scholarly journals The Transcription Factor Ventral Anterior Homeobox 1 Modulates Circadian Time-Keeping and Fertility Through Direct Regulation of Vasoactive Intestinal Polypeptide Expression in the Suprachiasmatic Nucleus

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A556-A556
Author(s):  
Brooke M Devries ◽  
Joseph Breuer ◽  
Alexandra Yaw ◽  
Brooke Jackson ◽  
Duong Nguyen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Circadian Rhythms ◽  
Suprachiasmatic Nucleus ◽  
Vasoactive Intestinal Polypeptide ◽  
Wheel Running ◽  
Constant Darkness ◽  
Hormone Release ◽  
Males And Females ◽  
Intestinal Polypeptide ◽  
Ventral Anterior Homeobox 1

Abstract Light provides the primary timing signal that enables fine-tuned behavioral and hormonal entrainment of circadian rhythms to the environment. Light is transmitted from the eye to the brain through the retinohypothalamic tract, where one target is the hypothalamic suprachiasmatic nucleus (SCN), which generates self-sustained circadian rhythms. The vasoactive intestinal polypeptide (VIP) expressing neurons of the SCN relay light information to peripheral cells and tissues through control of hormonal and nervous signals, allowing synchronization of molecular clocks located in individual cells throughout the body. Non-natural light cycles, ie shiftwork, and weakened SCN function through genetic manipulation, disrupt the body’s circadian rhythms, causing deregulated hormone release, metabolic disorders, and negative effects on reproductive systems such as irregular menstrual cycles and decreased sperm count. To further our understanding of how the SCN translates light information into neuroendocrine control of fertility, we conditionally deleted the SCN enriched transcription factor Ventral anterior homeobox 1 (Vax1) in post-developmental VIP neurons, generating Vax1-flox/flox:Vip-Cre+ (cKO) mice. To determine if the SCN timekeeping function was impacted in cKO mice, we single housed males and females with running wheels to examine activity during both 12-hour light/dark cycles and in constant darkness. Wheel-running behavior in constant darkness revealed a shortening of the endogenous free-running period (Tau) of the SCN. Aside from Tau, wheel running behaviors were comparable to controls. Weakened SCN output can negatively impact fertility. While on 12-hour light/dark cycles, we found a modest, but significant change in follicle stimulating hormone and estrogen in cKO females and a reduced sensitivity of GnRH neurons to kisspeptin in males. The changes in hormone release were associated with a slightly lengthened estrous cycle in cKO females and reduced sperm quality in cKO males. To identify the molecular origin of the shortened SCN period, we used immunohistochemistry and RNAscope to examine expression of Vip. We found that diestrus cKO females had a significant reduction in Vip expression at ZT16 and preliminary data suggest a reduction in the circadian clock gene Bmal1. Together, these studies identify a novel role of VAX1 in VIP neurons where VAX1 is required for VIP expression and circadian timekeeping. Loss of VAX1 in VIP neurons weakens SCN output, deregulating reproductive hormone release and modestly reducing reproductive function in both males and females.

Disrupted circadian rhythms in VIP- and PHI-deficient mice

2003 ◽  
Vol 285 (5) ◽  
pp. R939-R949 ◽  
Author(s):  
Christopher S. Colwell ◽  
Stephan Michel ◽  
Jason Itri ◽  
Williams Rodriguez ◽  
J. Tam ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Wheel Running ◽  
Activity Rhythm ◽  
Activity Patterns ◽  
Circadian System ◽  
Diurnal Rhythms ◽  
Constant Darkness ◽  
Light Cycle ◽  
Wild Type ◽  
Deficient Mice

The related neuropeptides vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are expressed at high levels in the neurons of the suprachiasmatic nucleus (SCN), but their function in the regulation of circadian rhythms is unknown. To study the role of these peptides on the circadian system in vivo, a new mouse model was developed in which both VIP and PHI genes were disrupted by homologous recombination. In a light-dark cycle, these mice exhibited diurnal rhythms in activity which were largely indistinguishable from wild-type controls. In constant darkness, the VIP/PHI-deficient mice exhibited pronounced abnormalities in their circadian system. The activity patterns started ∼8 h earlier than predicted by the previous light cycle. In addition, lack of VIP/PHI led to a shortened free-running period and a loss of the coherence and precision of the circadian locomotor activity rhythm. In about one-quarter of VIP/PHI mice examined, the wheel-running rhythm became arrhythmic after several weeks in constant darkness. Another striking example of these deficits is seen in the split-activity patterns expressed by the mutant mice when they were exposed to a skeleton photoperiod. In addition, the VIP/PHI-deficient mice exhibited deficits in the response of their circadian system to light. Electrophysiological analysis indicates that VIP enhances inhibitory synaptic transmission within the SCN of wild-type and VIP/PHI-deficient mice. Together, the observations suggest that VIP/PHI peptides are critically involved in both the generation of circadian oscillations as well as the normal synchronization of these rhythms to light.

scholarly journals Effects of neonatal alcohol exposure on vasoactive intestinal polypeptide neurons in the rat suprachiasmatic nucleus

Alcohol ◽  
2009 ◽  
Vol 43 (5) ◽  
pp. 387-396 ◽  
Author(s):  
Yuhua Z. Farnell ◽  
Gregg C. Allen ◽  
Nichole Neuendorff ◽  
James R. West ◽  
A. Chen Wei-Jung ◽  
...  
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Vasoactive Intestinal Polypeptide ◽  
Alcohol Exposure ◽  
Neonatal Alcohol Exposure ◽  
Intestinal Polypeptide

scholarly journals Arginine-Vasopressin Expressing Neurons in the Murine Suprachiasmatic Nucleus Exhibit a Circadian Rhythm in Network Coherence in vivo

2021 ◽  
Author(s):  
Adam Stowie ◽  
Zhimei Qiao ◽  
Daniella Do Carmo Buonfiglio ◽  
J. Christopher Ehlen ◽  
Morris Benveniste ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Suprachiasmatic Nucleus ◽  
Arginine Vasopressin ◽  
Single Cells ◽  
Circadian Variation ◽  
Population Level ◽  
Correlational Analysis ◽  
Constant Darkness ◽  
Peak Time

AbstractThe Suprachiasmatic Nucleus (SCN) is composed of functionally distinct sub-populations of GABAergic neurons such as vasoactive intestinal polypeptide (VIP)-, arginine vasopressin (AVP)-, gastrin releasing peptide (GRP)-, and neuromedin S (NMS)-expressing neurons which form a neural network responsible for synchronizing most physiological and behavioral circadian rhythms in mammals. To date, little is known regarding which aspects of SCN rhythmicity are generated by individual SCN neurons or neuronal sub-populations and which aspects result from neuronal interaction within a network. In this study, we address this question utilizing in vivo miniaturized microscopy to measure fluorescent GCaMP-mediated calcium dynamics in AVP neurons in the intact SCN of awake, behaving mice. This approach permits analysis of rhythms of single cells, populations, and correlational analysis among groups of AVP neurons in a field of view across the circadian and diurnal day and night. We report that AVP neurons in the murine SCN exhibit a periodic oscillatory increase in calcium of approximately 14 seconds across the day and night, in both constant darkness and under a 12:12 light-dark (LD) cycle. Using in vivo optogentically-targeted single unit activity recording, we demonstrated that these slow calcium waves are likely the result of burst-firing characteristic of AVP neurons previously reported for other brain regions. Rhythmicity analysis of several fluorescence measures suggests that individual AVP neurons exhibit unstable and stochastic rhythms, with approximately 30% of the neurons rhythmic during any given day across lighting conditions, and weak or absent rhythmicity at the population level. Network-level cross-correlational analysis revealed that coherence among neuron pairs also exhibited stochastic rhythms with about 25% of pairs rhythmic at any time. Notably, this analysis revealed a stronger rhythm at the population level than was observed in single cell analysis. The peak time of maximal coherence among AVP neuronal pairs occurs between CT/ZT 6 and 9, coinciding with the timing of maximal neuronal activity with the SCN as a whole. These results are the first to demonstrate robust circadian variation in the coordination between apparently weakly rhythmic or arrhythmic neurons suggesting that, for AVP neurons, interactions between neurons in the SCN are more influential than individual or single subpopulation activity in the regulation of mammalian circadian rhythms.

Vasoactive intestinal polypeptide neuron changes in the senile rat suprachiasmatic nucleus

1988 ◽  
Vol 9 ◽  
pp. 307-312 ◽  
Author(s):  
C.A. Chee ◽  
B. Roozendaal ◽  
D.F. Swaab ◽  
E. Goudsmit ◽  
M. Mirmiran
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Vasoactive Intestinal Polypeptide ◽  
Intestinal Polypeptide

scholarly journals Free-running circadian breathing rhythms are eliminated by suprachiasmatic nucleus lesion

2020 ◽  
Vol 129 (1) ◽  
pp. 49-57
Author(s):  
Benton S. Purnell ◽  
Gordon F. Buchanan
Keyword(s):  
Sleep Apnea ◽  
Circadian Rhythms ◽  
Suprachiasmatic Nucleus ◽  
Time Of Day ◽  
Sudden Unexpected Death ◽  
Constant Darkness ◽  
Unexpected Death ◽  
Treatment And Prevention ◽  
Free Running

It has long been appreciated that breathing is altered by time of day. This study demonstrates that rhythmicity in breathing persists in constant darkness but is dependent on the suprachiasmatic nucleus in the hypothalamus. Understanding circadian rhythms in breathing may be important for the treatment and prevention of diseases such as sleep apnea and sudden unexpected death in epilepsy.

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