Activation of GABAergic pathway by hypocretin in the median raphe nucleus (MRN) mediates stress-induced theta rhythm in rats

Hsiao, Yi‐Tse; Jou, Shuo-Bin; Yi, Pei-Lu; Chang, Fang‐Chia

doi:10.1016/j.bbr.2012.05.002

Cited by 23 publications

(21 citation statements)

References 36 publications

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“…Orexin A (0.1-10 mmol/L; Sigma-Aldrich) was microinjected into the RVLM using doses based on a previous study (21). Orexin receptors in the RVLM were blocked using the nonselective antagonist TCS 1102 (5 mmol/L; Tocris Bioscience), diluted in 50% DMSO (Sigma-Aldrich), using a dose based on a previous report (22).…”

Section: Glucoprivation and Microinjectionsmentioning

confidence: 99%

Orexinergic Activation of Medullary Premotor Neurons Modulates the Adrenal Sympathoexcitation to Hypothalamic Glucoprivation

et al. 2014

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Glucoprivation activates neurons in the perifornical hypothalamus (PeH) and in the rostral ventrolateral medulla (RVLM), which results in the release of adrenaline. The current study aimed to establish 1) whether neuroglucoprivation in the PeH or in the RVLM elicits adrenaline release in vivo and 2) whether direct activation by glucoprivation or orexin release in the RVLM modulates the adrenaline release. Neuroglucoprivation in the PeH or RVLM was elicited by microinjections of 2-deoxy-D-glucose or 5-thio-D-glucose in anesthetized, euglycemic rats. Firstly, inhibition of neurons in the PeH abolished the increase in adrenal sympathetic nerve activity (ASNA) to systemic glucoprivation. Secondly, glucoprivation of neurons in the PeH increased ASNA. Thirdly, in vivo or in vitro glucoprivation did not affect the activity of RVLM adrenal premotor neurons. Finally, blockade of orexin receptors in the RVLM abolished the increase in ASNA to neuroglucoprivation in the PeH. The evoked changes in ASNA were directly correlated to levels of plasma metanephrine but not to normetanephrine. These findings suggest that orexin release modulates the activation of adrenal presympathetic neurons in the RVLM.Glucoprivation is a metabolic challenge capable of eliciting adrenaline release, an important mechanism for the restoration of normal blood glucose levels. Additionally, neuroglucoprivation produced by 2-deoxy-D-glucose (2DG) is used as an experimental tool to study glucoregulatory neurons (1-4). Previous findings suggest that adrenaline release in response to glucoprivation involves activation of neurons in the perifornical hypothalamus (PeH) and rostral ventrolateral medulla (RVLM). Systemic glucoprivation using 2DG excites RVLM sympathetic premotor neurons (5,6) and orexinergic neurons (7) in the PeH (8). Additionally, neurotropic viruses injected into the adrenal gland transsynaptically label neurons in the RVLM (9) and PeH (10). Disinhibition of perifornical neurons produces an increase in endogenous glucose production in the liver, which is mediated by the autonomic nervous system (11). However, it remains unknown whether intrinsic glucose sensitivity or projections from hypothalamic glucose-sensitive neurons (4,12,13) play an important role in the excitation of RVLM adrenal premotor neurons in response to glucoprivation; in particular, whether the responses evoked in RVLM neurons are modulated by orexinergic inputs (14,15).In this study, we hypothesized that PeH neurons respond to neuroglucoprivation and elicit adrenaline release by orexinergic activation of sympathetic premotor neurons in the RVLM. To test this hypothesis, we used a combination of in vivo and in vitro electrophysiological techniques to first examine the role played by neurons in the PeH in driving adrenal sympathetic nerve activity (ASNA). We then demonstrate for the first time that these effects are independent of any intrinsic sensitivity

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Section: Glucoprivation and Microinjectionsmentioning

confidence: 99%

Orexinergic Activation of Medullary Premotor Neurons Modulates the Adrenal Sympathoexcitation to Hypothalamic Glucoprivation

et al. 2014

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“…Atropine-resistant theta became known as type I theta, since it occurred during Type I (voluntary) motor behaviors, such as walking, rearing and postural adjustments. These oscillations can be modulated by stress, in the case of type II theta, related to cognition (Hsiao et al, 2012 ) but also by other behavioral variables, in particular by locomotion, in the case of type I theta (Vanderwolf, 1969 ; Buzsáki, 2002 ). In the theta frequency range, Mu oscillations are thought to reflect the vigilance state (Kramis et al, 1975 ; Sakata et al, 2005 ; Popa et al, 2010 ) but can be affected by sensory inputs (Fanselow et al, 2001 ; Tort et al, 2010 ; Aitake et al, 2011 ; Fries, 2015 ).…”

Section: Methodsmentioning

confidence: 99%

Acute Stress Affects the Expression of Hippocampal Mu Oscillations in an Age-Dependent Manner

Takillah

Naudé

Didienne

et al. 2017

Front. Aging Neurosci.

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Anxiolytic drugs are widely used in the elderly, a population particularly sensitive to stress. Stress, aging and anxiolytics all affect low-frequency oscillations in the hippocampus and prefrontal cortex (PFC) independently, but the interactions between these factors remain unclear. Here, we compared the effects of stress (elevated platform, EP) and anxiolytics (diazepam, DZP) on extracellular field potentials (EFP) in the PFC, parietal cortex and hippocampus (dorsal and ventral parts) of adult (8 months) and aged (18 months) Wistar rats. A potential source of confusion in the experimental studies in rodents comes from locomotion-related theta (6–12 Hz) oscillations, which may overshadow the direct effects of anxiety on low-frequency and especially on the high-amplitude oscillations in the Mu range (7–12 Hz), related to arousal. Animals were restrained to avoid any confound and isolate the direct effects of stress from theta oscillations related to stress-induced locomotion. We identified transient, high-amplitude oscillations in the 7–12 Hz range (“Mu-bursts”) in the PFC, parietal cortex and only in the dorsal part of hippocampus. At rest, aged rats displayed more Mu-bursts than adults. Stress acted differently on Mu-bursts depending on age: it increases vs. decreases burst, in adult and aged animals, respectively. In contrast DZP (1 mg/kg) acted the same way in stressed adult and age animal: it decreased the occurrence of Mu-bursts, as well as their co-occurrence. This is consistent with DZP acting as a positive allosteric modulator of GABAA receptors, which globally potentiates inhibition and has anxiolytic effects. Overall, the effect of benzodiazepines on stressed animals was to restore Mu burst activity in adults but to strongly diminish them in aged rats. This work suggests Mu-bursts as a neural marker to study the impact of stress and DZP on age.

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“…A indução de úlceras foi replicada por outras pesquisas em ratos submetidos à restrição física -nas quais também se constatatou que sob efeito deste modelo de indução de estresse, a lesão do MnR induz maior supressão do sistema imunológico, maiores índices de corticosterona e de perda de peso em comparação aos animais controles falso operados (Andrade et al, 1999;Graeff, Guimaraes, De Andrade, & Deakin, 1996). Por fim, diversas pesquisas descreveram o papel do MnR no controle da atividade de ondas teta no hipocampo (Graeff et al, 1980;Hsiao, Jou, Yi, & Chang, 2012;Jackson, Dickson, & Bland, 2008;Kitchigina, Kudina, Kutyreva, & Vinogradova, 1999), demonstrando que a inativação deste núcleo desinibe a ocorrência destas ondas, promovendo constante atividade teta , 1995Vertes, Kinney, Kocsis, & Fortin, 1994). Com base nestes dados, o MnR exerceria o papel de pacemaker, dessincronizando a atividade hipocampal e inibindo a atividade teta -onda eletroencefalográfica que em ratos está fortemente associada ao sono REM, ao alerta diante de estímulos aversivos, à atividade locomotora, à atenção e à memória.…”

Section: O Núcleo Mediano Da Rafe (Mnr): Aspectos Funcionaisunclassified

Efeitos comportamentais da lesão eletrolítica da região do núcleo mediano da rafe como modelo experimental de mania no rato e no camundongo

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Activation of GABAergic pathway by hypocretin in the median raphe nucleus (MRN) mediates stress-induced theta rhythm in rats

Cited by 23 publications

References 36 publications

Orexinergic Activation of Medullary Premotor Neurons Modulates the Adrenal Sympathoexcitation to Hypothalamic Glucoprivation

Orexinergic Activation of Medullary Premotor Neurons Modulates the Adrenal Sympathoexcitation to Hypothalamic Glucoprivation

Acute Stress Affects the Expression of Hippocampal Mu Oscillations in an Age-Dependent Manner

Efeitos comportamentais da lesão eletrolítica da região do núcleo mediano da rafe como modelo experimental de mania no rato e no camundongo

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