GABAA, GABAC, and NMDA receptor subunit expression in the suprachiasmatic nucleus and other brain regions

O’Hara, Bruce F.; Andretic, Rozi; Heller, H. Craig; Carter, Donald B.; Kilduff, Thomas S.

doi:10.1016/0169-328x(94)00212-w

Cited by 97 publications

(68 citation statements)

References 61 publications

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“…Neuropeptide Y and ␥-aminobutyric acid (GABA) are putative transmitters of non-photic signals via the geniculohypothalamic tract to the SCN (77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91). We observed C-flanking peptide of neuropeptide Y, which was reported in geniculohypothalamic tract projections to the SCN (82), and the peptide fragment of GABA receptor subunit ␣-6.…”

Section: Discussionmentioning

confidence: 81%

Endogenous Peptide Discovery of the Rat Circadian Clock

Lee

Atkins

Hatcher

et al. 2010

Molecular & Cellular Proteomics

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Understanding how a small brain region, the suprachiasmatic nucleus (SCN), can synchronize the body's circadian rhythms is an ongoing research area. This important time-keeping system requires a complex suite of peptide hormones and transmitters that remain incompletely characterized. Here, capillary liquid chromatography and FTMS have been coupled with tailored software for the analysis of endogenous peptides present in the SCN of the rat brain. After ex vivo processing of brain slices, peptide extraction, identification, and characterization from tandem FTMS data with <5-ppm mass accuracy produced a hyperconfident list of 102 endogenous peptides, including 33 previously unidentified peptides, and 12 peptides that were post-translationally modified with amidation, phosphorylation, pyroglutamylation, or acetylation. This characterization of endogenous peptides from the SCN will aid in understanding the molecular mechanisms that mediate rhythmic behaviors in mammals. Molecular & Cellular Proteomics 9:285-297, 2010.

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Section: Discussionmentioning

confidence: 81%

Endogenous Peptide Discovery of the Rat Circadian Clock

Lee

Atkins

Hatcher

et al. 2010

Molecular & Cellular Proteomics

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“…␦-subunit was found to be undetectable by Western blot (41). However, we have found no studies which looked for the ␦-subunit in the hamster SCN.…”

Section: Discussionmentioning

confidence: 82%

“…The classical inhibitory neurotransmitter ␥-aminobutyric acid (GABA) (8,11,29,32), its receptors (16,35,41), synthesis enzymes (21,22,53), and transporters (4) are in nearly every cell in the SCN. There is substantial evidence both in vivo and in vitro that GABA plays a major role in the regulation of SCN neurons.…”

mentioning

confidence: 99%

Regulation of light's action in the mammalian circadian clock: role of the extrasynaptic GABA_A receptor

Ehlen¹,

Paul²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Over 90% of SCN neurons contain GABA as a neurotransmitter and express GABA A and GABA B receptors (8)(9)(10), and electrophysiological and pharmacological studies in vitro have pointed to GABA as a key signal mediating SCN neuronal network properties (11,12). Studies of mutant mice show that voltage-gated sodium channel type 1 (Na V 1.1) encoded by the Scn1a gene is the primary voltage-gated Na + channel in several classes of GABAergic interneurons (13,14).…”

mentioning

confidence: 99%

Na _V 1.1 channels are critical for intercellular communication in the suprachiasmatic nucleus and for normal circadian rhythms

Han

Yu²,

Schwartz³

et al. 2012

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

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Na V 1.1 is the primary voltage-gated Na + channel in several classes of GABAergic interneurons, and its reduced activity leads to reduced excitability and decreased GABAergic tone. Here, we show that Na V 1.1 channels are expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus. Mice carrying a heterozygous loss of function mutation in the Scn1a gene (Scn1a +/− ), which encodes the pore-forming α-subunit of the Na V 1.1 channel, have longer circadian period than WT mice and lack light-induced phase shifts. In contrast, Scn1a +/− mice have exaggerated light-induced negativemasking behavior and normal electroretinogram, suggesting an intact retina light response. Scn1a +/− mice show normal light induction of c-Fos and mPer1 mRNA in ventral SCN but impaired gene expression responses in dorsal SCN. Electrical stimulation of the optic chiasm elicits reduced calcium transients and impaired ventro-dorsal communication in SCN neurons from Scn1a +/− mice, and this communication is barely detectable in the homozygous gene KO (Scn1a −/− ). Enhancement of GABAergic transmission with tiagabine plus clonazepam partially rescues the effects of deletion of Na V 1.1 on circadian period and phase shifting. Our report demonstrates that a specific voltage-gated Na + channel and its associated impairment of SCN interneuronal communication lead to major deficits in the function of the master circadian pacemaker. Heterozygous loss of Na V 1.1 channels is the underlying cause for severe myoclonic epilepsy of infancy; the circadian deficits that we report may contribute to sleep disorders in severe myoclonic epilepsy of infancy patients. entrainment | neuronal oscillators | sodium channel T he mammalian suprachiasmatic nucleus (SCN) of the hypothalamus houses a master circadian clock that governs phase coordination between peripheral oscillators and overt circadian rhythms (1) as well as synchronization of these rhythms to the light-dark (LD) cycle through the retinohypothalamic tract (RHT) (2). Although SCN neurons are autonomous single-cell oscillators that rely on autoregulatory transcriptional/translational feedback loops of clock genes (3, 4), interneuronal synchronization is critical for the SCN to act as a tissue pacemaker with a coherent output (5, 6). Sodium-dependent action potentials are known to be essential for the synchronization between clock neurons in the SCN as well as necessary to maintain robust oscillations of clock gene expression (ref. 7 and reviewed in ref. 6), but the molecular identity of voltage-gated Na + channels contributing to the synchronization of the SCN neuronal network is currently unknown.Over 90% of SCN neurons contain GABA as a neurotransmitter and express GABA A and GABA B receptors (8-10), and electrophysiological and pharmacological studies in vitro have pointed to GABA as a key signal mediating SCN neuronal network properties (11,12). Studies of mutant mice show that voltage-gated sodium channel type 1 (Na V 1.1) encoded by the Scn1a gene is the primary voltage-gated Na + channel in...

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GABAA, GABAC, and NMDA receptor subunit expression in the suprachiasmatic nucleus and other brain regions

Cited by 97 publications

References 61 publications

Endogenous Peptide Discovery of the Rat Circadian Clock

Endogenous Peptide Discovery of the Rat Circadian Clock

Regulation of light's action in the mammalian circadian clock: role of the extrasynaptic GABA_A receptor

Na _V 1.1 channels are critical for intercellular communication in the suprachiasmatic nucleus and for normal circadian rhythms

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GABAA, GABAC, and NMDA receptor subunit expression in the suprachiasmatic nucleus and other brain regions

Cited by 97 publications

References 61 publications

Endogenous Peptide Discovery of the Rat Circadian Clock

Endogenous Peptide Discovery of the Rat Circadian Clock

Regulation of light's action in the mammalian circadian clock: role of the extrasynaptic GABAA receptor

Na V 1.1 channels are critical for intercellular communication in the suprachiasmatic nucleus and for normal circadian rhythms

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Regulation of light's action in the mammalian circadian clock: role of the extrasynaptic GABA_A receptor

Na _V 1.1 channels are critical for intercellular communication in the suprachiasmatic nucleus and for normal circadian rhythms