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Stephen C Gammie - One of the best experts on this subject based on the ideXlab platform.
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microrna expression is altered in Lateral Septum across reproductive stages
Neuroscience, 2016Co-Authors: Michael C Saul, Changjiu Zhao, Terri M Driessen, Brian E Eisinger, Stephen C GammieAbstract: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 significant alterations in the postpartum brain.
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Glutamate, GABA, and glutamine are synchronously upregulated in the mouse Lateral Septum during the postpartum period.
Brain research, 2014Co-Authors: Changjiu Zhao, Stephen C GammieAbstract:Dramatic structural and functional remodeling occurs in the postpartum brain for the establishment of maternal care, which is essential for the growth and development of young offspring. Glutamate and GABA signaling are critically important in modulating multiple behavioral performances. Large scale signaling changes occur in the postpartum brain, but it is still not clear to what extent the neurotransmitters glutamate and GABA change and whether the ratio of glutamate/GABA remains balanced. In this study, we examined the glutamate/GABA-glutamine cycle in the Lateral Septum (LS) of postpartum female mice. In postpartum females (relative to virgins), tissue levels of glutamate and GABA were elevated in LS and increased mRNA was found for the respective enzymes producing glutamate and GABA, glutaminase (Gls) and glutamate decarboxylase 1 and 2 (Gad1 and Gad2). The common precursor, glutamine, was elevated as was the enzyme that produces it, glutamate-ammonia ligase (Glul). Additionally, glutamate, GABA, and glutamine were positively correlated and the glutamate/GABA ratio was almost identical in the postpartum and virgin females. Collectively, these findings indicate that glutamate and GABA signaling are increased and that the ratio of glutamate/GABA is well balanced in the maternal LS. The postpartum brain may provide a useful model system for understanding how glutamate and GABA are linked despite large signaling changes. Given that some mental health disorders, including depression and schizophrenia display dysregulated glutamate/GABA ratio, and there is increased vulnerability to mental disorders in mothers, it is possible that these postpartum disorders emerge when glutamate and GABA changes are not properly coordinated.
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Maternal defense is modulated by beta adrenergic receptors in Lateral Septum in mice
Behavioral Neuroscience, 2011Co-Authors: Melissa Ann L Scotti, Grace Lee, Stephen C GammieAbstract: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.
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gabaa receptor signaling in the Lateral Septum regulates maternal aggression in mice
Behavioral Neuroscience, 2009Co-Authors: Grace Lee, Stephen C GammieAbstract:Maternal aggression (maternal defense) is a fierce aggression produced by lactating females toward intruders that plays an important role in protection of vulnerable offspring. Enhancement of GABA(A) receptor signaling by benzodiazepines increases maternal aggression, and we recently found indirect evidence that Lateral Septum (LS) could be a key site where benzodiazepines elevate aggression. In this study, we directly tested the hypothesis that activation of GABA(A) receptors in LS would promote maternal aggression while inhibition of this receptor would decrease aggression. Site-directed injections to LS were made using the GABA(A) receptor antagonist, bicuculline (3-30 ng), or the GABA(A) receptor agonists, chlordiazepoxide, a benzodiazepine (2.5-5 microg), and muscimol (0.05-5 ng). Maternal aggression and other behavioral measures were then evaluated in lactating mice. Neither GABA(A) receptor agonist elevated aggression, which could reflect a ceiling effect. However, 7 ng of the GABA(A) receptor antagonist, bicuculline, in LS significantly decreased maternal aggression without altering other maternal behaviors or light-dark box performance, suggesting some GABA(A) receptor signaling in LS is required for full maternal aggression expression. Together, these results confirm a role for GABA(A) receptor signaling in LS in the regulation of maternal aggression.
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activation of corticotropin releasing factor receptor 2 in Lateral Septum negatively regulates maternal defense
Behavioral Neuroscience, 2009Co-Authors: Kimberly L Danna, Stephen C GammieAbstract:Maternal defense (also known as maternal aggression) is impaired by corticotropin-releasing factor-(CRF) related peptides, but where these peptides inhibit defense is unknown. Lateral Septum (LS) gates reactivity to stressors, contains receptors to CRF-related peptides, and during lactation shows a decreased response to CRF, suggesting LS is a key site for regulating maternal aggression. In this study, the authors examined the effects of CRF-related peptides in LS on maternal defense. LS injections of CRF (0.2 microg), urocortin (Ucn) 1 (0.2 microg), and Ucn 3 (0.25 microg) all significantly impaired maternal defense behavior. However, LS injections of CRF receptor 2 antagonist astressin-2B, but not a CRF receptor 1 antagonist, reversed the inhibitory effects of both septal CRF and Ucn 3. After intra-LS injection of peptides, c-Fos immunoreactivity was increased in ventromedial hypothalamus, Lateral hypothalamus, and parabrachial nucleus, identifying these brain regions as possible downstream mediators of altered LS activity. Together, these findings indicate that CRF-related peptides similarly modulate maternal defense via CRF receptor 2, and that LS is a critical site for the negative regulation of maternal defense behavior.
Janet L. Menard - One of the best experts on this subject based on the ideXlab platform.
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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
Behavioural Brain Research, 2016Co-Authors: Steven J Lamontagne, Mary C Olmstead, Janet L. MenardAbstract: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.
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the Lateral Septum as a regulator of hippocampal theta oscillations and defensive behavior in rats
Journal of Neurophysiology, 2015Co-Authors: Sansan A Chee, Janet L. Menard, Hans C DringenbergAbstract:Hippocampal theta oscillations are linked to various processes, including locomotion, learning and memory, and defense and affect. The Lateral Septum (LS) has been implicated in the generation of the hippocampal theta rhythm, but its precise role in this process is not well understood. Here, we investigated the effects of direct pharmacological inhibition or disinhibition of the dorsal LS (dLS) on the frequency of hippocampal theta activity elicited by stimulation of the reticular formation in urethane-anesthetized rats. We found that biLateral infusions of the GABAA receptor agonist muscimol into the dLS significantly increased theta frequency. Strikingly, intra-dLS infusions of the GABAA receptor antagonist GABAzine largely abolished reticularly elicited theta activity. We also locally injected these same compounds into the medial Septum (MS) to test for neuroanatomical specificity. In contrast to the effects seen in the dLS, intra-MS infusions of muscimol had no effect on theta frequency, whereas intra-MS infusions of GABAzine increased theta frequency. Given the hypothesized role of hippocampal theta in behavioral defense, we also examined the effects of intra-dLS application of muscimol in two models of anxiety, the elevated plus maze and the novelty-induced suppression of feeding paradigm; both tests revealed clear, anxiolytic-like effects following muscimol infusions. The fact that dLS-muscimol increased theta frequency while also reducing anxiety-like behaviors challenges the influential theta suppression model of anxiolysis, which predicts a slowing of theta with anxiolytic compounds. More importantly, the experiments reveal a novel role of the LS, especially its dorsal aspects, as an important gating mechanism for the expression of theta oscillations in the rodent hippocampus.
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behavioral anxiolysis without reduction of hippocampal theta frequency after histamine application in the Lateral Septum of rats
Hippocampus, 2014Co-Authors: Sansan A Chee, Janet L. Menard, Hans C DringenbergAbstract:Hippocampal theta activity is linked to various processes, including locomotion, learning and memory, and defense and affect (i.e., fear and anxiety). Interestingly, all classes of clinically effective anxiolytics, as well as experimental compounds that decrease anxiety in pre-clinical animal models of anxiety, reduce the frequency of hippocampal theta activity elicited by stimulation of the reticular formation in freely behaving or anesthetized animals. In the present experiments, we found that biLateral histamine infusions (0.5 µg/hemisphere) into the Lateral Septum (LS) of rats decreased anxiety-like responses in two models of anxiety, the elevated plus maze and novelty-induced suppression of feeding test. Surprisingly, these same infusions significantly increased hippocampal theta frequency elicited by reticular stimulation in urethane-anesthetized rats. In contrast to these findings, additional experiments showed that the clinically effective anxiolytic buspirone (40 mg/kg, i.p.) reduced theta frequency, confirming previous observations. Taken together, the dissociation of behavioral anxiolysis and theta frequency reduction noted here suggest that hippocampal theta frequency is not a direct index of anxiety levels in rodents. Further, the mechanisms underlying the behavioral and physiological effects elicited by histamine in the LS require further study. © 2014 Wiley Periodicals, Inc.
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the histaminergic h1 h2 and h3 receptors of the Lateral Septum differentially mediate the anxiolytic like effects of histamine on rats defensive behaviors in the elevated plus maze and novelty induced suppression of feeding paradigm
Physiology & Behavior, 2013Co-Authors: Sansan A Chee, Janet L. MenardAbstract:The neural histaminergic system is involved in a wide range of physiological processes, including anxiety. Histaminergic neurons are localized in the tuberomammillary nucleus of the posterior hypothalamus and share bidirectional connections with the Lateral Septum, an area well implicated in anxiety. The current study examined whether the histaminergic system of the Lateral Septum regulates rats' defensive behaviors in two animal models of anxiety, the elevated plus maze (EPM) and novelty-induced suppression of feeding paradigm (NISF). We found that biLateral infusions of histamine (1.0 μg and 5.0 μg) into the Lateral Septum selectively decreased rats' defensive behaviors in the EPM (both doses) and NISF (1.0 μg only). Follow-up studies found that pre-infusions of the H1 and H2 antagonists, pyrilamine (20 μg) and ranitidine (20 μg) respectively, reversed the anxiolytic-like effects of intra-LS histamine (1.0 μg) in the NISF but not in the EPM, while pre-infusions of the H3 antagonist ciproxifan (200 pg) attenuated the anxiolytic-like effects of intra-LS histamine in the EPM but not in the NISF. This double dissociation suggests that H1 and H2 receptors in the Lateral Septum, likely via a post-synaptic mechanism, mediate the anxiolytic-like effects of histamine in the NISF but not in the EPM. In contrast, Lateral septal H3 receptors mediate, likely pre-synaptically, the anxiolytic-like effects of histamine in the EPM but not in the NISF. Our findings indicate that these receptors differentially contribute to rats' specific defensive behaviors in the EPM and NISF, that is, avoidance of open spaces and neophagia respectively.
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infusions of neuropeptide y into the Lateral Septum reduce anxiety related behaviors in the rat
Pharmacology Biochemistry and Behavior, 2011Co-Authors: Natalie L. Trent, Janet L. MenardAbstract:Abstract Neuropeptide Y (NPY) is one of the most abundant peptides in mammalian brain and NPY-like-immunoreactivity is highly expressed in the Lateral Septum, an area extensively involved in anxiety regulation. NPY counteracts the neurochemical and behavioral responses to acute threat in animal models, and intracerebroventricular (i.c.v.) administration of NPY at low doses is anxiolytic. Less is known about the specific contributions of the Lateral Septum to NPY-mediated anxiety regulation. In Experiment 1, the effects of infusions of NPY (1.5 μg) into the Lateral Septum were investigated in three animal models of anxiety: the elevated plus-maze, novelty-induced suppression of feeding, and shock-probe burying tests. Experiment 2 examined the role of the NPY Y1 receptor in these models by co-infusing the Y1 antagonist BIBO 3304 (0.15 μg, 0.30 μg) with NPY into the Lateral Septum. In the elevated plus-maze, there were no changes in rats' open arm exploration, the index of anxiety reduction in this test. In the novelty-induced suppression of feeding test, rats infused with NPY showed decreases in the latency to consume a palatable snack in a novel (but not familiar) environment, suggesting a reduction in anxiety independent of increases in appetite. This anxiolysis was attenuated by co-infusion with BIBO 3304 (0.30 μg) in Experiment 2. Lastly, rats infused with NPY showed decreases in the duration of burying behavior in the shock-probe burying test, also indicative of anxiety reduction. However, unlike in the feeding test, BIBO 3304 did not attenuate the NPY-induced anxiolysis in the shock-probe test. It is concluded that NPY produces anxiolytic-like actions in the Lateral Septum in two animal models of anxiety: the novelty-induced suppression of feeding, and shock-probe burying tests, and that this anxiolysis is dependent on Y1 receptor activation in the feeding test.
Andrey E. Ryabinin - One of the best experts on this subject based on the ideXlab platform.
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The Edinger-Westphal–Lateral Septum Urocortin Pathway and Its Relationship to Alcohol Consumption
2013Co-Authors: Ryan K Bachtell, Fred O Risinger, Adam Z. Weitemier, Agustin Galvan-rosas, Natalia O. Tsivkovskaia, Tamara J. Phillips, Nicholas J. Grahame, Andrey E. RyabininAbstract:Identifying and characterizing brain regions regulating alcohol consumption is beneficial for understanding the mechanisms of alcoholism. To this aim, we first identified brain regions changing in expression of the inducible transcription factor c-Fos in the alcoholpreferring C57BL/6J (B6) and alcohol-avoiding DBA/2J (D2) mice after ethanol consumption. Drinking a 5 % ethanol/10 % sucrose solution in a 30 min limited access procedure led to induction of c-Fos immunoreactivity in urocortin (Ucn)-positive cells of the Edinger-Westphal nucleus (EW), suppression of c-Fos immunoreactivity in the dorsal portion of the Lateral Septum (LS) of both strains of mice, and strain-specific suppression in the intermediate portion of the LS and the CA3 hippocampal region. Because the EW sends Ucn projections to the LS, and B6 and D2 mice differ dramatically in EW Ucn expression, we further analyzed the Ucn EW–LS pathway using several genetic approaches. We find that D2 mice have higher numbers of Ucn-immunoreactive processes than B6 mice in the LS and that consumption of ethanol/sucrose in the F2 offspring of a B6D2 intercross positively correlates with Ucn immunoreactivity in the EW and negatively correlates with Ucn immunoreactivity in the LS. In agreement with these findings, we find that alcohol-avoiding male B6.D2 Alcp1 line 2.2 congenic mice have lower Ucn immunoreactivity in the EW than male B6.B6 mice. Finally, we also find that HAP mice, selectively bred for high alcohol preference, have higher Ucn immunoreactivity in EW, than LAP mice, selectively bred for low alcohol preference. Taken together, these studies provide substantial evidence for involvement of the EW–LS Ucn pathway in alcohol consumption
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urocortin 1 microinjection into the mouse Lateral Septum regulates the acquisition and expression of alcohol consumption
Neuroscience, 2008Co-Authors: Andrey E. Ryabinin, Naomi Yoneyama, Michelle A Tanchuck, Gregory P Mark, Deborah A FinnAbstract:Abstract Previous studies using genetic and lesion approaches have shown that the neuropeptide urocortin 1 (Ucn1) is involved in regulating alcohol consumption. Ucn1 is a corticotropin releasing factor (CRF) –like peptide that binds CRF1 and CRF2 receptors. Perioculomotor urocortin-containing neurons (pIIIu), also known as the non-preganglionic Edinger-Westphal nucleus, are the major source of Ucn1 in the brain and are known to innervate the Lateral Septum. Thus, the present study tested whether Ucn1 could regulate alcohol consumption through the Lateral Septum. In a series of experiments Ucn1 or CRF was biLaterally injected at various doses into the Lateral Septum of male C57BL/6J mice. Consumption of 20% volume/volume ethanol or water was tested immediately after the injections using a modification of a 2-h limited access sweetener-free “drinking-in-the-dark” procedure. Ucn1 significantly suppressed ethanol consumption when administered prior to the third ethanol drinking session (the expression phase of ethanol drinking) at doses as low as 6 pmol. Ethanol intake was differentially sensitive to Ucn1, as equivalent doses of this peptide did not suppress water consumption. In contrast, CRF suppressed both ethanol and water intake at 40 and 60 pmol, but not at lower doses. Repeated administration of Ucn1 during the acquisition of alcohol consumption showed that 40 pmol (but not 2 or 0.1 pmol) significantly attenuated ethanol intake. Repeated administration of Ucn1 also resulted in a decrease of ethanol intake in sham-injected animals, a finding suggesting that the suppressive effect of Ucn1 on ethanol intake can be conditioned. Taken together, these studies confirm the importance of Lateral Septum innervation by Ucn1 in the regulation of alcohol consumption.
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the edinger westphal Lateral Septum urocortin pathway and its relationship to alcohol consumption
PMC, 2003Co-Authors: Ryan K Bachtell, Agustin Galvanrosas, Fred O Risinger, Adam Z. Weitemier, Natalia O. Tsivkovskaia, Tamara J. Phillips, Nicholas J. Grahame, Andrey E. RyabininAbstract:Identifying and characterizing brain regions regulating alcohol consumption is beneficial for understanding the mechanisms of alcoholism. To this aim, we first identified brain regions changing in expression of the inducible transcription factor c-Fos in the alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA/2J (D2) mice after ethanol consumption. Drinking a 5% ethanol/10% sucrose solution in a 30 min limited access procedure led to induction of c-Fos immunoreactivity in urocortin (Ucn)-positive cells of the Edinger-Westphal nucleus (EW), suppression of c-Fos immunoreactivity in the dorsal portion of the Lateral Septum (LS) of both strains of mice, and strain-specific suppression in the intermediate portion of the LS and the CA3 hippocampal region. Because the EW sends Ucn projections to the LS, and B6 and D2 mice differ dramatically in EW Ucn expression, we further analyzed the Ucn EW-LS pathway using several genetic approaches. We find that D2 mice have higher numbers of Ucn-immunoreactive processes than B6 mice in the LS and that consumption of ethanol/sucrose in the F2 offspring of a B6D2 intercross positively correlates with Ucn immunoreactivity in the EW and negatively correlates with Ucn immunoreactivity in the LS. In agreement with these findings, we find that alcohol-avoiding male B6.D2 Alcp1 line 2.2 congenic mice have lower Ucn immunoreactivity in the EW than male B6.B6 mice. Finally, we also find that HAP mice, selectively bred for high alcohol preference, have higher Ucn immunoreactivity in EW, than LAP mice, selectively bred for low alcohol preference. Taken together, these studies provide substantial evidence for involvement of the EW-LS Ucn pathway in alcohol consumption.
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high alcohol sucrose consumption during dark circadian phase in c57bl 6j mice involvement of hippocampus Lateral Septum and urocortin positive cells of the edinger westphal nucleus
Psychopharmacology, 2003Co-Authors: Andrey E. Ryabinin, Agustin Galvanrosas, Ryan K Bachtell, Fred O RisingerAbstract:Abstract Rationale. Identification of the neuroanatomical substrates regulating alcohol consumption is important for the understanding of alcoholism. Previous studies mapping changes in brain activity used rodent models of alcohol drinking with relatively low alcohol intakes. Objectives. This study was aimed to identify brain regions changing activity after high voluntary intake of alcohol-containing solutions. Methods. Adult male C57BL/6J mice were trained to drink a 10% ethanol/10% sucrose solution in daily 30-min limited-access sessions during the dark phase of the circadian cycle. Control groups of animals consumed 10% sucrose or water. Analysis of c-Fos immunohistochemistry (as a marker for neuronal activity) was performed at 90 min after the last alcohol drinking session. Results. The limited access procedure led to high intakes (2.9±0.3 g/kg) and blood alcohol concentrations of 251±46 mg%. Expression of c-Fos was significantly higher in the alcohol/sucrose group than both the water and sucrose groups in the Edinger-Westphal nucleus, and significantly lower in the alcohol/sucrose group than two control groups in hippocampal subregions, posterior hypothalamus and dorsal Lateral Septum. Double immunohistochemistry showed that alcohol-induced c-Fos-positive cells in the Edinger-Westphal nucleus co-localized with the neuropeptide urocortin. In addition, intake and/or blood alcohol concentrations correlated with c-Fos expression in specific subregions of the hippocampus, hypothalamus, prefrontal cortex, Lateral Septum and midbrain. Conclusions. The dark phase voluntary limited-access procedure in mice leads to intakes of alcohol-containing solutions that are considered highly intoxicating. Brain regions showing alcohol-specific changes in c-Fos expression after this procedure can be connected into a novel neurocircuit, including Lateral Septum, hippocampus, hypothalamus, and the Edinger-Westphal nucleus.
Diana L. Williams - One of the best experts on this subject based on the ideXlab platform.
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endogenous glp 1 in Lateral Septum promotes satiety and suppresses motivation for food in mice
Physiology & Behavior, 2019Co-Authors: Sarah J. Terrill, Calyn B. Maske, Marie K Holt, Nataly Abrams, Frank Reimann, Stefan Trapp, Diana L. WilliamsAbstract:Glucagon-like peptide 1 receptors (GLP-1R) are expressed in the Lateral Septum (LS) of rats and mice, and we have published that endogenous LS GLP-1 affects feeding and motivation for food in rats. Here we asked if these effects are also observed in mice. In separate dose-response studies using male C57Bl6J mice, intra-LS GLP-1 or the GLP-1R antagonist Exendin 9 (Ex9) was delivered shortly before dark onset, at doses subthreshold for effect when injected intracerebroventricularly (icv). Intra-LS GLP-1 significantly suppressed chow intake early in the dark phase and tended to reduce overnight intake. However, blockade of LS GLP-1R with Ex9 had no effect on ad libitum dark onset chow intake. We then asked if LS GLP-1R blockade blunts nutrient preload-induced intake suppression. Mice were trained to consume Ensure immediately before dark onset, which suppressed subsequent chow intake, and intra-LS Ex9 attenuated that preload-induced intake suppression. We also found that restraint stress robustly activates hindbrain GLP-1-producing neurons, and that LS GLP-1R blockade attenuates 30-min restraint stress-induced hypophagia in mice. Furthermore, we have reported that in the rat, GLP-1R in the dorsal subregion of the LS (dLS) affect motivation for food. We examined this in food-restricted mice responding for sucrose pellets on a progressive ratio (PR) schedule. Intra-dLS GLP-1R stimulation significantly suppressed, and Ex9 significantly increased, operant responding, and the Ex9 effect remained after mice returned to ad libitum conditions. Similarly, we found that stimulation of dLS GLP-1 suppressed licking for sucrose and conversely, Ex9 increased licking under ad libitum feeding conditions. Together, our data suggest that endogenous activation of LS GLP-1R plays a role in feeding in mice under some but not all conditions, and that these receptors strongly influence motivation for food.
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endogenous glp 1 in Lateral Septum contributes to stress induced hypophagia
Physiology & Behavior, 2018Co-Authors: Sarah J. Terrill, Calyn B. Maske, Diana L. WilliamsAbstract:Glucagon-like peptide 1 (GLP-1) neurons of the caudal brainstem project to many brain areas, including the Lateral Septum (LS), which has a known role in stress responses. Previously, we showed that endogenous GLP-1 in the LS plays a physiologic role in the control of feeding under non-stressed conditions, however, central GLP-1 is also involved in behavioral and endocrine responses to stress. Here, we asked whether LS GLP-1 receptors (GLP-1R) contribute to stress-induced hypophagia. Male rats were implanted with biLateral cannulas targeting the dorsal subregion of the LS (dLS). In a within-subjects design, shortly before the onset of the dark phase, rats received dLS injections of saline or the GLP-1R antagonist Exendin (9-39) (Ex9) prior to 30 min restraint stress. Food intake was measured continuously for the next 20 h. The stress-induced hypophagia observed within the first 30 min of dark was not influenced by Ex9 pretreatment, but Ex9 tended to blunt the effect of stress as early as 1 and 2 h into the dark phase. By 4-6 h, there were significant stress X drug interactions, and Ex9 pretreatment blocked the stress-induced suppression of feeding. These effects were mediated entirely through changes in average meal size; stress suppressed meal size while dLS Ex9 attenuated this effect. Using a similar design, we examined the role of dLS GLP-1R in the neuroendocrine response to acute restraint stress. As expected, stress potently increased serum corticosterone, but blockade of dLS GLP-1Rs did not affect this response. Together, these data show that endogenous GLP-1 action in the dLS plays a role in some but not all of the physiologic responses to acute stress.
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Role of Lateral Septum glucagon-like peptide 1 receptors in food intake
American journal of physiology. Regulatory integrative and comparative physiology, 2016Co-Authors: Sarah J. Terrill, Christine M. Jackson, Hayden E. Greene, Nicole Lilly, Calyn B. Maske, Samantha Vallejo, Diana L. WilliamsAbstract: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 (E...
Eric R Kandel - One of the best experts on this subject based on the ideXlab platform.
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a circuit from hippocampal ca2 to Lateral Septum disinhibits social aggression
Nature, 2018Co-Authors: Felix Leroy, Jung M Park, Arun Asok, David H Brann, Torcato Meira, Lara M Boyle, Eric W Buss, Eric R KandelAbstract:Although the hippocampus is known to be important for declarative memory, it is less clear how hippocampal output regulates motivated behaviours, such as social aggression. Here we report that pyramidal neurons in the CA2 region of the hippocampus, which are important for social memory, promote social aggression in mice. This action depends on output from CA2 to the Lateral Septum, which is selectively enhanced immediately before an attack. Activation of the Lateral Septum by CA2 recruits a circuit that disinhibits a subnucleus of the ventromedial hypothalamus that is known to trigger attack. The social hormone arginine vasopressin enhances social aggression by acting on arginine vasopressin 1b receptors on CA2 presynaptic terminals in the Lateral Septum to facilitate excitatory synaptic transmission. In this manner, release of arginine vasopressin in the Lateral Septum, driven by an animal's internal state, may serve as a modulatory control that determines whether CA2 activity leads to declarative memory of a social encounter and/or promotes motivated social aggression.
