GABA<sub>B</sub> receptor‐mediated modulation of hypocretin/orexin neurones in mouse hypothalamus

Xie, Xinmin; Crowder, Tara L.; Yamanaka, Akihiro; Morairty, Stephen R.; LeWinter, Robin D.; Sakurai, Takeshi; Kilduff, Thomas S.

doi:10.1113/jphysiol.2006.108266

Cited by 94 publications

(80 citation statements)

References 88 publications

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“…Next, we examined the effects of the GABA A and GABA B receptor antagonists, bicuculline (BIC) and CGP54626, respectively, on the activity of orexin neurons. Consistent with our previous study (9), orexin neurons in wild-type control slices did not respond to application of the antagonists BIC (25 M) (Fig. 3B) or CGP54626 (12 M) (data not shown).…”

Section: Elimination Of Gabab Receptors On Orexin Neurons Results In Ansupporting

confidence: 79%

“…EEG/EMG records were scored into 20-s epochs of each state. Brain slice preparations from oxGKO; orexin/eGFP mice subjected to patch-clamp recordings and electrophysiological analyses were as previously described (9,21). Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Orexin neurons also receive glutamatergic and GABAergic innervations from local interneurons (1,7). In vitro electrophysiological studies showed that both GABA A and GABA B agonists inhibit the activity of orexin neurons (7)(8)(9), but the physiological relevance of such regulation in vivo is unknown.…”

Section: Selective Loss Of Gaba B Receptors In Orexin-producing Neuromentioning

confidence: 99%

“…The partial GABA B R agonist gammahydroxybutyrate (GHB) (16) is used to treat both the excessive sleepiness and cataplexy symptoms of human narcolepsy. GAB-A B R activation inhibits presynaptic release of both glutamate and GABA onto orexin neurons (9) and both pre-and postsynaptic GABA B Rs modulate the activity of orexin neurons (9). In the present study, we engineered mice with a selective deletion of the GABA B1 gene specifically from orexin neurons (oxGKO mice) to study the consequences of the absence of GABA B Rs on orexin neuron function at the cellular and behavioral levels.…”

Section: Selective Loss Of Gaba B Receptors In Orexin-producing Neuromentioning

confidence: 99%

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Selective loss of GABA _B receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture

Matsuki

Nomiyama

Takahira³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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116

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Section: Elimination Of Gabab Receptors On Orexin Neurons Results In Ansupporting

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Selective Loss Of Gaba B Receptors In Orexin-producing Neuromentioning

confidence: 99%

Section: Selective Loss Of Gaba B Receptors In Orexin-producing Neuromentioning

confidence: 99%

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Selective loss of GABA _B receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture

Matsuki

Nomiyama

Takahira³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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116

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“…Bath application of GABA or GABA A receptor agonist muscimol could induce an early hyperpolarization mediated by Cl -and a late depolarization mediated by the efflux of bicarbonate. These GABA A receptor-mediated responses were blocked by Cl -channel blocker picrotoxin and GABA A receptor blocker bicuculline (Xie et al, 2006), picrotoxin and bicuculline could also induce seizure or convulsion (Cz³onkowska et al, 2000;Yamada et al, 2001). Recent investigation revealed that picrotoxin and bicuculline significantly antagonized the melatonin-induced increase in total sleep time, slow-wave sleep and paradoxical sleep, and the decrease in time to sleep onset and wakefulness (Wang et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Honokiol Potentiates Pentobarbital-Induced Sleeping Behaviors through GABA_AReceptor Cl^-Channel Activation

Ma¹,

Ma²,

Jo³

et al. 2008

Biomolecules and Therapeutics

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− This study was undertaken to investigate whether honokiol could enhance the pentobarbitalinduced sleeping behaviors through γ-aminobutyric acid (GABA) receptor Cl -channel activation. Thirty minutes after the oral administration of honokiol, mice were received sodium pentobarbital (42 mg/kg, i.p.). The time elapsed from pentobarbital injection to the loss of the righting reflex was taken as sleeping latency. The time elapsed between the loss and voluntary recovery of the righting reflex was considered as the total sleeping time. Western blot technique and Cl -sensitive fluorescence probe were used to detect the expression of GABA A receptor subunits and Cl -influx in the primary cultured cerebellar granule cells. Honokiol (0.1 and 0.2 mg/kg) prolonged the sleeping time induced by pentobarbital (42 mg/kg) in a dosage-dependent manner. Honokiol (20 and 50 µM) increased Cl -influx in primary cultured cerebellar granule cells, and selectively increased the GABA A receptor α-subunit expression, but had no effect on the abundance of β or γ-subunits. Chronic treatment with 20 µM honokiol in primary cultured cerebellar neurons did not affect the abundance of GAD65/67. The results suggested that honokiol could potentiate pentobarbital-induced sleeping through GABA A receptor Cl -channel activation.

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Descending projections from the basal forebrain to the orexin neurons in mice

Agostinelli

Ferrari

Mahoney

et al. 2017

J of Comparative Neurology

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The orexin (hypocretin) neurons play an essential role in promoting arousal, and loss of the orexin neurons results in narcolepsy, a condition characterized by chronic sleepiness and cataplexy. The orexin neurons excite wake-promoting neurons in the basal forebrain (BF), and a reciprocal projection from the BF back to the orexin neurons may help promote arousal and motivation. The BF contains at least three different cell types (cholinergic, glutamatergic, and GABAergic neurons) across its different regions (medial septum, diagonal band, magnocellular preoptic area, and substantia innominata). Given the neurochemical and anatomical heterogeneity of the BF, we mapped the pattern of BF projections to the orexin neurons across multiple BF regions and neuronal types. We performed conditional anterograde tracing using mice that express Cre recombinase only in neurons producing acetylcholine, glutamate, or GABA. We found that the orexin neurons are heavily apposed by axon terminals of glutamatergic and GABAergic neurons of the substantia innominata and magnocellular preoptic area, but there was no innervation by the cholinergic neurons. Channelrhodopsin-Assisted Circuit Mapping (CRACM) demonstrated that glutamatergic SI neurons frequently form functional synapses with the orexin neurons, but surprisingly, functional synapses from SI GABAergic neurons were rare. Considering their strong reciprocal connections, BF and orexin neurons likely work in concert to promote arousal, motivation, and other behaviors.

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GABA_B receptor‐mediated modulation of hypocretin/orexin neurones in mouse hypothalamus

Cited by 94 publications

References 88 publications

Selective loss of GABA _B receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture

Selective loss of GABA _B receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture

Honokiol Potentiates Pentobarbital-Induced Sleeping Behaviors through GABA_AReceptor Cl^-Channel Activation

Descending projections from the basal forebrain to the orexin neurons in mice

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GABAB receptor‐mediated modulation of hypocretin/orexin neurones in mouse hypothalamus

Cited by 94 publications

References 88 publications

Selective loss of GABA B receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture

Selective loss of GABA B receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture

Honokiol Potentiates Pentobarbital-Induced Sleeping Behaviors through GABAAReceptor Cl-Channel Activation

Descending projections from the basal forebrain to the orexin neurons in mice

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GABA_B receptor‐mediated modulation of hypocretin/orexin neurones in mouse hypothalamus

Selective loss of GABA _B receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture

Selective loss of GABA _B receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture

Honokiol Potentiates Pentobarbital-Induced Sleeping Behaviors through GABA_AReceptor Cl^-Channel Activation