demonstrate that repeated exposure to alcohol, nicotine, methamphetamine, and morphine upregulates α2δ-1 in reward-related brain regions, but it was unclear whether this alteration generalized to cocaine. Here, we show that α2δ-1 protein was increased in nucleus accumbens after cocaine self-administration and extinction compared with saline controls. Furthermore, the endogenous ligand thrombospondin-1, responsible for the synaptogenic properties of the α2δ-1 receptor, was likewise elevated. Using whole-cell patch-clamp recordings of EPSCs in nucleus accumbens, we demonstrated that gabapentin, a specific α2δ-1 antagonist, preferentially reduced the amplitude and increased the paired-pulse ratio of EPSCs evoked by electrical stimulation in slices from cocaine-experienced rats compared with controls. In vivo, gabapentin microinjected in the nucleus accumbens core attenuated cocaine-primed but not cue-induced reinstatement. Importantly, gabapentin's effects on drug seeking were not due to a general depression of spontaneous or cocaine-induced locomotor activity. Moreover, gabapentin had no effect on reinstatement of sucrose seeking. These data indicate that α2δ-1 contributes specifically to cocaine-reinstated drug seeking, and identifies this protein as a target for the development of cocaine relapse medications. These results also inform ongoing discussion in the literature regarding efficacy of gabapentin as a candidate addiction therapy. PMID:24948814

  10. α2δ-1 signaling in nucleus accumbens is necessary for cocaine-induced relapse.

    PubMed

    Spencer, Sade; Brown, Robyn M; Quintero, Gabriel C; Kupchik, Yonatan M; Thomas, Charles A; Reissner, Kathryn J; Kalivas, Peter W

    2014-06-18

    Relapse to cocaine seeking is associated with potentiated excitatory synapses in nucleus accumbens. α2δ-1 is an auxiliary subunit of voltage-gated calcium channels that affects calcium-channel trafficking and kinetics, initiates extracellular signaling cascades, and promotes excitatory synaptogenesis. Previous data demonstrate that repeated exposure to alcohol, nicotine, methamphetamine, and morphine upregulates α2δ-1 in reward-related brain regions, but it was unclear whether this alteration generalized to cocaine. Here, we show that α2δ-1 protein was increased in nucleus accumbens after cocaine self-administration and extinction compared with saline controls. Furthermore, the endogenous ligand thrombospondin-1, responsible for the synaptogenic properties of the α2δ-1 receptor, was likewise elevated. Using whole-cell patch-clamp recordings of EPSCs in nucleus accumbens, we demonstrated that gabapentin, a specific α2δ-1 antagonist, preferentially reduced the amplitude and increased the paired-pulse ratio of EPSCs evoked by electrical stimulation in slices from cocaine-experienced rats compared with controls. In vivo, gabapentin microinjected in the nucleus accumbens core attenuated cocaine-primed but not cue-induced reinstatement. Importantly, gabapentin's effects on drug seeking were not due to a general depression of spontaneous or cocaine-induced locomotor activity. Moreover, gabapentin had no effect on reinstatement of sucrose seeking. These data indicate that α2δ-1 contributes specifically to cocaine-reinstated drug seeking, and identifies this protein as a target for the development of cocaine relapse medications. These results also inform ongoing discussion in the literature regarding efficacy of gabapentin as a candidate addiction therapy. PMID:24948814

  11. The indirect pathway of the nucleus accumbens shell amplifies neuropathic pain

    PubMed Central

    Ren, Wenjie; Centeno, Maria Virginia; Berger, Sara; Wu, Ying; Na, Xiaodong; Liu, Xianguo; Kondapalli, Jyothisri; Apkarian, A Vania; Martina, Marco; Surmeier, D James

    2016-01-01

    We examined adaptations in nucleus accumbens (NAc) neurons in mouse and rat peripheral nerve injury models of neuropathic pain. Injury selectively increased excitability of NAc shell indirect pathway spiny projection neurons (iSPNs) and altered their synaptic connectivity. Moreover, injury-induced tactile allodynia was reversed by inhibiting and exacerbated by exciting iSPNs, indicating that they not only participated in the central representation of pain, but gated activity in ascending nociceptive pathways. PMID:26691834

  12. Framework for developing a hierarchical model of reward focusing on the nucleus accumbens.

    PubMed

    Smith, Wesley; Nair, Satish S; Xu, Dong; Nair, Jyotsna; Beitman, Bernard

    2004-01-01

    Computational modeling using GENESIS platform has led to advances in fabricating a model to test the influence of molecular/proteomic adaptations on behavior due to reward. The nucleus accumbens is an area of the brain that processes information from other parts of the brain and is an integral element of the 'reward pathway' in the brain. A simplified model of the accumbens using one neuron is developed as part of a larger effort to study reward and chemical dependency with a focus on cocaine addiction. A preliminary model of a biologically realistic neuron was developed with inhibitory and excitatory afferents as well as intrasynapse dynamics. The neuron displayed characteristic behavior of a neuron found in the nucleus accumbens including bistability. The neuron has afferents from other neurons via dendrites which carry the inputs relating to behavioral aspects and to learning. To add behavioral aspects to the model, a methodology is developed to model contexts and their reinforcing effects on behavior, similar to cocaine addiction. Results using both the biological and behavioral modeling are encouraging for this preliminary model. PMID:17271623

  13. TRH injected into the nucleus accumbens shell releases dopamine and reduces feeding motivation in rats.

    PubMed

    Puga, L; Alcántara-Alonso, V; Coffeen, U; Jaimes, O; de Gortari, P

    2016-06-01

    The thyrotropin-releasing hormone (TRH), an anorexigenic factor that reduces food intake in food-restricted animals, may be involved in motivation for food. Injected centrally, TRH impairs acquisition of food-rewarded behavior. Through the TRH-R1 receptors, TRH injected in the nucleus accumbens increases dopamine content-perhaps the mechanism by which the peptide modulates food motivation. This, however, is still to be demonstrated. We sought to evaluate dopamine release by microdialysis after a TRH injection into the nucleus accumbens shell in free-moving fasted rats. In addition, we assessed dopamine content and turnover by HPLC and the relationship with the motivation for food by analyzing the performance of rats during a progressive-ratio (PR) operant-conditioning test. Finally, we determined serum leptin and triiodothyronine (T3) levels in order to evaluate the animals' metabolic response to food restriction and the impact of intra-accumbal TRH administration on circulating hormones. Intra-accumbal injections of TRH reduced food intake in food-restricted rats-compared to counterparts treated with saline-, without further decreasing T3 or leptin levels, which dropped due to their dietary regime. TRH-injected rats had lower breaking points on the PR schedule, which indicated lower motivation to eat. Accordingly, compared to saline-treated animals, dopamine release and turnover increased in the nucleus accumbens of TRH-injected rats, a finding that suggests a relationship between motivation for food and TRH-induced release of dopamine. PMID:27006143

  14. Stimulation of the nucleus accumbens as behavioral reward in awake behaving monkeys.

    PubMed

    Bichot, Narcisse P; Heard, Matthew T; Desimone, Robert

    2011-08-15

    It has been known that monkeys will repeatedly press a bar for electrical stimulation in several different brain structures. We explored the possibility of using electrical stimulation in one such structure, the nucleus accumbens, as a substitute for liquid reward in animals performing a complex task, namely visual search. The animals had full access to water in the cage at all times on days when stimulation was used to motivate them. Electrical stimulation was delivered bilaterally at mirror locations in and around the accumbens, and the animals' motivation to work for electrical stimulation was quantified by the number of trials they performed correctly per unit of time. Acute mapping revealed that stimulation over a large area successfully supported behavioral performance during the task. Performance improved with increasing currents until it reached an asymptotic, theoretically maximal level. Moreover, stimulation with chronically implanted electrodes showed that an animal's motivation to work for electrical stimulation was at least equivalent to, and often better than, when it worked for liquid reward while on water control. These results suggest that electrical stimulation in the accumbens is a viable method of reward in complex tasks. Because this method of reward does not necessitate control over water or food intake, it may offer an alternative to the traditional liquid or food rewards in monkeys, depending on the goals and requirements of the particular research project. PMID:21704383

  15. Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving

    PubMed Central

    Lee, Brian R.; Ma, Yao-ying; Huang, Yanhua H.; Wang, Xiusong; Otaka, Mami; Ishikawa, Masago; Neumann, Peter A.; Graziane, Nicolas M.; Brown, Travis E.; Suska, Anna; Guo, Changyong; Lobo, Mary Kay; Sesack, Susan R.; Wolf, Marina E.; Nestler, Eric J.; Shaham, Yavin; Schlüter, Oliver M.; Dong, Yan

    2013-01-01

    In rat models of drug relapse and craving, cue-induced cocaine seeking progressively increases after drug withdrawal. This ‘incubation of cocaine craving’ is partially mediated by time-dependent adaptations at glutamatergic synapses in nucleus accumbens. However, the circuit-level adaptations mediating this plasticity remain elusive. Here we studied silent synapses—often regarded as immature synapses that express stable NMDA receptors with AMPA receptors either absent or labile—in basolateral amygdala-to-accumbens projection in incubation of cocaine craving. Silent synapses were detected within this projection during early withdrawal from cocaine. As the withdrawal period progressed, these silent synapses became ‘unsilenced’, a process involving synaptic insertion of calcium-permeable AMPA receptors (CP-AMPARs). In vivo optogenetic stimulation-induced downregulation of CP-AMPARs at amygdala-to-NAc synapses, which re-silenced some of the previously silent synapses after prolonged withdrawal, decreased cocaine incubation. Our finding indicates that silent synapse-based reorganization of the amygdala-to-accumbens projection is critical for persistent cocaine craving and relapse after withdrawal. PMID:24077564

  16. Chronic ethanol treatment potientials ethanol-induced increases in interstitial nucleus accumbens endocannabinoid levels in rats

    PubMed Central

    Alvarez-Jaimes, Lily; Stouffer, David G.; Parsons, Loren H.

    2013-01-01

    We employed in vivo microdialysis to characterize the effect of an ethanol challenge injection on endocannabinoid levels in the nucleus accumbens of ethanol-naïve and chronic ethanol-treated rats. Ethanol (0.75 and 2 g/kg, i.p.) dose-dependently increased dialysate 2-arachidonoylglycerol (to a maximum 157 ± 20% of baseline) and decreased anandamide (to a minimum 52 ± 9% of baseline) in ethanol-naïve rats. The endocannabinoid clearance inhibitor N-(4-hydrophenyl) arachidonoylamide (AM404; 3 mg/kg) potentiated ethanol effects on 2-arachidonoylglycerol levels but did not alter ethanol-induced decreases in anandamide. AM404 alone did not alter dialysate levels of either endocannabinoid. Then, we characterized the effect of ethanol challenge on nucleus accumbens endocannabinoid levels in rats previously maintained on an ethanol-containing liquid diet. Ethanol challenge produced a greater and more prolonged increase in 2-arach-idonoylglycerol (to a maximum 394 ± 135% of baseline) in ethanol-experienced than in ethanol-naïve rats. The profile in ethanol-experienced rats was similar to that produced by AM404 pre-treatment in ethanol-naïve rats. AM404 in ethanol-experienced rats led to a further enhancement in the 2-arachidonoylglycerol response to ethanol challenge (to a maximum 704 ± 174% of baseline). Our findings demonstrate that ethanol-induced increases in nucleus accumbens 2-arachidonoylglycerol are potentiated in animals with a history of ethanol consumption. PMID:19650871

  17. Estradiol in the Preoptic Area Regulates the Dopaminergic Response to Cocaine in the Nucleus Accumbens.

    PubMed

    Tobiansky, Daniel J; Will, Ryan G; Lominac, Kevin D; Turner, Jonathan M; Hattori, Tomoko; Krishnan, Krittika; Martz, Julia R; Nutsch, Victoria L; Dominguez, Juan M

    2016-06-01

    The sex-steroid hormone estradiol (E2) enhances the psychoactive effects of cocaine, as evidenced by clinical and preclinical studies. The medial preoptic area (mPOA), a region in the hypothalamus, is a primary neural locus for neuroendocrine integration, containing one of the richest concentrations of estrogen receptors in the CNS and also has a key role in the regulation of naturally rewarding behaviors. However, whether estradiol enhances the neurochemical response to cocaine by acting in the mPOA is still unclear. Using neurotoxic lesions and microdialysis, we examined whether the mPOA modulates cocaine-induced neurochemical activity in the nucleus accumbens. Tract tracing and immunohistochemical staining were used to determine whether projections from the mPOA to the ventral tegmental area (VTA) are sensitive to estrogen signaling. Finally, estradiol microinjections followed by microdialysis were used to determine whether estrogenic signaling in the mPOA modulates cocaine-induced changes of dopamine in the nucleus accumbens. Results showed that lesions of the mPOA or microinjections of estradiol directly into the mPOA increased cocaine-induced release of dopamine in the nucleus accumbens. Immunohistochemical analyses revealed that the mPOA modulates cocaine responsiveness via projections to both dopaminergic and GABAergic neurons in the VTA, and that these projections are sensitive to estrogenic stimulation. Taken together, these findings point to a novel estradiol-dependent pathway that modulates cocaine-induced neurochemical activity in the mesolimbic system. PMID:26647972

  18. Aphallia as part of urorectal septum malformation sequence in an infant of a diabetic mother.

    PubMed

    Gripp, K W; Barr, M; Anadiotis, G; McDonald-McGinn, D M; Zderic, S A; Zackai, E H

    1999-02-19

    A male patient with aphallia, anal stenosis, tetralogy of Fallot, multiple vertebral anomalies including sacral agenesis and central nervous system (CNS) malformations was born after a pregnancy complicated by poorly controlled maternal diabetes. Aphallia is an extremely rare abnormality and can be part of the urorectal septum malformation sequence (URSMS). While aphallia has not been reported in infants of diabetic mothers, urogenital malformations are known to occur with increased frequency. Two female products of pregnancies complicated by diabetes presented with multiple malformations including anal atresia and recto-vaginal fistula consistent with the diagnosis of URSMS. The three patients share CNS, cardiac, and vertebral anomalies, abnormalities secondary to abnormal blastogenesis and characteristic of diabetic embryopathy. URSMS is also caused by abnormal blastogenesis. Therefore, this particular malformation should be viewed in the context of the multiple blastogenetic abnormalities in the cases reported here. The overlap of findings of URSMS in our cases with other abnormalities of blastogenesis, such as VATER association or sacral agenesis is not surprising, as these associations are known to lack clear diagnostic boundaries. PMID:10069704

  19. Extracardiac septum transversum/proepicardial endothelial cells pattern embryonic coronary arterio-venous connections.

    PubMed

    Cano, Elena; Carmona, Rita; Ruiz-Villalba, Adrián; Rojas, Anabel; Chau, You-Ying; Wagner, Kay D; Wagner, Nicole; Hastie, Nicholas D; Muñoz-Chápuli, Ramón; Pérez-Pomares, José M

    2016-01-19

    Recent reports suggest that mammalian embryonic coronary endothelium (CoE) originates from the sinus venosus and ventricular endocardium. However, the contribution of extracardiac cells to CoE is thought to be minor and nonsignificant for coronary formation. Using classic (Wt1(Cre)) and previously undescribed (G2-Gata4(Cre)) transgenic mouse models for the study of coronary vascular development, we show that extracardiac septum transversum/proepicardium (ST/PE)-derived endothelial cells are required for the formation of ventricular coronary arterio-venous vascular connections. Our results indicate that at least 20% of embryonic coronary arterial and capillary endothelial cells derive from the ST/PE compartment. Moreover, we show that conditional deletion of the ST/PE lineage-specific Wilms' tumor suppressor gene (Wt1) in the ST/PE of G2-Gata4(Cre) mice and in the endothelium of Tie2(Cre) mice disrupts embryonic coronary transmural patterning, leading to embryonic death. Taken together, our results demonstrate that ST/PE-derived endothelial cells contribute significantly to and are required for proper coronary vascular morphogenesis. PMID:26739565

  20. Visualization and functional dissection of coaxial paired SpoIIIE channels across the sporulation septum

    DOE PAGESBeta

    Shin, Jae Yen; Lopez-Garrido, Javier; Lee, Sang-Hyuk; Diaz-Celis, Cesar; Fleming, Tinya; Bustamante, Carlos; Pogliano, Kit

    2015-05-07

    SpoIIIE is a membrane-anchored DNA translocase that localizes to the septal midpoint to mediate chromosome translocation and membrane fission during Bacillus subtilis sporulation. Here we use cell-specific protein degradation and quantitative photoactivated localization microscopy in strains with a thick sporulation septum to investigate the architecture and function of the SpoIIIE DNA translocation complex in vivo. We were able to visualize SpoIIIE complexes with approximately equal numbers of molecules in the mother cell and the forespore. Cell-specific protein degradation showed that only the mother cell complex is required to translocate DNA into the forespore, whereas degradation in either cell reversesmore » membrane fission. Our data suggest that SpoIIIE assembles a coaxially paired channel for each chromosome arm comprised of one hexamer in each cell to maintain membrane fission during DNA translocation. We show that SpoIIIE can operate, in principle, as a bi-directional motor that exports DNA.« less

  1. Interventricular Septum Hydatid Cyst: Successful Seven-Year Follow Up- Case Report

    PubMed Central

    MIRZAIE, Asadollah; ERFANIAN-TAGHVAEI, Majid Reza; MIRZAIE, Maryam; SHARIFI-NOGHABI, Reza

    2014-01-01

    Abstract Hydatid cyst disease should be considered in differential diagnosis in many doubtful clinical situations as can present with non-specific symptoms especially in the endemic areas. Cardiac involvement should be considered in patients with history of previous hydatid cyst disease.. Cardiac hydatid cysts account for less than 2% of all hydatid diseases. In this report we aimed to present a case of 14-year-old boy with the diagnosis of occlusion of artery of the right lower extremity. Surgical exploration of the femoral artery revealed multiple hydatid cysts. Echocardiography showed a mobile mixed mass lesion. Complete resection of the mass was done from interventricular septum. Histo-pathological examination of the removed tissue revealed a complicated hydatid cyst and complete mass excision was confirmed. In this case a 7 year clinical and serological tests evaluation follow-up after surgical treatment showed no evidence of recurrence. The finding of this case emphasizes that in endemic countries, primary cardiovascular echino-coccosis should be considered in differential diagnosis. PMID:26175985

  2. Novel technique for injecting and extracting beams in a circular hadron accelerator without using septum magnets

    NASA Astrophysics Data System (ADS)

    Franchi, Andrea; Giovannozzi, Massimo

    2015-07-01

    With a few exceptions, all on-axis injection and extraction schemes implemented in circular particle accelerators, synchrotrons, and storage rings, make use of magnetic and electrostatic septa with systems of slow-pulsing dipoles acting on tens of thousands of turns and fast-pulsing dipoles on just a few. The dipoles create a closed orbit deformation around the septa, usually referred to as an orbit bump. A new approach is presented which obviates the need for the septum deflectors. Fast-pulsing elements are still required, but their strength can be minimized by choosing appropriate local accelerator optics. This technique should increase the beam clearance and reduce the usually high radiation levels found around the septa and also reduce the machine impedance introduced by the fast-pulsing dipoles. The basis of the technique is the creation of stable islands around stable fixed points in horizontal phase space. The trajectories of these islands may then be adjusted to match the position and angle of the incoming or outgoing beam.

  3. Muscarinic acetylcholine receptors in the nucleus accumbens core and shell contribute to cocaine priming-induced reinstatement of drug seeking

    PubMed Central

    Yee, Judy; Famous, Katie R.; Hopkins, Thomas J.; McMullen, Michael C.; Pierce, R. Christopher; Schmidt, Heath D.

    2011-01-01

    Muscarinic acetylcholine receptors in the nucleus accumbens play an important role in mediating the reinforcing effects of cocaine. However, there is a paucity of data regarding the role of accumbal muscarinic acetylcholine receptors in the reinstatement of cocaine-seeking behavior. The goal of these experiments was to assess the role of muscarinic acetylcholine receptors in the nucleus accumbens core and shell in cocaine and sucrose priming-induced reinstatement. Rats were initially trained to self-administer cocaine or sucrose on a fixed-ratio schedule of reinforcement. Lever-pressing behavior was then extinguished and followed by a subsequent reinstatement phase during which operant responding was induced by either a systemic injection of cocaine in cocaine-experienced rats or non-contingent delivery of sucrose pellets in subjects with a history of sucrose self-administration. Results indicated that systemic administration of the muscarinic acetylcholine receptor antagonist scopolamine (5.0 mg/kg, i.p.) dose-dependently attenuated cocaine, but not sucrose, reinstatement. Furthermore, administration of scopolamine (36.0 μg) directly into the nucleus accumbens shell or core attenuated cocaine-priming induced reinstatement. In contrast, infusion of scopolamine (36.0 μg) directly into the accumbens core, but not shell, attenuated sucrose reinstatement, which suggests that muscarinic acetylcholine receptors in these two subregions of the nucleus accumbens have differential roles in sucrose seeking. Taken together, these results indicate that cocaine-priming induced reinstatement is mediated, in part, by increased signaling through muscarinic acetylcholine receptors in the shell subregion of the nucleus accumbens. Muscarinic acetylcholine receptors in the core of the accumbens, in contrast, appear to play a more general (i.e. not cocaine specific) role in motivated behaviors. PMID:21034738

  4. Platypnea-Orthodeoxia Syndrome Two Decades after Definitive Surgical Repair of Pulmonary Atresia with Intact Ventricular Septum

    PubMed Central

    Chiu, Ing-Sh

    2016-01-01

    A 20-year-old female had undergone definitive surgical repair for pulmonary atresia with intact ventricular septum soon after birth. She was referred to our institution with the chief complaint of clubbing fingers. A thorough examination revealed platypnea-orthodeoxia syndrome due to an interatrial right-to-left shunt through a secundum atrial septal defect. Percutaneous closure with an Amplatzer Septal Occluder resulted in resolution of the syndrome. PMID:26996585

  5. Echocardiography-guided percutaneous per-ventricular laser ablation of ventricular septum: in vivo study in a canine model.

    PubMed

    He, Guangbin; Sun, Chao; Zhang, Xiangkong; Zuo, Lei; Qin, Haiying; Zheng, Minjuan; Zhou, Xiaodong; Liu, Liwen

    2016-05-01

    Surgical myectomy and ethanol ablation are established intervention strategies for left ventricular outflow obstruction in hypertrophic cardiomyopathy. Safety and efficacy limitations of these interventions call for a minimally invasive, potentially safer, and more efficacious strategy. In this study, we aimed to evaluate the feasibility of echocardiography-guided percutaneous per-ventricular laser ablation of a ventricular septum in a canine model. Six domestic dogs were chosen for the study. A 21G needle was inserted into the right ventricle with its tip reaching the targeted basal to mid-septum, after which laser ablation was performed as follows: 1-W laser for 3 min (180 J) at the basal segment and 5 min (300 J) at middle segment of the septum, respectively. Echocardiography, blood chemistry tests, and pathology examination were performed to assess the results of laser ablation. No death or major complications, i.e., tamponade, pericardial effusion, or ventricular fibrillation, occurred. The laser-ablated areas were well demarcated in the results of the pathological examination. The diameters of the ablated regions were 4.42 ± 0.57 and 5.28 ± 0.83 mm for 3 and 5 min ablation, respectively. Pre-ablation and post-ablation, cardiac enzymes were found to increase significantly while no significant differences were found among M-mode, 2D (LVEF), pulsed-wave (PW) Doppler, and tissue Doppler imaging (TDI) measurements. Contrast echocardiography confirmed the perfusion defects in the ablated regions. Microscopically, the ablated myocardium showed coagulative changes and a sparse distribution of disappearing nuclei and an increase in eosinophil number were observed. Our study suggests that percutaneous and per-ventricular laser ablation of the septum is feasible, potentially safe and efficacious, and warrants further investigation and validation. PMID:26861985

  6. Abstinence from cocaine self-administration heightens neural encoding of goal-directed behaviors in the accumbens.

    PubMed

    Hollander, Jonathan A; Carelli, Regina M

    2005-08-01

    Cocaine addiction in humans is characterized by cycles of abstinence from drug-taking and relapse. Here, electrophysiological recording procedures were used to determine whether nucleus accumbens (Acb) neuronal firing properties are altered following interruption and resumption of cocaine self-administration. Rats (n = 12) were trained to self-administer cocaine (2 h daily sessions) then divided into two groups. Acb activity was recorded for Group 1 (controls) during two additional self-administration sessions completed over the next 2 days (test sessions 1 and 2). Acb activity was recorded for Group 2 (1-month) during one self-administration session completed the next day (test 1), and during a second self-administration session 1 month later (test 2). As in prior reports, a subset of Acb neurons exhibited patterned discharges (short duration and/or long-term cyclic alterations, termed 'phasically active') relative to cocaine-reinforced responding during test session 1. Remarkably, the percentage of phasically active cells dramatically increased (nearly two-fold) following 1-month abstinence, in the core but not the shell of the Acb. Likewise, the strength of the neural correlates (determined via signal-to-baseline ratios) also increased as a function of abstinence. Extinction experiments in another set of rats (n = 12) revealed an increased motivational state for the drug following abstinence. The results show that abstinence from cocaine self-administration causes a dramatic increase in the number and strength of Acb neurons that encode cocaine-related information, thus representing the first neurophysiological correlate of heightened activation of the 'brain reward system' following abstinence and resumption (relapse) of cocaine consumption. PMID:15856078

  7. Nucleus accumbens response to incentive stimuli anticipation in children of alcoholics: relationships with precursive behavioral risk and lifetime alcohol use.

    PubMed

    Yau, Wai-Ying Wendy; Zubieta, Jon-Kar; Weiland, Barbara J; Samudra, Preeti G; Zucker, Robert A; Heitzeg, Mary M

    2012-02-15

    Children of alcoholics (COAs) are at elevated risk to develop alcohol and other substance use disorders. The neurobiological underpinnings of this heightened vulnerability are presently not well understood. This study investigated whether, in humans, COAs have different functioning of the mesolimbic reward circuitry beyond previous substance use confounds and examined potential group differences in neural response in relation to alcohol use and behavioral risk. We studied 20 18- to 22-year-old COAs and 20 controls, developmentally well characterized for substance use and selected to match on sex, age, IQ, lifetime substance use and associated problems, and precursive (ages 12-14 years) externalizing behavioral risk. None met criteria for Diagnostic and Statistical Manual of Mental Disorders IV diagnosis. Neural responses to anticipation of reward and loss were assessed using functional magnetic resonance imaging during a monetary incentive delay task. Overall, COAs showed reduced ventral striatum activation during anticipation of monetary reward and loss compared with controls. However, additional analysis revealed that blunted nucleus accumbens (NAcc) response was only observed in COAs who have not demonstrated any problem drinking behavior. In addition, uniquely in COAs, NAcc activation was positively correlated with precursive externalizing risk, as well as current and lifetime alcohol consumption. These findings suggest a multilevel developmental process whereby lower precursive behavioral risk appears protective of later problem alcohol use in COAs, which is further associated with a blunted NAcc response to incentive anticipation, potentially reflecting a resilience mechanism. Moreover, the results suggest that a close association between motivational responses, alcohol consumption, and behavioral risk may underlie addiction vulnerability in COAs. PMID:22396427

  8. Dopamine receptor expression and distribution dynamically change in the rat nucleus accumbens after withdrawal from cocaine self-administration

    PubMed Central

    Conrad, Kelly L.; Ford, Kerstin; Marinelli, Michela; Wolf, Marina E.

    2010-01-01

    Dopamine receptors (DARs) in the nucleus accumbens (NAc) are critical for cocaine's actions but the nature of adaptations in DAR function after repeated cocaine exposure remains controversial. This may be due in part to the fact that different methods used in previous studies measured different DAR pools. In the present study, we used a protein crosslinking assay to make the first measurements of DAR surface expression in the NAc of cocaine-experienced rats. Intracellular and total receptor levels were also quantified. Rats self-administered saline or cocaine for ten days. The entire NAc, or core and shell subregions, were collected one or 45 days later, when rats are known to exhibit low and high levels of cue-induced drug seeking, respectively. We found increased cell surface D1 DARs in the NAc shell on the first day after discontinuing cocaine self-administration (designated withdrawal day 1, or WD1) but this normalized by WD45. Decreased intracellular and surface D2 DAR levels were observed in the cocaine group. In shell, both measures decreased on WD1 and WD45. In core, decreased D2 DAR surface expression was only observed on WD45. Similarly, WD45 but not WD1 was associated with increased D3 DAR surface expression in the core. Taking into account many other studies, we suggest that decreased D2 DAR and increased D3 DAR surface expression on WD45 may contribute to enhanced cocaine-seeking after prolonged withdrawal, although this is likely to be a modulatory effect, in light of the mediating effect previously demonstrated for AMPA-type glutamate receptors. PMID:20435100

  9. Role of Acetylcholine Transmission in Nucleus Accumbens and Ventral Tegmental Area in Heroin-Seeking Induced by Conditioned Cues

    PubMed Central

    Zhou, Wenhua; Liu, Huifen; Zhang, Fuqiang; Tang, Suien; Zhu, Huaqiang; Lai, Miaojun; Kalivas, Peter W.

    2007-01-01

    The involvement of cholinergic transmission in heroin self-administration and the reinstatement of heroin-seeking was examined in rats trained to nose-poke for intravenous heroin. Systemic treatment with physostigmine, an inhibitor of acetylcholinesterase, modestly reduced the acquisition and rate of heroin self-administration, and this suppression of heroin intake was reversed by pretreatment with scopolamine but not by mecamylamine. Following 10–14 days of self-administration, rats were left in the home environment for 14 days. Subsequently, rats were evaluated for extinction of nose-pokes during the first hour after being returned to the self-administration apparatus. One hr later a conditioned stimulus (house light, light in the nose-poke hole, sound of the infusion pump) was presented to initiate cue-induced reinstatement. Physostigmine produced a dose-dependent inhibition of cue-induced reinstatement, but only the dose of 0.5 mg/kg significantly decreased nose-poke responding in the extinction test. Chronic treatment with physostigmine (0.1 mg/kg) did not impair performance during acquisition of heroin self-administration. However, during a subsequent reinstatement test conducted in the absence of physostigmine pretreatment, heroin seeking was significantly below that of rats chronically pretreated with saline. To evaluate brain regions mediating the effects of systemic drug treatment on reinstatement, physostigmine was microinjected into the nucleus accumbens (NAc) or ventral tegmental area (VTA). Microinjection of physostigmine into the NAc prior to presenting conditioned cues inhibited the reinstatement of heroin-seeking, without affecting extinction responding. In contrast, microinjection of physostigmine into the VTA augmented the reinstatement induced by conditioned cues and extinction responding. Inactivation of either NAc or VTA by microinjecting tetrodotoxin blocked both extinction responding and cue-induced reinstatement. These data demonstrate

  10. Accessory lateral discoid meniscus.

    PubMed

    Saygi, Baransel; Yildirim, Yakup; Senturk, Salih; Sezgin Ramadan, Saime; Gundes, Hakan

    2006-12-01

    The lateral meniscus tends to have more developmental variation than the medial counterpart. This is a report of an accessory discoid layer of lateral meniscus. All arthroscopic, magnetic resonance imaging and histopathological views are presented. PMID:16710729

  11. Amyotrophic lateral sclerosis

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000688.htm Amyotrophic lateral sclerosis To use the sharing features on this page, please enable JavaScript. Amyotrophic lateral sclerosis, or ALS, is a disease of the nerve ...

  12. Septum and medial frontal cortex contribution to spatial problem-solving.

    PubMed

    Poucet, B; Herrmann, T

    1990-03-26

    An attempt was made to contrast the effects of lesions to the medial frontal cortex and septum in two spatial tasks. In the fixed-goal (FG) task, the food was located on the same table throughout testing, and the start table was randomly varied from day to day. In the variable-goal (VG) task, the start table remained constant but the food was randomly distributed on one or the other of the two remaining tables. In both tasks, normal animals performed better than frontal and septal rats whose performance, however, improved over days in the FG, but not in the VG, task. In both tasks, significant improvement within days was found in medial frontal animals, but not in septal animals. Additional analyses revealed that septal animals had a general pattern of disrupted exploration and a tendency to use a response strategy (i.e. to repeat the same response both within and between days) which decreased over days in the FG task. In contrast, medial frontal animals did not demonstrate disrupted exploration nor any response tendency. It is concluded that both septal and medial frontal cortical damage produce a common spatial working memory impairment. However, there is some evidence to suggest that this common memory impairment could result from disruption of distinct mechanisms in septal and frontal animals. It is proposed that medial frontal lesions could affect some specific mechanism related either to attentional processes or to the ability to anticipate future events, whereas septal damage would interfere with the building of comprehensive and flexible spatial memories. PMID:2340101

  13. Antiplatelet effects of clopidogrel and aspirin after interventional patent foramen ovale/ atrium septum defect closure.

    PubMed

    Polzin, Amin; Dannenberg, Lisa; Sophia Popp, Valérie-; Kelm, Malte; Zeus, Tobias

    2016-06-01

    The optimal antiplatelet therapy after patent foramen ovale (PFO)/ atrium septum defect (ASD) closure is a matter of discussion. It is challenging as inter-individual responses to antiplatelet medication vary significantly and common complications are bleeding and ischemic events. In this study, we aimed to analyze the incidence of high on-treatment platelet reactivity (HTPR) to antiplatelet medication in patients undergoing PFO/ASD closure as well as clinical complications and thrombus formation on the occluder during six-month follow-up. This hypothesis generating pilot study was observed, which included 140 patients undergoing PFO/ASD closure. The primary endpoint was pharmacodynamic response to antiplatelet medication. A composite of death, myocardial infarction, bleeding, stroke and thrombus formation on the occluder during six-month follow-up was the secondary endpoint. HTPR to clopidogrel was analyzed using the vasodilator-stimulated protein phosphorylation (VASP), HTPR to aspirin by light-transmission aggregometry (LTA). In 71% of patients HTPR to clopidogrel was detected, HTPR to aspirin in only 4%. We observed 12 complications, 9 bleeding events (including 3 major bleeding events) and 3 transient ischemic attacks. No stroke and no thrombus formation on the occluder occurred. The primary endpoint was not associated with the secondary endpoint. The incidence of HTPR to clopidogrel in PFO/ASD closure patients is very high. Despite this high incidence, no stroke or thrombus formation on the occluder occurred at all. This leads to the hypothesis, that the benefit of additional clopidogrel medication is questionable and has to be investigated in large-scale clinical trials. PMID:26556101

  14. The effect of microinjections of amphetamine into the neostriatum and the nucleus accumbens on self-stimulation behaviour.

    PubMed

    Broekkamp, C L; Pijnenburg, A J; Cools, A R; Van Rossum, J M

    1975-05-28

    The effect of micro-injections of dexamphetamine chloride into the neostriatum, the nucleus accumbens, the anterior hypothalamus, and the ventricular system on self-stimulation with electrodes in the ventral tegmentum was studied. Unilateral injections of 10 mug into the anterior hypothalamus produced no effect. Injections into the neostriatum tended to depress the self-stimulation rate, whereas injections into the nucleus accumbens increased the rate markedly. Bilateral injections (2 times 2.5 mug and 2 times 5 mug amph.) into the nucleus accumbens were more effective than unilateral injections and were as effective as systemic injections of 1 mg/kg amphetamine (i.p.). Bilateral injections into the neostriatum also increased the self-stimulation rate. Injections of 10 mug into the ventricular system resulted in a smaller increase which was not statistically significant. These results are discussed in relation to the involvement of the dopaminergic system in the maintenance of self-stimulation behaviour. PMID:1161977

  15. Infection of male rats with Toxoplasma gondii results in enhanced delay aversion and neural changes in the nucleus accumbens core

    PubMed Central

    Tan, Donna; Soh, Linda Jing Ting; Lim, Lee Wei; Daniel, Tan Chia Wei; Zhang, Xiaodong; Vyas, Ajai

    2015-01-01

    Rats infected with the protozoan parasite Toxoplasma gondii exhibit reduced avoidance of predator odours. This behavioural change is likely to increase transmission of the parasite from rats to cats. Here, we show that infection with T. gondii increases the propensity of the infected rats to make more impulsive choices, manifested as delay aversion in an intertemporal choice task. Concomitantly, T. gondii infection causes reduction in dopamine content and neuronal spine density of the nucleus accumbens core, but not of the nucleus accumbens shell. These results are consistent with a role of the nucleus accumbens dopaminergic system in mediation of choice impulsivity and goal-directed behaviours. Our observations suggest that T. gondii infection in rats causes a syndromic shift in related behavioural constructs of innate aversion and making foraging decisions. PMID:25994671

  16. Ultrastructural localization of tyrosine hydroxylase in tree shrew nucleus accumbens core and shell

    PubMed Central

    McCollum, Lesley A.; Roberts, Rosalinda C.

    2014-01-01

    Many behavioral, physiological, and anatomical studies utilize animal models to investigate human striatal pathologies. Although commonly used, rodent striatum may not present the optimal animal model for certain studies due to a lesser morphological complexity than that of non-human primates, which are increasingly restricted in research. As an alternative, the tree shrew could provide a beneficial animal model for studies of the striatum. The gross morphology of the tree shrew striatum resembles that of primates, with separation of the caudate and putamen by the internal capsule. The neurochemical anatomy of the ventral striatum, specifically the nucleus accumbens, has never been examined. This major region of the limbic system plays a role in normal physiological functioning and is also an area of interest for human striatal disorders. The current study uses immunohistochemistry of calbindin and tyrosine hydroxylase (TH) to determine the ultrastructural organization of the nucleus accumbens core and shell of the tree shrew (Tupaia glis belangeri). Stereology was used to quantify the ultrastructural localization of TH, which displays weaker immunoreactivity in the core and denser immunoreactivity in the shell. In both regions, synapses with TH-immunoreactive axon terminals were primarily symmetric and showed no preference for targeting dendrites versus dendritic spines. The results were compared to previous ultrastructural studies of TH and dopamine in rat and monkey nucleus accumbens. Tree shrew and monkey show no preference for the postsynaptic target in the shell, in contrast to rats which show a preference for synapsing with dendrites. Tree shrews have a ratio of asymmetric to symmetric synapses formed by TH-immunoreactive terminals that is intermediate between rats and monkey. The findings from this study support the tree shrew as an alternative model for studies of human striatal pathologies. PMID:24769226

  17. Lateral flow strip assay

    SciTech Connect

    Miles, Robin R.; Benett, William J.; Coleman, Matthew A.; Pearson, Francesca S.; Nasarabadi, Shanavaz L.

    2011-03-08

    A lateral flow strip assay apparatus comprising a housing; a lateral flow strip in the housing, the lateral flow strip having a receiving portion; a sample collection unit; and a reagent reservoir. Saliva and/or buccal cells are collected from an individual using the sample collection unit. The sample collection unit is immersed in the reagent reservoir. The tip of the lateral flow strip is immersed in the reservoir and the reagent/sample mixture wicks up into the lateral flow strip to perform the assay.

  18. Intrahypothalamic injection of cannabidiol increases the extracellular levels of adenosine in nucleus accumbens in rats.

    PubMed

    Mijangos-Moreno, Stephanie; Poot-Aké, Alwin; Arankowsky-Sandoval, Gloria; Murillo-Rodríguez, Eric

    2014-07-01

    Cannabidiol (CBD) is a constituent of Cannabis sativa that promotes wakefulness as well as enhances endogenous levels of wake-related neurotransmitters, including dopamine. However, at this date, the effects of CBD on the sleep-inducing molecules, such as adenosine (AD), are unknown. Here, we report that intrahypothalamic injection of CBD (10μg/1μL) increases the extracellular levels of AD collected from nucleus accumbens. Furthermore, the pharmacodynamic of this drug shows that effects on the contents of AD last 2h post-injection. These preliminary findings suggest that CBD promotes the endogenous accumulation of AD. PMID:24800644

  19. Cholecystokinin release mediated by 5-HT3 receptors in rat cerebral cortex and nucleus accumbens.

    PubMed Central

    Paudice, P.; Raiteri, M.

    1991-01-01

    1. The effects of 5-hydroxytryptamine (5-HT) on the release of cholexystokinin-like immunoreactivity (CCK-LI) were examined in synaptosomes prepared from rat cerebral cortex and nucleus accumbens and depolarized by superfusion with 15 mM KCl. 2. In both areas 5-HT, tested between 0.1 and 100 nM, increased the calcium-dependent, depolarization-evoked CCK-LI release in a concentration-related manner. The concentration-response curves did not differ significantly between the two brain areas (EC50: 0.4 +/- 0.045 nM and 0.48 +/- 0.053 nM, respectively, in cortical and n. accumbens synaptosomes; maximal effect: about 60% at 10 nM 5-HT). 3. The 5-HT1/5-HT2 receptor antagonist methiothepin (300 nM) did not affect the CCK-LI release elicited by 10 nM 5-HT. However, the effects of 10 nM 5-HT were antagonized in a concentration-dependent manner by the 5-HT3 receptor antagonists (3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205-930; 0.1-100 nM; IC50: 3.56 +/- 0.42 nM in the cortex and 3.90 +/- 0.50 nM in the n. accumbens) and ondasetron (IC50: 8.15 +/- 0.73 nM in the cerebral cortex). 5-HT (10 nM) was also strongly antagonized by 100 nM 1 alpha H, 3 alpha 5 alpha H-tropan-3-yl-3,5-dichlorobenzoate (MDL 72222) another blocker of the 5-HT3 receptor. Moreover, the 5-HT3 receptor agonist 1-phenylbiguanide (tested in the cerebral cortex between 0.1 and 100 nM) enhanced CCK-LI release in a manner almost identical to that of 5-HT (EC50 = 0.64 +/- 0.071 nM). 4. It is concluded that 5-HT can act as a potent releaser of CCK-LI in rat cerebrocortex and nucleus accumbens through the activation of receptors of the 5-HT3 type situated on the CCK-releasing terminals. This interaction may provide a rationale for the clinical development of both 5-HT3 and CCK receptor antagonists as novel anxiolytic drugs. PMID:1933141

  20. The dorsomedial shell of the nucleus accumbens facilitates cocaine-induced locomotor activity during the induction of behavioral sensitization.

    PubMed

    Todtenkopf, M S; Carreiras, T; Melloni, R H; Stellar, J R

    2002-04-01

    The mesolimbic dopamine system has been intensely studied as the neural circuit mediating the locomotor response to psychostimulants and behavioral sensitization. In particular, the dopaminergic innervation of the nucleus accumbens has been implicated as a site responsible for the manifestations of behavioral sensitization. Previous studies have demonstrated an augmented release of dopamine in the nucleus accumbens upon a systemic injection of a psychostimulant. In addition, alterations in the dopaminergic innervation patterns in this brain region have been demonstrated in animals that received repeated injections of cocaine. Furthermore, lesions of projection sites that have terminations in the nucleus accumbens have demonstrated alterations in psychostimulant induced locomotion, both acutely, as well as in sensitization paradigms. Since dopamine in the nucleus accumbens is believed to regulate several excitatory amino acid inputs, the present study examined the effects of a localized electrolytic lesion in the dorsomedial shell of the nucleus accumbens in order to better understand the functional role this brain region has in behavioral sensitization. All animals received bi-daily injections of 15 mg/kg i.p. cocaine. Only those demonstrating behavioral sensitization after a subsequent challenge dose were included in the analysis. Following acute exposure to cocaine, lesioned animals did not show any difference in their locomotor response when compared with sham controls. However, after repeated exposure to cocaine, sensitized animals demonstrated a significant attenuation in locomotor behavior when compared with sensitized sham controls. This decrease in horizontal locomotion persisted 2 days into withdrawal, yet dissipated in the sensitized animals that were challenged 2 weeks following their last injection. The data presented here demonstrate that the dorsomedial shell of the nucleus accumbens plays an important role in the initial stages of behavioral

  1. Lateral canthal surgery.

    PubMed

    Chong, Kelvin Kam-Lung; Goldberg, Robert A

    2010-08-01

    The lateral canthus is a delicate and complicated three-dimensional structure with function relevant to the health of the ocular surface. Dysfunction of the lateral canthus, due to aging changes or iatrogenic trauma, results in ocular morbidity ranging from chronic irritation to tearing to recalcitrant keratopathy. From an aesthetic standpoint, symmetric, normally positioned lateral canthi are cornerstones of youthful periorbital appearance, disruption of which leads to cosmetically significant deformity or asymmetry. Reconstruction of the lateral canthus is important in the rehabilitation of the aging eyelid and an unfortunate necessity after failed lateral canthal surgery. The common methods for improving or maintaining position, tone, and shape of the lower eyelid and lateral canthus use tightening or shortening the lower eyelid horizontally, keeping the canthal angle in an appropriate vertical level, and hugging the ocular surface. Many techniques have been described for the reconstruction of the lateral canthus in functional conditions or for aesthetic purposes. These methods have met with varying success. In this article, we begin with a discussion of the anatomy and physiology of the lateral canthus, followed by clinical examples of lateral canthal abnormalities and underlying pathophysiologies. A review of surgical options for the lateral canthus is presented with concluding remarks on postoperative complications. PMID:20524167

  2. Aneurysm of the Membranous Septum Causing Outflow Obstruction of the Venous Ventricle in Corrected Transposition of the Great Arteries

    PubMed Central

    Gunawan, Antonius; Krajcer, Zvonimir; Leachman, Robert D.

    1982-01-01

    A 58 year-old man with clinical and hemodynamic evidence of subpulmonic stenosis was admitted to our hospital. Angiography revealed corrected transposition of the great arteries and an aneurysm of membranous ventricular septum (AVS) that protruded into the venous outflow tract, causing severe subpulmonic obstruction during systole. The diagnosis was confirmed at surgery, and successful repair of the aneurysm was performed. This was an unusual case because the AVS caused such severe obstruction that the venous ventricular pressure was elevated to a value equal to the systemic level. Images PMID:15226819

  3. Reduced dopamine function within the medial shell of the nucleus accumbens enhances latent inhibition

    PubMed Central

    Nelson, A.J.D.; Thur, K.E.; Horsley, R.R.; Spicer, C.; Marsden, C.A.; Cassaday, H.J.

    2011-01-01

    Latent inhibition (LI) manifests as poorer conditioning to a CS that has previously been presented without consequence. There is some evidence that LI can be potentiated by reduced mesoaccumbal dopamine (DA) function but the locus within the nucleus accumbens of this effect is as yet not firmly established. Experiment 1 tested whether 6-hydroxydopamine (6-OHDA)-induced lesions of DA terminals within the core and medial shell subregions of the nucleus accumbens (NAc) would enhance LI under conditions that normally disrupt LI in controls (weak pre-exposure). LI was measured in a thirst motivated conditioned emotional response procedure with 10 pre-exposures (to a noise CS) and 2 conditioning trials. The vehicle-injected and core-lesioned animals did not show LI and conditioned to the pre-exposed CS at comparable levels to the non-pre-exposed controls. 6-OHDA lesions to the medial shell, however, produced potentiation of LI, demonstrated across two extinction tests. In a subsequent experiment, haloperidol microinjected into the medial shell prior to conditioning similarly enhanced LI. These results underscore the dissociable roles of core and shell subregions of the NAc in mediating the expression of LI and indicate that reduced DA function within the medial shell leads to enhanced LI. PMID:21146557

  4. Does incentive-elicited nucleus accumbens activation differ by substance of abuse? An examination with adolescents.

    PubMed

    Karoly, Hollis C; Bryan, Angela D; Weiland, Barbara J; Mayer, Andrew; Dodd, Andrew; Feldstein Ewing, Sarah W

    2015-12-01

    Numerous questions surround the nature of reward processing in the developing adolescent brain, particularly in regard to polysubstance use. We therefore sought to examine incentive-elicited brain activation in the context of three common substances of abuse (cannabis, tobacco, and alcohol). Due to the role of the nucleus accumbens (NAcc) in incentive processing, we compared activation in this region during anticipation of reward and loss using a monetary incentive delay (MID) task. Adolescents (ages 14-18; 66% male) were matched on age, gender, and frequency of use of any common substances within six distinct groups: cannabis-only (n=14), tobacco-only (n=34), alcohol-only (n=12), cannabis+tobacco (n=17), cannabis+tobacco+alcohol (n=17), and non-using controls (n=38). All groups showed comparable behavioral performance on the MID task. The tobacco-only group showed decreased bilateral nucleus accumbens (NAcc) activation during reward anticipation as compared to the alcohol-only group, the control group, and both polysubstance groups. Interestingly, no differences emerged between the cannabis-only group and any of the other groups. Results from this study suggest that youth who tend toward single-substance tobacco use may possess behavioral and/or neurobiological characteristics that differentiate them from both their substance-using and non-substance-using peers. PMID:26070843

  5. RAPID DOPAMINE TRANSMISSION WITHIN THE NUCLEUS ACCUMBENS DRAMATICALLY DIFFERS FOLLOWING MORPHINE AND OXYCODONE DELIVERY

    PubMed Central

    Mabrouk, Omar S.; Lovic, Vedran; Singer, Bryan F.; Kennedy, Robert T.; Aragona, Brandon J.

    2014-01-01

    While most drugs of abuse increase dopamine neurotransmission, rapid neurochemical measurements show that different drugs evoke distinct dopamine release patterns within the nucleus accumbens. Rapid changes in dopamine concentration following psychostimulant administration have been well studied; however, such changes have never been examined following opioid delivery. Here, we provide novel measures of rapid dopamine release following intravenous infusion of two opioids, morphine and oxycodone, in drug naïve rats using fast-scan cyclic voltammetry and rapid (1 min) microdialysis coupled with mass spectrometry. In addition to measuring rapid dopamine transmission, microdialysis HPLC-MS measures changes in GABA, glutamate, monoamines, monoamine metabolites, and several other neurotransmitters. Although both opioids increased dopamine release in the nucleus accumbens, their patterns of drug-evoked dopamine transmission differed dramatically. Oxycodone evoked a robust and stable increase in dopamine concentration and a robust increase in the frequency and amplitude of phasic dopamine release events. Conversely, morphine evoked a brief (~ 1 min) increase in dopamine that was coincident with a surge in GABA concentration and then both transmitters returned to baseline levels. Thus, by providing rapid measures of neurotransmission, this study reveals previously unknown differences in opioid-induced neurotransmitter signaling. Investigating these differences may be essential for understanding how these two drugs of abuse could differentially usurp motivational circuitry and powerfully influence behavior. PMID:25208732

  6. Protein Expression in the Nucleus Accumbens of Rats Exposed to Developmental Vitamin D Deficiency

    PubMed Central

    McGrath, John; Iwazaki, Takeshi; Eyles, Darryl; Burne, Thomas; Cui, Xiaoying; Ko, Pauline; Matsumoto, Izuru

    2008-01-01

    Introduction Developmental vitamin D (DVD) deficiency is a candidate risk factor for schizophrenia. Animal models have confirmed that DVD deficiency is associated with a range of altered genomic, proteomic, structural and behavioural outcomes in the rat. Because the nucleus accumbens has been implicated in neuropsychiatric disorders, in the current study we examined protein expression in this region in adult rats exposed to DVD deficiency Methods Female Sprague Dawley rats were maintained on a vitamin D deficient diet for 6 weeks, mated and allowed to give birth, after which a diet containing vitamin D was reintroduced. Male adult offspring (n = 8) were compared to control male (n = 8). 2-D gel electrophoresis-based proteomics and mass spectroscopy were used to investigate differential protein expression. Results There were 35 spots, mapped to 33 unique proteins, which were significantly different between the two groups. Of these, 22 were down-regulated and 13 up-regulated. The fold changes were uniformly small, with the largest FC being −1.67. Within the significantly different spots, three calcium binding proteins (calbindin1, calbindin2 and hippocalcin) were altered. Other proteins associated with DVD deficiency related to mitochondrial function, and the dynamin-like proteins. Conclusions Developmental vitamin D deficiency was associated with subtle changes in protein expression in the nucleus accumbens. Disruptions in pathways related to calcium-binding proteins and mitochondrial function may underlie some of the behavioural features associated with animal models of developmental vitamin D deficiency PMID:18545652

  7. The effect of ploidy and incubation temperature on survival and the prevalence of aplasia of the septum transversum in Atlantic salmon, Salmo salar L.

    PubMed

    Fraser, T W K; Fleming, M S; Poppe, T T; Hansen, T; Fjelldal, P G

    2014-03-01

    Heart deformities are a concern in aquaculture and are linked to egg incubation temperature. Diploid and triploid Atlantic salmon, Salmo salar L., were incubated at 6, 8 and 10 °C and analysed for aplasia of the septum transversum (n = 150 ploidy⁻¹ incubation temperature⁻¹). Heart morphology (size and shape) was assessed in fish incubated at 6 °C and in fish with and without aplasia of the septum transversum (n = 9 group⁻¹) incubated at 10 °C. Egg mortality was significantly higher in triploids than in diploids at all incubation temperatures, and increased egg incubation temperatures increased mortality in both ploidy. Triploids grew quicker than diploids after egg incubation at 10 °C, but not at 6 °C. Aplasia of the septum transversum occurred only in triploid fish after incubation at 6 °C and 8 °C (0.7% and 3.3%, respectively) and was significantly greater (P ≤ 0.05) in triploids after incubation at 10 °C compared with diploids (30% and 18%, respectively). Aplasia of the septum transversum significantly increased heart mass and resulted in a long flat ventricle compared with fish displaying a septum transversum. The results suggest triploid salmon should be incubated below 8 °C. PMID:23488808

  8. Drc1p/Cps1p, a 1,3-beta-glucan synthase subunit, is essential for division septum assembly in Schizosaccharomyces pombe.

    PubMed Central

    Liu, J; Wang, H; McCollum, D; Balasubramanian, M K

    1999-01-01

    Schizosaccharomyces pombe divides by medial fission through the use of an actomyosin-based contractile ring. A division septum is formed centripetally, concomitant with ring constriction. Although several genes essential for cytokinesis have been described previously, enzymes that participate in the assembly of the division septum have not been identified. Here we describe a temperature-sensitive mutation, drc1-191, that prevents division septum assembly and causes mutant cells to arrest with a stable actomyosin ring. Unlike the previously characterized cytokinesis mutants, which undergo multiple mitotic cycles, drc1-191 is the first cytokinesis mutant that arrests with two interphase nuclei. Interestingly, unlike drc1-191, drc1-null mutants proceed through multiple mitotic cycles, leading to the formation of large cells with many nuclei. drc1 is allelic to cps1, which encodes a 1,3-beta-glucan synthase subunit. We conclude that Drc1p/Cps1p is not required for cell elongation and cell growth, but plays an essential role in assembly of the division septum. Furthermore, it appears that constriction of the actomyosin ring might depend on assembly of the division septum. We discuss possible mechanisms that account for the differences in the phenotypes of the drc1-191 and the drc1-null mutants and also reflect the potential links between Drc1p and other cytokinesis regulators. PMID:10545452

  9. Tracking the Fear Memory Engram: Discrete Populations of Neurons within Amygdala, Hypothalamus, and Lateral Septum Are Specifically Activated by Auditory Fear Conditioning

    ERIC Educational Resources Information Center

    Butler, Christopher W.; Wilson, Yvette M.; Gunnersen, Jenny M.; Murphy, Mark

    2015-01-01

    Memory formation is thought to occur via enhanced synaptic connectivity between populations of neurons in the brain. However, it has been difficult to localize and identify the neurons that are directly involved in the formation of any specific memory. We have previously used "fos-tau-lacZ" ("FTL") transgenic mice to identify…

  10. The flexible approach hypothesis: unification of effort and cue-responding hypotheses for the role of nucleus accumbens dopamine in the activation of reward-seeking behavior.

    PubMed

    Nicola, Saleem M

    2010-12-01

    Dopamine released in the nucleus accumbens is thought to contribute to the decision to exert effort to seek reward. This hypothesis is supported by findings that performance of tasks requiring higher levels of effort is more susceptible to disruption by manipulations that reduce accumbens dopamine function than tasks that require less effort. However, performance of some low-effort cue-responding tasks is highly dependent on accumbens dopamine. To reconcile these disparate results, we made detailed behavioral observations of rats performing various operant tasks and determined how injection of dopamine receptor antagonists into the accumbens influenced specific aspects of the animals' behavior. Strikingly, once animals began a chain of operant responses, the antagonists did not affect the ability to continue the chain until reward delivery. Instead, when rats left the operandum, the antagonists severely impaired the ability to return. We show that this impairment is specific to situations in which the animal must determine a new set of approach actions on each approach occasion; this behavior is called "flexible approach." Both high-effort operant tasks and some low-effort cue-responding tasks require dopamine receptor activation in the accumbens because animals pause their responding and explore the chamber, and accumbens dopamine is required to terminate these pauses with flexible approach to the operandum. The flexible approach hypothesis provides a unified framework for understanding the contribution of the accumbens and its dopamine projection to reward-seeking behavior. PMID:21147998

  11. Nucleus accumbens response to gains in reputation for the self relative to gains for others predicts social media use.

    PubMed

    Meshi, Dar; Morawetz, Carmen; Heekeren, Hauke R

    2013-01-01

    Our reputation is important to us; we've experienced natural selection to care about our reputation. Recently, the neural processing of gains in reputation (positive social feedback concerning one's character) has been shown to occur in the human ventral striatum. It is still unclear, however, how individual differences in the processing of gains in reputation may lead to individual differences in real-world behavior. For example, in the real-world, one way that people currently maintain their reputation is by using social media websites, like Facebook. Furthermore, Facebook use consists of a social comparison component, where users observe others' behavior and can compare it to their own. Therefore, we hypothesized a relationship between the way the brain processes specifically self-relevant gains in reputation and one's degree of Facebook use. We recorded functional neuroimaging data while participants received gains in reputation, observed the gains in reputation of another person, or received monetary reward. We demonstrate that across participants, when responding to gains in reputation for the self, relative to observing gains for others, reward-related activity in the left nucleus accumbens predicts Facebook use. However, nucleus accumbens activity in response to monetary reward did not predict Facebook use. Finally, a control step-wise regression analysis showed that Facebook use primarily explains our results in the nucleus accumbens. Overall, our results demonstrate how individual sensitivity of the nucleus accumbens to the receipt of self-relevant social information leads to differences in real-world behavior. PMID:24009567

  12. No Evidence for Sex Differences in the Electrophysiological Properties and Excitatory Synaptic Input onto Nucleus Accumbens Shell Medium Spiny Neurons.

    PubMed

    Willett, Jaime A; Will, Tyler; Hauser, Caitlin A; Dorris, David M; Cao, Jinyan; Meitzen, John

    2016-01-01

    Sex differences exist in how the brain regulates motivated behavior and reward, both in normal and pathological contexts. Investigations into the underlying neural mechanisms have targeted the striatal brain regions, including the dorsal striatum and nucleus accumbens core and shell. These investigations yield accumulating evidence of sexually different electrophysiological properties, excitatory synaptic input, and sensitivity to neuromodulator/hormone action in select striatal regions both before and after puberty. It is unknown whether the electrical properties of neurons in the nucleus accumbens shell differ by sex, and whether sex differences in excitatory synaptic input are present before puberty. To test the hypothesis that these properties differ by sex, we performed whole-cell patch-clamp recordings on male and female medium spiny neurons (MSNs) in acute brain slices obtained from prepubertal rat nucleus accumbens shell. We analyzed passive and active electrophysiological properties, and miniature EPSCs (mEPSCs). No sex differences were detected; this includes those properties, such as intrinsic excitability, action potential afterhyperpolarization, threshold, and mEPSC frequency, that have been found to differ by sex in other striatal regions and/or developmental periods. These findings indicate that, unlike other striatal brain regions, the electrophysiological properties of nucleus accumbens shell MSNs do not differ by sex. Overall, it appears that sex differences in striatal function, including motivated behavior and reward, are likely mediated by other factors and striatal regions. PMID:27022621

  13. The Role of Nucleus Accumbens Shell in Learning about Neutral versus Excitatory Stimuli during Pavlovian Fear Conditioning

    ERIC Educational Resources Information Center

    Bradfield, Laura A.; McNally, Gavan P.

    2010-01-01

    We studied the role of nucleus accumbens shell (AcbSh) in Pavlovian fear conditioning. Rats were trained to fear conditioned stimulus A (CSA) in Stage I, which was then presented in compound with a neutral stimulus and paired with shock in Stage II. AcbSh lesions had no effect on fear-learning to CSA in Stage I, but selectively prevented learning…

  14. Interactions between Brainstem Noradrenergic Neurons and the Nucleus Accumbens Shell in Modulating Memory for Emotionally Arousing Events

    ERIC Educational Resources Information Center

    Kerfoot, Erin C.; Williams, Cedric L.

    2011-01-01

    The nucleus accumbens shell (NAC) receives axons containing dopamine-[beta]-hydroxylase that originate from brainstem neurons in the nucleus of the solitary tract (NTS). Recent findings show that memory enhancement produced by stimulating NTS neurons after learning may involve interactions with the NAC. However, it is unclear whether these…

  15. Dopamine D(2)/D(3)-receptor and transporter densities in nucleus accumbens and amygdala of type 1 and 2 alcoholics.

    PubMed

    Tupala, E; Hall, H; Bergström, K; Särkioja, T; Räsänen, P; Mantere, T; Callaway, J; Hiltunen, J; Tiihonen, J

    2001-05-01

    Alcohol acts through mechanisms involving the brain neurotransmitter dopamine (DA) with the nucleus accumbens as the key zone for mediating these effects. We evaluated the densities of DA D(2)/D(3) receptors and transporters in the nucleus accumbens and amygdala of post-mortem human brains by using [(125)l]epidepride and [(125)I]PE2I as radioligands in whole hemispheric autoradiography of Cloninger type 1 and 2 alcoholics and healthy controls. When compared with controls, the mean binding of [(125)I]epidepride to DA D(2)/D(3) receptors was 20% lower in the nucleus accumbens and 41% lower in the amygdala, and [(125)I]PE2I binding to DA transporters in the nucleus accumbens was 39% lower in type 1 alcoholics. These data indicate that dopaminergic functions in these limbic areas may be impaired among type 1 alcoholics, due to the substantially lower number of receptor sites. Our results suggest that such a reduction may result in the chronic overuse of alcohol as an attempt to stimulate DA function. PMID:11326293

  16. Nucleus accumbens response to gains in reputation for the self relative to gains for others predicts social media use

    PubMed Central

    Meshi, Dar; Morawetz, Carmen; Heekeren, Hauke R.

    2013-01-01

    Our reputation is important to us; we've experienced natural selection to care about our reputation. Recently, the neural processing of gains in reputation (positive social feedback concerning one's character) has been shown to occur in the human ventral striatum. It is still unclear, however, how individual differences in the processing of gains in reputation may lead to individual differences in real-world behavior. For example, in the real-world, one way that people currently maintain their reputation is by using social media websites, like Facebook. Furthermore, Facebook use consists of a social comparison component, where users observe others' behavior and can compare it to their own. Therefore, we hypothesized a relationship between the way the brain processes specifically self-relevant gains in reputation and one's degree of Facebook use. We recorded functional neuroimaging data while participants received gains in reputation, observed the gains in reputation of another person, or received monetary reward. We demonstrate that across participants, when responding to gains in reputation for the self, relative to observing gains for others, reward-related activity in the left nucleus accumbens predicts Facebook use. However, nucleus accumbens activity in response to monetary reward did not predict Facebook use. Finally, a control step-wise regression analysis showed that Facebook use primarily explains our results in the nucleus accumbens. Overall, our results demonstrate how individual sensitivity of the nucleus accumbens to the receipt of self-relevant social information leads to differences in real-world behavior. PMID:24009567

  17. Microstructural Abnormality in Left Nucleus Accumbens Predicts Dysfunctional Beliefs in Treatment-Resistant Obsessive-Compulsive Disorder

    PubMed Central

    Li, Zhongchun; Ji, Weidong; Li, Deqiang; Li, Xujuan; Feng, Wei

    2014-01-01

    Background The aim of this study was to determine whether dysfunctional beliefs might predict treatment-resistance and to examine the relationship between fractional anisotropy (FA) in diffusion tensor imaging (DTI) and cognitive biases for optimal treatment choice. Material/Methods We recruited 11 non-resistant obsessive-compulsive disorder (OCD) patients, 11 resistant OCD patients, and 11 healthy subjects. Results OCD patients had higher Obsessive Beliefs Questionnaire (OBQ-87) subscale scores than subjects in non-resistant and resistant groups. A significant difference was found between non-resistant and resistant OCD patients in R-Scale and I-Scale. A significant decrease in FA was found in left dorsal frontal gyrus and left inferior parietal lobule in the non-resistant group as compared to the control group. FA also decreased significantly in left anterior cingulate cortex, putamen, and nucleus accumbens in the resistant group as compared to the control group. There was a significant decrease in FA in nucleus accumbens in the resistant group as compared to the non-resistant group. Reduced FA in left nucleus accumbens was negatively associated with OBQ-87 factor R and I and the total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Conclusions Abnormalities in cortical-striatal white matter networks may contribute to the dysfunctional beliefs in patients with treatment-resistant OCD, and the left nucleus accumbens may be an important and promising target for the treatment of OCD. PMID:25393961

  18. A Study on the Role of the Dorsal Striatum and the Nucleus Accumbens in Allocentric and Egocentric Spatial Memory Consolidation

    ERIC Educational Resources Information Center

    De Leonibus, Elvira; Oliverio, Alberto; Mele, Andrea

    2005-01-01

    There is now accumulating evidence that the striatal complex in its two major components, the dorsal striatum and the nucleus accumbens, contributes to spatial memory. However, the possibility that different striatal subregions might modulate specific aspects of spatial navigation has not been completely elucidated. Therefore, in this study, two…

  19. Discoid lateral meniscus.

    PubMed

    Fritschy, D; Gonseth, D

    1991-01-01

    Discoid meniscus is uncommon and usually affects the lateral meniscus. We present 16 patients (8 male and 6 female) with tears of a discoid lateral meniscus occurring in 1800 arthroscopies. We carried out an arthroscopic partial meniscectomy leaving an intact peripheral rim. This is biomechanically satisfactory and the early results are encouraging. PMID:1917190

  20. Dysembryoplastic Neuroepithelial Tumor of the Septum Pellucidum and the Supratentorial Midline: Histopathologic, Neuroradiologic, and Molecular Features of 7 Cases.

    PubMed

    Gessi, Marco; Hattingen, Elke; Dörner, Evelyn; Goschzik, Tobias; Dreschmann, Verena; Waha, Andreas; Pietsch, Torsten

    2016-06-01

    Dysembryoplastic neuroepithelial tumors (DNTs) are one of the most common epilepsy-associated low-grade glioneuronal tumors of the central nervous system. Although most DNTs occur in the cerebral cortex, DNT-like tumors with unusual intraventricular or periventricular localizations have been reported. Most of them involve the septum pellucidum and the foramen of Monro. In this study, we have described the neuroradiologic, histopathologic, and molecular features of 7 cases (4 female and 3 male; patient age range, 3 to 34 y; mean age, 16.7 y). The tumors, all localized near the supratentorial midline structures in proximity to the foramen of Monro and septum pellucidum, appeared in magnetic resonance imaging as well-delimited cystic lesions with cerebrospinal fluid-like signal on T1-weighted and T2-weighted images, some of them with typical fluid-attenuated inversion recovery ring sign. Histologically, they shared features with classic cortical DNTs but did not display aspects of multinodularity. From a molecular point of view the cases investigated did not show KIAA1549-BRAF fusions or FGFR1 mutations, alterations otherwise observed in pilocytic astrocytomas, or MYB and MYBL1 alterations that have been identified in a large group of pediatric low-grade gliomas. Moreover, BRAF mutations, which so far represent the most common molecular alteration found in cortical DNTs, were absent in this group of rare periventricular tumors. PMID:26796505

  1. Normal development of the muscular region of the interventricular septum--I. The significance of the ventricular trabeculations.

    PubMed

    Contreras-Ramos, A; Sánchez-Gómez, C; García-Romero, H L; Cimarosti, L O

    2008-10-01

    The structures that participate in normal ventricular septation, and to what extent they do so, are questions not yet clarified. Even less is known about how much each of the embryonic structures contributes to the topography of the mature interventricular septum (IVS). The aim of the present paper is to investigate the significance of ventricular trabeculations in the normal development of the muscular region (the middle and apical thirds) of the IVS and to determine the direction in which it grows during cardiac septation. Anatomical studies and in vivo labelling were carried out in chicken embryo hearts at stage 18HH, tracing the labels up to stage 36HH. We analysed the results by measuring the distance between the labelled structures at the beginning and end of the experiments. We demonstrate that the muscular region of the septum originates by the fusion of the ventricular trabeculations with evidence that during cardiac development, the IVS as well as the ventricular cavities grow in opposite direction to the atria. PMID:18460050

  2. Distinct roles of Rho1, Cdc42, and Cyk3 in septum formation and abscission during yeast cytokinesis

    PubMed Central

    Onishi, Masayuki; Ko, Nolan; Nishihama, Ryuichi

    2013-01-01

    In yeast and animal cytokinesis, the small guanosine triphosphatase (GTPase) Rho1/RhoA has an established role in formation of the contractile actomyosin ring, but its role, if any, during cleavage-furrow ingression and abscission is poorly understood. Through genetic screens in yeast, we found that either activation of Rho1 or inactivation of another small GTPase, Cdc42, promoted secondary septum (SS) formation, which appeared to be responsible for abscission. Consistent with this hypothesis, a dominant-negative Rho1 inhibited SS formation but not cleavage-furrow ingression or the concomitant actomyosin ring constriction. Moreover, Rho1 is temporarily inactivated during cleavage-furrow ingression; this inactivation requires the protein Cyk3, which binds Rho1-guanosine diphosphate via its catalytically inactive transglutaminase-like domain. Thus, unlike the active transglutaminases that activate RhoA, the multidomain protein Cyk3 appears to inhibit activation of Rho1 (and thus SS formation), while simultaneously promoting cleavage-furrow ingression through primary septum formation. This work suggests a general role for the catalytically inactive transglutaminases of fungi and animals, some of which have previously been implicated in cytokinesis. PMID:23878277

  3. A sporulation-specific, sigF-dependent protein, SspA, affects septum positioning in Streptomyces coelicolor

    PubMed Central

    Tzanis, Angelos; Dalton, Kate A; Hesketh, Andrew; den Hengst, Chris D; Buttner, Mark J; Thibessard, Annabelle; Kelemen, Gabriella H

    2014-01-01

    The RNA polymerase sigma factor SigF controls late development during sporulation in the filamentous bacterium Streptomyces coelicolor. The only known SigF-dependent gene identified so far, SCO5321, is found in the biosynthetic cluster encoding spore pigment synthesis. Here we identify the first direct target for SigF, the gene sspA, encoding a sporulation-specific protein. Bioinformatic analysis suggests that SspA is a secreted lipoprotein with two PepSY signature domains. The sspA deletion mutant exhibits irregular sporulation septation and altered spore shape, suggesting that SspA plays a role in septum formation and spore maturation. The fluorescent translational fusion protein SspA–mCherry localized first to septum sites, then subsequently around the surface of the spores. Both SspA protein and sspA transcription are absent from the sigF null mutant. Moreover, in vitro transcription assay confirmed that RNA polymerase holoenzyme containing SigF is sufficient for initiation of transcription from a single sspA promoter. In addition, in vivo and in vitro experiments showed that sspA is a direct target of BldD, which functions to repress sporulation genes, including whiG, ftsZ and ssgB, during vegetative growth, co-ordinating their expression during sporulation septation. PMID:24261854

  4. In vitro study on the disinfectability of two split-septum needle-free connection devices using different disinfection procedures

    PubMed Central

    Engelhart, Steffen; Exner, Martin; Simon, Arne

    2015-01-01

    This in vitro study investigated the external disinfection of two needle-free connection devices (NFC) using Octeniderm® (spraying and wiping technique) vs. Descoderm® pads (wiping technique). The split-septum membrane of the NFC was contaminated with >105 CFU K. pneumoniae or S. epidermidis. The efficacy of the disinfection at 30 sec. exposure time was controlled by taking a swab sample and by flushing the NFC with sterile 0.9% sodium chloride solution. Disinfection with octenidine dihydrochloride 0.1 g, 1-Propanol 30.0 g, and 2-Propanol 45.0 g in 100 g solution was highly effective (CFU reduction ≥4 log) against both microorganisms, whereas the use of 63.1 g 2-Propanol in 100 ml solution led to residual contamination with S. epidermidis. Our investigation underlines that (i) in clinical practice disinfection of NFCs before use is mandatory, and that (ii) details of disinfection technique are of utmost importance regarding their efficacy. Our investigation revealed no significant differences between both split-septum NFC types. Clinical studies are needed to confirm a possible superiority of disinfectants with long-lasting residual antimicrobial activity. PMID:26693394

  5. Ovariectomy-associated changes in interradicular septum and in tibia metaphysis in different observation periods in rats.

    PubMed

    Esteves, Carina M; Moraes, Renata M; Gomes, Francine C; Marcondes, Meryenn S; Lima, Gabriela M G; Anbinder, Ana Lia

    2015-02-01

    In order to standardize an experimental model to study the effects of absence of ovarian hormones in maxillary bones compared with long bones, the aim of this research was to analyze the influence of ovariectomy (OVX) on rat alveolar bone and tibiae, in different observation periods. Thirty-six female rats were ovariectomized or sham operated. After 60, 90 or 120 days, the animals were sacrificed and their hemimandibles, maxillae and tibiae were removed and routinely prepared for hematoxylin and eosin staining. The percentage of bone matrix area in bone septum in the first molar furcation region, and in tibial metaphysis was calculated, and data were submitted to statistical analysis (p<0.05). As regards the histomorphometrical analysis in jaw bones, there was no statistical difference between groups, while the effects of ovariectomy on tibiae were seen as early as 60 days. According to the methods used, there was no significant influence of absence of ovarian hormones on interradicular septum of mandibular or maxillary first molars in the periods studied, despite the reduction in bone matrix area in tibia metaphysis as early as 60 days. PMID:25532670

  6. [Semidiscoid lateral meniscus].

    PubMed

    Araki, Y; Ishida, T; Ootani, M; Yamamoto, H; Yamamoto, T; Nakamura, H; Tsukaguchi, I

    1992-12-25

    We propose a new entity known as "semidiscoid lateral meniscus" of the knee. The diagnostic criteria for semidiscoid lateral meniscus is the appearance on a thin-sliced axial 3-D image of a crescent-shaped meniscus whose transverse width is within 11.6 mm to 14.3 mm on the coronal image. These numerical values were calculated by discriminant analysis. A retrospective review of MR examinations of the knees revealed 15 patients (15 knees) with this entity. These patients were our subjects. Of these 15 patients, complicated lateral meniscal tears were seen in only three cases. Nine knees were free from complications, and five were asymptomatic. Six patients were examined with MR on the contralateral side, and discoid lateral menisci were revealed in all cases. Thus semidiscoid lateral meniscus shows a cross-relationship with discoid menisci. PMID:1488290

  7. Dopaminergic effects of histamine administration in the nucleus accumbens and the impact of H1-receptor blockade.

    PubMed

    Galosi, R; Lenard, L; Knoche, A; Haas, H; Huston, J P; Schwarting, R K

    2001-03-01

    The mesolimbic dopamine system is thought to play a critical role in reward-related processes. A number of studies have shown that lesion or inhibition of histaminergic neurons acting through H1 receptors can potentiate the effects of drug-induced reward (e.g., psychostimulants and opioids) and can enhance the reinforcing effects of electrical stimulation of the brain. Since dopamine transmission in the nucleus accumbens is thought to provide a crucial link in these histaminergic actions, we examined the effects of local histamine application (0.1, 1.0 and 10.0 micromol/l) on dopamine and its metabolites in the nucleus accumbens of anesthetized rats by means of unilateral reverse dialysis. To study the influence of H1 receptors, we also applied the H1-receptor antagonist pyrilamine (10.0 and 20.0 mg/kg, intraperitoneally) 20 min before histamine administration (1 mmol/l). Finally, pyrilamine (0.1, 1.0 and 10.0 micromol/l) was locally administered into the nucleus accumbens. The data show that histamine can enhance extracellular dopamine levels in the nucleus accumbens in a dose-dependent way. This increase was partially antagonized by prior peripheral administration of 10 mg/kg, and was completely blocked by 20 mg/kg, of pyrilamine. Finally, intra-accumbens administration of pyrilamine locally decreased dopamine and increased dihydroxyphenylacetic acid and homovanillic acid levels. These data are discussed with respect to the possible interactions between dopaminergic and histaminergic mechanisms in the mesolimbic system and their relation to mechanisms of reinforcement. PMID:11249972

  8. Dual effects of limbic seizures on psychosis-relevant behaviors shown by nucleus accumbens kindling in rats

    PubMed Central

    Ma, Jingyi; Leung, L. Stan

    2016-01-01

    Background A paradox in epilepsy and psychiatry is that temporal lobe epilepsy is often predisposed to schizophrenic-like psychosis, whereas convulsive therapy can relieve schizophrenic symptoms. We have previously demonstrated that the nucleus accumbens is a key structure in mediating postictal psychosis induced by a hippocampal electrographic seizure. Objective/Hypothesis The purpose of this study is to test a hypothesis that accumbens kindling cumulating in a single (1-time) or repeated (5-times) convulsive seizures have different effects on animal models of psychosis. Methods Electrical stimulation at 60 Hz was applied to nucleus accumbens to evoke afterdischarges until one, or five, convulsive seizures that involved the hind limbs (stage 5 seizures) were attained. Behavioral tests, performed at 3 days after the last seizure, included gating of hippocampal auditory evoked potentials (AEP) and prepulse inhibition to an acoustic startle response (PPI), tested without drug injection or after ketamine (3 mg/kg s.c.) injection, as well as locomotion induced by ketamine or methamphetamine (1 mg/kg i.p.). Results Compared to non-kindled control rats, 1-time, but not 5-times, convulsive seizures induced PPI deficit and decreased gating of hippocampal AEP, without drug injection. Compared to non-kindled rats, 5-times, but not 1-time, convulsive seizures antagonized ketamine-induced hyperlocomotion, ketamine-induced PPI deficit and AEP gating decrease. However, both 1- and 5-times convulsive seizures, significantly enhanced methamphetamine-induced locomotion as compared to non-kindled rats. Conclusions Accumbens kindling ending with 1 convulsive seizure may induce schizophrenic-like behaviors, while repeated (≥ 5) convulsive seizures induced by accumbens kindling may have therapeutic effects on dopamine independent psychosis. PMID:27267861

  9. Active stimulation site of nucleus accumbens deep brain stimulation in obsessive-compulsive disorder is localized in the ventral internal capsule.

    PubMed

    van den Munckhof, Pepijn; Bosch, D Andries; Mantione, Mariska H M; Figee, Martijn; Denys, Damiaan A J P; Schuurman, P Richard

    2013-01-01

    Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder characterized by persistent thoughts and repetitive ritualistic behaviours. Despite optimal cognitive-behavioral and pharmacological therapy, approximately 10 % of patients remain treatment-resistant. Deep brain stimulation (DBS) is being investigated as experimental therapy for treatment-refractory OCD. In the current study, we determined the relationship between anatomical location of active electrode contacts and clinical outcome in 16 OCD patients undergoing bilateral nucleus accumbens (NAc) DBS. We found that most patients actually do not receive active stimulation in the NAc but in the more laterally, anteriorly and dorsally located ventral part of the anterior limb of the internal capsule, ventral ALIC (vALIC). Our nine patients receiving bilateral vALIC DBS improved on average 73 % on their Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores, whereas the six patients with their centers of stimulation located otherwise improved on average only 42 %. We therefore propose bilateral vALIC as a promising new DBS target for patients with treatment-refractory OCD. Future studies employing a direct vALIC targeting approach in larger patient numbers are needed to test whether this proposal holds true. PMID:23652657

  10. Dynorphin/KOP and nociceptin/NOP gene expression and epigenetic changes by cocaine in rat striatum and nucleus accumbens.

    PubMed

    Caputi, Francesca Felicia; Di Benedetto, Manuela; Carretta, Donatella; Bastias del Carmen Candia, Sussy; D'Addario, Claudio; Cavina, Chiara; Candeletti, Sanzio; Romualdi, Patrizia

    2014-03-01

    Cocaine induces neurochemical changes of endogenous prodynorphin-kappa opioid receptor (pDYN-KOP) and pronociceptin/orphaninFQ-nociceptin receptor (pN/OFQ-NOP) systems. Both systems play an important role in rewarding mechanisms and addictive stimulus processing by modulating drug-induced dopaminergic activation in the mesocortico-limbic brain areas. They are also involved in regulating stress mechanisms related to addiction. The aim of this study was to investigate possible changes of gene expression of the dynorphinergic and nociceptinergic system components in the nucleus accumbens (NA) and in medial and lateral caudate putamen (mCPu and lCPu, respectively) of rats, following chronic subcutaneous infusion of cocaine. In addition, the epigenetic histone modifications H3K4me3 and H3K27me3 (an activating and a repressive marker, respectively) at the promoter level of the pDYN, KOP, pN/OFQ and NOP genes were investigated. Results showed that cocaine induced pDYN gene expression up-regulation in the NA and lCPu, and its down-regulation in the mCPu, whereas KOP mRNA levels were unchanged. Moreover, cocaine exposure decreased pN/OFQ gene expression in the NA and lCPu, while NOP mRNA levels appeared significantly increased in the NA and decreased in the lCPu. Specific changes of the H3K4me3 and H3K27me3 levels were found at pDYN, pN/OFQ, and NOP gene promoter, consistent with the observed gene expression alterations. The present findings contribute to better define the role of endogenous pDYN-KOP and pN/OFQ-NOP systems in neuroplasticity mechanisms following chronic cocaine treatment. The epigenetic histone modifications underlying the gene expression changes likely mediate the effects of cocaine on transcriptional regulation of specific gene promoters that result in long-lasting drug-induced plasticity. PMID:24184686

  11. Increased extracellular dopamine in the nucleus accumbens of the rat during associative learning of neutral stimuli.

    PubMed

    Young, A M; Ahier, R G; Upton, R L; Joseph, M H; Gray, J A

    1998-04-01

    Brain microdialysis was used to study changes in dopamine in the nucleus accumbens and the dorsal striatum during associative learning between two neutral stimuli, flashing light and tone, presented on a paired schedule during stage 1 of a sensory preconditioning paradigm. The tone was subsequently paired with mild footshock using standard aversive conditioning procedures and the formation of a conditioned association between the flashing light and the tone in stage 1 was assessed by measuring the ability of the flashing light to elicit the same conditioned response as the tone when presented at test. The first experiment used behavioural monitoring only, to establish stimulus parameters for subsequent microdialysis experiments. Animals receiving paired presentation of the light and tone in stage 1 showed a conditioned suppression of licking to the light as well as to the tone, indicating that associative learning between the flashing light and the tone had occurred during stage 1, whilst in a separate group of animals given the same stimuli over the same time period but on an explicitly non-paired schedule, the conditioned emotional response was seen to the tone, but not to the light, showing that no association had been formed between the two stimuli during stage 1. In dialysis experiments using the same procedure, we measured a two-fold rise in dopamine in the nucleus accumbens during paired presentation of flashing light and tone, but not during non-paired presentation of the two stimuli. On subsequent test presentation of the two stimuli, we saw increases in accumbal dopamine on presentation of the tone in both groups, reflecting the formation of an association with the footshock in both. However the flashing light elicited an increase in dopamine only in the group which had received paired presentation at stage 1. Thus accumbal dopamine release at test is correlated to the ability of the stimulus to evoke a conditioned response measured behaviourally

  12. Synaptic and Behavioral Profile of Multiple Glutamatergic Inputs to the Nucleus Accumbens

    PubMed Central

    Britt, Jonathan P.; Benaliouad, Faiza; McDevitt, Ross A.; Stuber, Garret D.; Wise, Roy A.; Bonci, Antonello

    2013-01-01

    SUMMARY Excitatory afferents to the nucleus accumbens (NAc) are thought to facilitate reward seeking by encoding reward-associated cues. Selective activation of different glutamatergic inputs to the NAc can produce divergent physiological and behavioral responses, but mechanistic explanations for these pathway-specific effects are lacking. Here, we compared the innervation patterns and synaptic properties of ventral hippocampus, basolateral amygdala, and prefrontal cortex input to the NAc. Ventral hippocampal input was found to be uniquely localized to the medial NAc shell, where it was predominant and selectively potentiated following cocaine exposure. In vivo, bidirectional optogenetic manipulations of this pathway attenuated and enhanced cocaine-induced locomotion. Challenging the idea that any of these inputs encode motivationally-neutral information, activation of each discrete pathway reinforced instrumental behaviors. Finally, direct optical activation of medium spiny neurons proved to be capable of supporting self-stimulation, demonstrating that behavioral reinforcement is an explicit consequence of strong excitatory drive to the NAc. PMID:23177963

  13. A Primary Role for Nucleus Accumbens and Related Limbic Network in Vocal Tics.

    PubMed

    McCairn, Kevin W; Nagai, Yuji; Hori, Yukiko; Ninomiya, Taihei; Kikuchi, Erika; Lee, Ju-Young; Suhara, Tetsuya; Iriki, Atsushi; Minamimoto, Takafumi; Takada, Masahiko; Isoda, Masaki; Matsumoto, Masayuki

    2016-01-20

    Inappropriate vocal expressions, e.g., vocal tics in Tourette syndrome, severely impact quality of life. Neural mechanisms underlying vocal tics remain unexplored because no established animal model representing the condition exists. We report that unilateral disinhibition of the nucleus accumbens (NAc) generates vocal tics in monkeys. Whole-brain PET imaging identified prominent, bilateral limbic cortico-subcortical activation. Local field potentials (LFPs) developed abnormal spikes in the NAc and the anterior cingulate cortex (ACC). Vocalization could occur without obvious LFP spikes, however, when phase-phase coupling of alpha oscillations were accentuated between the NAc, ACC, and the primary motor cortex. These findings contrasted with myoclonic motor tics induced by disinhibition of the dorsolateral putamen, where PET activity was confined to the ipsilateral sensorimotor system and LFP spikes always preceded motor tics. We propose that vocal tics emerge as a consequence of dysrhythmic alpha coupling between critical nodes in the limbic and motor networks. VIDEO ABSTRACT. PMID:26796690

  14. Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward.

    PubMed

    Al-Hasani, Ream; McCall, Jordan G; Shin, Gunchul; Gomez, Adrian M; Schmitz, Gavin P; Bernardi, Julio M; Pyo, Chang-O; Park, Sung Il; Marcinkiewcz, Catherine M; Crowley, Nicole A; Krashes, Michael J; Lowell, Bradford B; Kash, Thomas L; Rogers, John A; Bruchas, Michael R

    2015-09-01

    The nucleus accumbens (NAc) and the dynorphinergic system are widely implicated in motivated behaviors. Prior studies have shown that activation of the dynorphin-kappa opioid receptor (KOR) system leads to aversive, dysphoria-like behavior. However, the endogenous sources of dynorphin in these circuits remain unknown. We investigated whether dynorphinergic neuronal firing in the NAc is sufficient to induce aversive behaviors. We found that photostimulation of dynorphinergic cells in the ventral NAc shell elicits robust conditioned and real-time aversive behavior via KOR activation, and in contrast, photostimulation of dorsal NAc shell dynorphin cells induced a KOR-mediated place preference and was positively reinforcing. These results show previously unknown discrete subregions of dynorphin-containing cells in the NAc shell that selectively drive opposing behaviors. Understanding the discrete regional specificity by which NAc dynorphinerigic cells regulate preference and aversion provides insight into motivated behaviors that are dysregulated in stress, reward, and psychiatric disease. PMID:26335648

  15. Cocaine Exposure Reorganizes Cell-Type and Input-Specific Connectivity in the Nucleus Accumbens

    PubMed Central

    MacAskill, Andrew F.; Cassel, John M.; Carter, Adam G.

    2014-01-01

    Exposure to cocaine alters the structural and functional properties of medium spiny neurons (MSNs) in the Nucleus Accumbens (NAc). These changes suggest a rewiring of the NAc circuit, with an enhancement of excitatory synaptic connections onto MSNs. However, it is unknown how drug exposure alters the balance of long-range afferents onto different cell types in the NAc. Here we use whole-cell recordings, two-photon microscopy, optogenetics and pharmacogenetics to show how repeated cocaine alters connectivity in the mouse NAc medial shell. We first determine that cocaine selectively enhances amygdala innervation of D1-MSNs relative to D2-MSNs. We then show that amygdala activity is required for cocaine-induced changes to behavior and connectivity. Finally, we establish how heightened amygdala innervation can explain the structural and functional changes induced by cocaine. Our findings reveal how exposure to drugs of abuse fundamentally reorganizes cell-type and input-specific connectivity in the NAc. PMID:25108911

  16. Relief learning is dependent on NMDA receptor activation in the nucleus accumbens

    PubMed Central

    Mohammadi, Milad; Fendt, Markus

    2015-01-01

    Background and Purpose Recently, we demonstrated that the nucleus accumbens (NAC) is required for the acquisition and expression of relief memory. The purpose of this study was to investigate the role of NMDA receptors within the NAC in relief learning. Experimental Approach The NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP-5) was injected into the NAC. The effects of these injections on the acquisition and expression of relief memory, as well as on the reactivity to aversive electric stimuli, were tested. Key Results Intra-accumbal AP-5 injections blocked the acquisition but not the expression of relief memory. Furthermore, reactivity to aversive electric stimuli was not affected by the AP-5 injections. Conclusion and Implication The present data indicate that NMDA-dependent plasticity within the NAC is crucial for the acquisition of relief memory. PMID:25572550

  17. Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward

    PubMed Central

    Al-Hasani, Ream; McCall, Jordan G.; Shin, Gunchul; Gomez, Adrian M.; Schmitz, Gavin P.; Bernardi, Julio M.; Pyo, Chang-O.; Park, Sung Il; Marcinkiewcz, Catherine M.; Crowley, Nicole A.; Krashes, Michael J.; Lowell, Bradford B.; Kash, Thomas L.; Rogers, John A.; Bruchas, Michael R.

    2015-01-01

    SUMMARY The nucleus accumbens (NAc) and the dynorphinergic system are widely implicated in motivated behaviors. Prior studies have shown that activation of the dynorphin-kappa opioid receptor (KOR) system leads to aversive, dysphoria-like behavior. However, the endogenous sources of dynorphin in these circuits remain unknown. We investigated whether dynorphinergic neuronal firing in the NAc is sufficient to induce aversive behaviors. We found that photostimulation of dynorphinergic cells in the ventral NAc shell elicits robust conditioned and real-time aversive behavior via KOR activation, and in contrast, photostimulation of dorsal NAc shell dynorphin cells induced a KOR-mediated place preference and were positively reinforcing. These results show previously unknown discrete subregions of dynorphin-containing cells in the NAc shell that selectively drive opposing behaviors. Understanding the discrete regional specificity by which NAc dynorphinerigic cells regulate preference and aversion provides insight into motivated behaviors that are dysregulated in stress, reward, and psychiatric disease. PMID:26335648

  18. Behavioural and physiological effects of electrical stimulation in the nucleus accumbens: a review.

    PubMed

    van Kuyck, K; Gabriëls, L; Cosyns, P; Arckens, L; Sturm, V; Rasmussen, S; Nuttin, B

    2007-01-01

    Electrical stimulation (ES) in the brain is becoming a new treatment option in patients with treatment-resistant obsessive-compulsive disorder (OCD). A possible brain target might be the nucleus accumbens (NACC). This review aims to summarise the behavioural and physiological effects of ES in the NACC in humans and in animals and to discuss these findings with regard to neuroanatomical, electrophysiological and behavioural insights. The results clearly demonstrate that ES in the NACC has an effect on reward, activity, fight-or-flight, exploratory behaviour and food intake, with evidence for only moderate physiological effects. Seizures were rarely observed. Finally, the results of ES studies in patients with treatment-resistant OCD and in animal models for OCD are promising. PMID:17691326

  19. [GABA-NO interaction in the N. Accumbens during danger-induced inhibition of exploratory behavior].

    PubMed

    2013-01-01

    In Sprague-Dawley rats by means of in vivo microdialysis combined with HPLC analysis, it was shown that presentation to rats during exploratory activity of a tone previously pared with footshock inhibited the exploration and prevented the exploration-induced increase in extracellular levels of citrulline (an NO co-product) in the medial n. accumbens. Intra-accumbal infusions of 20 μM bicuculline, a GABA(A)-receptor antagonist, firstly, partially restored the exploration-induced increase of extracellular citrulline levels in this brain area, which was inhibited by presentation of the tone, previously paired with foot-shock and, secondly, prevented the inhibition of exploratory behavior produced by this sound signal of danger. The data obtained indicate for the first time that signals of danger inhibit exploratory behavior and exploration-induced activation of the accumbal nitrergic system via GABA(A)-receptor mechanisms. PMID:25508395

  20. [GABA-NO interaction in the N. Accumbens during danger-induced inhibition of exploratory behavior].

    PubMed

    Saul'skaia, N V; Terekhova, E A

    2013-01-01

    In Sprague-Dawley rats by means of in vivo microdialysis combined with HPLC analysis, it was shown that presentation to rats during exploratory activity of a tone previously pared with footshock inhibited the exploration and prevented the exploration-induced increase in extracellular levels of citrulline (an NO co-product) in the medial n. accumbens. Intra-accumbal infusions of 20 μM bicuculline, a GABA(A)-receptor antagonist, firstly, partially restored the exploration-induced increase of extracellular citrulline levels in this brain area, which was inhibited by presentation of the tone, previously paired with foot-shock and, secondly, prevented the inhibition of exploratory behavior produced by this sound signal of danger. The data obtained indicate for the first time that signals of danger inhibit exploratory behavior and exploration-induced activation of the accumbal nitrergic system via GABA(A)-receptor mechanisms. PMID:25464764

  1. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.

    PubMed

    Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J

    2016-01-01

    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1-D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated. PMID:27337658

  2. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation

    PubMed Central

    Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J.

    2016-01-01

    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1–D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated. PMID:27337658

  3. Amyotrophic Lateral Sclerosis

    MedlinePlus

    Amyotrophic lateral sclerosis (ALS) is a nervous system disease that attacks nerve cells called neurons in your ... people with ALS die from respiratory failure. The disease usually strikes between age 40 and 60. More ...

  4. Amyotrophic Lateral Sclerosis

    MedlinePlus

    Amyotrophic lateral sclerosis (ALS) is a nervous system disease that attacks nerve cells called neurons in your brain and spinal cord. These neurons ... breathing machine can help, but most people with ALS die from respiratory failure. The disease usually strikes ...

  5. Primary Lateral Sclerosis

    MedlinePlus

    ... synthesizers, and wheelchairs ma help some people retain independence.. Speech therapy may be useful for those with ... prevent, and ultimately cure these devastating diseases. NIH Patient Recruitment for Primary Lateral Sclerosis Clinical Trials At ...

  6. Serotonergic antidepressants decrease hedonic signals but leave learning signals in the nucleus accumbens unaffected.

    PubMed

    Graf, Heiko; Metzger, Coraline D; Walter, Martin; Abler, Birgit

    2016-01-01

    Investigating the effects of serotonergic antidepressants on neural correlates of visual erotic stimulation revealed decreased reactivity within the dopaminergic reward network along with decreased subjective sexual functioning compared with placebo. However, a global dampening of the reward system under serotonergic drugs is not intuitive considering clinical observations of their beneficial effects in the treatment of depression. Particularly, learning signals as coded in prediction error processing within the dopaminergic reward system can be assumed to be rather enhanced as antidepressant drugs have been demonstrated to facilitate the efficacy of psychotherapeutic interventions relying on learning processes. Within the same study sample, we now explored the effects of serotonergic and dopaminergic/noradrenergic antidepressants on prediction error signals compared with placebo by functional MRI. A total of 17 healthy male participants (mean age: 25.4 years) were investigated under the administration of paroxetine, bupropion and placebo for 7 days each within a randomized, double-blind, within-subject cross-over design. During functional MRI, we used an established monetary incentive task to explore neural prediction error signals within the bilateral nucleus accumbens as region of interest within the dopaminergic reward system. In contrast to diminished neural activations and subjective sexual functioning under the serotonergic agent paroxetine under visual erotic stimulation, we revealed unaffected or even enhanced neural prediction error processing within the nucleus accumbens under this antidepressant along with unaffected behavioural processing. Our study provides evidence that serotonergic antidepressants facilitate prediction error signalling and may support suggestions of beneficial effects of these agents on reinforced learning as an essential element in behavioural psychotherapy. PMID:26555033

  7. Orbitofrontal or accumbens dopamine depletion does not affect risk-based decision making in rats.

    PubMed

    Mai, Bettina; Hauber, Wolfgang

    2015-09-01

    Considerable evidence has implicated dopamine (DA) signals in target regions of midbrain DA neurons such as the medial prefrontal cortex or the core region of the nucleus accumbens in controlling risk-based decision-making. However, to date little is known about the contribution of DA in the orbitofrontal cortex (OFC) and the medial shell region of the nucleus accumbens (AcbS) to risk-based decision-making. Here we examined in rats the effects of 6-hydroxydopamine-induced DA depletions of the OFC and AcbS on risky choice using an instrumental two-lever choice task that requires the assessment of fixed within-session reward probabilities that were shifted across subsequent sessions, i.e., rats had to choose between two levers, a small/certain lever that delivered one certain food reward (one pellet at p = 1) and a large/risky lever that delivered a larger uncertain food reward with decreasing probabilities across subsequent sessions (four pellets at p = 0.75, 0.5, 0.25, 0.125, 0.0625). Results show that systemic administration of amphetamine or cocaine increased the preference for the large/risky lever. Results further demonstrate that, like sham controls, rats with OFC or AcbS DA depletion were sensitive to changes in probabilities for obtaining the large/risky reward across sessions and displayed probabilistic discounting. These findings point to the view that the basal capacity to evaluate the magnitude and likelihood of rewards associated with alternative courses of action as well as long-term changes of reward probabilities does not rely on DA input to the AcbS or OFC. PMID:25860659

  8. The effect of N-acetylcysteine in the nucleus accumbens on neurotransmission and relapse to cocaine

    PubMed Central

    Kupchik, Yonatan M.; Moussawi, Khaled; Tang, Xing-Chun; Wang, Xiusong; Kalivas, Benjamin C.; Kolokithas, Rosalia; Ogburn, Katelyn B.; Kalivas, Peter W.

    2011-01-01

    Background Relapse to cocaine-seeking has been linked with low glutamate in the nucleus accumbens core (NAcore) causing potentiation of synaptic glutamate transmission from prefrontal cortex (PFC) afferents. Systemic N-acetylcysteine (NAC) has been shown to restore glutamate homeostasis, reduce relapse to cocaine-seeking and depotentiate PFC-NAcore synapses. Here we examine the effects of NAC applied directly to the NAcore on relapse and neurotransmission in PFC-NAcore synapses, as well as the involvement of the metabotropic glutamate receptors (mGluRs) mGluR2/3 and mGluR5. Methods Rats were trained to self-administer cocaine for 2 weeks and following extinction received either intra-accumbens NAC or systemic NAC 30 or 120 minutes, respectively, prior to inducing reinstatement with a conditioned cue or a combined cue and cocaine injection. We also recorded postsynaptic currents using in vitro whole cell recordings in acute slices and measured cystine and glutamate uptake in primary glial cultures. Results NAC microinjection into the NAcore inhibited the reinstatement of cocaine-seeking. In slices, a low concentration of NAC reduced the amplitude of evoked glutamatergic synaptic currents in the NAcore in a mGluR2/3-dependent manner, while high doses of NAC increased amplitude in a mGluR5-dependent manner. Both effects depended on NAC uptake through cysteine transporters and activity of the cysteine/glutamate exchanger. Finally, we showed that by blocking mGluR5 the inhibition of cocaine-seeking by NAC was potentiated. Conclusions The effect of NAC on relapse to cocaine-seeking depends on the balance between stimulating mGluR2/3 and mGluR5 in the NAcore, and the efficacy of NAC can be improved by simultaneously inhibiting mGluR5. PMID:22137594

  9. Familiar companions diminish cocaine conditioning and attenuate cocaine-stimulated dopamine release in the nucleus accumbens.

    PubMed

    Tzeng, Wen-Yu; Cherng, Chian-Fang G; Wang, Shyi-Wu; Yu, Lung

    2016-06-01

    This study aimed to assess the impact of companions on the rewarding effects of cocaine. Three cage mates, serving as companions, were housed with each experimental mouse throughout cocaine-place conditioning in a cocaine-induced conditioned place preference (CPP) paradigm using conditioning doses of 10 and 20mg/kg. The presence of companions decreased the magnitude of the CPP. At 20mg/kg, cocaine stimulated dopamine (DA) release in the nucleus accumbens as evidenced by a significant decrease in total (spontaneous and electrical stimulation-provoked) DA release in accumbal superfusate samples. The presence of companions prevented this cocaine-stimulated DA release; such a reduction in cocaine-induced DA release may account for the reduction in the magnitude of the CPP in the presence of the companions. Furthermore, cocaine pretreatment (2.5mg/kg) was found to prevent the companion-produced decreases in cocaine (10mg/kg/conditioning)-induced CPP as well as the cocaine (10mg/kg)-stimulated DA release. Moreover, the presence of methamphetamine (MA) (1mg/kg)-treated companions decreased cocaine (20mg/kg/conditioning)-induced CPP and prevented the cocaine (20mg/kg)-stimulated DA release. Finally, the presence of companions decreased the magnitude of the CPP could not seem to be accounted for by cocaine-stimulated corticosterone (CORT) release. Taken together, these results indicate that familiar companions, regardless of their pharmacological status, may exert dampening effects on CPP induced by moderate to high conditioning doses of cocaine, at least in part, by preventing cocaine-stimulated DA release in the nucleus accumbens. PMID:27001454

  10. Pathways of lateral spreading.

    PubMed

    Jacobi, U; Schanzer, S; Weigmann, H-J; Patzelt, A; Vergou, T; Sterry, W; Lademann, J

    2011-01-01

    In the case of topically applied substances, usually both lateral spreading and competitive penetration into the skin occur in parallel. In the present study, the pathways of lateral spreading were studied quantitatively and visually. The local distribution and lateral spreading of the UV filter substance butyl methoxydibenzoylmethane applied in an o/w emulsion was studied on the forearm and the back. The tape stripping procedure was used to determine the recovery rates inside and outside the area of application. The skin characteristics of transepidermal water loss, pH value, hydration of the stratum corneum and sebum rate were determined at both anatomic sites. Photography and laser scanning microscopy were used to visually investigate the lateral spreading of topically applied dyes. On the back, a preferred direction of lateral spreading parallel to the body axis was observed. This result was caused by differences in the network of furrows. The furrows functioned as a pathway for lateral spreading, whereas the follicles formed a reservoir for the topically applied substance. PMID:21455016

  11. 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

  12. Differential effect of viral overexpression of nucleus accumbens shell 5-HT1B receptors on stress- and cocaine priming-induced reinstatement of cocaine seeking

    PubMed Central

    Nair, Sunila G.; Furay, Amy R.; Liu, Yusha; Neumaier, John F.

    2013-01-01

    5-HT1B receptors are densely expressed on terminals of medium spiny neurons projecting from the nucleus accumbens shell (NAccSh) to the ventral tegmental area, where 5-HT1B receptors modulate GABA release directly, and firing of dopaminergic neurons indirectly. While interactions between NAccSh 5-HT1B receptors and stress have been reported in early stages of psychostimulant-induced neuroadaptations, specifically psychomotor sensitization, the effect of this interaction on later stages of drug seeking is currently unknown. Here, we examined the effect of herpes simplex virus (HSV)-mediated overexpression of NAccSh 5-HT1B receptors on reinstatement of cocaine seeking induced by exposure to stress or a cocaine prime. Rats were trained to self-administer cocaine (0.75 mg/kg/infusion) and the operant response was extinguished. Rats were then injected with viral vector expressing 5-HT1B and green fluorescent protein (GFP) or GFP alone into the NAccSh. The effect of 5-HT1B receptor overexpression was assessed on reinstatement induced by intermittent footshock (0.5 mA for 15 minutes) or a cocaine prime (10 mg/kg, ip). Results indicate that NAccSh 5-HT1B receptor overexpression had no effect on footshock reinstatement while significantly decreasing cocaine priming-induced reinstatement. We also found that NAccSh overexpression of 5-HT1B receptors had no effect on saccharin intake following social defeat stress. These results suggest that the efficacy of pharmacological agents targeting 5-HT1B receptors for the treatment of cocaine relapse will depend largely on the nature of the reinstating stimulus. Taken together with previous results it appears that NAccSh 5-HT1B receptors influence stress responses in early, but not in the later stages of psychostimulant-induced neuroadaptations. PMID:24075973

  13. A case report of aphallia with urorectal septum malformation sequence in a newborn: a very rarely seen condition

    PubMed Central

    Sharma, Deepak; Singh, Ravinder; Shastri, Sweta

    2015-01-01

    Aphallia (absence of penis) is an extremely rare abnormality which has rarely been described in medical literature and can be part of the urorectal septum malformation sequence (URSMS). URSMS has hardly been reported in medical literature and includes the absence of perineal and anal openings in association with ambiguous genitalia and urogenital, colonic, and lumbosacral anomalies. This case report tells the importance of detailed examination of infants that are diagnosed with aphallia. We report a case of a newborn who was diagnosed as aphallia with the URSMS syndrome after birth. The neonate had an endocardial cushion defect (atrial septal defect and ventricular septal defect) and bilateral agenesis of the kidney. The neonate succumbed to death secondary to hypoplastic lung leading to respiratory failure. PMID:26673776

  14. [Personal experiences with extended frontolateral laryngectomy and simultaneous reconstruction using a cartilage/mucous membrane transplant from the nasal septum].

    PubMed

    Szmeja, Z; Szyfter, W; Wójtowicz, J; Kruk-Zagajewska, A

    1994-04-01

    From 1979 to 1992, 219 extended frontolateral laryngectomies were performed in Poznań with simultaneous reconstruction of the larynx using a mucochondral nasal septum flap. During following examinations local recurrences were observed in 7 cases and metastases to regional lymph nodes were found in 3 cases. Complete healing of the flap was seen in 172 patients. In these cases the laryngeal lumen was found to be wide and the transplanted mucosa was normal. In 14 patients there appeared to be partial rotation of the flap, narrowing the reconstructed lumen. Among the causes of failure were the use of a too flexible, thin septal cartilage and wound infection. Detailed acoustic recordings of postoperative voices are presented as examples of successful surgery. PMID:8021157

  15. Mycobacterium tuberculosis Proteins Involved in Mycolic Acid Synthesis and Transport Localize Dynamically to the Old Growing Pole and Septum

    PubMed Central

    Cantaloube, Sylvain; Bonne, Mélanie; Diagne, Cheikh T.; Laval, Françoise; Daffé, Mamadou; Zerbib, Didier

    2014-01-01

    Understanding the mechanism that controls space-time coordination of elongation and division of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is critical for fighting the tubercle bacillus. Most of the numerous enzymes involved in the synthesis of Mycolic acid - Arabinogalactan-Peptidoglycan complex (MAPc) in the cell wall are essential in vivo. Using a dynamic approach, we localized Mtb enzymes belonging to the fatty acid synthase-II (FAS-II) complexes and involved in mycolic acid (MA) biosynthesis in a mycobacterial model of Mtb: M. smegmatis. Results also showed that the MA transporter MmpL3 was present in the mycobacterial envelope and was specifically and dynamically accumulated at the poles and septa during bacterial growth. This localization was due to its C-terminal domain. Moreover, the FAS-II enzymes were co-localized at the poles and septum with Wag31, the protein responsible for the polar localization of mycobacterial peptidoglycan biosynthesis. The dynamic localization of FAS-II and of the MA transporter with Wag31, at the old-growing poles and at the septum suggests that the main components of the mycomembrane may potentially be synthesized at these precise foci. This finding highlights a major difference between mycobacteria and other rod-shaped bacteria studied to date. Based on the already known polar activities of envelope biosynthesis in mycobacteria, we propose the existence of complex polar machinery devoted to the biogenesis of the entire envelope. As a result, the mycobacterial pole would represent the Achilles' heel of the bacillus at all its growing stages. PMID:24817274

  16. Laterally closed lattice homomorphisms

    NASA Astrophysics Data System (ADS)

    Toumi, Mohamed Ali; Toumi, Nedra

    2006-12-01

    Let A and B be two Archimedean vector lattices and let be a lattice homomorphism. We call that T is laterally closed if T(D) is a maximal orthogonal system in the band generated by T(A) in B, for each maximal orthogonal system D of A. In this paper we prove that any laterally closed lattice homomorphism T of an Archimedean vector lattice A with universal completion Au into a universally complete vector lattice B can be extended to a lattice homomorphism of Au into B, which is an improvement of a result of M. Duhoux and M. Meyer [M. Duhoux and M. Meyer, Extended orthomorphisms and lateral completion of Archimedean Riesz spaces, Ann. Soc. Sci. Bruxelles 98 (1984) 3-18], who established it for the order continuous lattice homomorphism case. Moreover, if in addition Au and B are with point separating order duals (Au)' and B' respectively, then the laterally closedness property becomes a necessary and sufficient condition for any lattice homomorphism to have a similar extension to the whole Au. As an application, we give a new representation theorem for laterally closed d-algebras from which we infer the existence of d-algebra multiplications on the universal completions of d-algebras.

  17. Laterally bendable belt conveyor

    DOEpatents

    Peterson, William J.

    1985-01-01

    An endless, laterally flexible and bendable belt conveyor particularly adapted for coal mining applications in facilitating the transport of the extracted coal up- or downslope and around corners in a continuous manner is disclosed. The conveying means includes a flat rubber belt reinforced along the middle portion thereof along which the major portion of the belt tension is directed so as to cause rotation of the tubular shaped belt when trammed around lateral turns thus preventing excessive belt bulging distortion between adjacent belt supports which would inhibit belt transport. Pretension induced into the fabric reinforced flat rubber belt by conventional belt take-up means supports the load conveyed when the belt conveyor is making lateral turns. The carrying and return portions of the belt are supported and formed into a tubular shape by a plurality of shapers positioned along its length. Each shaper is supported from above by a monorail and includes clusters of idler rollers which support the belt. Additional cluster rollers in each shaper permit the belt supporting roller clusters to rotate in response to the belt's operating tension imposed upon the cluster rollers by induced lateral belt friction forces. The freely rotating roller clusters thus permit the belt to twist on lateral curves without damage to itself while precluding escape of the conveyed material by effectively enclosing it in the tube-shaped, inner belt transport length.

  18. Hysteroscopy- and laparoscopy-based diagnosis and treatment of girls with unbroken hymen with an obstructing uterine septum: two case reports

    PubMed Central

    2014-01-01

    Introduction Obstructing uterine septum is a rare uterine malformation. Patients with obstructing uterine septum are usually treated with laparouterotomy, causing obvious injury to both the uterus and body of the patients. Therefore, using the natural channel of the vagina is undoubtedly the best way to carry out the surgery. However, obstructing uterine septum usually occurs in puberty in girls without a history of sexual intercourse, thus iatrogenic damage to the hymen during the diagnosis and treatment cannot probably be avoided. However, Chinese people traditionally tend to use hymen intactness as a standard to judge whether an unmarried woman is chaste. Therefore, in China, to protect the hymen from damage during hysteroscopic diagnosis and treatment is of special significance for girls and women with unbroken hymens. None of the previously reported cases were treated with electrosurgical obstructing uterine septum excision based on B-ultrasound-guided hymen-protecting hysteroscopy and laparoscopy. Case presentation Case 1 patient was a virgo intacta 13-year-old Chinese girl. She was admitted due to an 8-day post-menstruation lower abdominal pain. With the guidance of B-ultrasound, we observed a 30mm×20mm mixed echogenicity mass in her uterine cavity. Case 2 patient was a virgo intacta 14-year-old Chinese girl. She was admitted to our hospital more than 6 months after secondary dysmenorrhea and 6 days after B-ultrasound-diagnosed uterine malformations. We observed a 30mm×25mm mixed echoic area in her uterine cavity with the guidance of B-ultrasound. Both patients were surgically treated without hymen damage with B-ultrasound-guided combined therapy of hysteroscopy and laparoscopy. A needle electrode with an 8mm diameter was placed into their uterine cavities under hysteroscopy. After obstructing uterine septum removal, their uterine cavities showed normal morphology. To protect their hymens, misoprostol was placed into their rectums to soften their cervices

  19. Effects of reward anticipation, reward presentation, and spatial parameters on the firing of single neurons recorded in the subiculum and nucleus accumbens of freely moving rats.

    PubMed

    Martin, P D; Ono, T

    2000-11-15

    The subiculum is the major output of the hippocampal formation (involved in spatial processing). Subicular afferents innervate the nucleus accumbens, which is thought to integrate limbic reward information with motor output. Rats were chronically implanted with extra-cellular recording electrodes aimed at both structures to investigate the functional relationship between them. Animals were then trained on a spatial task in which they searched for random locations where they would receive rewarding medial forebrain bundle stimulation. At random times a cue tone was sounded, indicating that the reward location was in the center of the environment. Rats quickly learned to run to the center upon hearing the tone in order to receive a reward. Simultaneously recorded groups of up to eight subicular and accumbens neurons were found to display alterations in firing rate after rewarding medial forebrain bundle stimulation. Moreover, neurons in both subiculum and accumbens displayed alterations in firing rate prior to arrival at the center during cued runs, i.e. they anticipated predictable rewards. Subicular and accumbens firing was also correlated with spatial location. However, neurons in accumbens were more likely to respond to task events, and these responses were more varied, than those seen in subiculum. Thus, while convergence of spatial and reward information occurs at the level of single cells in both subiculum and nucleus accumbens, these structures also display functional localization. PMID:11090883

  20. Characterization of the effects of serotonin on the release of (/sup 3/H)dopamine from rat nucleus accumbens and striatal slices

    SciTech Connect

    Nurse, B.; Russell, V.A.; Taljaard, J.J.

    1988-05-01

    The effect of serotonin agonists on the depolarization (K+)-induced, calcium-dependent, release of (/sup 3/H)dopamine (DA) from rat nucleus accumbens and striatal slices was investigated. Serotonin enhanced basal /sup 3/H overflow and reduced K+-induced release of (/sup 3/H)DA from nucleus accumbens slices. The effect of serotonin on basal /sup 3/H overflow was not altered by the serotonin antagonist, methysergide, or the serotonin re-uptake blocker, chlorimipramine, but was reversed by the DA re-uptake carrier inhibitors nomifensine and benztropine. With the effect on basal overflow blocked, serotonin did not modulate K+-induced release of (/sup 3/H)DA in the nucleus accumbens or striatum. The serotonin agonists, quipazine (in the presence of nomifensine) and 5-methoxytryptamine, did not significantly affect K+-induced release of (/sup 3/H)DA in the nucleus accumbens. This study does not support suggestions that serotonin receptors inhibit the depolarization-induced release of dopamine in the nucleus accumbens or striatum of the rat brain. The present results do not preclude the possibility that serotonin may affect the mesolimbic reward system at a site which is post-synaptic to dopaminergic terminals in the nucleus accumbens.

  1. Hydatid cyst of the cardiac interventricular septum with complete atrioventricular block: a case report from Pakistan.

    PubMed

    Mustafa, Bilal; Ahmed, Waqas; Akbar, Mohammad Tauqeer

    2012-03-01

    Cardiac involvement in systemic echinococcosis is a rare phenomenon. Abnormalities of the cardiac conduction system are an exceptional feature of cardiac hydatidosis. We report, to the best of our knowledge, the first case of cardiac hydatidosis from Pakistan in a 30 year old male who presented with recurrent syncopal episodes due to complete atrioventricular conduction block and subsequently underwent implantation of dual chamber pacemaker. His transthoracic echocardiogram revealed a large, well circumscribed, interventricular septal mass which was avascular on subsequent perfusion imaging. Surgical resection of the mass three years later confirmed it to be a hydatid cyst. PMID:22764470

  2. Extensor tendon and fascia sectioning of extensors at the musculotendinous unit in lateral epicondylitis.

    PubMed

    Barth, Joeri; Mahieu, Peter; Hollevoet, Nadine

    2013-06-01

    Different surgical techniques exist to treat lateral epicondylitis. In most techniques, release of the common extensor origin is performed adjacent to the humeral epicondyle. The purpose of the present study was to assess the outcome of transverse sectioning of the intermuscular septum and the aponeuroses of the extensor carpi radialis brevis and extensor digitorum communis, 3 to 5 cm distally to the radial epicondyle. Forty-nine elbows were operated on in 44 patients. Subjective results were obtained after a mean followup of 33 months. Mean age of patients was 44 years. Mean disabilities of arm, shoulder and hand score was 6, mean visual analogue scale score for pain was 1 and for satisfaction 9. The result was excellent in 26, good in 15 and poor in 8 elbows following Spencer and Herndon. Mean absence from work was 40 days. We conclude that tendon release in the musculotendinous unit can be used to treat lateral epicondylitis. PMID:23926727

  3. Infrared lateral shearing interferometers

    NASA Astrophysics Data System (ADS)

    Kwon, O.

    1980-04-01

    Recently IR interferometry has received much attention for its special capabilities of testing IR materials, diamond-turned metal mirrors, deep aspherics, unpolished rough surface optics, and other unconventional optics. A CW CO2 laser is used as a coherent light source at 10.6 microns, and germanium and zinc selenide optics are used for lenses and beam splitters. A pyroelectric vidicon (PEV) detects the modulated interference pattern through a TV monitor and video recorder-player. This paper presents three methods of IR lateral shear interferometry using (1) a germanium plane-parallel plate, (2) a Ronchi ruling, and (3) a double-grating lateral shear interferometer.

  4. Left ventricular outflow tract obstruction in complete transposition of the great arteries with intact ventricular septum. A cross sectional echocardiography study.

    PubMed Central

    Robinson, P J; Wyse, R K; Macartney, F J

    1985-01-01

    The roles of posterior bulging of the interventricular septum (septal bulge) and of systolic septal mitral apposition in patients with simple transposition of the great arteries are not known. Cross sectional echocardiograms of 40 such patients were reviewed (after exclusion of those with fixed left ventricular outflow tract obstruction) and haemodynamic findings were compared with long and short axis measurements within the left ventricle. There was no significant correlation between the degree of septal bulge and systolic gradient across the left ventricular outflow tract, but septal bulge correlated weakly with systolic right ventricular pressure and inversely with pulmonary arteriolar resistance index. Systolic left ventricular outflow gradient was inversely related to the minimum systolic distance between the anterior mitral leaflet and interventricular septum. No patients without complete systolic apposition of the anterior mitral leaflet and interventricular septum had a left ventricular outflow gradient greater than 20 mm Hg. Conversely, even when cross sectional echocardiography showed apparently total obstruction of the left ventricular outflow tract at some time in systole there was often no significant gradient detected during haemodynamic study. In the short axis cuts closeness of the papillary muscles to the interventricular septum or to each other was unrelated to systolic gradient. This study shows that (a) cross sectional echocardiography can identify fixed obstruction of the left ventricular outflow tract in simple transposition of the great arteries; (b) the degree of septal bulge, unless complicated by fibrous thickening of the anterior mitral leaflet and interventricular septum, is unrelated to the gradient across the left ventricular outflow tract; (c) the absence of systolic septal/mitral apposition excludes a significant gradient at that site across the left ventricular outflow tract; and (d) papillary muscle geometry is unrelated to dynamic

  5. Lateral Thinking of Prospective Teachers

    ERIC Educational Resources Information Center

    Lawrence, A. S. Arul; Xavier, S. Amaladoss

    2013-01-01

    Edward de Bono who invented the term "lateral thinking" in 1967 is the pioneer of lateral thinking. Lateral thinking is concerned with the generation of new ideas. Liberation from old ideas and the stimulation of new ones are twin aspects of lateral thinking. Lateral thinking is a creative skills from which all people can benefit…

  6. Quinolinic acid lesion of nucleus accumbens reduces D sub 1 but not D sub 2 dopamine receptors: An autoradiographic study

    SciTech Connect

    Filloux, F.; Richards, T.J.; Huff, G.F. ); Wamsley, J.K. )

    1991-01-01

    Information concerning the cellular localization of dopamine receptor subtypes in the nucleus accumbens (NAcc) was obtained using receptor autoradiographic analysis. Unilateral, stereotaxic injection of the axonsparing neurotoxin, quinolinic acid, into the NAcc resulted in a prominent loss of dopamine D{sub 1} receptors (as labeled by ({sup 3}H)SCH 23390). Contrarily, no appreciable decrement in D{sub 2} receptors (labeled by ({sup 3}H)raclopride) could be identified within the same region of the NAcc. The findings support the view that accumbens D{sub 1} receptors are located postsynaptically on neurons or their processes, while D{sub 2} receptors within this nucleus are primarily located on afferent terminals.

  7. Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens

    PubMed Central

    Rose, Jamie H.; Karkhanis, Anushree N.; Chen, Rong; Gioia, Dominic; Lopez, Marcelo F.; Becker, Howard C.; McCool, Brian A.

    2016-01-01

    Background: Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the dopamine terminal and withdrawal-related behaviors were examined. Methods: Five weeks of chronic intermittent ethanol exposure in male C57BL/6 mice were used to examine the role of kappa opioid receptors in chronic ethanol-induced increases in ethanol intake and marble burying, a measure of anxiety/compulsive-like behavior. Drinking and marble burying were evaluated before and after chronic intermittent ethanol exposure, with and without kappa opioid receptor blockade by nor-binaltorphimine (10mg/kg i.p.). Functional alterations in kappa opioid receptors were assessed using fast scan cyclic voltammetry in brain slices containing the nucleus accumbens. Results: Chronic intermittent ethanol-exposed mice showed increased ethanol drinking and marble burying compared with controls, which was attenuated with kappa opioid receptor blockade. Chronic intermittent ethanol-induced increases in behavior were replicated with kappa opioid receptor activation in naïve mice. Fast scan cyclic voltammetry revealed that chronic intermittent ethanol reduced accumbal dopamine release and increased uptake rates, promoting a hypodopaminergic state of this region. Kappa opioid receptor activation with U50,488H concentration-dependently decreased dopamine release in both groups; however, this effect was greater in chronic intermittent ethanol-treated mice, indicating kappa opioid receptor supersensitivity in this group. Conclusions: These data suggest that the chronic intermittent ethanol-induced increase

  8. Neonatal Prefrontal Inactivation Results in Reversed Dopaminergic Responses in the Shell Subregion of the Nucleus Accumbens to NMDA Antagonists.

    PubMed

    Pouvreau, Tiphaine; Tagliabue, Emmanuelle; Usun, Yusuf; Eybrard, Séverine; Meyer, Francisca; Louilot, Alain

    2016-07-20

    Striatal dopaminergic dysregulation in schizophrenia could result from a prefronto-striatal dysconnectivity, of neurodevelopmental origin, involving N-methyl-d-aspartate (NMDA) receptors. The dorsomedian shell part of the nucleus accumbens is a striatal subregion of particular interest inasmuch as it has been described as the common target region for antipsychotics. Moreover, NMDA receptors located on the dopaminergic endings have been reported in the shell. The present study examines in adult rats the effects of early functional inactivation of the left prefrontal cortex on behavioral and dopaminergic responses in the dorsomedian shell part of the nucleus accumbens following administration of two noncompetitive NMDA receptor antagonists, ketamine, and dizocilpine (MK-801). The results showed that postnatal blockade of the prefrontal cortex led to increased locomotor activity as well as increased extracellular dopamine levels in the dorsomedian shell following administration of both noncompetitive NMDA receptor antagonists, and, more markedly, after treatment with the more specific one, MK-801, whereas decreased dopaminergic levels were observed in respective controls. These data suggest a link between NMDA receptor dysfunctioning and dopamine dysregulation at the level of the dorsomedian shell part of the nucleus accumbens. They may help to understand the pathophysiology of schizophrenia in a neurodevelopmental perspective. PMID:27145294

  9. Intra-Accumbens Baclofen, But Not Muscimol, Increases Second Order Instrumental Responding for Food Reward in Rats

    PubMed Central

    Pulman, Kim G. T.; Somerville, Elizabeth M.; Clifton, Peter G.

    2012-01-01

    Stimulation of either GABAA or GABAB receptors within the nucleus accumbens shell strongly enhances food intake in rats. However the effects of subtype-selective stimulation of GABA receptors on instrumental responses for food reward are less well characterized. Here we contrast the effects of the GABAA receptor agonist muscimol and GABAB receptor agonist baclofen on instrumental responding for food using a second order reinforcement schedule. Bilateral intra-accumbens administration of baclofen (220–440 pmol) stimulated responding but a higher dose (660 pmol) induced stereotyped oral behaviour that interfered with responding. Baclofen (220–660 pmol) also stimulated intake of freely available chow. Muscimol (220–660 pmol) was without effect on responding for food on this schedule but did stimulate intake of freely available chow. Unilateral administration of either baclofen or muscimol (220 pmol) induced similar patterns of c-fos immunoreactivity in several hypothalamic sites but differed in its induction in the central nucleus of the amygdala. We conclude that stimulation of GABAA or GABAB receptors in the nucleus accumbens shell of rats produces clearly distinguishable effects on operant responding for food. PMID:22808090

  10. [Adult lateral meniscus].

    PubMed

    Beaufils, P; Hardy, P; Chambat, P; Clavert, P; Djian, P; Frank, A; Hulet, C; Potel, J-F; Verdonk, R

    2006-09-01

    Meniscal lesion does not mean meniscectomy and this is particularly true for the lateral meniscus. The reputation of mildness of the meniscectomy is usurped. The rate of joint space narrowing after lateral meniscectomy is of 40% at a follow-up of 13 years compared to 28% for the medial meniscus (symposium SFA 1996). Several arguments explain those results: biomechanical: the lateral meniscus contributes to the congruence; particularly the lateral meniscus is the zone where antero-posterior translational during knee flexion is 12 mm. The pejorative effects of lateral meniscectomy have conducted, more though to the medial meniscus, to the concept of meniscal economy. Lateral meniscectomy must be as partial as possible. Particularly, a discoid meniscus presenting a complete tear should be treated by a meniscoplasty in order to shape the meniscus in a more anatomic form than a total meniscectomy. Lateral meniscectomy is indicated in complex or horizontal cleavage, symptomatic, on stable knees. A particular case is the cyst of the lateral meniscus. It is a cystic subcutaneous formation, usual consequence of a horizontal cleaved meniscus of which the particularity is that it opens besides the articulation. The strategy must not consist in the isolated treatment of the cyst. This pathology should be addressed by an arthroscopic meniscectomy reaching the meniscosynovial junction at the level of the cyst. Meniscal repair must be proposed every time if possible. Criteria of reparability are better studied on MRI. Preoperatively MRI is the first choice radiological exam. Two essential indications can be held back: the vertical peripheral longitudinal lesion is on the non-vascularized area, and the horizontal cleaving of the junior athlete (if the cleaving remains purely intra meniscal). Meniscal repair is highly performed when the meniscal tear is associated to a rupture of the ACL (simultaneous reconstruction of the LCA). Postoperative outcome is different of that of a

  11. GSK-3β inhibitors reverse cocaine-induced synaptic transmission dysfunction in the nucleus accumbens.

    PubMed

    Zhao, Rui; Chen, Jiaojiao; Ren, Zhaoxiang; Shen, Hui; Zhen, Xuechu

    2016-11-01

    Nucleus accumbens receives glutamatergic projection from the prefrontal cortex (PFC) and dopaminergic input from the Ventral tegmental area (VTA). Recent studies have suggested a critical role for serine/threonine kinase glycogen synthase kinase 3β (GSK3β) in cocaine-induced hyperactivity; however, the effect of GSK3β on the modulation of glutamatergic and dopaminergic afferents is unclear. In this study, we found that the GSK3 inhibitors, LiCl (100 mg/kg, i.p.) or SB216763 (2.5 mg/kg, i.p.), blocked the cocaine-induced hyperlocomotor activity in rats. By employing single-unit recordings in vivo, we found that pretreatment with either SB216763 or LiCl for 15 min reversed the cocaine-inhibited firing frequency of medium spiny neuron (MSN) in the nucleus accumbens (NAc). Preperfusion of SB216763 (5 μM) ameliorated the inhibitory effect of cocaine on both the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (up to 99 ± 6.8% inhibition) and N-methyl-D-aspartic acid receptor (NMDAR)-mediate EPSC (up to 73 ± 9.7% inhibition) in the NAc in brain slices. The effect of cocaine on AMPA and NMDA receptor-mediate excitatory postsynaptic current (EPSC) were mimicked by the D1 -like receptor agonist SKF 38393 and blocked by the D1 -like receptor antagonist SCH 23390, whereas D2 -like receptor agonist or antagonist failed to mimic or to block the action of cocaine. Preperfusion of SB216763 for 5 min also ameliorated the inhibitory effect of SKF38393 on both AMPA and NMDA receptor-mediated components of EPSC, indicate the effect of SB216763 on cocaine was via the D1 -like receptor. Moreover, cocaine inhibited the presynaptic release of glutamate in the NAc, and SB216763 reversed this effect. In conclusion, D1 receptor-GSK3β pathway, which mediates glutamatergic transmission in the NAc core through a presynaptic mechanism, plays an important role in acute cocaine-induced hyperlocomotion. PMID:27377051

  12. Nucleus Accumbens Core and Shell Differentially Encode Reward-Associated Cues after Reinforcer Devaluation

    PubMed Central

    West, Elizabeth A.

    2016-01-01

    Nucleus accumbens (NAc) neurons encode features of stimulus learning and action selection associated with rewards. The NAc is necessary for using information about expected outcome values to guide behavior after reinforcer devaluation. Evidence suggests that core and shell subregions may play dissociable roles in guiding motivated behavior. Here, we recorded neural activity in the NAc core and shell during training and performance of a reinforcer devaluation task. Long–Evans male rats were trained that presses on a lever under an illuminated cue light delivered a flavored sucrose reward. On subsequent test days, each rat was given free access to one of two distinctly flavored foods to consume to satiation and were then immediately tested on the lever pressing task under extinction conditions. Rats decreased pressing on the test day when the reinforcer earned during training was the sated flavor (devalued) compared with the test day when the reinforcer was not the sated flavor (nondevalued), demonstrating evidence of outcome-selective devaluation. Cue-selective encoding during training by NAc core (but not shell) neurons reliably predicted subsequent behavioral performance; that is, the greater the percentage of neurons that responded to the cue, the better the rats suppressed responding after devaluation. In contrast, NAc shell (but not core) neurons significantly decreased cue-selective encoding in the devalued condition compared with the nondevalued condition. These data reveal that NAc core and shell neurons encode information differentially about outcome-specific cues after reinforcer devaluation that are related to behavioral performance and outcome value, respectively. SIGNIFICANCE STATEMENT Many neuropsychiatric disorders are marked by impairments in behavioral flexibility. Although the nucleus accumbens (NAc) is required for behavioral flexibility, it is not known how NAc neurons encode this information. Here, we recorded NAc neurons during a training

  13. Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell.

    PubMed

    Rada, P; Avena, N M; Hoebel, B G

    2005-01-01

    Most drugs of abuse increase dopamine (DA) in the nucleus accumbens (NAc), and do so every time as a pharmacological response. Palatable food also releases accumbens-shell DA, but in naïve rats the effect can wane during a long meal and disappears with repetition. Under select dietary circumstances, sugar can have effects similar to a drug of abuse. Rats show signs of DA sensitization and opioid dependence when given intermittent access to sucrose, such as alterations in DA and mu-opioid receptors, cross-sensitization with amphetamine and alcohol, and behavioral and neurochemical signs of naloxone-precipitated withdrawal. The present experiment asks whether sucrose-dependent rats release DA each time they binge. We also predict that acetylcholine (ACh), which rises as the end of a meal, will be delayed in rats with intermittent access to sucrose. To create dependency, the experimental group (Daily Intermittent Sucrose) was maintained on a diet of 12-h food deprivation that extended 4 h into the dark, followed by 12-h access to a 10% sucrose solution and chow, daily, for 21 days. As the main result, these rats gradually increased their sucrose intake from 37 to 112 ml per day (from 13 to 20 ml in the first hour of access), and repeatedly increased extracellular DA to 130% of baseline as measured in the NAc shell by microdialysis during the first hour of sucrose access on day 1, day 2 and day 21. Three control groups failed to show a significant increase in extracellular DA on day 21: Sucrose only for 1 h on days 1 and 21 (Sucrose Twice), ad libitum access to sucrose and chow (Daily Ad libitum Sucrose), and intermittent chow instead of sucrose (Daily Intermittent Chow). Acetylcholine measured at the same time as DA, increased significantly toward the end and after each test meal in all groups. In the Daily Intermittent Sucrose group, the highest ACh levels (133%) occurred during the first sample after the sucrose meal ended. In summary, sucrose-dependent animals

  14. Rat nucleus accumbens core astrocytes modulate reward and the motivation to self-administer ethanol after abstinence.

    PubMed

    Bull, Cecilia; Freitas, Kelen C C; Zou, Shiping; Poland, Ryan S; Syed, Wahab A; Urban, Daniel J; Minter, Sabrina C; Shelton, Keith L; Hauser, Kurt F; Negus, S Stevens; Knapp, Pamela E; Bowers, M Scott

    2014-11-01

    Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH self-administration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with

  15. Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence

    PubMed Central

    Bull, Cecilia; Freitas, Kelen CC; Zou, Shiping; Poland, Ryan S; Syed, Wahab A; Urban, Daniel J; Minter, Sabrina C; Shelton, Keith L; Hauser, Kurt F; Negus, S Stevens; Knapp, Pamela E; Bowers, M Scott

    2014-01-01

    Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH self-administration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with

  16. Lateral flow assays

    PubMed Central

    Koczula, Katarzyna M.

    2016-01-01

    Lateral flow assays (LFAs) are the technology behind low-cost, simple, rapid and portable detection devices popular in biomedicine, agriculture, food and environmental sciences. This review presents an overview of the principle of the method and the critical components of the assay, focusing on lateral flow immunoassays. This type of assay has recently attracted considerable interest because of its potential to provide instantaneous diagnosis directly to patients. The range and interpretation of results and parameters used for evaluation of the assay will also be discussed. The main advantages and disadvantages of LFAs will be summarized and relevant future improvements to testing devices and strategies will be proposed. Finally, the major recent advances and future diagnostic applications in the LFA field will be explored. PMID:27365041

  17. Conjugal amyotrophic lateral sclerosis

    PubMed Central

    Dewitt, John D.; Kwon, Julia; Burton, Rebecca

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a disease characterized by progressive degeneration of motor neurons in the motor cortex, brainstem, and spinal cord. The incidence of sporadic ALS is 1.5 to 2.7 in 100,000, and the prevalence is 5.2 to 6.0 in 100,000. Conjugal ALS is even rarer than sporadic ALS. We report a case of conjugal ALS encountered in our outpatient neurology clinic. PMID:22275781

  18. Hemispheric lateralization in reasoning.

    PubMed

    Turner, Benjamin O; Marinsek, Nicole; Ryhal, Emily; Miller, Michael B

    2015-11-01

    A growing body of evidence suggests that reasoning in humans relies on a number of related processes whose neural loci are largely lateralized to one hemisphere or the other. A recent review of this evidence concluded that the patterns of lateralization observed are organized according to two complementary tendencies. The left hemisphere attempts to reduce uncertainty by drawing inferences or creating explanations, even at the cost of ignoring conflicting evidence or generating implausible explanations. Conversely, the right hemisphere aims to reduce conflict by rejecting or refining explanations that are no longer tenable in the face of new evidence. In healthy adults, the hemispheres work together to achieve a balance between certainty and consistency, and a wealth of neuropsychological research supports the notion that upsetting this balance results in various failures in reasoning, including delusions. However, support for this model from the neuroimaging literature is mixed. Here, we examine the evidence for this framework from multiple research domains, including an activation likelihood estimation analysis of functional magnetic resonance imaging studies of reasoning. Our results suggest a need to either revise this model as it applies to healthy adults or to develop better tools for assessing lateralization in these individuals. PMID:26426534

  19. Roles of Nucleus Accumbens CREB and Dynorphin in Dysregulation of Motivation

    PubMed Central

    Muschamp, John W.; Carlezon, William A.

    2013-01-01

    Psychostimulants such as amphetamine and cocaine are believed to produce dependence by causing rapid, supraphysiological elevations in synaptic dopamine (DA) within the nucleus accumbens (NAc) (Volkow et al. 2009, Neuropharmacology 56: 3–8). These changes in forebrain DA transmission are similar to those evoked by natural reinforcers (Louilot et al. 1991, Brain Res 553: 313–317; Roitman et al. 2004, J Neurosci 24: 1265–1271), but are of greater magnitude and longer duration. Repeated drug exposure causes compensatory neuroadaptations in neurons of the NAc, some of which may modulate excess DA in a homeostatic fashion. One such adaptation is the activation of the transcription factor CREB (cAMP response element-binding protein) within neurons of the NAc. Although elevated levels of transcriptionally active CREB appear to attenuate DA transmission by increasing expression of the endogenous κ opioid receptor (KOR) ligand dynorphin, increased dynorphin transmission may ultimately have undesirable effects that contribute to drug withdrawal states as well as comorbid psychiatric illnesses such as depression. This state may prompt a return to drug use to mitigate the adverse effects of withdrawal. This article summarizes our current understanding of how CREB and dynorphin contribute to the dysregulation of motivation and describes novel therapeutic strategies that derive from preclinical research in this area. PMID:23293139

  20. VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons.

    PubMed

    Qi, Jia; Zhang, Shiliang; Wang, Hui-Ling; Barker, David J; Miranda-Barrientos, Jorge; Morales, Marisela

    2016-05-01

    The ventral tegmental area (VTA) is best known for its dopamine neurons, some of which project to nucleus accumbens (nAcc). However, the VTA also has glutamatergic neurons that project to nAcc. The function of the mesoaccumbens glutamatergic pathway remains unknown. Here we report that nAcc photoactivation of mesoaccumbens glutamatergic fibers promotes aversion. Although we found that these mesoaccumbens glutamatergic fibers lack GABA, the aversion evoked by their photoactivation depended on glutamate- and GABA-receptor signaling, and not on dopamine-receptor signaling. We found that mesoaccumbens glutamatergic fibers established multiple asymmetric synapses on single parvalbumin GABAergic interneurons and that nAcc photoactivation of these fibers drove AMPA-mediated cellular firing of parvalbumin GABAergic interneurons. These parvalbumin GABAergic interneurons in turn inhibited nAcc medium spiny output neurons, thereby controlling inhibitory neurotransmission in nAcc. To our knowledge, the mesoaccumbens glutamatergic pathway is the first glutamatergic input to nAcc shown to mediate aversion instead of reward, and the first pathway shown to establish excitatory synapses on nAcc parvalbumin GABAergic interneurons. PMID:27019014

  1. Anabolic-androgenic steroids decrease dendritic spine density in the nucleus accumbens of male rats.

    PubMed

    Wallin-Miller, Kathryn; Li, Grace; Kelishani, Diana; Wood, Ruth I

    2016-08-25

    Recent studies have demonstrated that anabolic-androgenic steroids (AAS) modify cognitive processes such as decision making and behavioral flexibility. However, the neural mechanisms underlying these AAS-induced cognitive changes remain poorly understood. The mesocorticolimbic dopamine (DA) system, particularly the nucleus accumbens (Acb), is important for reward, motivated behavior, and higher cognitive processes such as decision making. Therefore, AAS-induced plasticity in the DA system is a potential structural substrate for the observed cognitive alterations. High doses of testosterone (the most commonly-used AAS) increase dendritic spine density in limbic regions including the amygdala and hippocampus. However, effects on Acb are unknown. This was the focus of the present study. Adolescent male Long-Evans rats were treated chronically for 8weeks with high-dose testosterone (7.5mg/kg in water with 13% cyclodextrin) or vehicle sc. Brains were stained by Golgi-Cox to analyze neuronal morphology in medium spiny neurons of the shell region of Acb (AcbSh). Eightweeks of testosterone treatment significantly decreased spine density in AcbSh compared to brains of vehicle-treated rats (F1,14=5.455, p<0.05). Testosterone did not significantly affect total spine number, dendritic length, or arborization measured by Sholl analysis. These results show that AAS alter neuronal morphology in AcbSh by decreasing spine density throughout the dendritic tree, and provides a potential mechanism for AAS to modify cognition and decision-making behavior. PMID:27238893

  2. Cocaine- and morphine-induced synaptic plasticity in the nucleus accumbens.

    PubMed

    Alcantara, Adriana A; Lim, Helen Y; Floyd, Christopher E; Garces, Juanita; Mendenhall, John M; Lyons, Chelsea L; Berlanga, Monica L

    2011-04-01

    The critical brain areas and molecular mechanisms involved in drug abuse and dependence have been extensively studied. Drug-induced persistent behaviors such as sensitization, tolerance, or relapse, however, far outlast any previously reported mechanisms. A challenge in the field of addiction, therefore, has been to identify drug-induced changes in brain circuitry that may subserve long-lasting changes in behavior. This study examined behavioral changes and electron microscopic evidence of altered synaptic connectivity within the nucleus accumbens (NAc) following repeated administration of cocaine or morphine. The unbiased quantitative stereological physical disector method was used to estimate the number of synapses per neuron. Increases in the synapse-to-neuron ratio were found in the NAc shell of cocaine-treated (49.1%) and morphine-treated (55.1%) rats and in the NAc core of cocaine-treated animals (49.1%). This study provides direct ultrastructural evidence of drug-induced synaptic plasticity and identifies synaptic remodeling as a potential neural substrate underlying drug-induced behavioral sensitization. PMID:20730804

  3. Transfer of neuroplasticity from nucleus accumbens core to shell is required for cocaine reward.

    PubMed

    Marie, Nicolas; Canestrelli, Corinne; Noble, Florence

    2012-01-01

    It is well established that cocaine induces an increase of dendritic spines density in some brain regions. However, few studies have addressed the role of this neuroplastic changes in cocaine rewarding effects and have often led to contradictory results. So, we hypothesized that using a rigorous time- and subject-matched protocol would demonstrate the role of this spine increase in cocaine reward. We designed our experiments such as the same animals (rats) were used for spine analysis and behavioral studies. Cocaine rewarding effects were assessed with the conditioned place preference paradigm. Spines densities were measured in the two subdivisions of the nucleus accumbens (NAcc), core and shell. We showed a correlation between the increase of spine density in NAcc core and shell and cocaine rewarding effects. Interestingly, when cocaine was administered in home cages, spine density was increase in NAcc core only. With anisomycin, a protein synthesis inhibitor, injected in the core we blocked spine increase in core and shell and also cocaine rewarding effects. Strikingly, whereas injection of this inhibitor in the shell immediately after conditioning had no effect on neuroplasticity or behavior, its injection 4 hours after conditioning was able to block neuroplasticity in shell only and cocaine-induced place preference. Thus, it clearly appears that the neuronal plasticity in the NAcc core is essential to induce plasticity in the shell, necessary for cocaine reward. Altogether, our data revealed a new mechanism in the NAcc functioning where a neuroplasticity transfer occurred from core to shell. PMID:22272316

  4. Delay of gratification in childhood linked to cortical interactions with the nucleus accumbens.

    PubMed

    Luerssen, Anna; Gyurak, Anett; Ayduk, Ozlem; Wendelken, Carter; Bunge, Silvia A

    2015-12-01

    Delay of gratification (DG) is the ability to forego immediate temptations in the service of obtaining larger, delayed rewards. An extensive body of behavioral research has revealed that DG ability in childhood is associated with a host of important outcomes throughout development, and that attentional focus away from temptations underlies this ability. In this study, we conducted a functional magnetic resonance imaging study to identify the neural underpinnings of individual differences in DG among children. We observed a relationship between behavior during the classic DG task, a well-studied and ecologically valid measure, and functional connectivity during a modified version of this task in the scanner. Specifically, greater attentional focus away from temptations was associated with stronger functional coupling between the nucleus accumbens, a brain region that supports approach behavior, and several regions within prefrontal and parietal cortex that support self-control. These results shed light on the network interactions that contribute to DG and that account for individual differences in this capacity. PMID:26048177

  5. Assessing Contributions of Nucleus Accumbens Shell Subregions to Reward-Seeking Behavior

    PubMed Central

    Reed, Michael D.; Hildebrand, David G. C.; Santangelo, Gabrielle; Moffa, Anthony; Pira, Ashley S.; Rycyna, Lisa; Radic, Mia; Price, Katherine; Archbold, Jonathan; McConnell, Kristi; Girard, Lauren; Morin, Kristen; Tang, Anna; Febo, Marcelo; Stellar, James R.

    2015-01-01

    Background The nucleus accumbens (NAc) plays a key role in brain reward processes including drug seeking and reinstatement. Several anatomical, behavioral, and neurochemical studies discriminate between the limbic-associated shell and the motor-associated core regions. Less studied is the fact that the shell can be further subdivided into a dorsomedial shell (NAcDMS) and an intermediate zone (NAcINT) based on differential expression of transient c-Fos and long-acting immediate-early gene ΔFosB upon cocaine sensitization. These disparate expression patterns suggest that NAc shell subregions may play distinct roles in reward-seeking behavior. In this study, we examined potential differences in the contributions of the NAcDMS and the NAcINT to reinstatement of reward-seeking behavior after extinction. Methods Rats were trained to intravenously self-administer cocaine, extinguished, and subjected to a reinstatement test session consisting of either an intracranial microinfusion of amphetamine or vehicle targeted to the NAcDMS or the NAcINT. Results Small amphetamine microinfusions targeted to the NAcDMS resulted in statistically significant reinstatement of lever pressing, whereas no statistical difference was observed for microinfusions targeted to the NAcINT. No significant difference was found for vehicle microinfusions in either case. Conclusion These results suggest heterogeneity in the behavioral relevance of NAc shell subregions, a possibility that can be tested in specific neuronal populations in the future with recently developed techniques including optogenetics. PMID:26048642

  6. Extinction and Reinstatement of Phasic Dopamine Signals in the Nucleus Accumbens Core during Pavlovian Conditioning

    PubMed Central

    Sunsay, Ceyhun; Rebec, George V.

    2014-01-01

    The prediction-error model of dopamine (DA) signaling has largely been confirmed with various appetitive Pavlovian conditioning procedures and has been supported in tests of Pavlovian extinction. Studies have repeatedly shown, however, that extinction does not erase the original memory of conditioning as the prediction-error model presumes, putting the model at odds with contemporary views that treat extinction as an episode of learning rather than unlearning of conditioning. Here, we combined fast-scan cyclic voltammetry (FSCV) with appetitive Pavlovian conditioning to assess DA release directly during extinction and reinstatement. DA was monitored in the nucleus accumbens core (NAc), which plays a key role in reward processing. Following at least 4 daily sessions of 16 tone-food pairings, FSCV was performed while rats received additional tone-food pairings followed by tone alone presentations (i.e., extinction). Acquisition memory was reinstated with non-contingent presentations of reward and then tested with cue presentation. Tone-food pairings produced transient (1–3 s) DA release in response to tone. During extinction, the amplitude of the DA response decreased significantly. Following presentation of two non-contingent food pellets, subsequent tone presentation reinstated the DA signal. Our results support the prediction-error model for appetitive Pavlovian extinction but not for reinstatement. PMID:25111335

  7. Dendritic morphology of neurons in medial prefrontal cortex, hippocampus, and nucleus accumbens in adult SH rats.

    PubMed

    Sánchez, Fremioth; Gómez-Villalobos, María de Jesús; Juarez, Ismael; Quevedo, Lucía; Flores, Gonzalo

    2011-03-01

    We have studied, in spontaneously hypertensive (SH) rats at different ages (2, 4, and 8 months old), the dendritic morphological changes of the pyramidal neurons of the medial prefrontal cortex (mPFC) and hippocampus and medium spiny neurons of the nucleus accumbens (NAcc) induced by the chronic effect of high-blood pressure. As control animals, we used Wistar-Kioto (WK) rats. Blood pressure was measured every 2 months to confirm the increase in arterial blood pressure. Spontaneous locomotor activity was assessed, and then brains were removed to study the dendritic morphology by the Golgi-Cox stain method followed by Sholl analysis. SH animals at 4 and 8 months of age showed decreased spine density in pyramidal neurons from the mPFC and in medium spiny cells from the NAcc. At 8 months of age as well the pyramidal neurons from the hippocampus exhibited a reduction in the number of dendritic spines. An increase in locomotion in a novel environment at all ages in the SH rats was observed. Our results indicate that high-blood pressure alters the neuronal dendrite morphology of the mPFC, hippocampus, and NAcc. The increased locomotion behavior supports the idea that dopaminergic transmission is altered in the SH rats. This could enhance our understanding of the consequences of chronic high-blood pressure on brain structure, which may implicate cognitive impairment in hypertensive patients. PMID:20665725

  8. Active Avoidance Requires a Serial Basal Amygdala to Nucleus Accumbens Shell Circuit

    PubMed Central

    Ramirez, Franchesca; Moscarello, Justin M.; LeDoux, Joseph E.

    2015-01-01

    Freezing is a species-typical defensive reaction to conditioned threats. While the neural circuitry of aversive Pavlovian behavior has been extensively studied, less is known about the circuitry underlying more active responses to danger. Here we show that the flow of information between the basal amygdala (BA) and the nucleus accumbens (NAcc) is necessary for signaled active avoidance behavior. Rats trained to avoid shock by shuttling during an auditory conditioned stimulus showed increased expression of the activity-dependent protein c-Fos in the NAcc, specifically the shell subregion (NAccSh). Silencing neural activity in the NAccSh, but not in the adjacent NAcc core, disrupted avoidance behavior. Disconnection of the BA and the NAccSh was just as effective at disrupting avoidance behavior as bilateral NAccSh inactivations, suggesting learned avoidance behavior requires an intact BA-NAccSh circuit. Together, these data highlight an essential role for the amygdalar projection to the ventral striatum in aversively motivated actions. PMID:25716846

  9. Chronic cocaine administration induces opposite changes in dopamine receptors in the striatum and nucleus accumbens

    SciTech Connect

    Goeders, N.E.; Kuhar, M.J.

    1987-01-01

    A variety of clinical and animal data suggest that the repeated administration of cocaine and related psychomotor stimulants may be associated with a behavioral sensitization whereby the same dose of the drug results in increasing behavioral pathology. This investigation was designed to determine the effects of chronic cocaine administration on the binding of (/sup 3/H)sulpiride, a relatively specific ligand for D2 dopaminergic receptors, in the rat brain using in vitro homogenate binding and light microscopic quantitative autoradiographic methodologies. Chronic daily injections of cocaine (10 mg/kg, i.p.) for 15 days resulted in a significant decrease in the maximum concentration of sulpiride binding sites in the striatum and a significant increase in the maximum number of these binding sites in the nucleus accumbens. No significant differences in binding affinity were observed in either brain region. These data suggest that chronic cocaine administration may result in differential effects on D2 receptors in the nigro-striatal and mesolimbic dopaminergic systems.

  10. D2R DNA Transfer Into the Nucleus Accumbens Attenuates Cocaine Self-Administration in Rats

    PubMed Central

    THANOS, PANAYOTIS K.; MICHAELIDES, MICHAEL; UMEGAKI, HIROYUKI; VOLKOW, NORA D.

    2009-01-01

    Dopamine (DA) D2 receptor (D2R) agonists and antagonists can modulate self-administration behavior, conditioned place preference, and locomotor responses to cocaine. Low levels of D2R have also been observed in cocaine addicted subjects and in non human primates after chronic cocaine exposures. Prior studies had shown that D2R upregulation in the nucleus accumbens (NAc) in rodents trained to self-administer alcohol markedly attenuated alcohol preference and intake. Here we assess the effects of D2R upregulation in the NAc on cocaine intake in rats trained to self-administer cocaine. Following 2 weeks of i.v. cocaine self-administration (CSA), rats were stereotaxically treated with an adenovirus that carried the D2R gene to upregulate D2R in the NAc. D2R vector treatment resulted in a significant decrease (75%) in cocaine infusions and lever presses (70%) for cocaine. This effect lasted 6 days before cocaine consumption returned to baseline levels, which corresponds roughly to the time it takes D2R to return to baseline levels. These findings show that CSA and D2R in the NAc are negatively correlated and suggest that cocaine intake is modulated in part by D2R levels in NAc. Thus strategies aimed at increasing D2R expression in NAc may be beneficial in treating cocaine abuse and addiction. PMID:18418874

  11. Nucleus accumbens core acetylcholine is preferentially activated during acquisition of drug- vs food-reinforced behavior.

    PubMed

    Crespo, Jose A; Stöckl, Petra; Zorn, Katja; Saria, Alois; Zernig, Gerald

    2008-12-01

    Acquisition of drug-reinforced behavior is accompanied by a systematic increase of release of the neurotransmitter acetylcholine (ACh) rather than dopamine, the expected prime reward neurotransmitter candidate, in the nucleus accumbens core (AcbC), with activation of both muscarinic and nicotinic ACh receptors in the AcbC by ACh volume transmission being necessary for the drug conditioning. The present findings suggest that the AcbC ACh system is preferentially activated by drug reinforcers, because (1) acquisition of food-reinforced behavior was not paralleled by activation of ACh release in the AcbC whereas acquisition of morphine-reinforced behavior, like that of cocaine or remifentanil (tested previously), was, and because (2) local intra-AcbC administration of muscarinic or nicotinic ACh receptor antagonists (atropine or mecamylamine, respectively) did not block the acquisition of food-reinforced behavior whereas acquisition of drug-reinforced behavior had been blocked. Interestingly, the speed with which a drug of abuse distributed into the AcbC and was eliminated from the AcbC determined the size of the AcbC ACh signal, with the temporally more sharply delineated drug stimulus producing a more pronounced AcbC ACh signal. The present findings suggest that muscarinic and nicotinic ACh receptors in the AcbC are preferentially involved during reward conditioning for drugs of abuse vs sweetened condensed milk as a food reinforcer. PMID:18418362

  12. Influence of olfactory bulbectomy on maternal behavior and dopaminergic function in nucleus accumbens in mice.

    PubMed

    Sato, Atsushi; Nakagawasai, Osamu; Tan-No, Koichi; Onogi, Hiroshi; Niijima, Fukie; Tadano, Takeshi

    2010-12-20

    Olfactory bulbectomy (OBX) induces behavioral, physiological, and neurochemical alterations resembling clinical depression and is widely used as an animal model of depression. It has been reported that depression is a critical cause of child abuse and neglect and that maternal behavior involves dopaminergic neurons of the mesolimbic pathway. In a previous study we found that OBX mice show maternal behavior deficits which are improved by administration of apomorphine, a non-selective dopamine agonist. Therefore, in this study, we investigated the effect of l-3,4-dihydroxyphenylalanine (l-DOPA) on maternal behavior deficits to examine the influence of pre-synaptic dopaminergic function in OBX mice. Furthermore, we measured tyrosine hydroxylase (TH) levels using microphotometry and quantified dopamine D1- and D2-like receptors using autoradiography in the nucleus accumbens (NAc). As a result, 25mg/kg l-DOPA with 12.5mg/kg benserazide improved disrupted maternal behavior in OBX mice and there are no changes in TH levels or number of D1- and D2-like receptors between sham and OBX mothers. The behavioral data support the hypothesis that changed dopaminergic function may contribute to maternal behavior deficits in OBX mice. However, our findings concerning dopaminergic function suggest that the deficits in OBX mice are not simply due to changes in TH levels or dopamine receptor number in the NAc. PMID:20638419

  13. Reduced Nucleus Accumbens Reactivity and Adolescent Depression following Early-life Stress

    PubMed Central

    Goff, Bonnie; Gee, Dylan G.; Telzer, Eva H.; Humphreys, Kathryn L.; Gabard-Durnam, Laurel; Flannery, Jessica; Tottenham, Nim

    2013-01-01

    Depression is a common outcome for those having experienced early life stress (ELS). For those individuals, depression typically increases during adolescence and appears to endure into adulthood, suggesting alterations in the development of brain systems involved in depression. Developmentally, the nucleus accumbens (NAcc), a limbic structure associated with reward learning and motivation, typically undergoes dramatic functional change during adolescence; therefore, age-related changes in NAcc function may underlie increases in depression in adolescence following ELS. The current study examined the effects of ELS in 38 previously institutionalized children and adolescents in comparison to a group of 31 youth without a history of ELS. Consistent with previous research, the findings showed that depression was higher in adolescents than children with a history of ELS. Additionally, fMRI results showed atypical NAcc development, where the ELS group did not show a typical increase in NAcc reactivity during adolescence. Consequently, the ELS group showed NAcc hypoactivation during adolescence, and lower NAcc reactivity was correlated with higher depression scores. The results have important implications for understanding how ELS may influence increases in depression via neural development during the transition to adolescence and highlight the importance of identifying at-risk individuals in childhood, a potential critical period for depression-targeted intervention. PMID:23262241

  14. Dynamic changes in accumbens dopamine correlate with learning during intracranial self-stimulation

    PubMed Central

    Owesson-White, Catarina A.; Cheer, Joseph F.; Beyene, Manna; Carelli, Regina M.; Wightman, R. Mark

    2008-01-01

    Dopamine in the nucleus accumbens (NAc) is an important neurotransmitter for reward-seeking behaviors such as intracranial self-stimulation (ICSS), although its precise role remains unclear. Here, dynamic fluctuations in extracellular dopamine were measured during ICSS in the rat NAc shell with fast-scan cyclic voltammetry at carbon-fiber microelectrodes. Rats were trained to press a lever to deliver electrical stimulation to the substantia nigra (SNc)/ventral tegmental area (VTA) after the random onset of a cue that predicted reward availability. Latency to respond after cue onset significantly declined across trials, indicative of learning. Dopamine release was evoked by the stimulation but also developed across trials in a time-locked fashion to the cue. Once established, the cue-evoked dopamine transients continued to grow in amplitude, although they were variable from trial to trial. The emergence of cue-evoked dopamine correlated with a decline in electrically evoked dopamine release. Extinction of ICSS resulted in a significant decline in goal-directed behavior coupled to a significant decrease in cue-evoked phasic dopamine across trials. Subsequent reinstatement of ICSS was correlated with a return to preextinction transient amplitudes in response to the cue and reestablishment of ICSS behavior. The results show the dynamic nature of chemical signaling in the NAc during ICSS and provide new insight into the role of NAc dopamine in reward-related behaviors. PMID:18689678

  15. Differential Dopamine Regulation of Ca2+ Signaling and Its Timing Dependence in the Nucleus Accumbens

    PubMed Central

    Swapna, Immani; Bondy, Brian; Morikawa, Hitoshi

    2016-01-01

    SUMMARY Dopamine action in the nucleus accumbens (NAc) is thought to drive appetitive behavior and Pavlovian reward learning. However, it remains controversial how dopamine achieves these behavioral effects by regulating medium spiny projection neurons (MSNs) of the NAc, especially on a behaviorally relevant timescale. Metabotropic glutamate receptor (mGluR)-induced Ca2+ signaling dependent on the Ca2+- releasing messenger inositol 1,4,5-triphosphate (IP3) plays a critical role in controlling neuronal excitability and synaptic plasticity. Here, we show that transient dopamine application facilitates mGluR/IP3-induced Ca2+ signals within a time window of ~2–10 s in a subpopulation of MSNs in the NAc core. Dopamine facilitation of IP3-induced Ca2+ signaling is mediated by D1 dopamine receptors. In dopamine-insensitive MSNs, activation of A2A adenosine receptors causes enhancement of IP3-evoked Ca2+ signals, which is reversed by D2 dopamine receptor activation. These results show that dopamine differentially regulates Ca2+ signaling on the order of seconds in two distinct MSN subpopulations. PMID:27068462

  16. Experience-Dependent Effects of Cocaine Self-Administration/Conditioning on Prefrontal and Accumbens Dopamine Responses

    PubMed Central

    Ikegami, Aiko; Olsen, Christopher M.; D’Souza, Manoranjan S.; Duvauchelle, Christine L.

    2008-01-01

    Experiments were performed to examine the effects of cocaine self-administration and conditioning experience on operant behavior, locomotor activity, and nucleus accumbens (NAcc) and prefrontal cortex (PFC) dopamine (DA) responses. Sensory cues were paired with alternating cocaine and nonreinforcement during 12 (limited training) or 40 (long-term training) daily operant sessions. After limited training, NAcc DA responses to cocaine were significantly enhanced in the presence of cocaine-associated cues compared with nonreward cues and significantly depressed after cocaine-paired cues accompanied a nonreinforced lever response. PFC DA levels were generally nonresponsive to cues after the same training duration. However, after long-term training, cocaine-associated cues increased the magnitude of cocaine-stimulated PFC DA levels significantly over levels observed with nonreinforcement cues. Conversely, conditioned cues no longer influenced NAcc DA levels after long-term training. In addition, cocaine-stimulated locomotor activity was enhanced by cocaine-paired cues after long-term, but not after limited, training. Findings demonstrate that cue-induced cocaine expectation exerts a significant impact on dopaminergic and behavioral systems, progressing from mesolimbic to mesocortical regions and from latent to patent behaviors as cocaine and associative experiences escalate. PMID:17469929

  17. AMPA receptor plasticity in the nucleus accumbens after repeated exposure to cocaine

    PubMed Central

    Wolf, Marina E.; Ferrario, Carrie R.

    2010-01-01

    This review focuses on cocaine-induced postsynaptic plasticity in the nucleus accumbens (NAc) involving changes in AMPA receptor (AMPAR) transmission. First, fundamental properties of AMPAR in the NAc are reviewed. Then, we provide a detailed and critical analysis of literature demonstrating alterations in AMPAR transmission in association with behavioral sensitization to cocaine and cocaine self-administration. We conclude that cocaine exposure leads to changes in AMPAR transmission that depend on many factors including whether exposure is contingent or non-contingent, the duration of withdrawal, and whether extinction training has occurred. The relationship between changes in AMPAR transmission and responding to cocaine or cocaine-paired cues can also be affected by these variables. However, after prolonged withdrawal in the absence of extinction training, our findings and others lead us to propose that AMPAR transmission is enhanced, resulting in stronger responding to drug-paired cues. Finally, many results indicate that the state of synaptic transmission in the NAc after cocaine exposure is associated with impairment of AMPAR-dependent plasticity. This may contribute to a broad range of addiction-related behavioral changes. PMID:20109488

  18. The rat nucleus accumbens is involved in guiding of instrumental responses by stimuli predicting reward magnitude.

    PubMed

    Giertler, Christian; Bohn, Ines; Hauber, Wolfgang

    2003-10-01

    The present study examined the involvement of N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionate/kainate (AMPA/KA) and dopamine receptors in the nucleus accumbens (ACB) in influencing reaction times of instrumental responses by the expectancy of reward. A simple reaction time task demanding conditioned lever release was used in which the upcoming reward magnitude was signalled in advance by discriminative cues. After training, in control rats with vehicle infusions (0.5 micro L) into the ACB, reaction times of responses were significantly shorter to the discriminative cue predictive of high reward magnitude. Indirect stimulation of dopamine receptors in the ACB by d-amphetamine (20 micro g/0.5 micro L) decreased reaction times, impaired their guidance by cue-associated reward magnitudes and reduced the accuracy of task performance. Blockade of AMPA/KA receptors in the ACB by 6-cyano-7-nitroquino-xaline-2,3-dione (0.75 and 2.5 micro g/0.5 micro L) or NMDA receptors by d(-)-2-amino-5-phosphonopentanoic acid (5 micro g/0.5 micro L) produced a general increase in reaction times, but left guidance of reaction times by cue-associated reward magnitudes unaffected. Thus, stimulation of intra-ACB ionotropic glutamate receptors is critically involved in modulating the speed of instrumental responding to cues predictive for reward magnitude, but is not required for intact performance of previously learned instrumental behaviour. PMID:14622231

  19. Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression

    PubMed Central

    Bagot, Rosemary C.; Parise, Eric M.; Peña, Catherine J.; Zhang, Hong-Xing; Maze, Ian; Chaudhury, Dipesh; Persaud, Brianna; Cachope, Roger; Bolaños-Guzmán, Carlos A.; Cheer, Joseph; Deisseroth, Karl; Han, Ming-Hu; Nestler, Eric J.

    2015-01-01

    Enhanced glutamatergic transmission in the nucleus accumbens (NAc), a region critical for reward and motivation, has been implicated in the pathophysiology of depression; however, the afferent source of this increased glutamate tone is not known. The NAc receives glutamatergic inputs from the medial prefrontal cortex (mPFC), ventral hippocampus (vHIP) and basolateral amygdala (AMY). Here, we demonstrate that glutamatergic vHIP afferents to NAc regulate susceptibility to chronic social defeat stress (CSDS). We observe reduced activity in vHIP in mice resilient to CSDS. Furthermore, attenuation of vHIP-NAc transmission by optogenetic induction of long-term depression is pro-resilient, whereas acute enhancement of this input is pro-susceptible. This effect is specific to vHIP afferents to the NAc, as optogenetic stimulation of either mPFC or AMY afferents to the NAc is pro-resilient. These data indicate that vHIP afferents to NAc uniquely regulate susceptibility to CSDS, highlighting an important, novel circuit-specific mechanism in depression. PMID:25952660

  20. Desoxypipradrol is more potent than cocaine on evoked dopamine efflux in the nucleus accumbens.

    PubMed

    Davidson, Colin; Ramsey, John

    2012-07-01

    Desoxypipradrol is a methylphenidate-like drug that has been recently found in a number of 'legal highs'. Evidence from emergency room toxicology reports suggests that this drug might have led to a number of psychotic events in drug abusers in the UK and elsewhere. However, very little research has been done on the effects of this drug on the brain. Here we used rat brain slices from the nucleus accumbens core, which were exposed to either cocaine (1, 3 or 10 µM) or desoxypipradrol (1, 3 or 10 µM) for 60 min. Dopamine efflux was electrically evoked and recorded using fast cyclic voltammetry. Both drugs increased the peak dopamine efflux and also slowed dopamine re-uptake. Desoxypipradrol was more potent than cocaine causing a sevenfold increase in peak dopamine levels (versus a threefold increase for cocaine) and increasing dopamine re-uptake half-life 15-fold (versus fivefold for cocaine). These data suggest that desoxypipradrol is more potent than cocaine at dopamine terminals, and this could account for its psychotogenic effects. PMID:22158543

  1. Essential Role of SIRT1 Signaling in the Nucleus Accumbens in Cocaine and Morphine Action

    PubMed Central

    Ferguson, Deveroux; Koo, Ja Wook; Feng, Jian; Heller, Elizabeth; Rabkin, Jacqui; Heshmati, Mitra; Renthal, William; Neve, Rachael; Liu, Xiaochuan; Shao, Ningyi; Sartorelli, Vittorio; Shen, Li

    2013-01-01

    Sirtuins (SIRTs), class III histone deacetylases, are well characterized for their control of cellular physiology in peripheral tissues, but their influence in brain under normal and pathological conditions remains poorly understood. Here, we establish an essential role for SIRT1 and SIRT2 in regulating behavioral responses to cocaine and morphine through actions in the nucleus accumbens (NAc), a key brain reward region. We show that chronic cocaine administration increases SIRT1 and SIRT2 expression in the mouse NAc, while chronic morphine administration induces SIRT1 expression alone, with no regulation of all other sirtuin family members observed. Drug induction of SIRT1 and SIRT2 is mediated in part at the transcriptional level via the drug-induced transcription factor ΔFosB and is associated with robust histone modifications at the Sirt1 and Sirt2 genes. Viral-mediated overexpression of SIRT1 or SIRT2 in the NAc enhances the rewarding effects of both cocaine and morphine. In contrast, the local knockdown of SIRT1 from the NAc of floxed Sirt1 mice decreases drug reward. Such behavioral effects of SIRT1 occur in concert with its regulation of numerous synaptic proteins in NAc as well as with SIRT1-mediated induction of dendritic spines on NAc medium spiny neurons. These studies establish sirtuins as key mediators of the molecular and cellular plasticity induced by drugs of abuse in NAc, and of the associated behavioral adaptations, and point toward novel signaling pathways involved in drug action. PMID:24107942

  2. Individual Variations in Nucleus Accumbens Responses Associated with Major Depressive Disorder Symptoms

    PubMed Central

    Misaki, Masaya; Suzuki, Hideo; Savitz, Jonathan; Drevets, Wayne C.; Bodurka, Jerzy

    2016-01-01

    Abnormal reward-related responses in the nucleus accumbens (NAcc) have been reported for major depressive disorder (MDD) patients. However, variability exists in the reported results, which could be due to heterogeneity in neuropathology of depression. To parse the heterogeneity of MDD we investigated variation of NAcc responses to gain and loss anticipations using fMRI. We found NAcc responses to monetary gain and loss were significantly variable across subjects in both MDD and healthy control (HC) groups. The variations were seen as a hyperactive response subtype that showed elevated activation to the anticipation of both gain and loss, an intermediate response with greater activation to gain than loss, and a suppressed-activity with reduced activation to both gain and loss compared to a non-monetary condition. While these response variability were seen in both MDD and HC subjects, specific symptoms were significantly associated with the right NAcc variation in MDD. Both the hyper- and suppressed-activity subtypes of MDD patients had severe suicidal ideation and anhedonia symptoms. The intermediate subjects had less severity in these symptoms. These results suggest that differing propensities in reward responsiveness in the NAcc may affect the development of specific symptoms in MDD. PMID:26880358

  3. Hyperammonaemia alters the mechanisms by which metabotropic glutamate receptors in nucleus accumbens modulate motor function.

    PubMed

    Cauli, Omar; Mlili, Nisrin; Rodrigo, Regina; Felipo, Vicente

    2007-10-01

    Activation of metabotropic glutamate receptors by injecting (S)3,5-dihydroxyphenylglycine (DHPG) in nucleus accumbens (NAcc) increases motor activity by different mechanisms in control rats and in rats with chronic liver failure due to portacaval shunt. In control rats DHPG increases extracellular dopamine in NAcc and induces locomotion by activating the 'normal' circuit: NAcc-->ventral pallidum-->medial-dorsal thalamus-->prefrontal cortex, which is not activated in portacaval shunt rats. In these rats, DHPG activates an 'alternative' circuit: NAcc-->substantia nigra pars reticulata-->ventro-medial thalamus-->prefrontal cortex, which is not activated in control rats. The reasons by which liver failure leads to activation of this 'alternative' circuit remain unclear. The aim of this work was to assess whether hyperammonaemia could be responsible for the alterations found in chronic liver failure. We injected DHPG in NAcc of control or hyperammonaemic rats and analysed, by in vivo brain microdialysis, the neurochemical responses of the 'normal' and 'alternative' circuits. In hyperammonaemic rats DHPG injection in NAcc activates both the 'normal' and 'alternative' circuits. In hyperammonaemia, activation of the 'alternative' circuit and increased motor response following metabotropic glutamate receptors activation in NAcc seem due to an increase in extracellular glutamate which activates AMPA receptors. PMID:17587309

  4. Dopamine and opioid systems interact within the nucleus accumbens to maintain monogamous pair bonds

    PubMed Central

    Resendez, Shanna L; Keyes, Piper C; Day, Jeremy J; Hambro, Caely; Austin, Curtis J; Maina, Francis K; Eidson, Lori N; Porter-Stransky, Kirsten A; Nevárez, Natalie; McLean, J William; Kuhnmuench, Morgan A; Murphy, Anne Z; Mathews, Tiffany A; Aragona, Brandon J

    2016-01-01

    Prairie vole breeder pairs form monogamous pair bonds, which are maintained through the expression of selective aggression toward novel conspecifics. Here, we utilize behavioral and anatomical techniques to extend the current understanding of neural mechanisms that mediate pair bond maintenance. For both sexes, we show that pair bonding up-regulates mRNA expression for genes encoding D1-like dopamine (DA) receptors and dynorphin as well as enhances stimulated DA release within the nucleus accumbens (NAc). We next show that D1-like receptor regulation of selective aggression is mediated through downstream activation of kappa-opioid receptors (KORs) and that activation of these receptors mediates social avoidance. Finally, we also identified sex-specific alterations in KOR binding density within the NAc shell of paired males and demonstrate that this alteration contributes to the neuroprotective effect of pair bonding against drug reward. Together, these findings suggest motivational and valence processing systems interact to mediate the maintenance of social bonds. DOI: http://dx.doi.org/10.7554/eLife.15325.001 PMID:27371827

  5. Nucleus accumbens associated 1 is recruited within the promyelocytic leukemia nuclear body through SUMO modification

    PubMed Central

    Tatemichi, Yoshinori; Shibazaki, Masahiko; Yasuhira, Shinji; Kasai, Shuya; Tada, Hiroshi; Oikawa, Hiroki; Suzuki, Yuji; Takikawa, Yasuhiro; Masuda, Tomoyuki; Maesawa, Chihaya

    2015-01-01

    Nucleus accumbens associated 1 (NACC1) is a cancer-associated BTB/POZ (pox virus and zinc finger/bric-a-brac tramtrack broad complex) gene, and is involved in several cellular functions in neurons, cancer and stem cells. Some of the BTB/POZ proteins associated with cancer biology are SUMOylated, which appears to play an important role in transcription regulation. We show that NACC1 is SUMOylated on a phylogenetically conserved lysine (K167) out of three consensus SUMOylation motif sites. Amino acid substitution in the SIM sequence (SIM/M) within the BTB/POZ domain partially reduced K167 SUMOylation activity of NACC1. Overexpression of GFP-NACC1 fusion protein leads to formation of discrete nuclear foci similar to promyelocytic leukemia nuclear bodies (PML-NB), which colocalized with SUMO paralogues (SUMO1/2/3). Both NACC1 nuclear body formation and colocalization with SUMO paralogues were completely suppressed in the GFP-NACC1-SIM/M mutant, whereas they were partially maintained in the NACC1 K167R mutant. Confocal immunofluorescence analysis showed that endogenous and exogenous NACC1 proteins colocalized with endogenous PML protein. A pull-down assay revealed that the consensus motifs of the SUMO acceptor site at K167 and the SIM within the BTB/POZ domain were both necessary for efficient binding to PML protein. Our study demonstrates that NACC1 can be modified by SUMO paralogues, and cooperates with PML protein. PMID:25891951

  6. Neural mechanisms of the nucleus accumbens circuit in reward and aversive learning.

    PubMed

    Hikida, Takatoshi; Morita, Makiko; Macpherson, Tom

    2016-07-01

    The basal ganglia are key neural substrates not only for motor function, but also cognitive functions including reward and aversive learning. Critical for these processes are the functional role played by two projection neurons within nucleus accumbens (NAc); the D1- and D2-expressing neurons. Recently, we have developed a novel reversible neurotransmission blocking technique that specifically blocks neurotransmission from NAc D1- and D2-expressing neurons, allowing for in vivo analysis. In this review, we outline the functional dissociation of NAc D1- and D2-expressing neurons of the basal ganglia in reward and aversive learning, as well as drug addiction. These studies have revealed the importance of activation of NAc D1 receptors for reward learning and drug addiction, and inactivation of NAc D2 receptors for aversive learning and flexibility. Based on these findings, we propose a neural mechanism, in which dopamine neurons in the ventral tegmental area that send inputs to the NAc work as a switch between D1- and D2-expressing neurons. These basal ganglia neural mechanisms will give us new insights into the pathophysiology of neuropsychiatric diseases. PMID:26827817

  7. Transfer of Neuroplasticity from Nucleus Accumbens Core to Shell Is Required for Cocaine Reward

    PubMed Central

    Marie, Nicolas; Canestrelli, Corinne; Noble, Florence

    2012-01-01

    It is well established that cocaine induces an increase of dendritic spines density in some brain regions. However, few studies have addressed the role of this neuroplastic changes in cocaine rewarding effects and have often led to contradictory results. So, we hypothesized that using a rigorous time- and subject-matched protocol would demonstrate the role of this spine increase in cocaine reward. We designed our experiments such as the same animals (rats) were used for spine analysis and behavioral studies. Cocaine rewarding effects were assessed with the conditioned place preference paradigm. Spines densities were measured in the two subdivisions of the nucleus accumbens (NAcc), core and shell. We showed a correlation between the increase of spine density in NAcc core and shell and cocaine rewarding effects. Interestingly, when cocaine was administered in home cages, spine density was increase in NAcc core only. With anisomycin, a protein synthesis inhibitor, injected in the core we blocked spine increase in core and shell and also cocaine rewarding effects. Strikingly, whereas injection of this inhibitor in the shell immediately after conditioning had no effect on neuroplasticity or behavior, its injection 4 hours after conditioning was able to block neuroplasticity in shell only and cocaine-induced place preference. Thus, it clearly appears that the neuronal plasticity in the NAcc core is essential to induce plasticity in the shell, necessary for cocaine reward. Altogether, our data revealed a new mechanism in the NAcc functioning where a neuroplasticity transfer occurred from core to shell. PMID:22272316

  8. Activation of Dopamine Receptors in the Nucleus Accumbens Promotes Sucrose-Reinforced Cued Approach Behavior

    PubMed Central

    du Hoffmann, Johann; Nicola, Saleem M.

    2016-01-01

    Dopamine receptor activation in the nucleus accumbens (NAc) promotes vigorous environmentally-cued food-seeking in hungry rats. Rats fed ad libitum, however, respond to fewer food-predictive cues, particularly when the value of food reward is low. Here, we investigated whether this difference could be due to differences in the degree of dopamine receptor activation in the NAc. First, we observed that although rats given ad libitum access to chow in their home cages approached a food receptacle in response to reward-predictive cues, the number of such approaches declined as animals accumulated food rewards. Intriguingly, cued approach to food occurred in clusters, with several cued responses followed by successive non-responses. This pattern suggested that behavior was dictated by transitions between two states, responsive and non-responsive. Injection of D1 or D2 dopamine receptor agonists into the NAc dose-dependently increased cue responding by promoting transitions to the responsive state and by preventing transitions to the non-responsive state. In contrast, antagonists of either D1 or D2 receptors promoted long bouts of non-responding by inducing transitions to the non-responsive state and by preventing transitions to the responsive state. Moreover, locomotor behavior during the inter-trial interval was correlated with the responsive state, and was also increased by dopamine receptor agonists. These results suggest that activation of NAc dopamine receptors plays an important role in regulating the probability of approach to food under conditions of normative satiety. PMID:27471453

  9. Nucleus accumbens shell, but not core, tracks motivational value of salt.

    PubMed

    Loriaux, Amy L; Roitman, Jamie D; Roitman, Mitchell F

    2011-09-01

    To appropriately respond to an affective stimulus, we must be able to track its value across changes in both the external and internal environment. The nucleus accumbens (NAc) is a critical component of reward circuitry, but recent work suggests that the NAc encodes aversion as well as reward. It remains unknown whether differential NAc activity reflects flexible changes in stimulus value when it is altered due to a change in physiological state. We measured the activity of individual NAc neurons when rats were given intraoral infusions of a hypertonic salt solution (0.45 M NaCl) across multiple sessions in which motivational state was manipulated. This normally nonpreferred taste was made rewarding via sodium depletion, which resulted in a strong motivation to seek out and consume salt. Recordings were made in three conditions: while sodium replete (REP), during acute sodium depletion (DEP), and following replenishment of salt to normal sodium balance (POST). We found that NAc neurons in the shell and core subregions responded differently across the three conditions. In the shell, we observed overall increases in NAc activity when the salt solution was nonpreferred (REP) but decreases when the salt solution was preferred (DEP). In the core, overall activity was significantly altered only after sodium balance was restored (POST). The results lend further support to the selective encoding of affective stimuli by the NAc and suggest that NAc shell is particularly involved in flexibly encoding stimulus value based on motivational state. PMID:21697439

  10. Butorphanol Suppression of Histamine Itch is Mediated by Nucleus Accumbens and Septal Nuclei

    PubMed Central

    Papoiu, Alexandru D.P.; Kraft, Robert A.; Coghill, Robert C.; Yosipovitch, Gil

    2014-01-01

    Opioid receptors in the central nervous system are important modulators of itch transmission. In this study, we examined the effect of mixed-action opioid butorphanol on histamine itch, cowhage itch and heat pain in healthy volunteers. Using functional MRI, we investigated significant changes in cerebral perfusion to identify the critical brain centers mediating the antipruritic effect of butorphanol. Butorphanol suppressed the itch induced experimentally with histamine, reduced the intensity of cowhage itch by approximately 35%, and did not affect heat pain sensitivity. In comparison with the placebo, butorphanol produced a bilateral deactivation of claustrum, insula and putamen, areas activated during itch processing. Analysis of cerebral perfusion patterns of brain processing of itch vs. itch inhibition under the effect of the drug, revealed that the reduction of cowhage itch by butorphanol was correlated with changes in cerebral perfusion in the midbrain, thalamus, S1, insula and cerebellum. The suppression of histamine itch by butorphanol was paralleled by the activation of nucleus accumbens and septal nuclei, structures expressing high levels of kappa opioid receptors. In conclusion, important relays of the mesolimbic circuit were involved in the inhibition of itch by butorphanol and could represent potential targets for the development of antipruritic therapy. PMID:25211175

  11. HIV-1 Transgenic Female Rat: Synaptodendritic Alterations of Medium Spiny Neurons in the Nucleus Accumbens

    PubMed Central

    Roscoe, Robert F.; Mactutus, Charles F.

    2015-01-01

    HIV-1 associated neurocognitive deficits are increasing in prevalence, although the neuronal basis for these deficits is unclear. HIV-1 Tg rats constitutively express 7 of 9 HIV-associated proteins, and may be useful for studying the neuropathological substrates of HIV-1 associated neurocognitive disorders (HAND). In this study, adult female HIV-1 Tg rats and F344 control rats had similar growth rates, estrous cyclicity and startle reflex inhibition to a visual prepulse stimulus. Medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) were ballistically-labeled utilizing the indocarbocyanine dye DiI. The branching complexity of MSNs in the NAcc was significantly decreased in HIV-1 Tg rats, relative to controls; moreover, the shorter length and decreased volume of dendritic spines, but unchanged head diameter, in HIV-1 Tg rats suggested a reduction of longer spines and an increase in shorter, less projected spines, indicating a population shift to a more immature spine phenotype. Collectively, these results from HIV-1 Tg female rats indicated significant synaptodendritic alterations of MSNs in the NAcc occur as a consequence of chronic, low-level, exposure to HIV-1 associated proteins. PMID:25037595

  12. Dopamine invigorates reward seeking by promoting cue-evoked excitation in the nucleus accumbens.

    PubMed

    du Hoffmann, Johann; Nicola, Saleem M

    2014-10-22

    Approach to reward is a fundamental adaptive behavior, disruption of which is a core symptom of addiction and depression. Nucleus accumbens (NAc) dopamine is required for reward-predictive cues to activate vigorous reward seeking, but the underlying neural mechanism is unknown. Reward-predictive cues elicit both dopamine release in the NAc and excitations and inhibitions in NAc neurons. However, a direct link has not been established between dopamine receptor activation, NAc cue-evoked neuronal activity, and reward-seeking behavior. Here, we use a novel microelectrode array that enables simultaneous recording of neuronal firing and local dopamine receptor antagonist injection. We demonstrate that, in the NAc of rats performing a discriminative stimulus task for sucrose reward, blockade of either D1 or D2 receptors selectively attenuates excitation, but not inhibition, evoked by reward-predictive cues. Furthermore, we establish that this dopamine-dependent signal is necessary for reward-seeking behavior. These results demonstrate a neural mechanism by which NAc dopamine invigorates environmentally cued reward-seeking behavior. PMID:25339748

  13. Modulation of medial geniculate nucleus neuronal activity by electrical stimulation of the nucleus accumbens.

    PubMed

    Barry, K M; Paolini, A G; Robertson, D; Mulders, W H A M

    2015-11-12

    Dysfunctional sensory gating has been proposed to result in the generation of phantom perceptions. In agreement, it has been recently suggested that tinnitus, a phantom perception of sound commonly associated with hearing loss, is the result of a breakdown of circuitry involving the limbic system and the medial geniculate nucleus (MGN) of the thalamus. In humans with tinnitus, structural changes and abnormal activity have been found to occur in the auditory pathway as well as parts of the limbic system such as the nucleus accumbens (NAc). However, at present, no studies have been conducted on the influence of the NAc on the MGN. We investigated the functional connectivity between the NAc and MGN single neurons. Bipolar electrical stimulation was delivered to the NAc while recording single neuron activity in MGN in anesthetized Wistar rats. Histological analysis was used to confirm placement of electrodes. NAc electrical stimulation generally decreased spontaneous firing rates in MGN neurons and, in a limited number of neurons, caused an increase in firing rate. This suggests that NAc can modulate the activity of auditory neurons in the MGN and may play a role in the development of tinnitus. PMID:26349008

  14. AUTS2 in the nucleus accumbens is essential for heroin-induced behavioral sensitization.

    PubMed

    Zhu, Yongsheng; Xing, Bo; Dang, Wei; Ji, Yuanyuan; Yan, Peng; Li, Yunxiao; Qiao, Xiaomeng; Lai, Jianghua

    2016-10-01

    Autism susceptibility candidate 2 (AUTS2) is a gene associated with autism and mental retardation. Recent studies have suggested an association of the AUTS2 gene with heroin dependence, and reduced AUTS2 gene expression may confer increased susceptibility to heroin dependence. However, the functional role of the AUTS2 protein in regulating enduring neuroadaptations in response to heroin exposure has not been established. Here, we investigated the effects of acute and chronic heroin exposure on AUTS2 mRNA and protein expression in the nucleus accumbens (NAc) and caudate-putamen (CPu) to determine whether changes in AUTS2 expression are associated with heroin-induced locomotor sensitization in mice. Moreover, we explored whether AUST2 knockdown affects heroin-induced locomotor sensitization. AUTS2 mRNA and protein expression in the NAc, but not the CPu, was decreased after chronic heroin (1mg/kg) administration. In the NAc, the expression of heroin-induced locomotor sensitization was enhanced through the lentiviral-AUTS2-shRNA-mediated knockdown of AUTS2, while the overexpression of AUTS2 attenuated the locomotor-stimulant effects of heroin. Together, these results indicate that AUTS2 in the NAc, but not the CPu, suppresses the initiation and expression of heroin-induced behavioral sensitization, suggesting that AUST2 may be a potential target for the treatment of heroin dependence. PMID:27423627

  15. Circadian genes Period 1 and Period 2 in the nucleus accumbens regulate anxiety-related behavior

    PubMed Central

    Spencer, Sade; Falcon, Edgardo; Kumar, Jaswinder; Krishnan, Vaishnav; Mukherjee, Shibani; Birnbaum, Shari G.; McClung, Colleen A.

    2013-01-01

    It has been suggested for some time that circadian rhythm abnormalities underlie the development of multiple psychiatric disorders. However, it is unclear how disruptions in individual circadian genes might regulate mood and anxiety. Here we found that mice lacking functional mPeriod 1 (mPer1) or mPeriod 2 (mPer2) individually did not have consistent behavioral abnormalities in measures of anxiety-related behavior. However, mice deficient in both mPer1 and mPer2 had an increase in levels of anxiety-like behavior in multiple measures. Moreover, we found that mPer1 and mPer2 expression was reduced in the nucleus accumbens (NAc) after exposure to chronic social defeat stress, a paradigm that led to increased anxiety-related behavior. Following social defeat, chronic treatment with fluoxetine normalized Per gene expression towards wild-type levels. Knockdown of both mPer1 and mPer2 expression via RNA interference specifically in the NAc led to a similar increase in anxiety-like behavior as seen in the mutant animals. Taken together, these results implicate the Per genes in the NAc in response to stress and the development of anxiety. PMID:23039899

  16. The effect of Gly-Gln [ß-endorphin30-31] on morphine-evoked serotonin and GABA efflux in the nucleus accumbens of conscious rats.

    PubMed

    Basaran, Nesrin F; Buyukuysal, R Levent; Sertac Yilmaz, M; Aydin, Sami; Cavun, Sinan; Millington, William R

    2016-08-01

    Glycyl-L-glutamine (Gly-Gln; β-endorphin30-31) is an endogenous dipeptide synthesized through the post-translational processing of β-endorphin1-31. Central Gly-Gln administration inhibits the rewarding properties of morphine and attenuates morphine tolerance, dependence and withdrawal although it does not interfere with morphine analgesia. In an earlier study, we found that Gly-Gln inhibits morphine-induced dopamine efflux in the nucleus accumbens (NAc), consistent with its ability to inhibit morphine reward. To further investigate the mechanism responsible for its central effects we tested whether i.c.v. Gly-Gln administration influences the rise in extracellular serotonin and GABA concentrations evoked by morphine in the NAc. Conscious rats were treated with Gly-Gln (100nmol/5μl) or saline i.c.v. followed, 2min later, by morphine (2.5mg/kg) or saline i.p. and extracellular serotonin and GABA concentrations were analyzed by microdialysis and HPLC. Morphine administration increased extracellular serotonin and GABA concentrations significantly within 20min, as shown previously. Unexpectedly, Gly-Gln also increased extracellular serotonin concentrations significantly in control animals. Combined treatment with Gly-Gln+morphine also elevated extracellular serotonin concentrations although the magnitude of the response did not differ significantly from the effect of Gly-Gln or morphine, given alone suggesting that Gly-Gln suppressed morphine induced serotonin efflux. Gly-Gln abolished the morphine-induced rise in extracellular GABA concentrations but had no effect on extracellular GABA when given alone to otherwise untreated animals. These data show that Gly-Gln stimulates NAc serotonin efflux and, together with earlier studies, support the hypothesis that Gly-Gln inhibits the rewarding effects of morphine by modulating morphine induced dopamine, GABA and serotonin efflux in the NAc. PMID:26861257

  17. Alterations in blood glucose and plasma glucagon concentrations during deep brain stimulation in the shell region of the nucleus accumbens in rats

    PubMed Central

    Diepenbroek, Charlene; van der Plasse, Geoffrey; Eggels, Leslie; Rijnsburger, Merel; Feenstra, Matthijs G. P.; Kalsbeek, Andries; Denys, Damiaan; Fliers, Eric; Serlie, Mireille J.; la Fleur, Susanne E.

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is an effective therapy for obsessive compulsive disorder (OCD) and is currently under investigation as a treatment for eating disorders. DBS of this area is associated with altered food intake and pharmacological treatment of OCD is associated with the risk of developing type 2 diabetes. Therefore we examined if DBS of the NAc-shell (sNAc) influences glucose metabolism. Male Wistar rats were subjected to DBS, or sham stimulation, for a period of 1 h. To assess the effects of stimulation on blood glucose and glucoregulatory hormones, blood samples were drawn before, during and after stimulation. Subsequently, all animals were used for quantitative assessment of Fos immunoreactivity in the lateral hypothalamic area (LHA) using computerized image analysis. DBS of the sNAc rapidly increased plasma concentrations of glucagon and glucose while sham stimulation and DBS outside the sNAc were ineffective. In addition, the increase in glucose was dependent on DBS intensity. In contrast, the DBS-induced increase in plasma corticosterone concentrations was independent of intensity and region, indicating that the observed DBS-induced metabolic changes were not due to corticosterone release. Stimulation of the sNAc with 200 μA increased Fos immunoreactivity in the LHA compared to sham or 100 μA stimulated animals. These data show that DBS of the sNAc alters glucose metabolism in a region- and intensity- dependent manner in association with neuronal activation in the LHA. Moreover, these data illustrate the need to monitor changes in glucose metabolism during DBS-treatment of OCD patients. PMID:24339800

  18. Nucleus accumbens NMDA receptor activation regulates amphetamine cross-sensitization and deltaFosB expression following sexual experience in male rats.

    PubMed

    Beloate, Lauren N; Weems, Peyton W; Casey, Graham R; Webb, Ian C; Coolen, Lique M

    2016-02-01

    Sexual experience in male rats followed by a period of abstinence causes sensitization to d-Amphetamine (Amph) reward, evidenced by an increased conditioned place preference (CPP) for low doses of Amph. Moreover, sexual experience induces neural plasticity within the nucleus accumbens (NAc), including induction of deltaFosB, which plays a key role in Amph reward cross-sensitization. The NMDA receptor subunit NR1 is also upregulated by mating, but the functional relevance of NMDA receptors in sex experience-induced effects is unknown. Here, we examined the influence of intra-NAc MK 801 infusions on sex experience-induced NAc deltaFosB and cFos expression, as well as mating- and Amph-induced CPP in adult male rats. In experiment 1, males received MK 801 or saline into the NAc during each of 4 consecutive days of mating or handling and were tested for Amph CPP and experience-induced deltaFosB 10 days later. Intra-NAc MK 801 during sexual behavior prevented experience-induced increases in Amph CPP and NAc deltaFosB expression without affecting sexual behavior. In experiment 2, the effects of intra-NAc MK 801 on mating-induced CPP were examined by intra-NAc infusion of MK 801 or saline prior to mating on conditioning days. Intra-NAc MK 801 did not affect mating-induced CPP. Next, effects of intra-NAc MK 801 on mating-induced cFos immunoreactivity were examined. MK 801 prevented mating-induced cFos expression in NAc shell and core. Together, these results provide evidence that NAc NMDA receptor activation during sexual behavior plays a key role in mating-induced cFos and deltaFosB expression and subsequent experience-induced cross-sensitization to Amph reward. PMID:26391065

  19. Alterations in blood glucose and plasma glucagon concentrations during deep brain stimulation in the shell region of the nucleus accumbens in rats.

    PubMed

    Diepenbroek, Charlene; van der Plasse, Geoffrey; Eggels, Leslie; Rijnsburger, Merel; Feenstra, Matthijs G P; Kalsbeek, Andries; Denys, Damiaan; Fliers, Eric; Serlie, Mireille J; la Fleur, Susanne E

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is an effective therapy for obsessive compulsive disorder (OCD) and is currently under investigation as a treatment for eating disorders. DBS of this area is associated with altered food intake and pharmacological treatment of OCD is associated with the risk of developing type 2 diabetes. Therefore we examined if DBS of the NAc-shell (sNAc) influences glucose metabolism. Male Wistar rats were subjected to DBS, or sham stimulation, for a period of 1 h. To assess the effects of stimulation on blood glucose and glucoregulatory hormones, blood samples were drawn before, during and after stimulation. Subsequently, all animals were used for quantitative assessment of Fos immunoreactivity in the lateral hypothalamic area (LHA) using computerized image analysis. DBS of the sNAc rapidly increased plasma concentrations of glucagon and glucose while sham stimulation and DBS outside the sNAc were ineffective. In addition, the increase in glucose was dependent on DBS intensity. In contrast, the DBS-induced increase in plasma corticosterone concentrations was independent of intensity and region, indicating that the observed DBS-induced metabolic changes were not due to corticosterone release. Stimulation of the sNAc with 200 μA increased Fos immunoreactivity in the LHA compared to sham or 100 μA stimulated animals. These data show that DBS of the sNAc alters glucose metabolism in a region- and intensity- dependent manner in association with neuronal activation in the LHA. Moreover, these data illustrate the need to monitor changes in glucose metabolism during DBS-treatment of OCD patients. PMID:24339800

  20. Outcome of Fetuses with Cerebral Ventriculomegaly and Septum Pellucidum Leaflet Abnormalities

    PubMed Central

    Li, Y; Sansgiri, R; Estroff, JA; Mehta, TS; Poussaint, TY; Robertson, RL; Robson, CD; Feldman, HA; Barnewolt, C; Levine, D

    2013-01-01

    Objective To assess outcomes of prenatal diagnosis of septal leaflet abnormality in fetuses referred for ventriculomegaly (VM). Methods In a prospective IRB-approved study with written informed consent, between 7/1/2003 to 5/15/2009, 425 pregnant women with 433 fetuses referred for VM were imaged with US and MRI. Four to six radiologists independently reviewed sonographic and MR images and recorded lateral ventricular diameters at the atrium and frontal horns, ventricular configuration, and the presence of VM and other CNS abnormalities. Final US, MR, and overall prenatal diagnoses were decided by consensus. Fetuses coded for septal leaflet abnormality were identified, and birth outcome, autopsy, postnatal imaging, and postnatal follow-up were obtained. Log-transformed ANCOVA, controlling for GA, was used to compare ventricular dimensions between fetuses with septal leaflet abnormalities and fetuses with isolated VM. Inter-rater agreement of septal leaflet abnormality was assessed with kappa statistics. Results 23 fetuses had septal leaflet abnormalities and 229 had isolated VM. Atrial and frontal horn diameters, adjusted for GA, were 77% and 98% larger, respectively, in fetuses with septal leaflet abnormalities than in fetuses with isolated VM (p<0.0001). Pre-conference consensus among US readers was moderate (kappa = 0.54) and among MR readers was good (kappa = 0.69). Additional MR CNS findings were seen in 12/23 (52%) fetuses. Eleven pregnancies with septal leaflet abnormalities underwent termination and 12 progressed to live birth with 3 neonatal demise. Neurodevelopmental follow-up was abnormal in all surviving children. Conclusion Even when septal leaflet abnormality is an isolated finding, developmental delay can occur postnatally. PMID:21178039

  1. Deep brain stimulation of the nucleus accumbens shell attenuates cue-induced reinstatement of both cocaine and sucrose seeking in rats.

    PubMed

    Guercio, Leonardo A; Schmidt, Heath D; Pierce, R Christopher

    2015-03-15

    Stimuli previously associated with drug taking can become triggers that can elicit craving and lead to relapse of drug-seeking behavior. Here, we examined the influence of deep brain stimulation (DBS) in the nucleus accumbens shell on cue-induced reinstatement of cocaine seeking, an animal model of relapse. Rats were allowed to self-administer cocaine (0.254 mg, i.v.) for 2 h daily for 21 days, with each infusion of cocaine being paired with a cue light. After 21 days of self-administration, cocaine-taking behavior was extinguished by replacing cocaine with saline in the absence of the cue light. Next, during the reinstatement phase, DBS was administered bilaterally into the nucleus accumbens shell through bipolar stainless steel electrodes immediately prior to re-exposure to cues previously associated with cocaine reinforcement. DBS continued throughout the 2 h reinstatement session. Parallel studies examined the influence of accumbens shell DBS on reinstatement induced by cues previously associated with sucrose reinforcement. Results indicated that DBS of the nucleus accumbens shell significantly attenuated cue-induced reinstatement of cocaine and sucrose seeking. Together, these results indicate that DBS of the accumbens shell disrupts cue-induced reinstatement associated with both a drug and a natural reinforcer. PMID:25529183

  2. Deep Brain Stimulation of the Nucleus Accumbens Shell Attenuates Cue-Induced Reinstatement of Both Cocaine and Sucrose Seeking in Rats

    PubMed Central

    Guercio, Leonardo A.; Schmidt, Heath D.; Pierce, R. Christopher

    2015-01-01

    Stimuli previously associated with drug taking can become triggers that can elicit craving and lead to relapse of drug-seeking behavior. Here, we examined the influence of deep brain stimulation (DBS) in the nucleus accumbens shell on cue-induced reinstatement of cocaine seeking, an animal model of relapse. Rats were allowed to self-administer cocaine (0.254 mg, i.v.) for 2 h daily for 21 d, with each infusion of cocaine being paired with a cue light. After 21 d of self-administration, cocaine-taking behavior was extinguished by replacing cocaine with saline in the absence of the cue light. Next, during the reinstatement phase, DBS was administered bilaterally into the nucleus accumbens shell through bipolar stainless steel electrodes immediately prior to re-exposure to cues previously associated with cocaine reinforcement. DBS continued throughout the 2 h reinstatement session. Parallel studies examined the influence of accumbens shell DBS on reinstatement induced by cues previously associated with sucrose reinforcement. Results indicated that DBS of the nucleus accumbens shell significantly attenuated cue-induced reinstatement of cocaine and sucrose seeking. Together, these results indicate that DBS of the accumbens shell disrupts cue-induced reinstatement associated with both a drug and a natural reinforcer. PMID:25529183

  3. Medial Septum-Diagonal Band of Broca (MSDB) GABAergic Regulation of Hippocampal Acetylcholine Efflux Is Dependent on Cognitive Demands

    PubMed Central

    Roland, Jessica J.; Stewart, Amanda L.; Janke, Kellie L.; Gielow, Matthew R.; Kostek, John A.; Savage, Lisa M.; Servatius, Richard J.

    2014-01-01

    The septohippocampal pathway contains cholinergic, GABAergic, and glutamatergic projections and has an established role in learning, memory, and hippocampal theta rhythm. Both GABAergic and cholinergic neurons in the medial septum-diagonal band of Broca (MSDB) have been associated with spatial memory, but the relationship between the two neuronal populations is not fully understood. The present study investigated the effect of selective GABAergic MSDB lesions on hippocampal acetylcholine (ACh) efflux and spatial memory during tasks that varied in memory demand. Male Sprague Dawley rats were given GABAergic lesions of the MSDB using GAT1-saporin (GAT1-SAP) and examined on spontaneous exploration (Experiment 1) and non-matching to position without (NMTP; Experiment 2) and with a delay (DNMTP; Experiment 3), while concurrently using in vivo microdialysis to measure hippocampal ACh efflux. Intraseptal GAT1-SAP treatment did not alter baseline or behaviorally stimulated hippocampal ACh efflux or maze exploration (Experiment 1). Moreover, GAT1-SAP did not alter evoked hippocampal ACh efflux related to NMTP nor did it impair working memory in NMTP (Experiment 2). In contrast, both ACh efflux and performance in DNMTP were impaired by intraseptal GAT1-SAP. Thus, GABAergic MSDB neurons are important for spatial working memory and modulate hippocampal ACh efflux under conditions of high memory load. The relationship between the septohippocampal cholinergic and GABAergic systems and working memory will be discussed. PMID:24403150

  4. Garvicin A, a Novel Class IId Bacteriocin from Lactococcus garvieae That Inhibits Septum Formation in L. garvieae Strains

    PubMed Central

    Cárdenas, Nivia; Martínez, Beatriz; Ruiz-Barba, José Luis; Fernández-Garayzábal, José F.; Rodríguez, Juan M.; Gibello, Alicia

    2013-01-01

    Lactococcus garvieae 21881, isolated in a human clinical case, produces a novel class IId bacteriocin, garvicin A (GarA), which is specifically active against other L. garvieae strains, including fish- and bovine-pathogenic isolates. Purification from active supernatants, sequence analyses, and plasmid-curing experiments identified pGL5, one of the five plasmids found in L. garvieae [M. Aguado-Urda et al., PLoS One 7(6):e40119, 2012], as the coding plasmid for the structural gene of GarA (lgnA), its putative immunity protein (lgnI), and the ABC transporter and its accessory protein (lgnC and lgnD). Interestingly, pGL5-cured strains were still resistant to GarA. Other putative bacteriocins encoded by the remaining plasmids were not detected during purification, pointing to GarA as the main inhibitor secreted by L. garvieae 21881. Mode-of-action studies revealed a potent bactericidal activity of GarA. Moreover, transmission microscopy showed that GarA seems to act by inhibiting septum formation in L. garvieae cells. This potent and species-specific inhibition by GarA holds promise for applications in the prevention or treatment of infections caused by pathogenic strains of L. garvieae in both veterinary and clinical settings. PMID:23666326

  5. Loss of medial septum cholinergic neurons in THY-Tau22 mouse model: what links with tau pathology?

    PubMed

    Belarbi, K; Burnouf, S; Fernandez-Gomez, F-J; Desmercières, J; Troquier, L; Brouillette, J; Tsambou, L; Grosjean, M-E; Caillierez, R; Demeyer, D; Hamdane, M; Schindowski, K; Blum, D; Buée, L

    2011-09-01

    Alzheimer's disease (AD) is a neurodegenerative disorder histologically defined by the cerebral accumulation of amyloid deposits and neurofibrillary tangles composed of hyperphosphorylated tau proteins. Loss of basal forebrain cholinergic neurons is another hallmark of the disease thought to contribute to the cognitive dysfunctions. To this date, the mechanisms underlying cholinergic neurons degeneration remain uncertain. The present study aimed to investigate the relationship between neurofibrillary degeneration and cholinergic defects in AD using THY-Tau22 transgenic mouse model exhibiting a major hippocampal AD-like tau pathology and hyperphosphorylated tau species in the septohippocampal pathway. Here, we report that at a time THY-Tau22 mice display strong reference memory alterations, the retrograde transport of fluorogold through the septohippocampal pathway is altered. This impairment is associated with a significant reduction in the number of choline acetyltransferase (ChAT)-immunopositive cholinergic neurons in the medial septum. Analysis of nerve growth factor (NGF) levels supports an accumulation of the mature neurotrophin in the hippocampus of THY-Tau22 mice, consistent with a decrease of its uptake or retrograde transport by cholinergic terminals. Finally, our data strongly support that tau pathology could be instrumental in the cholinergic neuronal loss observed in AD. PMID:21605043

  6. [Anesthesia Management of a Patient with Pulmonary Atresia, Intact Ventricular Septum, Major Aortopulmonary Collateral Artery and Tetralogy of Fallot].

    PubMed

    Hitosugi, Takashi; Tsukamoto, Masanori; Ishii, Kentaro; Kadowaki, Masanori; Fujiwara, Shigeki; Yokoyama, Takeshi

    2016-03-01

    The patient was a 6-year-old girl with pulmonary atresia, intact ventricular septum and major aortopulmonary collateral artery with tetralogy of Fallot Her Sp(O2) was around 60% under room air, and she could not walk long. She underwent dental treatment under general anesthesia. Invasive monitoring using pulmonary artery catheter should have been avoided, since the risk of monitoring greatly exceeds that of the treatment. The patient entered the operating room with her mother, and anesthesia was induced with intravenous midazolam, propofol and vecuronium. She was intubated orally first and impedance cardiography monitoring was started. FI(O2) was maintained at 0.5-1.0. Increases in airway pressure and Pa(CO2) were appropriately avoided. Dental treatment is important for infants with cardiac disease not only to reduce their pain, but also to reduce the risk of infection. It often requires general anesthesia. We have to conduct it with less invasiveness and less stress. PMID:27097511

  7. Lateral Lumbar Interbody Fusion

    PubMed Central

    Hughes, Alexander; Girardi, Federico; Sama, Andrew; Lebl, Darren; Cammisa, Frank

    2015-01-01

    The lateral lumbar interbody fusion (LLIF) is a relatively new technique that allows the surgeon to access the intervertebral space from a direct lateral approach either anterior to or through the psoas muscle. This approach provides an alternative to anterior lumbar interbody fusion with instrumentation, posterior lumbar interbody fusion, and transforaminal lumbar interbody fusion for anterior column support. LLIF is minimally invasive, safe, better structural support from the apophyseal ring, potential for coronal plane deformity correction, and indirect decompression, which have has made this technique popular. LLIF is currently being utilized for a variety of pathologies including but not limited to adult de novo lumbar scoliosis, central and foraminal stenosis, spondylolisthesis, and adjacent segment degeneration. Although early clinical outcomes have been good, the potential for significant neurological and vascular vertebral endplate complications exists. Nevertheless, LLIF is a promising technique with the potential to more effectively treat complex adult de novo scoliosis and achieve predictable fusion while avoiding the complications of traditional anterior surgery and posterior interbody techniques. PMID:26713134

  8. Lateral Lumbar Interbody Fusion.

    PubMed

    Pawar, Abhijit; Hughes, Alexander; Girardi, Federico; Sama, Andrew; Lebl, Darren; Cammisa, Frank

    2015-12-01

    The lateral lumbar interbody fusion (LLIF) is a relatively new technique that allows the surgeon to access the intervertebral space from a direct lateral approach either anterior to or through the psoas muscle. This approach provides an alternative to anterior lumbar interbody fusion with instrumentation, posterior lumbar interbody fusion, and transforaminal lumbar interbody fusion for anterior column support. LLIF is minimally invasive, safe, better structural support from the apophyseal ring, potential for coronal plane deformity correction, and indirect decompression, which have has made this technique popular. LLIF is currently being utilized for a variety of pathologies including but not limited to adult de novo lumbar scoliosis, central and foraminal stenosis, spondylolisthesis, and adjacent segment degeneration. Although early clinical outcomes have been good, the potential for significant neurological and vascular vertebral endplate complications exists. Nevertheless, LLIF is a promising technique with the potential to more effectively treat complex adult de novo scoliosis and achieve predictable fusion while avoiding the complications of traditional anterior surgery and posterior interbody techniques. PMID:26713134

  9. Creativity in later life.

    PubMed

    Price, K A; Tinker, A M

    2014-08-01

    The ageing population presents significant challenges for the provision of social and health services. Strategies are needed to enable older people to cope within a society ill prepared for the impacts of these demographic changes. The ability to be creative may be one such strategy. This review outlines the relevant literature and examines current public health policy related to creativity in old age with the aim of highlighting some important issues. As well as looking at the benefits and negative aspects of creative activity in later life they are considered in the context of the theory of "successful ageing". Creative activity plays an important role in the lives of older people promoting social interaction, providing cognitive stimulation and giving a sense of self-worth. Furthermore, it is shown to be useful as a tool in the multi-disciplinary treatment of health problems common in later life such as depression and dementia. There are a number of initiatives to encourage older people to participate in creative activities such as arts-based projects which may range from visual arts to dance to music to intergenerational initiatives. However, participation shows geographical variation and often the responsibility of provision falls to voluntary organisations. Overall, the literature presented suggests that creative activity could be a useful tool for individuals and society. However, further research is needed to establish the key factors which contribute to patterns of improved health and well-being, as well as to explore ways to improve access to services. PMID:24974278

  10. 8. UPPER INSIDE CHORD, VERTICAL, LATERAL STRUT, UPPER LATERAL & ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. UPPER INSIDE CHORD, VERTICAL, LATERAL STRUT, UPPER LATERAL & GUSSET PLATE, ONE DIAGONAL BRACE - Enterprise Parker Truss Bridge, Spanning Smoky Hill River on K-43 Highway, Enterprise, Dickinson County, KS

  11. 7. UPPER INSIDE CHORD, VERTICAL, LATERAL STRUT, UPPER LATERAL & ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. UPPER INSIDE CHORD, VERTICAL, LATERAL STRUT, UPPER LATERAL & GUSSET PLATE, TWO DIAGONAL BRACES - Enterprise Parker Truss Bridge, Spanning Smoky Hill River on K-43 Highway, Enterprise, Dickinson County, KS

  12. Role of Dopamine Receptors Subtypes, D1-Like and D2-Like, within the Nucleus Accumbens Subregions, Core and Shell, on Memory Consolidation in the One-Trial Inhibitory Avoidance Task

    ERIC Educational Resources Information Center

    Manago, Francesca; Castellano, Claudio; Oliverio, Alberto; Mele, Andrea; De Leonibus, Elvira

    2009-01-01

    Recent evidence demonstrated that dopamine within the nucleus accumbens mediates consolidation of both associative and nonassociative memories. However, the specific contribution of the nucleus accumbens subregions, core and shell, and of D1 and D2 receptors subtypes has not been yet clarified. The aim of this study was, therefore, to directly…

  13. Lateral conduction infrared photodetector

    DOEpatents

    Kim, Jin K.; Carroll, Malcolm S.

    2011-09-20

    A photodetector for detecting infrared light in a wavelength range of 3-25 .mu.m is disclosed. The photodetector has a mesa structure formed from semiconductor layers which include a type-II superlattice formed of alternating layers of InAs and In.sub.xGa.sub.1-xSb with 0.ltoreq.x.ltoreq.0.5. Impurity doped regions are formed on sidewalls of the mesa structure to provide for a lateral conduction of photo-generated carriers which can provide an increased carrier mobility and a reduced surface recombination. An optional bias electrode can be used in the photodetector to control and vary a cut-off wavelength or a depletion width therein. The photodetector can be formed as a single-color or multi-color device, and can also be used to form a focal plane array which is compatible with conventional read-out integrated circuits.

  14. Laterality and language experience.

    PubMed

    Hull, Rachel; Vaid, Jyotsna

    2006-09-01

    A meta-analysis was conducted on studies that examined hemispheric functional asymmetry for language in brain-intact monolingual and bilingual adults. Data from 23 laterality studies that directly compared bilingual and monolingual speakers on the same language were analysed (n = 1234). Variables examined were language experience (monolingual, bilingual), experimental paradigm (dichotic listening, visual hemifield presentation, and dual task) and, among bilinguals, the influence of second language proficiency (proficient vs nonproficient) and onset of bilingualism (early, or before age 6; and late, or after age 6). Overall, monolinguals and late bilinguals showed reliable left hemisphere dominance, while early bilinguals showed reliable bilateral hemispheric involvement. Within bilinguals, there was no reliable effect of language proficiency when age of L2 acquisition was controlled. The findings indicate that early learning of one vs. two languages predicts divergent patterns of cerebral language lateralisation in adulthood. PMID:16882556

  15. Lateral Flow Immunoassay.

    PubMed

    Ching, Kathryn H

    2015-01-01

    Lateral flow immunoassays (LFIAs) are a staple in the field of rapid diagnostics. These small handheld devices require no specialized training or equipment to operate, and generate a result within minutes of sample application. They are an ideal format for many types of home test kits, for emergency responders and for food manufacturers and producers looking for a quick evaluation of a given sample. LFIAs rely on high quality monoclonal antibodies that recognize the analyte of interest. As monoclonal antibody technology becomes more accessible to smaller laboratories, there has been increased interest in developing LFIA prototypes for potential commercial manufacture. In this chapter, the basics of designing and building an LFIA prototype are described. PMID:26160571

  16. Role of Mu and Delta Opioid Receptors in the Nucleus Accumbens in Cocaine-Seeking Behavior

    PubMed Central

    Simmons, Diana; Self, David W.

    2009-01-01

    Previous studies suggest that opioid receptors in the ventral tegmental area (VTA), but not the nucleus accumbens (NAc), play a role in relapse to drug-seeking behavior. However, environmental stimuli that elicit relapse also release the endogenous opioid β-endorphin in the NAc. Using a within–session extinction/reinstatement paradigm in rats that self-administer cocaine, we found that NAc infusions of the mu opioid receptor (MOR) agonist DAMGO moderately reinstated responding on the cocaine-paired lever at low doses (1.0–3.0 ng/side), whereas the delta opioid receptor (DOR) agonist DPDPE induced greater responding at higher doses (300–3000 ng/side) that also enhanced inactive lever responding. Using doses of either agonist that induced responding on only the cocaine-paired lever, we found that DAMGO-induced responding was blocked selectively by pretreatment with the MOR antagonist CTAP, while DPDPE-induced responding was selectively blocked by the DOR antagonist naltrindole. Cocaine-primed reinstatement was blocked by intra-NAc CTAP but not naltrindole, indicating a role for endogenous MOR-acting peptides in cocaine-induced reinstatement of cocaine-seeking behavior. In this regard, intra-NAc infusions of β-endorphin (100–1000 ng/side) induced marked cocaine-seeking behavior, an effect blocked by intra-NAc pretreatment with the MOR but not DOR antagonist. Conversely, cocaine seeking elicited by the enkephalinase inhibitor thiorphan (1–10 μg/side) was blocked by naltrindole but not CTAP. MOR stimulation in more dorsal caudate-putamen sites was ineffective, while DPDPE infusions induced cocaine seeking. Together, these findings establish distinct roles for MOR and DOR in cocaine relapse, and suggest that NAc MOR could be an important therapeutic target to neutralize the effects of endogenous β-endorphin release on cocaine relapse. PMID:19279569

  17. Cannabinoids and Glucocorticoids in the Basolateral Amygdala Modulate Hippocampal-Accumbens Plasticity After Stress.

    PubMed

    Segev, Amir; Akirav, Irit

    2016-03-01

    Acute stress results in release of glucocorticoids, which are potent modulators of learning and plasticity. This process is presumably mediated by the basolateral amygdala (BLA) where cannabinoids CB1 receptors have a key role in regulating the hypothalamic-pituitary-adrenal (HPA) axis. Growing attention has been focused on nucleus accumbens (NAc) plasticity, which regulates mood and motivation. The NAc integrates affective and context-dependent input from the BLA and ventral subiculum (vSub), respectively. As our previous data suggest that the CB1/2 receptor agonist WIN55,212-2 (WIN) and glucocorticoid receptor (GR) antagonist RU-38486 (RU) can prevent the effects of stress on emotional memory, we examined whether intra-BLA WIN and RU can reverse the effects of acute stress on NAc plasticity. Bilateral, ipsilateral, and contralateral BLA administration of RU or WIN reversed the stress-induced impairment in vSub-NAc long-term potentiation (LTP) and the decrease in cAMP response element-binding protein (CREB) activity in the NAc. BLA CB1 receptors were found to mediate the preventing effects of WIN on plasticity, but not the preventing effects of RU, after stress. Inactivating the ipsilateral BLA, but not the contralateral BLA, impaired LTP. The possible mechanisms underlying the effects of BLA on NAc plasticity are discussed; the data suggest that BLA-induced changes in the NAc may be mediated through neural pathways in the brain's stress circuit rather than peripheral pathways. The results suggest that glucocorticoid and cannabinoid systems in the BLA can restore normal function of the NAc and hence may have a central role in the treatment of a variety of stress-related disorders. PMID:26289146

  18. Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making.

    PubMed

    Zalocusky, Kelly A; Ramakrishnan, Charu; Lerner, Talia N; Davidson, Thomas J; Knutson, Brian; Deisseroth, Karl

    2016-03-31

    A marked bias towards risk aversion has been observed in nearly every species tested. A minority of individuals, however, instead seem to prefer risk (repeatedly choosing uncertain large rewards over certain but smaller rewards), and even risk-averse individuals sometimes opt for riskier alternatives. It is not known how neural activity underlies such important shifts in decision-making--either as a stable trait across individuals or at the level of variability within individuals. Here we describe a model of risk-preference in rats, in which stable individual differences, trial-by-trial choices, and responses to pharmacological agents all parallel human behaviour. By combining new genetic targeting strategies with optical recording of neural activity during behaviour in this model, we identify relevant temporally specific signals from a genetically and anatomically defined population of neurons. This activity occurred within dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens (NAc), signalled unfavourable outcomes from the recent past at a time appropriate for influencing subsequent decisions, and also predicted subsequent choices made. Having uncovered this naturally occurring neural correlate of risk selection, we then mimicked the temporally specific signal with optogenetic control during decision-making and demonstrated its causal effect in driving risk-preference. Specifically, risk-preferring rats could be instantaneously converted to risk-averse rats with precisely timed phasic stimulation of NAc D2R cells. These findings suggest that individual differences in risk-preference, as well as real-time risky decision-making, can be largely explained by the encoding in D2R-expressing NAc cells of prior unfavourable outcomes during decision-making. PMID:27007845

  19. Nucleus accumbens neuronal maturation differences in young rats bred for low versus high voluntary running behaviour

    PubMed Central

    Roberts, Michael D; Toedebusch, Ryan G; Wells, Kevin D; Company, Joseph M; Brown, Jacob D; Cruthirds, Clayton L; Heese, Alexander J; Zhu, Conan; Rottinghaus, George E; Childs, Thomas E; Booth, Frank W

    2014-01-01

    We compared the nucleus accumbens (NAc) transcriptomes of generation 8 (G8), 34-day-old rats selectively bred for low (LVR) versus high voluntary running (HVR) behaviours in rats that never ran (LVRnon-run and HVRnon-run), as well as in rats after 6 days of voluntary wheel running (LVRrun and HVRrun). In addition, the NAc transcriptome of wild-type Wistar rats was compared. The purpose of this transcriptomics approach was to generate testable hypotheses as to possible NAc features that may be contributing to running motivation differences between lines. Ingenuity Pathway Analysis and Gene Ontology analyses suggested that ‘cell cycle’-related transcripts and the running-induced plasticity of dopamine-related transcripts were lower in LVR versus HVR rats. From these data, a hypothesis was generated that LVR rats might have less NAc neuron maturation than HVR rats. Follow-up immunohistochemistry in G9–10 LVRnon-run rats suggested that the LVR line inherently possessed fewer mature medium spiny (Darpp-32-positive) neurons (P < 0.001) and fewer immature (Dcx-positive) neurons (P < 0.001) than their G9–10 HVR counterparts. However, voluntary running wheel access in our G9–10 LVRs uniquely increased their Darpp-32-positive and Dcx-positive neuron densities. In summary, NAc cellularity differences and/or the lack of running-induced plasticity in dopamine signalling-related transcripts may contribute to low voluntary running motivation in LVR rats. PMID:24665095

  20. Changes in dopamine transporter binding in nucleus accumbens following chronic self-administration cocaine: heroin combinations.

    PubMed

    Pattison, Lindsey P; McIntosh, Scot; Sexton, Tammy; Childers, Steven R; Hemby, Scott E

    2014-10-01

    Concurrent use of cocaine and heroin (speedball) has been shown to exert synergistic effects on dopamine neurotransmission in the nucleus accumbens (NAc), as observed by significant increases in extracellular dopamine levels and compensatory elevations in the maximal reuptake rate of dopamine. The present studies were undertaken to determine whether chronic self-administration of cocaine, heroin or a combination of cocaine:heroin led to compensatory changes in the abundance and/or affinity of high- and low-affinity DAT binding sites. Saturation binding of the cocaine analog [(125) I] 3β-(4-iodophenyl)tropan-2β-carboxylic acid methyl ester ([(125) I]RTI-55) in rat NAc membranes resulted in binding curves that were best fit to two-site binding models, allowing calculation of dissociation constant (Kd ) and binding density (Bmax ) values corresponding to high- and low-affinity DAT binding sites. Scatchard analysis of the saturation binding curves clearly demonstrate the presence of high- and low- affinity binding sites in the NAc, with low-affinity sites comprising 85 to 94% of the binding sites. DAT binding analyses revealed that self-administration of cocaine and a cocaine:heroin combination increased the affinity of the low-affinity site for the cocaine congener RTI-55 compared to saline. These results indicate that the alterations observed following chronic speedball self-administration are likely due to the cocaine component alone; thus further studies are necessary to elaborate upon the synergistic effect of cocaine:heroin combinations on the dopamine system in the NAc. PMID:24916769

  1. Nucleus accumbens neuronal activity in freely behaving rats is modulated following acute and chronic methylphenidate administration.

    PubMed

    Chong, Samuel L; Claussen, Catherine M; Dafny, Nachum

    2012-03-10

    Methylphenidate (MPD) is a psychostimulant that enhances dopaminergic neurotransmission in the central nervous system by using mechanisms similar to cocaine and amphetamine. The mode of action of brain circuitry responsible for an animal's neuronal response to MPD is not fully understood. The nucleus accumbens (NAc) has been implicated in regulating the rewarding effects of psychostimulants. The present study used permanently implanted microelectrodes to investigate the acute and chronic effects of MPD on the firing rates of NAc neuronal units in freely behaving rats. On experimental day 1 (ED1), following a saline injection (control), a 30 min baseline neuronal recording was obtained immediately followed by a 2.5 mg/kg i.p. MPD injection and subsequent 60 min neuronal recording. Daily 2.5 mg/kg MPD injections were given on ED2 through ED6 followed by 3 washout days (ED7 to ED9). On ED10, neuronal recordings were resumed from the same animal after a saline and MPD (rechallenge) injection exactly as obtained on ED1. Sixty-seven NAc neuronal units exhibited similar wave shape, form and amplitude on ED1 and ED10 and their firing rates were used for analysis. MPD administration on ED1 elicited firing rate increases and decreases in 54% of NAc units when compared to their baselines. Six consecutive MPD administrations altered the neuronal baseline firing rates of 85% of NAc units. MPD rechallenge on ED10 elicited significant changes in 63% of NAc units. These alterations in firing rates are hypothesized to be through mechanisms that include D1 and D2-like DA receptor induced cellular adaptation and homeostatic adaptations/deregulation caused by acute and chronic MPD administration. PMID:22248440

  2. Assessment of individual differences in the rat nucleus accumbens transcriptome following taste-heroin extended access.

    PubMed

    Imperio, Caesar G; McFalls, Ashley J; Colechio, Elizabeth M; Masser, Dustin R; Vrana, Kent E; Grigson, Patricia S; Freeman, Willard M

    2016-05-01

    Heroin addiction is a disease of chronic relapse that harms the individual through devaluation of personal responsibilities in favor of finding and using drugs. Only some recreational heroin users devolve into addiction but the basis of these individual differences is not known. We have shown in rats that avoidance of a heroin-paired taste cue reliably identifies individual animals with greater addiction-like behavior for heroin. Here rats received 5min access to a 0.15% saccharin solution followed by the opportunity to self-administer either saline or heroin for 6h. Large Suppressors of the heroin-paired taste cue displayed increased drug escalation, motivation for drug, and drug loading behavior compared with Small Suppressors. Little is known about the molecular mechanisms of these individual differences in addiction-like behavior. We examined the individual differences in mRNA expression in the nucleus accumbens (NAc) of rats that were behaviorally stratified by addiction-like behavior using next-generation sequencing. We hypothesized that based on the avoidance of the drug-paired cue there will be a unique mRNA profile in the NAc. Analysis of strand-specific whole genome RNA-Seq data revealed a number of genes differentially regulated in NAc based on the suppression of the natural saccharine reward. Large Suppressors exhibited a unique mRNA prolife compared to Saline controls and Small Suppressors. Genes related to immunity, neuronal activity, and behavior were differentially expressed among the 3 groups. In total, individual differences in avoidance of a heroin-paired taste cue are associated with addiction-like behavior along with differential NAc gene expression. PMID:26733446

  3. Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence.

    PubMed

    Garbusow, Maria; Schad, Daniel J; Sebold, Miriam; Friedel, Eva; Bernhardt, Nadine; Koch, Stefan P; Steinacher, Bruno; Kathmann, Norbert; Geurts, Dirk E M; Sommer, Christian; Müller, Dirk K; Nebe, Stephan; Paul, Sören; Wittchen, Hans-Ulrich; Zimmermann, Ulrich S; Walter, Henrik; Smolka, Michael N; Sterzer, Philipp; Rapp, Michael A; Huys, Quentin J M; Schlagenhauf, Florian; Heinz, Andreas

    2016-05-01

    In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence. PMID:25828702

  4. Serotonin-2C Receptor Agonists Decrease Potassium-Stimulated GABA Release In the Nucleus Accumbens

    PubMed Central

    Kasper, James M; Booth, Raymond G; Peris, Joanna

    2014-01-01

    The serotonin 5-HT2C receptor has shown promise in vivo as a pharmacotherapeutic target for alcoholism. For example, recently, a novel 4-phenyl-2-N,N-dimethylaminotetralin (PAT) drug candidate, that demonstrates 5-HT2C receptor agonist activity together with 5-HT2A/2B receptor inverse agonist activity, was shown to reduce operant responding for ethanol after peripheral administration to rats. Previous studies have shown that the 5-HT2C receptor is found throughout the mesoaccumbens pathway and that 5-HT2C receptor agonism causes activation of ventral tegmental area (VTA) GABA neurons. It is unknown what effect 5-HT2C receptor modulation has on GABA release in the nucleus accumbens core (NAcc). To this end, microdialysis coupled to capillary electrophoresis with laser-induced fluorescence was used to quantify extracellular neurotransmitter concentrations in the NAcc under basal and after potassium stimulation conditions, in response to PAT analogs and other 5-HT2C receptor modulators administered by reverse dialysis to rats. 5-HT2C receptor agonists specifically attenuated stimulated GABA release in the NAcc while 5-HT2C antagonists or inverse agonists had no effect. Agents with activity at 5-HT2A receptors had no effect on GABA release. Thus, in contrast to results reported for the VTA, current results suggest 5-HT2C receptor agonists decrease stimulated GABA release in the NAcc, and provide a possible mechanism of action for 5HT2C-mediated negative modulation of ethanol self-administration. PMID:25382408

  5. The role of nucleus accumbens and dorsolateral striatal D2 receptors in active avoidance conditioning.

    PubMed

    Boschen, Suelen Lucio; Wietzikoski, Evellyn Claudia; Winn, Philip; Da Cunha, Claudio

    2011-09-01

    The role of dopamine (DA) in rewarding motivated actions is well established but its role in learning how to avoid aversive events is still controversial. Here we tested the role of D2-like DA receptors in the nucleus accumbens (NAc) and the dorsolateral striatum (DLS) of rats in the learning and performance of conditioned avoidance responses (CAR). Adult male Wistar rats received systemic, intra-NAc or intra-DLS (pre- or post-training) administration of a D2-like receptor agonist (quinpirole) or antagonist ((-)sulpiride) and were given two sessions in the two-way active avoidance task. The main effects observed were: (i) sulpiride and lower (likely pre-synaptic) doses of quinpirole decreased the number of CARs and increased the number of escape failures; (ii) higher doses of quinpirole (likely post-synaptic) increased inter-trial crossings and failures; (iii) pre-training administration of sulpiride decreased the number of CARs in both training and test sessions when infused into the NAc, but this effect was observed only in the test session when it was infused into the DLS; (iv) post-training administration of sulpiride decreased CARs in the test session when infused into the NAc but not DLS. These findings suggest that activation of D2 receptors in the NAc is critical for fast adaptation to responding to unconditioned and conditioned aversive stimuli while activation of these receptors in the DLS is needed for a slower learning of how to respond to the same stimuli based on previous experiences. PMID:21619938

  6. Addiction and reward-related genes show altered expression in the postpartum nucleus accumbens

    PubMed Central

    Zhao, Changjiu; Eisinger, Brian Earl; Driessen, Terri M.; Gammie, Stephen C.

    2014-01-01

    Motherhood involves a switch in natural rewards, whereby offspring become highly rewarding. Nucleus accumbens (NAC) is a key CNS region for natural rewards and addictions, but to date no study has evaluated on a large scale the events in NAC that underlie the maternal change in natural rewards. In this study we utilized microarray and bioinformatics approaches to evaluate postpartum NAC gene expression changes in mice. Modular Single-set Enrichment Test (MSET) indicated that postpartum (relative to virgin) NAC gene expression profile was significantly enriched for genes related to addiction and reward in five of five independently curated databases (e.g., Malacards, Phenopedia). Over 100 addiction/reward related genes were identified and these included: Per1, Per2, Arc, Homer2, Creb1, Grm3, Fosb, Gabrb3, Adra2a, Ntrk2, Cry1, Penk, Cartpt, Adcy1, Npy1r, Htr1a, Drd1a, Gria1, and Pdyn. ToppCluster analysis found maternal NAC expression profile to be significantly enriched for genes related to the drug action of nicotine, ketamine, and dronabinol. Pathway analysis indicated postpartum NAC as enriched for RNA processing, CNS development/differentiation, and transcriptional regulation. Weighted Gene Coexpression Network Analysis (WGCNA) identified possible networks for transcription factors, including Nr1d1, Per2, Fosb, Egr1, and Nr4a1. The postpartum state involves increased risk for mental health disorders and MSET analysis indicated postpartum NAC to be enriched for genes related to depression, bipolar disorder (BPD), and schizophrenia. Mental health related genes included: Fabp7, Grm3, Penk, and Nr1d1. We confirmed via quantitative PCR Nr1d1, Per2, Grm3, Penk, Drd1a, and Pdyn. This study indicates for the first time that postpartum NAC involves large scale gene expression alterations linked to addiction and reward. Because the postpartum state also involves decreased response to drugs, the findings could provide insights into how to mitigate addictions. PMID:25414651

  7. Opposing Role for Egr3 in Nucleus Accumbens Cell Subtypes in Cocaine Action

    PubMed Central

    Chandra, Ramesh; Francis, T. Chase; Konkalmatt, Prasad; Amgalan, Ariunzaya; Gancarz, Amy M.; Dietz, David M.

    2015-01-01

    An imbalance in molecular signaling cascades and transcriptional regulation in nucleus accumbens (NAc) medium spiny neuron (MSN) subtypes, those enriched in dopamine D1 versus D2 receptors, is implicated in the behavioral responses to psychostimulants. To provide further insight into the molecular mechanisms occurring in MSN subtypes by cocaine, we examined the transcription factor early growth response 3 (Egr3). We evaluated Egr3 because it is a target of critical cocaine-mediated signaling pathways and because Egr3-binding sites are found on promoters of key cocaine-associated molecules. We first used a RiboTag approach to obtain ribosome-associated transcriptomes from each MSN subtype and found that repeated cocaine administration induced Egr3 ribosome-associated mRNA in NAc D1-MSNs while reducing Egr3 in D2-MSNs. Using Cre-inducible adeno-associated viruses combined with D1-Cre and D2-Cre mouse lines, we observed that Egr3 overexpression in D1-MSNs enhances rewarding and locomotor responses to cocaine, whereas overexpression in D2-MSNs blunts these behaviors. miRNA knock-down of Egr3 in MSN subtypes produced opposite behavioral responses from those observed with overexpression. Finally, we found that repeated cocaine administration altered Egr3 binding to promoters of genes that are important for cocaine-mediated cellular and behavioral plasticity. Genes with increased Egr3 binding to promoters, Camk2α, CREB, FosB, Nr4a2, and Sirt1, displayed increased mRNA in D1-MSNs and, in some cases, a reduction in D2-MSNs. Histone and the DNA methylation enzymes G9a and Dnmt3a displayed reduced Egr3 binding to their promoters and reduced mRNA in D1-MSNs. Our study provides novel insight into an opposing role of Egr3 in select NAc MSN subtypes in cocaine action. PMID:25995477

  8. Central and peripheral contributions to dynamic changes in nucleus accumbens glucose induced by intravenous cocaine

    PubMed Central

    Wakabayashi, Ken T.; Kiyatkin, Eugene A.

    2015-01-01

    The pattern of neural, physiological and behavioral effects induced by cocaine is consistent with metabolic neural activation, yet direct attempts to evaluate central metabolic effects of this drug have produced controversial results. Here, we used enzyme-based glucose sensors coupled with high-speed amperometry in freely moving rats to examine how intravenous cocaine at a behaviorally active dose affects extracellular glucose levels in the nucleus accumbens (NAc), a critical structure within the motivation-reinforcement circuit. In drug-naive rats, cocaine induced a bimodal increase in glucose, with the first, ultra-fast phasic rise appearing during the injection (latency 6–8 s; ~50 μM or ~5% of baseline) followed by a larger, more prolonged tonic elevation (~100 μM or 10% of baseline, peak ~15 min). While the rapid, phasic component of the glucose response remained stable following subsequent cocaine injections, the tonic component progressively decreased. Cocaine-methiodide, cocaine's peripherally acting analog, induced an equally rapid and strong initial glucose rise, indicating cocaine's action on peripheral neural substrates as its cause. However, this analog did not induce increases in either locomotion or tonic glucose, suggesting direct central mediation of these cocaine effects. Under systemic pharmacological blockade of dopamine transmission, both phasic and tonic components of the cocaine-induced glucose response were only slightly reduced, suggesting a significant role of non-dopamine mechanisms in cocaine-induced accumbal glucose influx. Hence, intravenous cocaine induces rapid, strong inflow of glucose into NAc extracellular space by involving both peripheral and central, non-dopamine drug actions, thus preventing a possible deficit resulting from enhanced glucose use by brain cells. PMID:25729349

  9. Dopaminergic Neurotransmission in the Nucleus Accumbens Modulates Social Play Behavior in Rats.

    PubMed

    Manduca, Antonia; Servadio, Michela; Damsteegt, Ruth; Campolongo, Patrizia; Vanderschuren, Louk Jmj; Trezza, Viviana

    2016-08-01

    Social play behavior is a highly rewarding form of social interaction displayed by young mammals. Social play is important for neurobehavioral development and it has been found to be impaired in several developmental psychiatric disorders. In line with the rewarding properties of social play, we have previously identified the nucleus accumbens (NAc) as an important site of action for endocannabinoid and opioid modulation of this behavior. NAc dopamine has a well-known role in certain components of reward processes, such as incentive motivation. However, its contribution to the positive emotional aspects of social interactions is less clear. Therefore, we investigated the role of dopaminergic neurotransmission in the NAc in social play behavior in rats. We found that intra-NAc infusion of the dopamine releaser/reuptake inhibitor amphetamine increased social play behavior that was dependent on activation of both D1 and D2 dopamine receptors. This increase in social play behavior was mimicked by intra-NAc infusion of the dopamine receptor agonist apomorphine, but not of the dopamine reuptake inhibitor GBR-12909. Blockade of either D1 or D2 NAc dopamine receptors reduced social play in animals highly motivated to play as a result of longer social isolation before testing. Last, blockade of NAc dopamine receptors prevented the play-enhancing effects of endocannabinoid and opioid receptor stimulation. These findings demonstrate an important modulatory role of NAc dopaminergic neurotransmission in social play. Thus, functional activity in the mesolimbic dopamine pathway plays an important role in adaptive social development, whereas abnormal NAc dopamine function may underlie the social impairments observed in developmental psychiatric disorders such as autism, attention deficit hyperactivity disorder or early-onset schizophrenia. PMID:26860202

  10. κ Opioid Receptors in the Nucleus Accumbens Shell Mediate Escalation of Methamphetamine Intake

    PubMed Central

    Schlosburg, Joel E.; Wee, Sunmee; Gould, Adam; George, Olivier; Grant, Yanabel; Zamora-Martinez, Eva R.; Edwards, Scott; Crawford, Elena; Vendruscolo, Leandro F.; Koob, George F.

    2015-01-01

    Given that the κ opioid receptor (KOR) system has been implicated in psychostimulant abuse, we evaluated whether the selective KOR antagonist norbinaltorphimine dihydrochloride (nor-BNI) would attenuate the escalation of methamphetamine (METH) intake in an extended-access self-administration model. Systemic nor-BNI decreased the escalation of intake of long-access (LgA) but not short-access (ShA) self-administration. nor-BNI also decreased elevated progressive-ratio (PR) breakpoints in rats in the LgA condition and continued to decrease intake after 17 d of abstinence, demonstrating that the effects of a nor-BNI injection are long lasting. Rats with an ShA history showed an increase in prodynorphin immunoreactivity in both the nucleus accumbens (NAc) core and shell, but LgA animals showed a selective increase in the NAc shell. Other cohorts of rats received nor-BNI directly into the NAc shell or core and entered into ShA or LgA. nor-BNI infusion in the NAc shell, but not NAc core, attenuated escalation of intake and PR responding for METH in LgA rats. These data indicate that the development and/or expression of compulsive-like responding for METH under LgA conditions depends on activation of the KOR system in the NAc shell and suggest that the dynorphin–KOR system is a central component of the neuroplasticity associated with negative reinforcement systems that drive the dark side of addiction. PMID:25762676

  11. κ Opioid receptors in the nucleus accumbens shell mediate escalation of methamphetamine intake.

    PubMed

    Whitfield, Timothy W; Schlosburg, Joel E; Wee, Sunmee; Gould, Adam; George, Olivier; Grant, Yanabel; Zamora-Martinez, Eva R; Edwards, Scott; Crawford, Elena; Vendruscolo, Leandro F; Koob, George F

    2015-03-11

    Given that the κ opioid receptor (KOR) system has been implicated in psychostimulant abuse, we evaluated whether the selective KOR antagonist norbinaltorphimine dihydrochloride (nor-BNI) would attenuate the escalation of methamphetamine (METH) intake in an extended-access self-administration model. Systemic nor-BNI decreased the escalation of intake of long-access (LgA) but not short-access (ShA) self-administration. nor-BNI also decreased elevated progressive-ratio (PR) breakpoints in rats in the LgA condition and continued to decrease intake after 17 d of abstinence, demonstrating that the effects of a nor-BNI injection are long lasting. Rats with an ShA history showed an increase in prodynorphin immunoreactivity in both the nucleus accumbens (NAc) core and shell, but LgA animals showed a selective increase in the NAc shell. Other cohorts of rats received nor-BNI directly into the NAc shell or core and entered into ShA or LgA. nor-BNI infusion in the NAc shell, but not NAc core, attenuated escalation of intake and PR responding for METH in LgA rats. These data indicate that the development and/or expression of compulsive-like responding for METH under LgA conditions depends on activation of the KOR system in the NAc shell and suggest that the dynorphin-KOR system is a central component of the neuroplasticity associated with negative reinforcement systems that drive the dark side of addiction. PMID:25762676

  12. Regulation of nucleus accumbens transcript levels in mice by early-life social stress and cocaine.

    PubMed

    Lo Iacono, Luisa; Valzania, Alessandro; Visco-Comandini, Federica; Viscomi, Maria Teresa; Felsani, Armando; Puglisi-Allegra, Stefano; Carola, Valeria

    2016-04-01

    Much interest has been piqued regarding the quality of one's environment at early ages in modulating the susceptibility to drug addiction in adulthood. However, the molecular mechanisms that are engaged during early trauma and mediate the risk for drug addiction are poorly understood. In rodents, exposure to early-life stress alters the rewarding effects of cocaine, amphetamine, and morphine in adulthood. Recently, we demonstrated that the exposure of juvenile mice to social threat (Social Stress, S-S) promoted cocaine-seeking behavior and relapse of cocaine-seeking after periods of withdrawal, compared with unhandled controls (UN) and with juvenile mice that experienced only daily isolation in a novel environment (no social stress, NS-S). Interestingly, while the exposure to NS-S slightly increased cocaine-seeking behavior compared with UN, the same was not sufficient to promote cocaine reinstatement. In this study, we examined the long-term transcriptional changes that are induced by S-S compared to NS-S and linked the increased susceptibility of S-S mice to cocaine reinstatement. To this end, we performed genome-wide RNA sequencing analysis in the nucleus accumbens (NAC), which revealed that 89 transcripts were differentially expressed between S-S and NS-S mice. By Gene Ontology classification, these hits were enriched in genes that mediate cell proliferation, neuronal differentiation, and neuron/forebrain development. Eleven of these genes have been reported to be involved in substance use disorders, and the remaining genes are novel candidates in this area. We characterized 4 candidates with regard to their significant neurobiological relevance (ZIC1, ZIC2, FABP7, and PRDM12) and measured their expression in the NAC by immunohistochemistry. These findings provide insights into novel molecular mechanisms in NAC that might be associated with the risk of relapse in cocaine-dependent individuals. PMID:26706499

  13. Gene expression changes in the nucleus accumbens of alcohol-preferring rats following chronic ethanol consumption

    PubMed Central

    Bell, Richard L.; Kimpel, Mark W.; McClintick, Jeanette N.; Strother, Wendy N.; Carr, Lucinda G.; Liang, Tiebing; Rodd, Zachary A.; Mayfield, R. Dayne; Edenberg, Howard J.; McBride, William J.

    2009-01-01

    The objective of this study was to determine the effects of binge-like alcohol drinking on gene expression changes in the nucleus accumbens (ACB) of alcohol-preferring (P) rats. Adult male P rats were given ethanol under multiple scheduled access (MSA; three 1-hr dark-cycle sessions/day) conditions for 8 weeks. For comparison purposes, a second ethanol drinking group was given continuous/daily alcohol access (CA; 24 hr/day). A third group was ethanol-naïve (W group). Average ethanol intakes for the CA and MSA groups were approximately 9.5 and 6.5 g/kg/day, respectively. Fifteen hr after the last drinking episode, rats were euthanized, the brains extracted, and the ACB dissected. RNA was extracted and purified for microarray analysis. The only significant differences were between the CA and W groups (p < 0.01; Storey false discovery rate = 0.15); there were 374 differences in named genes between these 2 groups. There were 20 significant Gene Ontology (GO) categories, which included negative regulation of protein kinase activity, anti-apoptosis, and regulation of G-protein-coupled receptor signaling. Ingenuity® analysis indicated a network of transcription factors, involving oncogenes (Fos, Jun, Junb had higher expression in the ACB of the CA group), suggesting increased neuronal activity. There were 43 genes located within rat QTLs for alcohol consumption and preference; 4 of these genes (Tgfa, Hspa5, Mtus1 and Creb3l2) are involved in anti-apoptosis and increased transcription, suggesting that they may be contributing to cellular protection and maintaining high alcohol intakes. Overall, these findings suggest that chronic CA drinking results in genomic changes that can be observed during the early acute phase of ethanol withdrawal. Conversely, chronic MSA drinking, with its associated protracted withdrawal periods, results in genomic changes that may be masked by tight regulation of these genes following repeated experiences of ethanol withdrawal. PMID:19666046

  14. Nucleus accumbens neuronal maturation differences in young rats bred for low versus high voluntary running behaviour.

    PubMed

    Roberts, Michael D; Toedebusch, Ryan G; Wells, Kevin D; Company, Joseph M; Brown, Jacob D; Cruthirds, Clayton L; Heese, Alexander J; Zhu, Conan; Rottinghaus, George E; Childs, Thomas E; Booth, Frank W

    2014-05-15

    We compared the nucleus accumbens (NAc) transcriptomes of generation 8 (G8), 34-day-old rats selectively bred for low (LVR) versus high voluntary running (HVR) behaviours in rats that never ran (LVR(non-run) and HVR(non-run)), as well as in rats after 6 days of voluntary wheel running (LVR(run) and HVR(run)). In addition, the NAc transcriptome of wild-type Wistar rats was compared. The purpose of this transcriptomics approach was to generate testable hypotheses as to possible NAc features that may be contributing to running motivation differences between lines. Ingenuity Pathway Analysis and Gene Ontology analyses suggested that 'cell cycle'-related transcripts and the running-induced plasticity of dopamine-related transcripts were lower in LVR versus HVR rats. From these data, a hypothesis was generated that LVR rats might have less NAc neuron maturation than HVR rats. Follow-up immunohistochemistry in G9-10 LVR(non-run) rats suggested that the LVR line inherently possessed fewer mature medium spiny (Darpp-32-positive) neurons (P < 0.001) and fewer immature (Dcx-positive) neurons (P < 0.001) than their G9-10 HVR counterparts. However, voluntary running wheel access in our G9-10 LVRs uniquely increased their Darpp-32-positive and Dcx-positive neuron densities. In summary, NAc cellularity differences and/or the lack of running-induced plasticity in dopamine signalling-related transcripts may contribute to low voluntary running motivation in LVR rats. PMID:24665095

  15. Plasticity of GABAA receptor-mediated neurotransmission in the nucleus accumbens of alcohol-dependent rats

    PubMed Central

    Liang, Jing; Lindemeyer, A. Kerstin; Suryanarayanan, Asha; Meyer, Edward M.; Marty, Vincent N.; Ahmad, S. Omar; Shao, Xuesi Max; Olsen, Richard W.

    2014-01-01

    Chronic alcohol exposure-induced changes in reinforcement mechanisms and motivational state are thought to contribute to the development of cravings and relapse during protracted withdrawal. The nucleus accumbens (NAcc) is a key structure of the mesolimbic dopaminergic reward system and plays an important role in mediating alcohol-seeking behaviors. Here we describe the long-lasting alterations of γ-aminobutyric acid type A receptors (GABAARs) of medium spiny neurons (MSNs) in the NAcc after chronic intermittent ethanol (CIE) treatment, a rat model of alcohol dependence. CIE treatment and withdrawal (>40 days) produced decreases in the ethanol and Ro15-4513 potentiation of extrasynaptic GABAARs, which mediate the picrotoxin-sensitive tonic current (Itonic), while potentiation of synaptic receptors, which give rise to miniature inhibitory postsynaptic currents (mIPSCs), was increased. Diazepam sensitivity of both Itonic and mIPSCs was decreased by CIE treatment. The average magnitude of Itonic was unchanged, but mIPSC amplitude and frequency decreased and mIPSC rise time increased after CIE treatment. Rise-time histograms revealed decreased frequency of fast-rising mIPSCs after CIE treatment, consistent with possible decreases in somatic GABAergic synapses in MSNs from CIE rats. However, unbiased stereological analysis of NeuN-stained NAcc neurons did not detect any decreases in NAcc volume, neuronal numbers, or neuronal cell body volume. Western blot analysis of surface subunit levels revealed selective decreases in α1 and δ and increases in α4, α5, and γ2 GABAAR subunits after CIE treatment and withdrawal. Similar, but reversible, alterations occurred after a single ethanol dose (5 g/kg). These data reveal CIE-induced long-lasting neuroadaptations in the NAcc GABAergic neurotransmission. PMID:24694935

  16. Distribution and compartmental organization of GABAergic medium-sized spiny neurons in the mouse nucleus accumbens

    PubMed Central

    Gangarossa, Giuseppe; Espallergues, Julie; de Kerchove d'Exaerde, Alban; El Mestikawy, Salah; Gerfen, Charles R.; Hervé, Denis; Girault, Jean-Antoine; Valjent, Emmanuel

    2012-01-01

    The nucleus accumbens (NAc) is a critical brain region involved in many reward-related behaviors. The NAc comprises major compartments the core and the shell, which encompass several subterritories. GABAergic medium-sized spiny neurons (MSNs) constitute the output neurons of the NAc core and shell. While the functional organization of the NAc core outputs resembles the one described for the dorsal striatum, a simple classification of the NAc shell neurons has been difficult to define due to the complexity of the compartmental segregation of cells. We used a variety of BAC transgenic mice expressing enhanced green fluorescence (EGFP) or the Cre-recombinase (Cre) under the control of the promoter of dopamine D1, D2, and D3 receptors and of adenosine A2a receptor to dissect the microanatomy of the NAc. Moreover, using various immunological markers we characterized in detail the distribution of MSNs in the mouse NAc. In addition, cell-type specific extracellular signal-regulated kinase (ERK) phosphorylation in the NAc subterritories was analyzed following acute administration of SKF81297 (a D1R-like agonist), quinpirole (a D2 receptors (D2R)-like agonist), apomorphine (a non-selective DA receptor agonist), raclopride (a D2R-like antagonist), and psychostimulant drugs, including cocaine and d-amphetamine. Each drug generated a unique topography and cell-type specific activation of ERK in the NAc. Our results show the existence of marked differences in the receptor expression pattern and functional activation of MSNs within the shell subterritories. This study emphasizes the anatomical and functional heterogeneity of the NAc, which will have to be considered in its further study. PMID:23423476

  17. Distribution and compartmental organization of GABAergic medium-sized spiny neurons in the mouse nucleus accumbens.

    PubMed

    Gangarossa, Giuseppe; Espallergues, Julie; de Kerchove d'Exaerde, Alban; El Mestikawy, Salah; Gerfen, Charles R; Hervé, Denis; Girault, Jean-Antoine; Valjent, Emmanuel

    2013-01-01

    The nucleus accumbens (NAc) is a critical brain region involved in many reward-related behaviors. The NAc comprises major compartments the core and the shell, which encompass several subterritories. GABAergic medium-sized spiny neurons (MSNs) constitute the output neurons of the NAc core and shell. While the functional organization of the NAc core outputs resembles the one described for the dorsal striatum, a simple classification of the NAc shell neurons has been difficult to define due to the complexity of the compartmental segregation of cells. We used a variety of BAC transgenic mice expressing enhanced green fluorescence (EGFP) or the Cre-recombinase (Cre) under the control of the promoter of dopamine D1, D2, and D3 receptors and of adenosine A2a receptor to dissect the microanatomy of the NAc. Moreover, using various immunological markers we characterized in detail the distribution of MSNs in the mouse NAc. In addition, cell-type specific extracellular signal-regulated kinase (ERK) phosphorylation in the NAc subterritories was analyzed following acute administration of SKF81297 (a D1R-like agonist), quinpirole (a D2 receptors (D2R)-like agonist), apomorphine (a non-selective DA receptor agonist), raclopride (a D2R-like antagonist), and psychostimulant drugs, including cocaine and d-amphetamine. Each drug generated a unique topography and cell-type specific activation of ERK in the NAc. Our results show the existence of marked differences in the receptor expression pattern and functional activation of MSNs within the shell subterritories. This study emphasizes the anatomical and functional heterogeneity of the NAc, which will have to be considered in its further study. PMID:23423476

  18. Nucleus accumbens cocaine-amphetamine regulated transcript mediates food intake during novelty conflict.

    PubMed

    Burghardt, P R; Krolewski, D M; Dykhuis, K E; Ching, J; Pinawin, A M; Britton, S L; Koch, L G; Watson, S J; Akil, H

    2016-05-01

    Obesity is a persistent and pervasive problem, particularly in industrialized nations. It has come to be appreciated that the metabolic health of an individual can influence brain function and subsequent behavioral patterns. To examine the relationship between metabolic phenotype and central systems that regulate behavior, we tested rats with divergent metabolic phenotypes (Low Capacity Runner: LCR vs. High Capacity Runner: HCR) for behavioral responses to the conflict between hunger and environmental novelty using the novelty suppressed feeding (NSF) paradigm. Additionally, we measured expression of mRNA, for peptides involved in energy management, in response to fasting. Following a 24-h fast, LCR rats showed lower latencies to begin eating in a novel environment compared to HCR rats. A 48-h fast equilibrated the latency to begin eating in the novel environment. A 24-h fast differentially affected expression of cocaine-amphetamine regulated transcript (CART) mRNA in the nucleus accumbens (NAc), where 24-h of fasting reduced CART mRNA in LCR rats. Bilateral microinjections of CART 55-102 peptide into the NAc increased the latency to begin eating in the NSF paradigm following a 24-h fast in LCR rats. These results indicate that metabolic phenotype influences how animals cope with the conflict between hunger and novelty, and that these differences are at least partially mediated by CART signaling in the NAc. For individuals with poor metabolic health who have to navigate food-rich and stressful environments, changes in central systems that mediate conflicting drives may feed into the rates of obesity and exacerbate the difficulty individuals have in maintaining weight loss. PMID:26926827

  19. Dysregulation of AMPA receptor transmission in the nucleus accumbens in animal models of cocaine addiction

    PubMed Central

    Wolf, Marina E.

    2014-01-01

    Plasticity of glutamate transmission in neuronal circuits involving the nucleus accumbens (NAc) is now recognized to play a critical role in cocaine addiction. NAc neurons are excited primarily by AMPA-type glutamate receptors (AMPAR) and this is required for cocaine seeking. This review will briefly describe AMPAR properties and trafficking, with a focus on studies in NAc neurons, and then consider mechanisms by which cocaine may alter AMPAR transmission. Two examples will be discussed that may be important in two different stages of addiction: learning about drugs and drug-related cues during the period of drug exposure, and persistent vulnerability to craving and relapse after abstinence is achieved. The first example is drawn from studies of cultured NAc neurons. Elevation of DA levels (as would occur following cocaine exposure) facilitates activity-dependent strengthening of excitatory synapses onto medium spiny neurons, the main cell type and projection neuron of the NAc. This occurs because activation of D1-class receptors primes AMPAR for synaptic insertion, creating a temporal window in which stimuli related to cocaine-taking are more efficacious at eliciting synaptic plasticity and thus being encoded into memory. The second example involves rat models of cocaine addiction. Cell surface and synaptic expression of AMPAR on NAc neurons is persistently increased after withdrawal from repeated cocaine exposure. We hypothesize that this increases the reactivity of NAc neurons to glutamate inputs from cortex and limbic structures, facilitating the ability of these inputs to trigger cocaine seeking and thus contributing to the persistent vulnerability to relapse that characterizes addiction. PMID:20361291

  20. Glucocorticoid receptor mediated the propofol self-administration by dopamine D1 receptor in nucleus accumbens.

    PubMed

    Wu, Binbin; Liang, Yuyuan; Dong, Zhanglei; Chen, Zhichuan; Zhang, Gaolong; Lin, Wenxuan; Wang, Sicong; Wang, Benfu; Ge, Ren-Shan; Lian, Qingquan

    2016-07-22

    Propofol, a widely used anesthetic, can cause addictive behaviors in both human and experimental animals. In the present study, we examined the involvement of glucocorticoid receptor (GR) signaling in the molecular process by which propofol may cause addiction. The propofol self-administration model was established by a fixed ratio 1 (FR1) schedule of reinforced dosing over successive 14days in rats. On day 15, the rats were treated with dexamethasone, a GR agonist (10-100μg/kg), or RU486, a GR antagonist (10-100μg/kg) at 1h prior to the last training. The animal behaviors were recorded automatically by the computer. The expression of dopamine D1 receptor in the nucleus accumbens (NAc) was examined by Western blot and the concentrations of plasma corticosterone were measured by enzyme-linked immunosorbent assay (ELISA). To further examine the specificity of GR in the process, mineralocorticoid receptor (MR) antagonist, spironolactone, and dexamethasone plus MR agonist, aldosterone, were also tested. Administration of dexamethasone (100μg/kg) or RU486 (⩾10mg/kg) significantly attenuated the rate of propofol maintained active nose-poke responses and infusions, which were accompanied by reductions in both plasma corticosterone level and the expression of D1 receptor in the NAc. Neither spironolactone alone nor dexamethasone combined with aldosterone affected the propofol-maintaining self-administrative behavior, indicating GR, but not MR, modulates the propofol reward in rats. In addition, neither the food-maintaining sucrose responses under FR1 schedule nor the locomotor activity was affected by any doses of dexamethasone or RU486 tested. These findings provide evidence that GR signaling may play an important role in propofol reward. PMID:27126557

  1. Oscillatory Activity in the Medial Prefrontal Cortex and Nucleus Accumbens Correlates with Impulsivity and Reward Outcome

    PubMed Central

    Rich, P. Dylan; Nevado-Holgado, Alejo J.; Fernando, Anushka B. P.; Van Dijck, Gert; Holzhammer, Tobias; Paul, Oliver; Ruther, Patrick; Paulsen, Ole; Robbins, Trevor W.; Dalley, Jeffrey W.

    2014-01-01

    Actions expressed prematurely without regard for their consequences are considered impulsive. Such behaviour is governed by a network of brain regions including the prefrontal cortex (PFC) and nucleus accumbens (NAcb) and is prevalent in disorders including attention deficit hyperactivity disorder (ADHD) and drug addiction. However, little is known of the relationship between neural activity in these regions and specific forms of impulsive behaviour. In the present study we investigated local field potential (LFP) oscillations in distinct sub-regions of the PFC and NAcb on a 5-choice serial reaction time task (5-CSRTT), which measures sustained, spatially-divided visual attention and action restraint. The main findings show that power in gamma frequency (50–60 Hz) LFP oscillations transiently increases in the PFC and NAcb during both the anticipation of a cue signalling the spatial location of a nose-poke response and again following correct responses. Gamma oscillations were coupled to low-frequency delta oscillations in both regions; this coupling strengthened specifically when an error response was made. Theta (7–9 Hz) LFP power in the PFC and NAcb increased during the waiting period and was also related to response outcome. Additionally, both gamma and theta power were significantly affected by upcoming premature responses as rats waited for the visual cue to respond. In a subgroup of rats showing persistently high levels of impulsivity we found that impulsivity was associated with increased error signals following a nose-poke response, as well as reduced signals of previous trial outcome during the waiting period. Collectively, these in-vivo neurophysiological findings further implicate the PFC and NAcb in anticipatory impulsive responses and provide evidence that abnormalities in the encoding of rewarding outcomes may underlie trait-like impulsive behaviour. PMID:25333512

  2. CRF receptors in the nucleus accumbens modulate partner preference in prairie voles

    PubMed Central

    Lim, Miranda M.; Liu, Yan; Ryabinin, Andrey E.; Bai, Yaohui; Wang, Zuoxin; Young, Larry J.

    2007-01-01

    Recent evidence suggests a role for corticotropin-releasing factor (CRF) in the regulation of pair bonding in prairie voles. We have previously shown that monogamous and non-monogamous vole species have dramatically different distributions of CRF receptor type 1 (CRF1) and CRF receptor type 2 (CRF2) in the brain, and that CRF1 and CRF2 receptor densities in the nucleus accumbens (NAcc) are correlated with social organization. Monogamous prairie and pine voles have significantly lower levels of CRF receptor type 1 (CRF1), and significantly higher levels of type 2 (CRF2) binding, in NAcc than non-monogamous meadow and montane voles. Here, we report that microinjections of CRF directly into the NAcc accelerate partner preference formation in male prairie voles. Control injections of CSF into NAcc, and CRF into caudate-putamen, did not facilitate partner preference. Likewise, CRF injections into NAcc of non-monogamous meadow voles also did not facilitate partner preference. In prairie voles, this CRF-facilitation effect was blocked by co-injection of either CRF1 or CRF2 receptor antagonists into NAcc. Immunocytochemical staining for CRF and Urocortin-1 (Ucn-1), two endogenous ligands for CRF1 or CRF2 receptors in the brain, revealed that CRF, but not Ucn-1, immunoreactive fibers were present in NAcc. This supports the hypothesis that local CRF release into NAcc could activate CRF1 or CRF2 receptors in the region. Taken together, our results reveal a novel role for accumbal CRF systems in social behavior. PMID:17320879

  3. Metabotropic Glutamate Receptor 5 within Nucleus Accumbens Shell modulates environment-elicited cocaine conditioning expression

    PubMed Central

    Martínez-Rivera, Arlene; Rodríguez-Borrero, Enrique; Matías-Alemán, Maria; Montalvo-Acevedo, Alexandra; Guerrero-Figuereo, Kathleen; Febo-Rodriguez, Liz. J; Morales-Rivera, Amarilys; Maldonado-Vlaar, Carmen S.

    2014-01-01

    The metabotropic glutamate receptors 5 (mGluRs5) within the Nucleus Accumbens (NAc) have been implicated in the modulation of psychostimulant reward. We hypothesized that blockade of mGluR5 within the NAc shell would impair cocaine conditioning in rats. For this study, animals were implanted with cannulae within the NAc shell, and separate groups were exposed to a multimodal environment within activity chambers that signaled cocaine (cocaine-paired) or saline (controls, cocaine-unpaired) injections. Prior to placing the animals in the chambers, rats received systemic intraperitoneal injections of saline or cocaine for 10 consecutive sessions. In the test session (D12), animals were exposed to the multimodal environment without any cocaine or saline pre-treatment. Before placing the rats in the chambers, separate groups of animals were infused within the NAc shell with 2.5, 12 or 25nmol/0.5μl/side of 2-methyl-6- (phenylethynyl) pyridine (MPEP), an antagonist of mGluR5 or with vehicle. Blockade of the mGluR5 subtype at a 2.5nmol dose showed no significant difference in either the ambulatory distance (AD) or the vertical plane move time (VPT). In contrast, mGluR5 blockade at 12nmol and 25nmol decreased conditioned locomotion in the cocaine-paired groups. An association of the environmental cues with the effects of cocaine implies the involvement of memory process during the conditioning response. Our results suggest that mGluR5 within the NAc shell could be modulating the expression of memory related to the association of environmental cues with the effects of cocaine. We suggest that mGluR5 could be taking into account to further studies related with cocaine exposure and cocaine addiction treatments. PMID:23850523

  4. Differential neuronal changes in medial prefrontal cortex, basolateral amygdala and nucleus accumbens after postweaning social isolation.

    PubMed

    Wang, Yu-Chun; Ho, Ue-Cheung; Ko, Meng-Ching; Liao, Chun-Chieh; Lee, Li-Jen

    2012-04-01

    The mesocorticolimbic system contains dopamine (DA)-producing neurons in the ventral tegmental area (VTA) and their projection targets, including the medial prefrontal cortex (mPFC), amygdala (AMY) and nucleus accumbens (NAc). Disruption of this system might attribute to mental illnesses. In the present study, we adopted the postweaning social isolation paradigm to model neuropsychiatric disorders and studied the functional and structural changes of the mesocorticolimbic system. After 8-9 weeks of isolation, rats exhibited hyperlocomotor activity and impaired sensorimotor gating compared to group-reared controls. However, the number of tyrosine hydroxylase-positive VTA neurons and the volume of VTA were not affected. Comparing with group-reared controls, the DA levels in the isolation-reared were not altered in the VTA, mPFC and NAc but decreased in the AMY. In the structural aspect, dendritic features of layer II/III pyramidal mPFC neurons; pyramidal neurons in the basolateral nucleus of amygdala (BLA) and medium spiny neurons in the core region of the NAc (NAcc) were examined. Interestingly, the neuronal changes were region-specific. The mPFC neurons had reduced dendritic complexity, spine density and elongated terminal branches. The BLA neurons had extensive dendritic arbors with short branches but unchanged spine density. The NAcc neurons had reduced total dendritic length but the segment length and spine density remained the same. Together, the results demonstrated the structural and functional changes in the mesocorticolimbic DA system of socially isolated rats. These changes may account for the behavioral impairments in these rats and attribute to the susceptibility to mental disorders related to schizophrenia and depression. PMID:22002740

  5. Nucleus accumbens responses differentiate execution and restraint in reward-directed behavior

    PubMed Central

    Loriaux, Amy L.

    2013-01-01

    Our behavior is powerfully driven by environmental cues that signal the availability of rewarding stimuli. We frequently encounter stimuli—a bowl of candy or an alert from our smartphone—that trigger actions to obtain those rewards, even though there may be positive outcomes associated with not acting. The inability to restrain one's action in the presence of reward-associated cues is one type of impulsive behavior and a component of such maladaptive behaviors as overeating, gambling, and substance abuse. The nucleus accumbens (NAc) is ideally situated to integrate multiple cognitive and affective inputs to bias action via outputs through the basal ganglia. NAc neurons have been shown to respond to cues that predict reward availability, goal-directed behaviors aimed at obtaining them, and delivery of the reward itself. As these processes are typically associated, it is difficult to discern whether signals in the NAc are more closely related to processing reward-predictive aspects of goal-directed behavior or selection of behavioral response. To dissociate these possibilities, we recorded the activity of NAc neurons while rats performed a task in which two different cues both informed rats of reward availability but required them to either press a lever (Go) or withhold pressing (NoGo) to obtain the reward. Individual cue-responsive neurons showed either increases or decreases in activity at cue onset. Increases in activity were larger, and decreases smaller, when rats withheld lever pressing, whether correctly for NoGo trials or in error on Go trials. Thus NAc cue responses correlated with action, regardless of cue type or accuracy. PMID:24174652

  6. Endocannabinoids in amygdala and nucleus accumbens mediate social play reward in adolescent rats

    PubMed Central

    Trezza, Viviana; Damsteegt, Ruth; Manduca, Antonia; Petrosino, Stefania; Van Kerkhof, Linda W.M.; Pasterkamp, R. Jeroen; Zhou, Yeping; Campolongo, Patrizia; Cuomo, Vincenzo; Di Marzo, Vincenzo; Vanderschuren, Louk J.M.J.

    2012-01-01

    The brain endocannabinoid system plays a crucial role in emotional processes. We have previously identified an important role for endocannabinoids in social play behavior, a highly rewarding form of social interaction in adolescent rats. Here, we tested the hypothesis that endocannabinoid modulation of social play behavior occurs in brain regions implicated in emotion and motivation. Social play increased levels of the endocannabinoid anandamide in the amygdala and nucleus accumbens (NAc), but not in prefrontal cortex or hippocampus of 4–5 week old male Wistar rats. Furthermore, social play increased phosphorylation of CB1 cannabinoid receptors in the amygdala. Systemic administration of the anandamide hydrolysis inhibitor URB597 increased social play behavior, and augmented the associated elevation in anandamide levels in the amygdala, but not the NAc. Infusion of URB597 into the basolateral amygdala (BLA) increased social play behavior, and blockade of BLA CB1 cannabinoid receptors with the antagonist/inverse agonist SR141716A prevented the play-enhancing effects of systemic administration of URB597. Infusion of URB597 into the NAc also increased social play, but blockade of NAc CB1 cannabinoid receptors did not antagonize the play-enhancing effects of systemic URB597 treatment. Last, SR141716A did not affect social play after infusion into the core and shell subregions of the NAc, while it reduced social play when infused into the BLA. These data show that increased anandamide signalling in the amygdala and NAc augments social play, and identify the BLA as a prominent site of action for endocannabinoids to modulate the rewarding properties of social interactions in adolescent rats. PMID:23100412

  7. Neonatal Masculinization Blocks Increased Excitatory Synaptic Input in Female Rat Nucleus Accumbens Core.

    PubMed

    Cao, Jinyan; Dorris, David M; Meitzen, John

    2016-08-01

    Steroid sex hormones and genetic sex regulate the phenotypes of motivated behaviors and relevant disorders. Most studies seeking to elucidate the underlying neuroendocrine mechanisms have focused on how 17β-estradiol modulates the role of dopamine in striatal brain regions, which express membrane-associated estrogen receptors. Dopamine action is an important component of striatal function, but excitatory synaptic neurotransmission has also emerged as a key striatal substrate and target of estradiol action. Here, we focus on excitatory synaptic input onto medium spiny neurons (MSNs) in the striatal region nucleus accumbens core (AcbC). In adult AcbC, miniature excitatory postsynaptic current (mEPSC) frequency is increased in female compared with male MSNs. We tested whether increased mEPSC frequency in female MSNs exists before puberty, whether this increased excitability is due to the absence of estradiol or testosterone during the early developmental critical period, and whether it is accompanied by stable neuron intrinsic membrane properties. We found that mEPSC frequency is increased in female compared with male MSNs before puberty. Increased mEPSC frequency in female MSNs is abolished after neonatal estradiol or testosterone exposure. MSN intrinsic membrane properties did not differ by sex. These data indicate that neonatal masculinization via estradiol and/or testosterone action is sufficient for down-regulating excitatory synaptic input onto MSNs. We conclude that excitatory synaptic input onto AcbC MSNs is organized long before adulthood via steroid sex hormone action, providing new insight into a mechanism by which sex differences in motivated behavior and other AbcC functions may be generated or compromised. PMID:27285859

  8. mGluR5 stimulates gliotransmission in the nucleus accumbens

    PubMed Central

    D'Ascenzo, Marcello; Fellin, Tommaso; Terunuma, Miho; Revilla-Sanchez, Raquel; Meaney, David F.; Auberson, Yves P.; Moss, Stephen J.; Haydon, Philip G.

    2007-01-01

    Although metabotropic glutamate receptor 5 (mGluR5) is essential for cocaine self-administration and drug-seeking behavior, there is limited knowledge of the cellular actions of this receptor in the nucleus accumbens (NAc). Although mGluR5 has the potential to regulate neurons directly, recent studies have shown the importance of mGluR5 in regulating Ca2+ signaling in astrocytes and, as a consequence, the Ca2+-dependent release of excitatory transmitters from these glia. In this study, we demonstrate that activation of mGluR5 induces Ca2+ oscillations in NAc astrocytes with the correlated appearance of NMDA receptor-dependent slow inward currents detected in medium spiny neurons (MSNs). Photolysis of caged Ca2+ loaded specifically into astrocytes evoked slow inward currents demonstrating that Ca2+ elevations in astrocytes are responsible for these excitatory events. Pharmacological evaluation of these glial-evoked NMDA currents shows that they are mediated by NR2B-containing NMDA receptors, whereas synaptic NMDA receptors rely on NR2A-containing receptors. Stimulation of glutamatergic afferents activates mGluR5-dependent astrocytic Ca2+ oscillations and gliotransmission that is sustained for minutes beyond the initial stimulus. Because gliotransmission is mediated by NMDA receptors, depolarized membrane potentials exhibited during up-states augment excitation provided by gliotransmission, which drives bursts of MSN action potentials. Because the predominant mGluR5-dependent action of glutamatergic afferents is to cause the sustained activation of astrocytes, which in turn excite MSNs through extrasynaptic NMDA receptors, our results raise the potential for gliotransmission being involved in prolonged mGluR5-dependent adaptation in the NAc. PMID:17259307

  9. Cocaine-Induced Synaptic Alterations in Thalamus to Nucleus Accumbens Projection.

    PubMed

    Neumann, Peter A; Wang, Yicun; Yan, Yijin; Wang, Yao; Ishikawa, Masago; Cui, Ranji; Huang, Yanhua H; Sesack, Susan R; Schlüter, Oliver M; Dong, Yan

    2016-08-01

    Exposure to cocaine induces addiction-associated behaviors partially through remodeling neurocircuits in the nucleus accumbens (NAc). The paraventricular nucleus of thalamus (PVT), which projects to the NAc monosynaptically, is activated by cocaine exposure and has been implicated in several cocaine-induced emotional and motivational states. Here we show that disrupting synaptic transmission of select PVT neurons with tetanus toxin activated via retrograde trans-synaptic transport of cre from NAc efferents decreased cocaine self-administration in rats. This projection underwent complex adaptations after self-administration of cocaine (0.75 mg/kg/infusion; 2 h/d × 5 d, 1d overnight training). Specifically, 1d after cocaine self-administration, we observed increased levels of AMPA receptor (AMPAR)-silent glutamatergic synapses in this projection, accompanied by a decreased ratio of AMPAR-to-NMDA receptor (NMDAR)-mediated EPSCs. Furthermore, the decay kinetics of NMDAR EPSCs was significantly prolonged, suggesting insertion of new GluN2B-containing NMDARs to PVT-to-NAc synapses. After 45-d withdrawal, silent synapses within this projection returned to the basal levels, accompanied by a return of the AMPAR/NMDAR ratio and NMDAR decay kinetics to the basal levels. In amygdala and infralimbic prefrontal cortical projections to the NAc, a portion of cocaine-generated silent synapses becomes unsilenced by recruiting calcium-permeable AMPARs (CP-AMPARs) after drug withdrawal. However, the sensitivity of PVT-to-NAc synapses to CP-AMPAR-selective antagonists was not changed after withdrawal, suggesting that CP-AMPAR trafficking is not involved in the evolution of cocaine-generated silent synapses within this projection. Meanwhile, the release probability of PVT-to-NAc synapses was increased after short- and long-term cocaine withdrawal. These results reveal complex and profound alterations at PVT-to-NAc synapses after cocaine exposure and withdrawal. PMID:27074816

  10. Glutamate release in the nucleus accumbens core is necessary for heroin seeking.

    PubMed

    LaLumiere, Ryan T; Kalivas, Peter W

    2008-03-19

    Long-term changes in glutamate transmission in the nucleus accumbens core (NAcore) contribute to the reinstatement of drug seeking after extinction of cocaine self-administration. Whether similar adaptations in glutamate transmission occur during heroin and cue-induced reinstatement of heroin seeking is unknown. After 2 weeks of heroin self-administration and 2 weeks of subsequent extinction training, heroin seeking was induced by a noncontingent injection of heroin or by presentation of light/tone cues previously paired with heroin infusions. Microdialysis was conducted in the NAcore during reinstatement of heroin seeking in animals extinguished from heroin self-administration or in subjects receiving parallel (yoked) noncontingent saline or heroin. Reinstatement by either heroin or cue increased extracellular glutamate in the NAcore in the self-administration group, but no increase was elicited during heroin-induced reinstatement in the yoked control groups. The increase in glutamate during heroin-induced drug seeking was abolished by inhibiting synaptic transmission in the NAcore with tetrodotoxin or by inhibiting glutamatergic afferents to the NAcore from the prelimbic cortex. Supporting critical involvement of glutamate release, heroin seeking induced by cue or heroin was blocked by inhibiting AMPA/kainate glutamate receptors in the NAcore. Interestingly, although a heroin-priming injection increased dopamine equally in animals trained to self-administer heroin and in yoked-saline subjects, inhibition of dopamine receptors in the NAcore also blocked heroin- and cue-induced drug seeking. Together, these findings show that recruitment of the glutamatergic projection from the prelimbic cortex to NAcore is necessary to initiate the reinstatement of heroin seeking. PMID:18354020

  11. Resting-State Functional Connectivity of the Nucleus Accumbens in Auditory and Visual Hallucinations in Schizophrenia

    PubMed Central

    Rolland, Benjamin; Amad, Ali; Poulet, Emmanuel; Bordet, Régis; Vignaud, Alexandre; Bation, Rémy; Delmaire, Christine; Thomas, Pierre; Cottencin, Olivier; Jardri, Renaud

    2015-01-01

    Both auditory hallucinations (AH) and visual hallucinations may occur in schizophrenia. One of the main hypotheses underlying their occurrence involves the increased activity of the mesolimbic pathway, which links the ventral tegmental area (VTA) and the nucleus accumbens (NAcc). However, the precise contribution of the mesolimbic pathway in hallucinations across various sensory modalities has not yet been explored. We compared the resting-state functional connectivity (rs-FC) of the NAcc among 16 schizophrenia patients with pure AH, 15 with both visuoauditory hallucinations (VAH), and 14 without hallucinations (NoH). A between-group comparison was performed using random-effects ANCOVA (rs-FC of the bilateral NAcc as the dependent variable, groups as the between-subjects factor, age and Positive and Negative Syndrome Scale scores as covariates; q(false discovery rate [FDR]) < .05). Compared to the NoH group, the AH group exhibited significantly enhanced NAcc rs-FC with the left temporal superior gyrus, the cingulate gyri, and the VTA, whereas the VAH group, compared to the AH group, exhibited significantly enhanced NAcc rs-FC with the bilateral insula, putamen, parahippocampal gyri, and VTA. The strength in rs-FC between the NAcc and the VTA appeared to be positively associated with the presence of hallucinations, but the NAcc FC patterns changed with the complexity of these experiences (ie, 0, 1, or 2 sensory modalities), rather than with severity. This might support the aberrant salience hypothesis of schizophrenia. Moreover, these findings suggest that future clinical and neurobiological studies of hallucinations should evaluate not only the global severity of symptoms but also their sensorial features. PMID:25053649

  12. NMR-based metabonomic in hippocampus, nucleus accumbens and prefrontal cortex of methamphetamine-sensitized rats.

    PubMed

    Bu, Qian; Lv, Lei; Yan, Guangyan; Deng, Pengchi; Wang, Yanli; Zhou, Jiaqing; Yang, Yanzhu; Li, Yan; Cen, Xiaobo

    2013-05-01

    (1)H NMR spectroscopy was applied to investigate the changes of cerebral metabolites in brain hippocampus, nucleus accumbens (NAC) and prefrontal cortex (PFC) of the rats subjected to subcutaneous twice-daily injections of 2.5mg/kg methamphetamine (MAP) for 7 days. The results indicated that MAP exposure induced significant behavioral sensitization and altered cerebral metabolites in rats. The neurotransmitters glutamate, glutamine and GABA significantly decreased in hippocampus, NAC and PFC. Specifically, increased succinic acid semialdehyde, a metabolism product of GABA, was observed in hippocampus. Additionally, decreased serotonin was observed in both NAC and PFC, whereas decreased dopamine was only observed in NAC after repeated MAP treatment. Glutathione obviously decreased in above brain regions, whereas acetylcysteine declined in hippocampus and NAC, and taurine declined in NAC and PFC. Homocysteic acid was elevated in hippocampus and NAC by repeated MAP administration. Membrane ingredients like phosphocholine elevated in response to MAP administration in NAC and PFC. N-Acetyl-aspartate, a marker of neuronal viability, decreased in the three regions; however, myo-inositol, a glial cell marker, increased in hippocampus and PFC. Tricarboxylic acid cycle intermediate products, such as α-ketoglutarate, succinate, citrate and the methionine significantly decreased in above three brain regions after MAP administration; however, ADP decreased in hippocampus. These results indicate that repeated MAP treatment causes neurotransmitters disturbance, imbalance between oxidative stress and antioxidants, and gliosis in hippocampus, NAC and PFC. Profound metabolic changes detected across brain regions provide the first evidence of metabonomic changes in MAP-induced sensitized rats. PMID:23462569

  13. Neuropeptide Y Activity in the Nucleus Accumbens Modulates Feeding Behavior and Neuronal Activity

    PubMed Central

    van den Heuvel, José K.; Furman, Kara; Gumbs, Myrtille C.R.; Eggels, Leslie; Opland, Darren M.; Land, Benjamin B.; Kolk, Sharon M.; Narayanan, Nandakumar; Fliers, Eric; Kalsbeek, Andries; DiLeone, Ralph J.; la Fleur, Susanne E.

    2014-01-01

    Background Neuropeptide Y (NPY) is a hypothalamic neuropeptide that plays a prominent role in feeding and energy homeostasis. Expression of the NPY Y1 receptor (Y1R) is highly concentrated in the nucleus accumbens (Acb), a region important in the regulation of palatable feeding. In this study, we performed a number of experiments to investigate the actions of NPY in the Acb. Methods First, we determined caloric intake and food choice after bilateral administration of NPY in the Acb in rats on a free-choice diet of saturated fat, 30% sucrose solution, and standard chow and whether this was mediated by the Y1R. Second, we measured the effect of intra-Acb NPY on neuronal activity using in vivo electrophysiology. Third, we examined co-localization of Y1R with enkephalin and dynorphin neurons and the effect of NPY on preproenkephalin messenger RNA levels in the striatum using fluorescent and radioactive in situ hybridization. Finally, using retrograde tracing, we examined whether NPY neurons in the arcuate nucleus projected to the Acb. Results In rats on the free-choice, high-fat, high-sugar diet, intra-Acb NPY increased intake of fat, but not sugar or chow, and this was mediated by the Y1R. Intra-Acb NPY reduced neuronal firing, as well as preproenkephalin messenger RNA expression in the striatum. Moreover, Acb enkephalin neurons expressed Y1R and arcuate nucleus NPY neurons projected to the Acb. Conclusions NPY reduces neuronal firing in the Acb resulting in increased palatable food intake. Together, our neuroanatomical, pharmacologic, and neuronal activity data support a role and mechanism for intra-Acb NPY-induced fat intake. PMID:25109664

  14. From ventral-medial to dorsal-lateral striatum: neural correlates of reward-guided decision-making.

    PubMed

    Burton, Amanda C; Nakamura, Kae; Roesch, Matthew R

    2015-01-01

    The striatum is critical for reward-guided and habitual behavior. Anatomical and interference studies suggest a functional heterogeneity within striatum. Medial regions, such as nucleus accumbens core and dorsal medial striatum play roles in goal-directed behavior, while dorsal lateral striatum is critical for control of habitual action. Subdivisions of striatum are topographically connected with different cortical and subcortical structures forming channels that carry information related to limbic, associative, and sensorimotor functions. Here, we describe data showing that as one progresses from ventral-medial to dorsal-lateral striatum, there is a shift from more prominent value encoding to activity more closely related to associative and motor aspects of decision-making. In addition, we will describe data suggesting that striatal circuits work in parallel to control behavior and that regions within striatum can compensate for each other when functions are disrupted. PMID:24858182

  15. From ventral-medial to dorsal-lateral striatum: Neural correlates of reward-guided decision-making

    PubMed Central

    Burton, Amanda C.; Nakamura, Kae; Roesch, Matthew R.

    2014-01-01

    The striatum is critical for reward-guided and habitual behavior. Anatomical and interference studies suggest a functional heterogeneity within striatum. Medial regions, such as nucleus accumbens core and dorsal medial striatum play roles in goal-directed behavior, while dorsal lateral striatum is critical for control of habitual action. Subdivisions of striatum are topographically connected with different cortical and subcortical structures forming channels that carry information related to limbic, associative, and sensorimotor functions. Here, we describe data showing that as one progresses from ventral-medial to dorsal-lateral striatum, there is a shift from more prominent value encoding to activity more closely related to associative and motor aspects of decision-making. In addition, we will describe data suggesting that striatal circuits work in parallel to control behavior and that regions within striatum can compensate for each other when functions are disrupted. PMID:24858182

  16. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

    PubMed

    Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A

    2016-06-01

    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

  17. Prenatal cocaine alters dopamine and sigma receptor binding in nucleus accumbens and striatum in dams and adolescent offspring.

    PubMed

    Silvers, J M; Wallace, D R; Harrod, S B; Mactutus, C F; Booze, R M

    2006-01-01

    Maternal cocaine abuse is a societal problem with serious impact on both mother and child. Few studies exist that study the mother/offspring dyad of neurological effects of maternal cocaine abuse. The present study was designed to study alterations in D2, D3 and sigma receptor density in nucleus accumbens and striatum of dams and male and female offspring following gestational cocaine. Long-Evans female rats were implanted with an intravenous (i.v.) access port prior to breeding and were administered saline or 3.0 mg/kg of cocaine from gestational day (GD) GD8-20 (1 injection/day-GD8-14, 2 injections/day-GD15-20). Offspring were raised by maternal dams and allowed to mature until postnatal days 31-35, at which time dams and offspring were sacrificed for assay of radioligand binding. In dams, decreased D2 (24.6%) and D3 (36.9%) binding was observed in striatum. Female offspring displayed no differences in receptor binding in either region. Male offspring displayed decreased D2 receptor binding (27.1%) in nucleus accumbens and increased D3 (75.2% and 33.5%) and sigma receptor binding (73.4% and 53.1%) in accumbens and striatum, respectively. Collectively, these data clearly demonstrate that male offspring exhibit significant alterations in D2, D3 and sigma receptor binding. These results suggest that dams and offspring display long-lasting alterations (5 weeks) in dopamine receptor binding. These alterations in dopamine and sigma receptor binding in offspring following prenatal cocaine and rearing by maternal dams are sex specific and could have profound effects on the development of behavior. PMID:16529908

  18. Nucleus accumbens core dopamine signaling tracks the need-based motivational value of food-paired cues.

    PubMed

    Aitken, Tara J; Greenfield, Venuz Y; Wassum, Kate M

    2016-03-01

    Environmental reward-predictive stimuli provide a major source of motivation for instrumental reward-seeking activity and this has been linked to dopamine signaling in the nucleus accumbens (NAc) core. This cue-induced incentive motivation can be quite general, not restricted to instrumental actions that earn the same unique reward, and is also typically regulated by one's current need state, such that cues only motivate actions when this is adaptive. But it remains unknown whether cue-evoked dopamine signaling is similarly regulated by need state. Here, we used fast-scan cyclic voltammetry to monitor dopamine concentration changes in the NAc core of rats during a Pavlovian-to-instrumental transfer task in which the motivating influence of two cues, each signaling a distinct food reward (sucrose or food pellets), over an action earning a third unique food reward (polycose) was assessed in a state of hunger and of satiety. Both cues elicited a robust NAc dopamine response when hungry. The magnitude of the sucrose cue-evoked dopamine response correlated with the Pavlovian-to-instrumental transfer effect that was selectively induced by this stimulus. Satiety attenuated these cue-evoked dopamine responses and behavioral responding, even though rats had never experienced the specific food rewards in this state. These data demonstrate that cue-evoked NAc core responses are sensitive to current need state, one critical variable that determines the current adaptive utility of cue-motivated behavior. Food-predictive stimuli motivate food-seeking behavior. Here, we show that food cues evoke a robust nucleus accumbens core dopamine response when hungry that correlates with the cue's ability to invigorate general food seeking. This response is attenuated when sated, demonstrating that food cue-evoked accumbens dopamine responses are sensitive to the need state information that determines the current adaptive utility of cue-motivated action. PMID:26715366

  19. Stimulated dopamine overflow and alpha-synuclein expression in the nucleus accumbens core distinguish rats bred for differential ethanol preference.

    PubMed

    Pelkonen, Anssi; Hiltunen, Mikko; Kiianmaa, Kalervo; Yavich, Leonid

    2010-08-01

    The key neurochemical systems and structures involved in the predisposition to substance abuse and preference to ethanol (EtOH) are not known in detail but clearly dopamine (DA) is an important modulator of addiction. Recent data indicate that alpha-synuclein (alpha-syn), a pre-synaptic protein, plays a role in regulation of DA release from the pre-synaptic terminals in striatum and the expression of this protein is different after drug abuse or following abstinence. In the present work, we analysed stimulated DA overflow in the dorsal and ventral striatum in EtOH naïve alko alchohol (AA) and alko non-alchohol (ANA) rats selected for more than 100 generations for their differential EtOH preference. In the same structures, we studied the expression of alpha-syn using western blotting. AA rats, in comparison with ANA rats, showed a marked reduction of stimulated peak DA overflow and higher levels of alpha-syn in the nucleus accumbens core. In the same structure, DA re-uptake was increased in AA rats in comparison with ANA rats. The effects of EtOH at low (0.1 g/kg) and higher (3 mg/kg) doses on DA overflow measured in the nucleus accumbens shell were similar in both lines. These results indicate that high expression of alpha-syn may contribute to the reduced DA overflow and the possible activation of re-uptake in the nucleus accumbens core of AA rats in comparison with ANA rats. PMID:20533994

  20. Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine.

    PubMed

    Dobbs, Lauren K; Kaplan, Alanna R; Lemos, Julia C; Matsui, Aya; Rubinstein, Marcelo; Alvarez, Veronica A

    2016-06-01

    Striatal medium spiny neurons (MSNs) form inhibitory synapses on neighboring striatal neurons through axon collaterals. The functional relevance of this lateral inhibition and its regulation by dopamine remains elusive. We show that synchronized stimulation of collateral transmission from multiple indirect-pathway MSNs (iMSNs) potently inhibits action potentials in direct-pathway MSNs (dMSNs) in the nucleus accumbens. Dopamine D2 receptors (D2Rs) suppress lateral inhibition from iMSNs to disinhibit dMSNs, which are known to facilitate locomotion. Surprisingly, D2R inhibition of synaptic transmission was larger at axon collaterals from iMSNs than their projections to the ventral pallidum. Targeted deletion of D2Rs from iMSNs impaired cocaine's ability to suppress lateral inhibition and increase locomotion. These impairments were rescued by chemogenetic activation of Gi-signaling in iMSNs. These findings shed light on the functional significance of lateral inhibition between MSNs and offer a novel synaptic mechanism by which dopamine gates locomotion and cocaine exerts its canonical stimulant response. VIDEO ABSTRACT. PMID:27181061

  1. Theta-rhythmic drive between medial septum and hippocampus in slow-wave sleep and microarousal: a Granger causality analysis.

    PubMed

    Kang, D; Ding, M; Topchiy, I; Shifflett, L; Kocsis, B

    2015-11-01

    Medial septum (MS) plays a critical role in controlling the electrical activity of the hippocampus (HIPP). In particular, theta-rhythmic burst firing of MS neurons is thought to drive lasting HIPP theta oscillations in rats during waking motor activity and REM sleep. Less is known about MS-HIPP interactions in nontheta states such as non-REM sleep, in which HIPP theta oscillations are absent but theta-rhythmic burst firing in subsets of MS neurons is preserved. The present study used Granger causality (GC) to examine the interaction patterns between MS and HIPP in slow-wave sleep (SWS, a nontheta state) and during its short interruptions called microarousals (a transient theta state). We found that during SWS, while GC revealed a unidirectional MS→HIPP influence over a wide frequency band (2-12 Hz, maximum: ∼8 Hz), there was no theta peak in the hippocampal power spectra, indicating a lack of theta activity in HIPP. In contrast, during microarousals, theta peaks were seen in both MS and HIPP power spectra and were accompanied by bidirectional GC with MS→HIPP and HIPP→MS theta drives being of equal magnitude. Thus GC in a nontheta state (SWS) vs. a theta state (microarousal) primarily differed in the level of HIPP→MS. The present findings suggest a modification of our understanding of the role of MS as the theta generator in two regards. First, a MS→HIPP theta drive does not necessarily induce theta field oscillations in the hippocampus, as found in SWS. Second, HIPP theta oscillations entail bidirectional theta-rhythmic interactions between MS and HIPP. PMID:26354315

  2. Significance of Late Gadolinium Enhancement at Right Ventricular Attachment to Ventricular Septum in Patients With Hypertrophic Cardiomyopathy.

    PubMed

    Chan, Raymond H; Maron, Barry J; Olivotto, Iacopo; Assenza, Gabriele E; Haas, Tammy S; Lesser, John R; Gruner, Christiane; Crean, Andrew M; Rakowski, Harry; Rowin, Ethan; Udelson, James; Lombardi, Massimo; Tomberli, Benedetta; Spirito, Paolo; Formisano, Francesco; Marra, Martina P; Biagini, Elena; Autore, Camillo; Manning, Warren J; Appelbaum, Evan; Roberts, William C; Basso, Cristina; Maron, Martin S

    2015-08-01

    Cardiovascular magnetic resonance (CMR) with extensive late gadolinium enhancement (LGE) is a novel marker for increased risk for sudden death (SD) in patients with hypertrophic cardiomyopathy (HC). Small focal areas of LGE confined to the region of right ventricular (RV) insertion to ventricular septum (VS) have emerged as a frequent and highly visible CMR imaging pattern of uncertain significance. The aim of this study was to evaluate the prognostic significance of LGE confined to the RV insertion area in patients with HC. CMR was performed in 1,293 consecutive patients with HC from 7 HC centers, followed for 3.4 ± 1.7 years. Of 1,293 patients (47 ± 14 years), 134 (10%) had LGE present only in the anterior and/or inferior areas of the RV insertion to VS, occupying 3.7 ± 2.9% of left ventricular myocardium. Neither the presence nor extent of LGE in these isolated areas was a predictor of adverse HC-related risk, including SD (adjusted hazard ratio 0.82, 95% confidence interval 0.45 to 1.50, p = 0.53; adjusted hazard ratio 1.16/10% increase in LGE, 95% confidence interval 0.29 to 4.65, p = 0.83, respectively). Histopathology in 20 HC hearts show the insertion areas of RV attachment to be composed of a greatly expanded extracellular space characterized predominantly by interstitial-type fibrosis and interspersed disorganized myocyte patterns and architecture. In conclusion, LGE confined to the insertion areas of RV to VS was associated with low risk of adverse events (including SD). Gadolinium pooling in this region of the left ventricle does not reflect myocyte death and repair with replacement fibrosis or scarring. PMID:26026863

  3. Atrial septum defect closure device in a beating heart, from the perspective of a researcher in artificial organs.

    PubMed

    Tomizawa, Yasuko

    2012-12-01

    Transcatheter closure of atrial septum defect (ASD) with a closure device is increasing, but the history of clinical use of this procedure is still short, and the efficacy and long-term safety remain unproved. The total number of closure devices implanted throughout the world has not been counted accurately. Therefore, the probability of complications occurring after implantation is uncertain. Device-related complications that occur suddenly late after implantation are life-threatening, and quite often necessitate emergency surgical intervention. In Japanese medical journals, authors reporting closure devices have mentioned no complications and problems in their facilities. Detailed studies of device-related complications and device removal have not been reported in Japan. In fact, this literature search found an unexpectedly large number of reports of various adverse events from many overseas countries. When follow-up duration is short and the number of patients is small, the incidence of complications cannot be determined. Rare complications may emerge in a large series with a long observation period. Consequently, the actual number of incidents related to ASD closure devices is possibly several times higher than the number reported. Guidelines for long-term patient management for patients with an implanted closure device are necessary and post-marketing surveillance is appropriate. Development of a national database, a worldwide registration system, and continuous information disclosure will improve the quality of treatment. The devices currently available are not ideal in view of reports of late complications requiring urgent surgery and the need for life-long follow-up. An ideal device should be free from complications during life, and reliability is indispensable. PMID:22729293

  4. Functional cooperation between the hippocampal subregions and the medial septum in unreinforced and reinforced spatial memory tasks.

    PubMed

    Okada, Kana; Okaichi, Hiroshige

    2010-06-19

    Anatomical connections between the medial septum (MS) and hippocampus (Hipp) via the fimbria-fornix suggest that functional cooperation between these structures may be important for the acquisition and use of spatial reference memories. The present study examined the extent to which this was true for both an unreinforced learning task (object exploration task) and a reinforced learning task (Morris water maze task). In Experiment 1, we compared the performance of MS/Hipp contralateral- and MS/Hipp ipsilateral-lesioned rats. MS/Hipp contralateral-lesioned rats exhibited deficient performance in both the object exploration and Morris water maze tasks. In Experiment 2, we examined the task performance of MS/CA1 contralateral-, MS/CA1 ipsilateral-, MS/CA3 contralateral- and MS/CA3 ipsilateral-lesioned rats. Contralateral MS/CA3 and MS/CA1 lesions were respectively associated with deficient performance at the spatial recognition test and object recognition test in the object exploration task. None of the lesioned rats performed deficiently in the Morris water maze task. These results indicate the importance of spatial reference memory of a functional cooperation between the MS and Hipp as a whole, irrespective of reward contingency. In contrast, functional cooperation between the MS and each of CA1 and CA3 played an important role in the performance of the unreinforced voluntary task, but not in the reinforced task. Further, the functional cooperation of both MS/CA3 and MA/CA1 were important in the spatial reference memory with the unreinforced task. PMID:20144657

  5. Our experience with transcanalicular laser-assisted endoscopic dacryocystorhinostomy (TCLADCR) in patients of chronic dacryocystitis with deviated nasal septum.

    PubMed

    Goel, Ruchi; Nagpal, Smriti; Kumar, Sushil; Kamal, Saurabh; Dangda, Sonal; Bodh, Sonam Angmo

    2015-12-01

    The purpose of this study is to study the operative difficulties and success rate of transcanalicular laser-assisted endoscopic dacryocystorhinostomy in patients of chronic dacryocystitis with deviated nasal septum (DNS). A prospective interventional clinical study of 36 consecutive patients suffering from chronic dacryocystitis with nasolacrimal duct obstruction with DNS undergoing primary TCLADCR from March to June 2011 was carried out. Diode laser was used to create a 16-mm(2) ostium which was enlarged to 64 mm(2) using Blakesley's forceps. Success was defined as anatomical patency and absence of symptoms at 12 months of follow-up. Out of the 36 patients, 25 were females with ages 20-72 years, and 19 were left sided. There were 12 high, 12 mid and 12 basal DNS towards the side of surgery, mild to moderate in severity. Intraoperatively there was difficulty in visualising the aiming beam in the nose, tedious manipulation of endoscope and excessive bleeding in 3 patients. Increased bleeding and failures were significantly higher in high DNS (Fisher exact test-2 tailed: 0.0045). The procedure was successful in 94.4 % cases with average ostium size of 21.94 mm(2) at 12 months and no statistically significant difference in success rates between mild and moderate DNS (Fisher exact test-2 tailed: 1.000). Also there was no difference in the complication rate between mild and moderate DNS (Fisher exact test-2 tailed: 0.0841). TCLADCR is an effective procedure in patients with mild to moderate mid and basal DNS and obviates the need for multiple procedures and a cutaneous scar. PMID:25702037

  6. Laterally oscillating nitinol engine

    SciTech Connect

    Banks, R.

    1987-09-08

    This patent describes a laterally oscillating nitinol engine comprising: a first L-shaped drive member journalled for pivoting horizontal oscillation about the juncture of the legs of the L-shaped member, a second drive member journalled for pivoting about a point proximate the outboard end of the shorter leg of the L-shaped member at a distance from the pivot journal of the L-shaped member, a bearing block secured to the end of longer leg of the L-shaped and having a guide hole. The second member extending through the guide hole and arranged to reciprocate therein, a shape memory alloy power element disposed in flexure secured at its ends to the bearing block and to the second member intermediate the sliding connection with the bearing block and the pivotal connection of the second member, means for disposing different temperature baths below the element whereby as the drive members oscillate about their journals the element alternately dips into one bath and then the other, and means for absorbing a portion of the energy developed by the engine and moving the power element from the cold bath to the hot bath.

  7. Investigating the dynamics of the brain response to music: A central role of the ventral striatum/nucleus accumbens.

    PubMed

    Mueller, Karsten; Fritz, Thomas; Mildner, Toralf; Richter, Maxi; Schulze, Katrin; Lepsien, Jöran; Schroeter, Matthias L; Möller, Harald E

    2015-08-01

    Ventral striatal activity has been previously shown to correspond well to reward value mediated by music. Here, we investigate the dynamic brain response to music and manipulated counterparts using functional magnetic resonance imaging (fMRI). Counterparts of musical excerpts were produced by either manipulating the consonance/dissonance of the musical fragments or playing them backwards (or both). Results show a greater involvement of the ventral striatum/nucleus accumbens both when contrasting listening to music that is perceived as pleasant and listening to a manipulated version perceived as unpleasant (backward dissonant), as well as in a parametric analysis for increasing pleasantness. Notably, both analyses yielded a ventral striatal response that was strongest during an early phase of stimulus presentation. A hippocampal response to the musical stimuli was also observed, and was largely mediated by processing differences between listening to forward and backward music. This hippocampal involvement was again strongest during the early response to the music. Auditory cortex activity was more strongly evoked by the original (pleasant) music compared to its manipulated counterparts, but did not display a similar decline of activation over time as subcortical activity. These findings rather suggest that the ventral striatal/nucleus accumbens response during music listening is strongest in the first seconds and then declines. PMID:25976924

  8. Reversal of morphine-induced cell-type-specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement.

    PubMed

    Hearing, Matthew C; Jedynak, Jakub; Ebner, Stephanie R; Ingebretson, Anna; Asp, Anders J; Fischer, Rachel A; Schmidt, Clare; Larson, Erin B; Thomas, Mark John

    2016-01-19

    Drug-evoked plasticity at excitatory synapses on medium spiny neurons (MSNs) of the nucleus accumbens (NAc) drives behavioral adaptations in addiction. MSNs expressing dopamine D1 (D1R-MSN) vs. D2 receptors (D2R-MSN) can exert antagonistic effects in drug-related behaviors, and display distinct alterations in glutamate signaling following repeated exposure to psychostimulants; however, little is known of cell-type-specific plasticity induced by opiates. Here, we find that repeated morphine potentiates excitatory transmission and increases GluA2-lacking AMPA receptor expression in D1R-MSNs, while reducing signaling in D2-MSNs following 10-14 d of forced abstinence. In vivo reversal of this pathophysiology with optogenetic stimulation of infralimbic cortex-accumbens shell (ILC-NAc shell) inputs or treatment with the antibiotic, ceftriaxone, blocked reinstatement of morphine-evoked conditioned place preference. These findings confirm the presence of overlapping and distinct plasticity produced by classes of abused drugs within subpopulations of MSNs that may provide targetable molecular mechanisms for future pharmacotherapies. PMID:26739562

  9. RNAi knockdown of oxytocin receptor in the nucleus accumbens inhibits social attachment and parental care in monogamous female prairie voles

    PubMed Central

    Keebaugh, Alaine C.; Barrett, Catherine E.; LaPrairie, Jamie L.; Jenkins, Jasmine J.; Young, Larry J.

    2015-01-01

    Oxytocin modulates many aspects of social cognition and behaviors, including maternal nurturing, social recognition and bonding. Natural variation in oxytocin receptor (OXTR) density in the nucleus accumbens (NAcc) is associated with variation in alloparental behavior, and artificially enhancing OXTR expression in the NAcc enhances alloparental behavior and pair bonding in socially monogamous prairie voles. Furthermore, infusion of an OXTR antagonist into the nucleus accumbens (NAcc) inhibits alloparental behavior and partner preference formation. However, antagonists can promiscuously interact with other neuropeptide receptors. To directly examine the role of OXTR signaling in social bonding, we used RNA interference to selectively knockdown, but not eliminate, OXTR in the NAcc of female prairie voles and examined the impact on social behaviors. Using an adeno-associated viral vector expressing a short hairpin RNA (shRNA) targeting Oxtr mRNA, we reduced accumbal OXTR density in female prairie voles from juvenile age through adulthood. Females receiving the shRNA vector displayed a significant reduction in alloparental behavior and disrupted partner preference formation. These are the first direct demonstrations that OXTR plays a critical role in alloparental behavior and adult social attachment, and suggest that natural variation in OXTR expression in this region alone can create variation in social behavior. PMID:25874849

  10. Effect of haloperidol and clozapine on the density of "perforated" synapses in caudate, nucleus accumbens, and medial prefrontal cortex.

    PubMed

    Meshul, C K; Janowsky, A; Casey, D E; Stallbaumer, R K; Taylor, B

    1992-01-01

    Perforated synapses, which contain a discontinuous density along the postsynaptic membrane, can increase or decrease in numbers following various behavioral and biochemical manipulations. We have previously established that 14-day treatment with haloperidol causes an increase in the number of perforated synapses within the caudate nucleus (dorsolateral region) but not the nucleus accumbens (Meshul and Casey 1989). This effect was reversed if the animals were withdrawn from the drug for an equivalent period of time. We have now further examined the effects of haloperidol administration, which is associated with a high incidence of extrapyramidal side effects (EPS) and tardive dyskinesia (TD), and assessed the effects of clozapine, which appears to have a lower potential for inducing EPS and TD. Administration of haloperidol for 2 weeks significantly increased the percentage of perforated synapses in the caudate, but not in the nucleus accumbens or layer VI of medial prefrontal cortex (MPCx). There was an increase in specific [125I]epidepride binding to D-2 receptors in the caudate nucleus and MPCx following haloperidol. Administration of clozapine for 2 weeks did not affect the percentage of perforated synapses in any of the three dopamine (DA)-rich regions that were examined. There was an increase in specific [3H]SCH 23390 binding to D-1 receptors and in specific [125I]epidepride binding to D-2 receptors only within MPCx following clozapine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1531388

  11. Underweight rats have enhanced dopamine release and blunted acetylcholine response in the nucleus accumbens while bingeing on sucrose.

    PubMed

    Avena, N M; Rada, P; Hoebel, B G

    2008-10-28

    The present study tested whether rats release more accumbens dopamine (DA) during a sugar binge when they are underweight vs. normal weight. Since acetylcholine (ACh) in the nucleus accumbens (NAc) normally increases as a meal progresses and satiety ensues, we also tested whether ACh release is altered when an animal has lost weight. Rats were maintained on daily 8-h access to chow, with 10% sucrose solution available for the first 2 h. Microdialysis performed on day 21, at normal body weight, revealed an increase in extracellular DA to 122% of baseline in response to drinking sucrose. Extracellular ACh peaked at the end of the meal. Next, the rats were food and sucrose restricted so that by day 28 they were at 85% body weight. When retested, these animals released significantly more DA when drinking sucrose (179%), but ACh release failed to rise. A control group was tested in the same manner but given sugar only on days 1, 21 and 28. At normal body weight, control animals showed a non-significant rise in DA when drinking sucrose on day 21. On day 28, at 85% body weight, the controls showed a small increase (124%) in DA release; however, this was significantly lower than the 179% observed in the underweight rats with daily sugar access. These findings suggest that when an animal binges on sugar and then loses weight, the binge releases significantly more DA and less ACh than when animals are at a normal body weight. PMID:18790017

  12. A high-fat meal, or intraperitoneal administration of a fat emulsion, increases extracellular dopamine in the nucleus accumbens.

    PubMed

    Rada, Pedro; Avena, Nicole M; Barson, Jessica R; Hoebel, Bartley G; Leibowitz, Sarah F

    2012-01-01

    Evidence links dopamine (DA) in the nucleus accumbens (NAc) shell to the ingestion of palatable diets. Less is known, however, about the specific relation of DA to dietary fat and circulating triglycerides (TG), which are stimulated by fat intake and promote overeating. The present experiments tested in Sprague-Dawley rats whether extracellular levels of NAc DA increase in response to acute access to fat-rich food or peripheral injection of a fat emulsion and, if so, whether this is related to caloric intake or elevated circulating lipids. When rats consumed more calories of a high-fat meal compared with a low-fat meal, there was a significant increase in extracellular accumbens DA (155% vs. 119%). Systemic injection of a fat emulsion, which like a high-fat diet raises circulating TG but eliminates the factor of taste and allows for the control of caloric intake, also significantly increased extracellular levels of DA (127%) compared to an equicaloric glucose solution (70%) and saline (85%). Together, this suggests that a rise in circulating TG may contribute to the stimulatory effect of a high-fat diet on NAc DA. PMID:24962774

  13. A High-Fat Meal, or Intraperitoneal Administration of a Fat Emulsion, Increases Extracellular Dopamine in the Nucleus Accumbens

    PubMed Central

    Rada, Pedro; Avena, Nicole M.; Barson, Jessica R.; Hoebel, Bartley G.; Leibowitz, Sarah F.

    2012-01-01

    Evidence links dopamine (DA) in the nucleus accumbens (NAc) shell to the ingestion of palatable diets. Less is known, however, about the specific relation of DA to dietary fat and circulating triglycerides (TG), which are stimulated by fat intake and promote overeating. The present experiments tested in Sprague-Dawley rats whether extracellular levels of NAc DA increase in response to acute access to fat-rich food or peripheral injection of a fat emulsion and, if so, whether this is related to caloric intake or elevated circulating lipids. When rats consumed more calories of a high-fat meal compared with a low-fat meal, there was a significant increase in extracellular accumbens DA (155% vs. 119%). Systemic injection of a fat emulsion, which like a high-fat diet raises circulating TG but eliminates the factor of taste and allows for the control of caloric intake, also significantly increased extracellular levels of DA (127%) compared to an equicaloric glucose solution (70%) and saline (85%). Together, this suggests that a rise in circulating TG may contribute to the stimulatory effect of a high-fat diet on NAc DA. PMID:24962774

  14. After daily bingeing on a sucrose solution, food deprivation induces anxiety and accumbens dopamine/acetylcholine imbalance

    PubMed Central

    Avena, Nicole M.; Bocarsly, Miriam E.; Rada, Pedro; Kim, Agnes; Hoebel, Bartley G.

    2015-01-01

    Bingeing on sugar may activate neural pathways in a manner similar to taking drugs of abuse, resulting in related signs of dependence. The present experiments test whether rats that have been bingeing on sucrose and then fasted demonstrate signs of opiate-like withdrawal. Rats were maintained on 12-h deprivation followed by 12-h access to a 10% sucrose solution and chow for 28 days, then fasted for 36 h. These animals spent less time on the exposed arm of an elevated plus-maze compared with a similarly deprived ad libitum chow group, suggesting anxiety. Microdialysis revealed a concomitant increase in extracellular acetylcholine and decrease in dopamine release in the nucleus accumbens shell. These results did not appear to be due to hypoglycemia. The findings suggest that a diet of bingeing on sucrose and chow followed by fasting creates a state that involves anxiety and altered accumbens dopamine and acetylcholine balance. This is similar to the effects of naloxone, suggesting opiate-like withdrawal. This may be a factor in some eating disorders. PMID:18325546

  15. After daily bingeing on a sucrose solution, food deprivation induces anxiety and accumbens dopamine/acetylcholine imbalance.

    PubMed

    Avena, Nicole M; Bocarsly, Miriam E; Rada, Pedro; Kim, Agnes; Hoebel, Bartley G

    2008-06-01

    Bingeing on sugar may activate neural pathways in a manner similar to taking drugs of abuse, resulting in related signs of dependence. The present experiments test whether rats that have been bingeing on sucrose and then fasted demonstrate signs of opiate-like withdrawal. Rats were maintained on 12-h deprivation followed by 12-h access to a 10% sucrose solution and chow for 28 days, then fasted for 36 h. These animals spent less time on the exposed arm of an elevated plus-maze compared with a similarly deprived ad libitum chow group, suggesting anxiety. Microdialysis revealed a concomitant increase in extracellular acetylcholine and decrease in dopamine release in the nucleus accumbens shell. These results did not appear to be due to hypoglycemia. The findings suggest that a diet of bingeing on sucrose and chow followed by fasting creates a state that involves anxiety and altered accumbens dopamine and acetylcholine balance. This is similar to the effects of naloxone, suggesting opiate-like withdrawal. This may be a factor in some eating disorders. PMID:18325546

  16. UNDERWEIGHT RATS HAVE ENHANCED DOPAMINE RELEASE AND BLUNTED ACETYLCHOLINE RESPONSE IN THE NUCLEUS ACCUMBENS WHILE BINGEING ON SUCROSE

    PubMed Central

    AVENA, N. M.; RADA, P.; HOEBEL, B. G.

    2015-01-01

    The present study tested whether rats release more accumbens dopamine (DA) during a sugar binge when they are underweight vs. normal weight. Since acetylcholine (ACh) in the nucleus accumbens (NAc) normally increases as a meal progresses and satiety ensues, we also tested whether ACh release is altered when an animal has lost weight. Rats were maintained on daily 8-h access to chow, with 10% sucrose solution available for the first 2 h. Microdialysis performed on day 21, at normal body weight, revealed an increase in extracellular DA to 122% of baseline in response to drinking sucrose. Extracellular ACh peaked at the end of the meal. Next, the rats were food and sucrose restricted so that by day 28 they were at 85% body weight. When retested, these animals released significantly more DA when drinking sucrose (179%), but ACh release failed to rise. A control group was tested in the same manner but given sugar only on days 1, 21 and 28. At normal body weight, control animals showed a non-significant rise in DA when drinking sucrose on day 21. On day 28, at 85% body weight, the controls showed a small increase (124%) in DA release; however, this was significantly lower than the 179% observed in the underweight rats with daily sugar access. These findings suggest that when an animal binges on sugar and then loses weight, the binge releases significantly more DA and less ACh than when animals are at a normal body weight. PMID:18790017

  17. Reversal of morphine-induced cell-type–specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement

    PubMed Central

    Hearing, Matthew C.; Jedynak, Jakub; Ebner, Stephanie R.; Ingebretson, Anna; Asp, Anders J.; Fischer, Rachel A.; Schmidt, Clare; Larson, Erin B.; Thomas, Mark John

    2016-01-01

    Drug-evoked plasticity at excitatory synapses on medium spiny neurons (MSNs) of the nucleus accumbens (NAc) drives behavioral adaptations in addiction. MSNs expressing dopamine D1 (D1R-MSN) vs. D2 receptors (D2R-MSN) can exert antagonistic effects in drug-related behaviors, and display distinct alterations in glutamate signaling following repeated exposure to psychostimulants; however, little is known of cell-type–specific plasticity induced by opiates. Here, we find that repeated morphine potentiates excitatory transmission and increases GluA2-lacking AMPA receptor expression in D1R-MSNs, while reducing signaling in D2-MSNs following 10–14 d of forced abstinence. In vivo reversal of this pathophysiology with optogenetic stimulation of infralimbic cortex-accumbens shell (ILC-NAc shell) inputs or treatment with the antibiotic, ceftriaxone, blocked reinstatement of morphine-evoked conditioned place preference. These findings confirm the presence of overlapping and distinct plasticity produced by classes of abused drugs within subpopulations of MSNs that may provide targetable molecular mechanisms for future pharmacotherapies. PMID:26739562

  18. Cage-induced stereotypic behaviour in laboratory mice covaries with nucleus accumbens FosB/ΔFosB expression.

    PubMed

    Phillips, Danielle; Choleris, Elena; Ervin, Kelsy S J; Fureix, Carole; Harper, Laura; Reynolds, Kathryn; Niel, Lee; Mason, Georgia J

    2016-03-15

    Stereotypic behaviour (SB) occurs in certain human disorders (e.g. autism), and animals treated with stimulants or raised in impoverished conditions, including laboratory mice in standard cages. Dysfunctional cortico-basal ganglia pathways have been implicated in these examples, but for cage-induced forms of SB, the relative roles of ventral versus dorsal striatum had not been fully ascertained. Here, we used immunohistochemical staining of FosB and ΔFosB to assess long-term activation within the nucleus accumbens and caudate-putamen of C57BL/6 mice. Housed in typical laboratory cages, these mice spontaneously developed different degrees of route-tracing, bar-mouthing and other forms of SB (spending 0% to over 50% of their active time budgets in this behaviour). The most highly stereotypic mice showed the most elevated FosB/ΔFosB activity in the nucleus accumbens. No such patterns occurred in the caudate-putamen. The cage-induced SB common in standard-housed mice thus involves elevated activity within the ventral striatum, suggesting an aetiology closer to compulsive gambling, eating and drug-seeking than to classic amphetamine stereotypies and other behaviours induced by motor loop over-activation. PMID:26731014

  19. Effect of ethanol on (/sup 3/H)dopamine release in rat nucleus accumbens and striatal slices

    SciTech Connect

    Russell, V.A.; Lamm, M.C.; Taljaard, J.J.

    1988-05-01

    Ethanol (10-200 mM) transiently increased tritium overflow from superfused rat nucleus accumbens slices previously incubated with (/sup 3/H)dopamine (DA) and (/sup 14/C)choline. The effect was greater in striatal tissue and did not appear to be a non-specific membrane effect since (/sup 14/C)acetylcholine (ACh) release was not affected. Lack of antagonism by picrotoxin suggested that gamma-aminobutyric acid (GABA) receptors were not involved. Calcium was not a requirement and the DA uptake blocker, nomifensine, was without effect. Ethanol appeared to be causing (/sup 3/H)DA release into the cytoplasm. K+ -stimulated release of (/sup 3/H)DA and (/sup 14/C)ACh from nucleus accumbens and striatal slices was not affected. Clonidine-mediated inhibition of the K+-evoked release of (/sup 3/H)DA remained unaltered. Ethanol attenuated the isoproterenol-induced enhancement of (/sup 3/H)DA release. Ethanol therefore appeared to interact with components of the DA terminal causing a transient increase in the release of neurotransmitter without impairing K+-evoked release but apparently interfering with the isoproterenol-induced effect.

  20. Diamond heteroepitaxial lateral overgrowth

    NASA Astrophysics Data System (ADS)

    Tang, Yung-Hsiu

    This dissertation describes improvements in the growth of single crystal diamond by microwave plasma-assisted chemical vapor deposition (CVD). Heteroepitaxial (001) diamond was grown on 1 cm. 2 a-plane sapphiresubstrates using an epitaxial (001) Ir thin-film as a buffer layer. Low-energy ion bombardment of the Ir layer, a process known as bias-enhanced nucleation, is a key step in achieving a high density of diamond nuclei. Bias conditions were optimized to form uniformly-high nucleation densities across the substrates, which led to well-coalesced diamond thin films after short growth times. Epitaxial lateral overgrowth (ELO) was used as a means of decreasing diamond internal stress by impeding the propagation of threading dislocations into the growing material. Its use in diamond growth requires adaptation to the aggressive chemical and thermal environment of the hydrogen plasma in a CVD reactor. Three ELO variants were developed. The most successful utilized a gold (Au) mask prepared by vacuum evaporation onto the surface of a thin heteroepitaxial diamond layer. The Au mask pattern, a series of parallel stripes on the micrometer scale, was produced by standard lift-off photolithography. When diamond overgrows the mask, dislocations are largely confined to the substrate. Differing degrees of confinement were studied by varying the stripe geometry and orientation. Significant improvement in diamond quality was found in the overgrown regions, as evidenced by reduction of the Raman scattering linewidth. The Au layer was found to remain intact during diamond overgrowth and did not chemically bond with the diamond surface. Besides impeding the propagation of threading dislocations, it was discovered that the thermally-induced stress in the CVD diamond was significantly reduced as a result of the ductile Au layer. Cracking and delamination of the diamond from the substrate was mostly eliminated. When diamond was grown to thicknesses above 0.1 mm it was found that

  1. Thinking laterally about genomes.

    PubMed

    Ragan, Mark A

    2009-10-01

    Perhaps the most-surprising discovery of the genome era has been the extent to which prokaryotic and many eukaryotic genomes incorporate genetic material from sources other than their parent(s). Lateral genetic transfer (LGT) among bacteria was first observed about 100 years ago, and is now accepted to underlie important phenomena including the spread of antibiotic resistance and ability to degrade xenobiotics. LGT is invoked, perhaps too readily, to explain a breadth of awkward data including compositional heterogeneity of genomes, disagreement among gene-sequence trees, and mismatch between physiology and systematics. At the same time many details of LGT remain unknown or controversial, and some key questions have scarcely been asked. Here I critically review what we think we know about the existence, extent, mechanism and impact of LGT; identify important open questions; and point to research directions that hold particular promise for elucidating the role of LGT in genome evolution. Evidence for LGT in nature is not only inferential but also direct, and potential vectors are ubiquitous. Genetic material can pass between diverse habitats and be significantly altered during residency in viruses, complicating the inference of donors, In prokaryotes about twice as many genes are interrupted by LGT as are transferred intact, and about 5Short protein domains can be privileged units of transfer. Unresolved phylogenetic issues include the correct null hypothesis, and genes as units of analysis. Themes are beginning to emerge regarding the effect of LGT on cellular networks, but I show why generalization is premature. LGT can associate with radical changes in physiology and ecological niche. Better quantitative models of genome evolution are needed, and theoretical frameworks remain to be developed for some observations including chromosome assembly by LGT. PMID:20180279

  2. Amylin Receptor Signaling in the Nucleus Accumbens Negatively Modulates μ-opioid-Driven Feeding

    PubMed Central

    Baisley, Sarah K; Baldo, Brian A

    2014-01-01

    Amylin is a peptide co-secreted with insulin that penetrates into the brain, and produces satiation-like effects via actions in the brainstem, hypothalamus, and mesencephalon. Little is known, however, about the effects of amylin in the nucleus accumbens shell (AcbSh), where a circumscribed zone of intense amylin receptor (AMY-R) binding overlaps reported mappings of a ‘hotspot' for μ-opioid receptor (μ-OR) amplification of food reward. Here, the ability of intra-AcbSh AMY-R signaling to modulate μ-OR-driven feeding was explored. Amylin (1–30 ng) was administered with the μ-OR agonist, D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) (0.25 μg), directly into the AcbSh of ad libitum-maintained rats. Amylin dose-dependently reversed DAMGO-induced hyperphagia; 3 ng of amylin reduced DAMGO-mediated feeding by nearly 50%. This dose was, however, completely ineffective at altering DAMGO-induced feeding in the anterior dorsal striatum. Intra-AcbSh amylin alone (3–30 ng) modestly suppressed 10% sucrose intake in ad libitum-maintained rats, and chow in food-deprived rats, but only at the 30-ng dose. This result indicates that reversal of AcbSh DAMGO-induced feeding at a 10-fold lower dose was neither due to malaise nor motoric impairment. Finally, intra-AcbSh infusion of the AMY-R antagonist, AC187 (20 μg), significantly attenuated the ability of prefeeding to suppress DAMGO-induced food intake, with no effects in non-prefed rats. Hence, AMY-R signaling negatively modulates μ-OR-mediated appetitive responses at the level of the AcbSh. The results with AC187 indicate that endogenous AMY-R transmission in the AcbSh curtails opioid function in the postprandial period, suggesting a novel pathway for peripheral-central integration in the control of appetitive motivation and opioid reward. PMID:24957819

  3. Nucleus accumbens core lesions retard instrumental learning and performance with delayed reinforcement in the rat

    PubMed Central

    Cardinal, Rudolf N; Cheung, Timothy HC

    2005-01-01

    Background Delays between actions and their outcomes severely hinder reinforcement learning systems, but little is known of the neural mechanism by which animals overcome this problem and bridge such delays. The nucleus accumbens core (AcbC), part of the ventral striatum, is required for normal preference for a large, delayed reward over a small, immediate reward (self-controlled choice) in rats, but the reason for this is unclear. We investigated the role of the AcbC in learning a free-operant instrumental response using delayed reinforcement, performance of a previously-learned response for delayed reinforcement, and assessment of the relative magnitudes of two different rewards. Results Groups of rats with excitotoxic or sham lesions of the AcbC acquired an instrumental response with different delays (0, 10, or 20 s) between the lever-press response and reinforcer delivery. A second (inactive) lever was also present, but responding on it was never reinforced. As expected, the delays retarded learning in normal rats. AcbC lesions did not hinder learning in the absence of delays, but AcbC-lesioned rats were impaired in learning when there was a delay, relative to sham-operated controls. All groups eventually acquired the response and discriminated the active lever from the inactive lever to some degree. Rats were subsequently trained to discriminate reinforcers of different magnitudes. AcbC-lesioned rats were more sensitive to differences in reinforcer magnitude than sham-operated controls, suggesting that the deficit in self-controlled choice previously observed in such rats was a consequence of reduced preference for delayed rewards relative to immediate rewards, not of reduced preference for large rewards relative to small rewards. AcbC lesions also impaired the performance of a previously-learned instrumental response in a delay-dependent fashion. Conclusions These results demonstrate that the AcbC contributes to instrumental learning and performance by

  4. Frequency Dependent Effects of Ethanol on Dopamine Release in the Nucleus Accumbens

    PubMed Central

    Yorgason, Jordan T.; Ferris, Mark J.; Steffensen, Scott C.; Jones, Sara R.

    2014-01-01

    Background Ethanol is known to have excitatory effects on dopamine (DA) release, with moderate to high doses (0.5–2.5 g/kg) of acute ethanol enhancing DA neuron firing rates in the ventral tegmental area (VTA) and DA levels in the nucleus accumbens (NAc). Ethanol has also been shown to reduce DA activity, with moderate doses (1–2 g/kg) attenuating electrically evoked release, and higher doses (5 g/kg) decreasing NAc DA levels, demonstrating a biphasic effect of ethanol on DA release. The purpose of the current study was to evaluate ethanol’s inhibitory effects on NAc DA terminal release under low- and high-frequency stimulation conditions. Methods Using fast-scan cyclic voltammetry in NAc slices from C57BL/6J mice, we examined ethanol’s (40–160 mM) effects on DA release under several different stimulation parameters, varying frequency (5–125 Hz), number of pulses (1–10), and stimulation intensity (50–350 µA). Additionally, calcium concentrations were manipulated under high-frequency stimulation conditions (20 Hz, 10 pulses, 350 µA) in order to determine if ethanol’s effects were dependent upon calcium concentration, and by extension, the amount of DA release. Results Acute ethanol (40–160 mM) inhibited DA release to a greater extent under high-frequency, multiple-pulse stimulation conditions, with increased sensitivity at 5 and 10 pulses and frequencies of 20 Hz or higher. High-frequency, multiple-pulse stimulations also resulted in greater DA release compared to single-pulse release, which was controlled by reducing stimulation intensity. Under reduced DA conditions, high-frequency stimulations still showed increased ethanol sensitivity. Reducing calcium levels also decreased DA release at high-frequency stimulations, but did not affect ethanol sensitivity. Conclusions Ethanol appears to inhibit DA release at NAc terminals under high-frequency stimulation conditions that are similar to release events observed during phasic burst firing in

  5. Integrative proteomic analysis of the nucleus accumbens in rhesus monkeys following cocaine self-administration.

    PubMed

    Tannu, N S; Howell, L L; Hemby, S E

    2010-02-01

    The reinforcing effects and long-term consequences of cocaine self-administration have been associated with brain regions of the mesolimbic dopamine pathway, namely the nucleus accumbens (NAc). Studies of cocaine-induced biochemical adaptations in rodent models have advanced our knowledge; however, unbiased detailed assessments of intracellular alterations in the primate brain are scarce, yet essential, to develop a comprehensive understanding of cocaine addiction. To this end, two-dimensional difference in gel electrophoresis (2D-DIGE) was used to compare changes in cytosolic protein abundance in the NAc between rhesus monkeys self-administering cocaine and controls. Following image normalization, spots with significantly differential image intensities (P<0.05) were identified, excised, trypsin digested and analyzed by matrix-assisted laser-desorption ionization time-of-flight time-of-flight (MALDI-TOF-TOF). In total, 1098 spots were subjected to statistical analysis with 22 spots found to be differentially abundant of which 18 proteins were positively identified by mass spectrometry. In addition, approximately 1000 protein spots were constitutively expressed of which 21 proteins were positively identified by mass spectrometry. Increased levels of proteins in the cocaine-exposed monkeys include glial fibrillary acidic protein, syntaxin-binding protein 3, protein kinase C isoform, adenylate kinase isoenzyme 5 and mitochondrial-related proteins, whereas decreased levels of proteins included beta-soluble N-ethylmaleimide-sensitive factor attachment protein and neural and non-neural enolase. Using a complimentary proteomics approach, the differential expression of phosphorylated proteins in the cytosolic fraction of these subjects was examined. Two-dimensional gel electrophoresis (2DGE) was followed by gel staining with Pro-Q Diamond phosphoprotein gel stain, enabling differentiation of approximately 150 phosphoprotein spots between the groups. Following excision and

  6. Oxytocin in the nucleus accumbens core reduces reinstatement of methamphetamine-seeking behaviour in rats.

    PubMed

    Baracz, Sarah J; Everett, Nicholas A; McGregor, Iain S; Cornish, Jennifer L

    2016-03-01

    The psychostimulant methamphetamine (METH) is an addictive illicit drug. Systemic administration of the neuropeptide oxytocin modulates METH-related reward and METH-seeking behaviour. Recent findings demonstrated a reduction in METH-induced reward by oxytocin administration into the nucleus accumbens (NAc) core. It is not known, however, if oxytocin acts in this region to reduce relapse to METH-seeking behaviour. Using the drug reinstatement paradigm in rats experienced at METH self-administration, we aimed to determine whether oxytocin pre-treatment within the NAc core would reduce relapse to METH use and if this could be reversed by the co-administration of the oxytocin receptor (OTR) antagonist desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT. Male Sprague-Dawley rats underwent surgery to implant an intravenous jugular vein catheter and bilateral microinjection cannulae in the NAc core. Rats were then trained to self-administer intravenous METH (0.1 mg/kg/infusion) by lever press during 2-hour fixed ratio 1 scheduled sessions for 20 days. Following extinction of lever press activity, the effect of microinjecting saline, oxytocin (0.5 pmol, 1.5 pmol, 4.5 pmol) or co-administration of oxytocin (1.5 pmol) and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT (1 nmol, 3 nmol) in the NAc core (500 nl/side) was examined on METH-primed (1 mg/kg, i.p.) reinstatement of drug-seeking behaviour. Our results showed oxytocin directly administered into the NAc core decreased METH-primed reinstatement in a dose-dependent manner. Co-administration of the selective OTR antagonist did not specifically reverse the inhibitory effects of oxytocin on METH priming, suggesting mediation by receptors other than the OTR. These findings highlight an important modulatory effect of oxytocin in the NAc core on relapse to METH seeking. PMID:25399704

  7. Cosmetic Lateral Canthoplasty: Preserving the Lateral Canthal Angle.

    PubMed

    Kim, Yeon-Jun; Lee, Kyu Ho; Choi, Hong Lim; Jeong, Eui Cheol

    2016-07-01

    Cosmetic lateral canthoplasty, in which the size of the eye is increased by extending the palpebral fissure and decreasing the degree of the eye slant, has become a prevalent procedure for East Asians. However, it is not uncommon for there to be complications or unfavorable results after the surgery. With this in mind, the authors have designed a surgical method to reduce complications in cosmetic lateral canthoplasty by preserving the lateral canthal angle. We discuss here the anatomy required for surgery, the surgical methods, and methods for reducing complications during cosmetic lateral canthoplasty. PMID:27462563

  8. Cosmetic Lateral Canthoplasty: Preserving the Lateral Canthal Angle

    PubMed Central

    Lee, Kyu Ho; Choi, Hong Lim; Jeong, Eui Cheol

    2016-01-01

    Cosmetic lateral canthoplasty, in which the size of the eye is increased by extending the palpebral fissure and decreasing the degree of the eye slant, has become a prevalent procedure for East Asians. However, it is not uncommon for there to be complications or unfavorable results after the surgery. With this in mind, the authors have designed a surgical method to reduce complications in cosmetic lateral canthoplasty by preserving the lateral canthal angle. We discuss here the anatomy required for surgery, the surgical methods, and methods for reducing complications during cosmetic lateral canthoplasty. PMID:27462563

  9. Amyotrophic lateral sclerosis

    PubMed Central

    Wijesekera, Lokesh C; Leigh, P Nigel

    2009-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by progressive muscular paralysis reflecting degeneration of motor neurones in the primary motor cortex, corticospinal tracts, brainstem and spinal cord. Incidence (average 1.89 per 100,000/year) and prevalence (average 5.2 per100,000) are relatively uniform in Western countries, although foci of higher frequency occur in the Western Pacific. The mean age of onset for sporadic ALS is about 60 years. Overall, there is a slight male prevalence (M:F ratio~1.5:1). Approximately two thirds of patients with typical ALS have a spinal form of the disease (limb onset) and present with symptoms related to focal muscle weakness and wasting, where the symptoms may start either distally or proximally in the upper and lower limbs. Gradually, spasticity may develop in the weakened atrophic limbs, affecting manual dexterity and gait. Patients with bulbar onset ALS usually present with dysarthria and dysphagia for solid or liquids, and limbs symptoms can develop almost simultaneously with bulbar symptoms, and in the vast majority of cases will occur within 1–2 years. Paralysis is progressive and leads to death due to respiratory failure within 2–3 years for bulbar onset cases and 3–5 years for limb onset ALS cases. Most ALS cases are sporadic but 5–10% of cases are familial, and of these 20% have a mutation of the SOD1 gene and about 2–5% have mutations of the TARDBP (TDP-43) gene. Two percent of apparently sporadic patients have SOD1 mutations, and TARDBP mutations also occur in sporadic cases. The diagnosis is based on clinical history, examination, electromyography, and exclusion of 'ALS-mimics' (e.g. cervical spondylotic myelopathies, multifocal motor neuropathy, Kennedy's disease) by appropriate investigations. The pathological hallmarks comprise loss of motor neurones with intraneuronal ubiquitin-immunoreactive inclusions in upper motor neurones and TDP-43 immunoreactive inclusions in

  10. Nucleus Accumbens Dopamine D2-Receptor Expressing Neurons Control Behavioral Flexibility in a Place Discrimination Task in the IntelliCage

    ERIC Educational Resources Information Center

    Macpherson, Tom; Morita, Makiko; Wang, Yanyan; Sasaoka, Toshikuni; Sawa, Akira; Hikida, Takatoshi

    2016-01-01

    Considerable evidence has demonstrated a critical role for the nucleus accumbens (NAc) in the acquisition and flexibility of behavioral strategies. These processes are guided by the activity of two discrete neuron types, dopamine D1- or D2-receptor expressing medium spiny neurons (D1-/D2-MSNs). Here we used the IntelliCage, an automated…

  11. AMPA/Kainate, NMDA, and Dopamine D1 Receptor Function in the Nucleus Accumbens Core: A Context-Limited Role in the Encoding and Consolidation of Instrumental Memory

    ERIC Educational Resources Information Center

    Hernandez, Pepe J.; Andrzejewski, Matthew E.; Sadeghian, Kenneth; Panksepp, Jules B.; Kelley, Ann E.

    2005-01-01

    Neural integration of glutamate- and dopamine-coded signals within the nucleus accumbens (NAc) is a fundamental process governing cellular plasticity underlying reward-related learning. Intra-NAc core blockade of NMDA or D1 receptors in rats impairs instrumental learning (lever-pressing for sugar pellets), but it is not known during which phase of…

  12. Modulation of Memory Consolidation by the Basolateral Amygdala or Nucleus Accumbens Shell Requires Concurrent Dopamine Receptor Activation in Both Brain Regions

    ERIC Educational Resources Information Center

    LaLumiere, Ryan T.; Nawar, Erene M.; McGaugh, James L.

    2005-01-01

    Previous findings indicate that the basolateral amygdala (BLA) and the nucleus accumbens (NAc) interact in influencing memory consolidation. The current study investigated whether this interaction requires concurrent dopamine (DA) receptor activation in both brain regions. Unilateral, right-side cannulae were implanted into the BLA and the…

  13. Intermittent-access binge consumption of sweet high-fat liquid does not require opioid or dopamine receptors in the nucleus accumbens.

    PubMed

    Lardeux, Sylvie; Kim, James J; Nicola, Saleem M

    2015-10-01

    Binge eating disorders are characterized by episodes of intense consumption of high-calorie food. In recently developed animal models of binge eating, rats given intermittent access to such food escalate their consumption over time. Consumption of calorie-dense food is associated with neurochemical changes in the nucleus accumbens, including dopamine release and alterations in dopamine and opioid receptor expression. Therefore, we hypothesized that binge-like consumption on intermittent access schedules is dependent on opioid and/or dopamine neurotransmission in the accumbens. To test this hypothesis, we asked whether injection of dopamine and opioid receptor antagonists into the core and shell of the accumbens reduced consumption of a sweet high-fat liquid in rats with and without a history of intermittent binge access to the liquid. Although injection of a μ opioid agonist increased consumption, none of the antagonists (including μ opioid, δ opioid, κ opioid, D1 dopamine and D2 dopamine receptor antagonists, as well as the broad-spectrum opioid receptor antagonist naltrexone) reduced consumption, and this was the case whether or not the animals had a prior history of intermittent access. These results suggest that consumption of sweet, fatty food does not require opioid or dopamine receptor activation in the accumbens even under intermittent access conditions that resemble human binge episodes. PMID:26097003

  14. No Evidence for Sex Differences in the Electrophysiological Properties and Excitatory Synaptic Input onto Nucleus Accumbens Shell Medium Spiny Neurons123

    PubMed Central

    Will, Tyler; Hauser, Caitlin A.; Cao, Jinyan

    2016-01-01

    Sex differences exist in how the brain regulates motivated behavior and reward, both in normal and pathological contexts. Investigations into the underlying neural mechanisms have targeted the striatal brain regions, including the dorsal striatum and nucleus accumbens core and shell. These investigations yield accumulating evidence of sexually different electrophysiological properties, excitatory synaptic input, and sensitivity to neuromodulator/hormone action in select striatal regions both before and after puberty. It is unknown whether the electrical properties of neurons in the nucleus accumbens shell differ by sex, and whether sex differences in excitatory synaptic input are present before puberty. To test the hypothesis that these properties differ by sex, we performed whole-cell patch-clamp recordings on male and female medium spiny neurons (MSNs) in acute brain slices obtained from prepubertal rat nucleus accumbens shell. We analyzed passive and active electrophysiological properties, and miniature EPSCs (mEPSCs). No sex differences were detected; this includes those properties, such as intrinsic excitability, action potential afterhyperpolarization, threshold, and mEPSC frequency, that have been found to differ by sex in other striatal regions and/or developmental periods. These findings indicate that, unlike other striatal brain regions, the electrophysiological properties of nucleus accumbens shell MSNs do not differ by sex. Overall, it appears that sex differences in striatal function, including motivated behavior and reward, are likely mediated by other factors and striatal regions. PMID:27022621

  15. Matrix-assisted laser desorption/ionization tissue profiling of secretoneurin in the nucleus accumbens shell from cocaine-sensitized rats

    PubMed Central

    Uys, Joachim D.; Grey, Angus C.; Wiggins, Armina; Schwacke, John H.; Schey, Kevin L.; Kalivas, Peter W.

    2014-01-01

    Proteins in the nucleus accumbens mediate many cocaine-induced behaviors. In an effort to measure changes in nucleus accumbens protein expression as potential biomarkers for addiction, coronal tissue sections were obtained from rats that developed behavioral sensitization after daily administration of cocaine, or from daily saline-treated controls. The tissue sections were subjected to matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) profiling and tissue imaging. For profiling experiments, brain sections were manually spotted with matrix over the nucleus accumbens, a brain region known to regulate cocaine sensitization. Summed mass spectra (10 000 laser shots, grid) were acquired and spectra were aligned to reference peaks. Using bioinformatics tools, eight spectral features were found to be altered by cocaine treatment. Based on additional sequencing experiments with MALDI tandem MS and database searches of measured masses, secretoneurin (m/z 3653) was identified as having an increased expression. In addition, the distribution of m/z 3653 in the nucleus accumbens was determined by MALDI tissue imaging, and the increased expression of its precursor protein, secretogranin II, was verified by immunoblotting. PMID:19918966

  16. Matrix-assisted laser desorption/ionization tissue profiling of secretoneurin in the nucleus accumbens shell from cocaine-sensitized rats.

    PubMed

    Uys, Joachim D; Grey, Angus C; Wiggins, Armina; Schwacke, John H; Schey, Kevin L; Kalivas, Peter W

    2010-01-01

    Proteins in the nucleus accumbens mediate many cocaine-induced behaviors. In an effort to measure changes in nucleus accumbens protein expression as potential biomarkers for addiction, coronal tissue sections were obtained from rats that developed behavioral sensitization after daily administration of cocaine, or from daily saline-treated controls. The tissue sections were subjected to matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) profiling and tissue imaging. For profiling experiments, brain sections were manually spotted with matrix over the nucleus accumbens, a brain region known to regulate cocaine sensitization. Summed mass spectra (10,000 laser shots, grid) were acquired and spectra were aligned to reference peaks. Using bioinformatics tools, eight spectral features were found to be altered by cocaine treatment. Based on additional sequencing experiments with MALDI tandem MS and database searches of measured masses, secretoneurin (m/z 3653) was identified as having an increased expression. In addition, the distribution of m/z 3653 in the nucleus accumbens was determined by MALDI tissue imaging, and the increased expression of its precursor protein, secretogranin II, was verified by immunoblotting. PMID:19918966

  17. Prenatal choline deficiency increases choline transporter expression in the septum and hippocampus during postnatal development and in adulthood in rats.

    PubMed

    Mellott, Tiffany J; Kowall, Neil W; Lopez-Coviella, Ignacio; Blusztajn, Jan Krzysztof

    2007-06-01

    Supplementation of maternal diet with the essential nutrient, choline, during the second half of pregnancy in rats causes long-lasting improvements in spatial memory in the offspring and protects them from the memory decline characteristic of old age. In contrast, prenatal choline deficiency is associated with poor performance in certain cognitive tasks. The mechanism by which choline influences learning and memory remains unclear; however, it may involve changes to the hippocampal cholinergic system. Previously, we showed that the hippocampi of prenatally [embryonic days (E) 11-17] choline-deficient animals have increased synthesis of acetylcholine (ACh) from choline transported by the high-affinity choline transporter (CHT) and reduced ACh content relative to the control and to the E11-17 choline-supplemented rats. In the current study, we found that, during postnatal period [postnatal days (P) 18-480], prenatal choline deficiency increased the expression of CHT mRNA in the septum and CHT mRNA and protein levels in the hippocampus and altered the pattern of CHT immunoreactivity in the dentate gyrus. CHT immunoreactivity was more prominent in the inner molecular layer in prenatally choline-deficient rats compared to controls and prenatally choline-supplemented animals. In addition, in all groups, we observed a population of hilar interneurons that were CHT-immunoreactive. These neurons are the likely source of the hippocampal CHT mRNA as their number correlated with the levels of this mRNA. The abundance of hippocampal CHT mRNA rose between P1 and P24 and then declined reaching 60% of the P1 value by P90. These