Regulation of Inhibitory Synaptic Transmission by Vasoactive Intestinal Peptide (VIP) in the Mouse Suprachiasmatic Nucleus

Itri, Jason N.; Colwell, Christopher S.

doi:10.1152/jn.00332.2003

Cited by 76 publications

(77 citation statements)

References 53 publications

(46 reference statements)

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“…Rhythmic GABA application has been shown to synchronize the firing of SCN neurons in vitro, making this signal a possible intermediary, although it is unknown whether GABA in the SCN is required for synchronization 11 . Alternatively, VIP signaling could directly activate clock gene transcription in neurons through its effects on intracellular calcium and cAMP signaling [42][43][44] . Future experiments should resolve whether VIP acts in a circadian manner or constitutively and whether it directly establishes and entrains rhythms in SCN neurons.…”

Section: Discussionmentioning

confidence: 99%

Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons

et al. 2005

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The mammalian suprachiasmatic nucleus (SCN) is a master circadian pacemaker. It is not known which SCN neurons are autonomous pacemakers or how they synchronize their daily firing rhythms to coordinate circadian behavior. Vasoactive intestinal polypeptide (VIP) and the VIP receptor VPAC 2 (encoded by the gene Vipr2) may mediate rhythms in individual SCN neurons, synchrony between neurons, or both. We found that Vip −/− and Vipr2 −/− mice showed two daily bouts of activity in a skeleton photoperiod and multiple circadian periods in constant darkness. Loss of VIP or VPAC 2 also abolished circadian firing rhythms in approximately half of all SCN neurons and disrupted synchrony between rhythmic neurons. Critically, daily application of a VPAC 2 agonist restored rhythmicity and synchrony to VIP −/− SCN neurons, but not to Vipr2 −/− neurons. We conclude that VIP coordinates daily rhythms in the SCN and behavior by synchronizing a small population of pacemaking neurons and maintaining rhythmicity in a larger subset of neurons.The SCN of the mammalian hypothalamus coordinates diverse daily rhythms, including states of vigilance, locomotor activity and hormonal release, through rhythms in neuronal firing 1 . These rhythms 'free-run' with a circadian period in the absence of synchronizing (or entraining) cues such as environmental light cycles. When the SCN are electrically silenced or lesioned, behavioral and physiologic rhythms disappear 2 .Rhythmic circadian firing within the SCN is dependent on cyclic expression of a family of 'clock genes'. Mutations of period 1 (Per1) or Per2, cryptochrome 1 (Cry 1) or Cry2, casein kinase Iε (Csnk1e), RevErbα (Nr1d1), BMAL1 (MOP3, Arntl) or clock lead to altered or abolished circadian periodicity 3 . These results have led to a model in which circadian rhythms are generated and sustained by an intracellular transcription-translation negative feedback loop. In support of this model for cell-autonomous pacemaking, single SCN neurons dispersed at low density onto a multielectrode array (MEA) can express firing rate patterns with different circadian periods 4 , leading to the suggestion that all 20,000 SCN neurons are autonomous circadian pacemakers 4-6 . In the intact SCN, these neurons usually synchronize to one another with defined phase relationships 7-10 . How synchrony is maintained between SCN neurons is Correspondence should be addressed to E.D.H. (herzog@wustl.edu).. COMPETING INTERESTS STATEMENTThe authors declare that they have no competing financial interests. Notably, rhythmicity and synchrony were restored to Vip −/− neurons by daily application of a VPAC 2 agonist. Our data show that many SCN neurons require VIP for rhythmicity, whereas others require it for synchrony. We conclude that a minority of SCN neurons are cellautonomous circadian pacemakers, which coordinate rhythms in the majority through VIP. NIH Public Access RESULTS Mice lacking VIP or VPAC 2 show multiple circadian periodsPrevious studies of locomotor activity in Vip −/− and Vipr2 −/− mutant mice ha...

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Section: Discussionmentioning

confidence: 99%

Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons

et al. 2005

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“…To record miniature and spontaneous postsynaptic currents (mPSCs and sPSCs, respectively), patch pipettes (4 -6 M⍀) were filled with an internal solution that was identical to the one used in current-clamp recordings, except for 120 mM K-gluconate and 20 KCl mM. In SCN neurons, this concentration of Cl Ϫ in the intracellular pipette solution causes the IPSCs to reverse between Ϫ40 to Ϫ50 mV (data not shown; but see Itri and Colwell, 2003). This positive shift in Cl Ϫ reversal potential causes both GABA and glutamate PSCs to appear as inward currents when membrane voltage is clamped at Ϫ70 mV.…”

Section: Whole-cell Recordingsmentioning

confidence: 99%

“…To discriminate between excitatory and inhibitory PSCs, a mixture of receptor antagonists (D-2-amino-5-phosphonopentanoate, AP-5; 6-cyano-7-nitroquinoxaline-2,3-dione, CNQX; and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide, NBQX) for the glutamate receptors and/or for the GABA A receptor (gabazine) were used. All recording protocols were similar to established methods for measuring PSCs in SCN neurons (Itri and Colwell, 2003).…”

Section: Whole-cell Recordingsmentioning

confidence: 99%

Acute Suppressive and Long-Term Phase Modulation Actions of Orexin on the Mammalian Circadian Clock

et al. 2014

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Circadian and homeostatic neural circuits organize the temporal architecture of physiology and behavior, but knowledge of their interactions is imperfect. For example, neurons containing the neuropeptide orexin homeostatically control arousal and appetitive states, while neurons in the suprachiasmatic nuclei (SCN) function as the brain's master circadian clock. The SCN regulates orexin neurons so that they are much more active during the circadian night than the circadian day, but it is unclear whether the orexin neurons reciprocally regulate the SCN clock. Here we show both orexinergic innervation and expression of genes encoding orexin receptors (OX 1 and OX 2 ) in the mouse SCN, with OX 1 being upregulated at dusk. Remarkably, we find through in vitro physiological recordings that orexin predominantly suppresses mouse SCN Period1 (Per1)-EGFP-expressing clock cells. The mechanisms underpinning these suppressions vary across the circadian cycle, from presynaptic modulation of inhibitory GABAergic signaling during the day to directly activating leak K ϩ currents at night. Orexin also augments the SCN clock-resetting effects of neuropeptide Y (NPY), another neurochemical correlate of arousal, and potentiates NPY's inhibition of SCN Per1-EGFP cells. These results build on emerging literature that challenge the widely held view that orexin signaling is exclusively excitatory and suggest new mechanisms for avoiding conflicts between circadian clock signals and homeostatic cues in the brain.

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“…VIP is necessary for synchrony between SCN neurons in vitro (5,6) and for coherent behavioral rhythmicity in vivo (7,8). GABA has been implicated because most (if not all) SCN neurons express GABA and its receptors (9)(10)(11), GABA is released in a daily rhythm within the SCN (12), and daily application of exogenous GABA synchronizes firing-rate rhythms of SCN neurons (13). How VIP mediates circadian synchrony and the necessity of GABA in this process have not been tested.…”

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confidence: 99%

GABA and G _i/o differentially control circadian rhythms and synchrony in clock neurons

Aton¹,

Huettner

Straume

et al. 2006

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

146

134

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Neurons in the mammalian suprachiasmatic nuclei (SCN) generate daily rhythms in physiology and behavior, but it is unclear how they maintain and synchronize these rhythms in vivo. We hypothesized that parallel signaling pathways in the SCN are required to synchronize rhythms in these neurons for coherent output. We recorded firing and clock-gene expression patterns while blocking candidate signaling pathways for at least 8 days. GABA A and GABA B antagonism increased circadian peak firing rates and rhythm precision of cultured SCN neurons, but G i/o did not impair synchrony or rhythmicity. In contrast, inhibiting G i/o with pertussis toxin abolished rhythms in most neurons and desynchronized the population, phenocopying the loss of vasoactive intestinal polypeptide (VIP). Daily VIP receptor agonist treatment restored synchrony and rhythmicity to VIP ؊/؊ SCN cultures during continuous GABA receptor antagonism but not during G i/o blockade. Pertussis toxin did not affect circadian cycling of the liver, suggesting that G i/o plays a specialized role in maintaining SCN rhythmicity. We conclude that endogenous GABA controls the amplitude of SCN neuronal rhythms by reducing daytime firing, whereas G i/o signaling suppresses nighttime firing, and it is necessary for synchrony among SCN neurons. We propose that G i/o, not GABA activity, converges with VIP signaling to maintain and coordinate rhythms among SCN neurons.luciferase ͉ multielectrode array ͉ Period gene ͉ suprachiasmatic nucleus ͉ vasoactive intestinal polypeptide T he suprachiasmatic nuclei (SCN) of the mammalian hypothalamus serve as a master circadian pacemaker, mediating daily rhythms in behavior and physiology. SCN pacemaker function depends on near-24-h oscillations in expression of ''clock genes'' and in firing rate (1). Previous studies have shown that of the nearly 20,000 neurons in the bilateral SCN, one subset comprises cell-autonomous circadian clocks, and another subset requires vasoactive intestinal polypeptide (VIP) signaling to maintain daily rhythms (2).For the SCN to coordinate coherent behavioral rhythms, SCN neurons must synchronize to one another in vivo. Blocking action potentials desynchronizes circadian rhythms among SCN neurons (3, 4). Neurotransmitters likely mediating synchrony within the SCN include VIP and GABA (2). VIP is necessary for synchrony between SCN neurons in vitro (5, 6) and for coherent behavioral rhythmicity in vivo (7,8). GABA has been implicated because most (if not all) SCN neurons express GABA and its receptors (9-11), GABA is released in a daily rhythm within the SCN (12), and daily application of exogenous GABA synchronizes firing-rate rhythms of SCN neurons (13). How VIP mediates circadian synchrony and the necessity of GABA in this process have not been tested.To examine the roles of endogenous GABA and G protein signaling, we recorded Period1::luciferase (Per1::luc) expression from SCN slices and firing rate and PERIOD2::luciferase (PER2::LUC) expression from individual SCN neurons. We find that long-term ant...

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Regulation of Inhibitory Synaptic Transmission by Vasoactive Intestinal Peptide (VIP) in the Mouse Suprachiasmatic Nucleus

Cited by 76 publications

References 53 publications

Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons

Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons

Acute Suppressive and Long-Term Phase Modulation Actions of Orexin on the Mammalian Circadian Clock

GABA and G _i/o differentially control circadian rhythms and synchrony in clock neurons

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Regulation of Inhibitory Synaptic Transmission by Vasoactive Intestinal Peptide (VIP) in the Mouse Suprachiasmatic Nucleus

Cited by 76 publications

References 53 publications

Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons

Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons

Acute Suppressive and Long-Term Phase Modulation Actions of Orexin on the Mammalian Circadian Clock

GABA and G i/o differentially control circadian rhythms and synchrony in clock neurons

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GABA and G _i/o differentially control circadian rhythms and synchrony in clock neurons