Estrous cycle plasticity in the central clock output to kisspeptin neurons: Implications for the preovulatory surge

Endocrinology ◽  
2021 ◽  
Author(s):  
Bradley B Jamieson ◽  
Gregory T Bouwer ◽  
Rebecca E Campbell ◽  
Richard Piet
Keyword(s):  
Estrous Cycle ◽  
Third Ventricle ◽  
Brain Slices ◽  
Neuron Activity ◽  
Sex Behavior ◽  
Ovulatory Cycle ◽  
Cellular Mechanisms ◽  
Action Potential Firing ◽  
Gonadotropin Secretion ◽  
Estrous Cycle Stage

Abstract Coordination of ovulation and behavior is critical to reproductive success in many species. During the female estrous cycle, the preovulatory gonadotropin surge occurs when ovarian follicles reach maturity and, in rodents, begins just before the daily onset of activity, ensuring ovulation coincides with sex behavior. Timing of the surge relies on projections from the suprachiasmatic nucleus (SCN), the locus of the central circadian clock, to hypothalamic circuits that regulate gonadotropin secretion. The cellular mechanisms through which the SCN controls these circuits and gates the preovulatory surge to the appropriate estrous cycle stage, however, are poorly understood. We investigated in mice the functional impact of SCN arginine-vasopressin (AVP) neuron projections to kisspeptin (Kiss1) neurons in the rostral periventricular area of the third ventricle (RP3V Kiss1), responsible for generating the preovulatory surge. Conditional anterograde tracing revealed that SCN AVP neurons innervate approximately half of the RP3V Kiss1 neurons. Optogenetic activation of SCN AVP projections in brain slices caused an AVP-mediated stimulation of RP3V Kiss1 action potential firing in proestrus, the cycle stage when the surge is generated. This effect was less prominent in diestrus, the preceding cycle stage, and absent in estrus, following ovulation. Remarkably, in estrus, activation of SCN AVP projections resulted in GABA-mediated inhibition of RP3V Kiss1 neuron firing, an effect rarely encountered in other cycle stages. Together, these data reveal functional plasticity in SCN AVP neuron output that drives opposing effects on RP3V Kiss1 neuron activity across the ovulatory cycle. This might contribute to gating activation of the preovulatory surge to the appropriate estrous cycle stage.

scholarly journals Changes in RFamide-Related Peptide-1 (RFRP-1)-Immunoreactivity During Postnatal Development and the Estrous Cycle

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4402-4410 ◽  
Author(s):  
Sara R. Jørgensen ◽  
Mille D. Andersen ◽  
Agnete Overgaard ◽  
Jens D. Mikkelsen
Keyword(s):  
Postnatal Development ◽  
Estrous Cycle ◽  
Third Ventricle ◽  
Female Rats ◽  
Male Rats ◽  
Relative Distribution ◽  
Gonadotropin Secretion ◽  
Related Peptide

Abstract GnRH is a key player in the hypothalamic control of gonadotropin secretion from the anterior pituitary gland. It has been shown that the mammalian counterpart of the avian gonadotropin inhibitory hormone named RFamide-related peptide (RFRP) is expressed in hypothalamic neurons that innervate and inhibit GnRH neurons. The RFRP precursor is processed into 2 mature peptides, RFRP-1 and RFRP-3. These are characterized by a conserved C-terminal motif RF-NH2 but display highly different N termini. Even though the 2 peptides are equally potent in vitro, little is known about their relative distribution and their distinct roles in vivo. In this study, we raised an antiserum selective for RFRP-1 and defined the distribution of RFRP-1-immunoreactive (ir) neurons in the rat brain. Next, we analyzed the level of RFRP-1-ir during postnatal development in males and females and investigated changes in RFRP-1-ir during the estrous cycle. RFRP-1-ir neurons were distributed along the third ventricle from the caudal part of the medial anterior hypothalamus throughout the medial tuberal hypothalamus and were localized in, but mostly in between, the dorsomedial hypothalamic, ventromedial hypothalamic, and arcuate nuclei. The number of RFRP-1-ir neurons and the density of cellular immunoreactivity were unchanged from juvenile to adulthood in male rats during the postnatal development. However, both parameters were significantly increased in female rats from peripuberty to adulthood, demonstrating prominent gender difference in the developmental control of RFRP-1 expression. The percentage of c-Fos-positive RFRP-1-ir neurons was significantly higher in diestrus as compared with proestrus and estrus. In conclusion, we found that adult females, as compared with males, have significantly more RFRP-1-ir per cell, and these cells are regulated during the estrous cycle.

scholarly journals Sex Hormones Regulate Rat Hepatic Monocarboxylate Transporter Expression and Membrane Trafficking

2017 ◽  
Vol 20 (1) ◽  
pp. 435 ◽  
Author(s):  
Jieyun Cao ◽  
Michael Ng ◽  
Melanie A Felmlee
Keyword(s):  
Sex Differences ◽  
Membrane Protein ◽  
Protein Expression ◽  
Estrous Cycle ◽  
Sex Hormones ◽  
Membrane Trafficking ◽  
Drug Disposition ◽  
Membrane Expression ◽  
Membrane Protein Expression ◽  
Estrous Cycle Stage

Purpose: Monocarboxylate transporters (MCTs) are involved in the transport of monocarboxylates such as ketone bodies, lactate, and pharmaceutical agents. CD147 functions as an ancillary protein for MCT1 and MCT4 for plasma membrane trafficking. Sex differences in MCT1 and MCT4 have been observed in muscle and reproductive tissues; however, there is a paucity of information on MCT sex differences in tissues involved in drug disposition. The objective of the present study was to quantify hepatic MCT1, MCT4 and CD147 mRNA, total cellular and membrane protein expression in males, over the estrous cycle in females and in ovariectomized (OVX) females. Method: Liver samples were collected from females at the four estrous cycle stages (proestrus, estrus, metestrus, diestrus), OVX females and male Sprague-Dawley rats (N = 3 – 5). Estrus cycle stage of females was determined by vaginal lavage. mRNA and protein (total and membrane) expression of MCT1, MCT4 and CD147 was evaluated by qPCR and western blot analysis. Results: MCT1 mRNA and membrane protein expression varied with estrous cycle stage, with OVX females having higher expression than males, indicating that female sex hormones may play a role in MCT1 regulation. MCT4 membrane expression varied with estrous cycle stage with expression significantly lower than males. MCT4 membrane expression in OVX females was also lower than males, suggesting that androgens play a role in membrane expression of MCT4. Males had higher membrane CD147 expression, whereas there was no difference in whole cell protein and mRNA levels suggesting that androgens are involved in regulating CD147 membrane localization. Conclusions: This study demonstrates hepatic expression and membrane localization of MCT1, MCT4 and CD147 are regulated by sex hormones. Sex differences in hepatic MCT expression may lead to altered drug disposition, so it is critical to elucidate the underlying mechanisms in the sex hormone-dependent regulation of MCT expression. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Agrp neuron activity is required for alcohol-induced overeating

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Sarah Cains ◽  
Craig Blomeley ◽  
Mihaly Kollo ◽  
Romeo Rácz ◽  
Denis Burdakov
Keyword(s):  
Alcohol Intake ◽  
Cell Activity ◽  
Brain Slices ◽  
Biological Factor ◽  
Calorie Intake ◽  
Neuron Activity ◽  
Biological Factors ◽  
Societal Factors ◽  
Core Elements

Abstract Alcohol intake associates with overeating in humans. This overeating is a clinical concern, but its causes are puzzling, because alcohol (ethanol) is a calorie-dense nutrient, and calorie intake usually suppresses brain appetite signals. The biological factors necessary for ethanol-induced overeating remain unclear, and societal causes have been proposed. Here we show that core elements of the brain’s feeding circuits—the hypothalamic Agrp neurons that are normally activated by starvation and evoke intense hunger—display electrical and biochemical hyperactivity on exposure to dietary doses of ethanol in brain slices. Furthermore, by circuit-specific chemogenetic interference in vivo, we find that the Agrp cell activity is essential for ethanol-induced overeating in the absence of societal factors, in single-housed mice. These data reveal how a widely consumed nutrient can paradoxically sustain brain starvation signals, and identify a biological factor required for appetite evoked by alcohol.

AV3V neurons that send axons to hypothalamic nuclei respond to the systemic injection of IL-1beta

1997 ◽  
Vol 272 (2) ◽  
pp. R532-R540 ◽  
Author(s):  
K. Ota ◽  
T. Katafuchi ◽  
A. Takaki ◽  
T. Hori
Keyword(s):  
Single Neuron ◽  
Sodium Salicylate ◽  
Third Ventricle ◽  
Neuron Activity ◽  
Systemic Injection ◽  
Local Synthesis ◽  
Hypothalamic Nuclei ◽  
Alpha Chloralose ◽  
Single Neuron Activity ◽  
Stimulation Of

The single neuron activity in the anteroventral region of the third ventricle (AV3V) was extracellularly recorded in urethan and alpha-chloralose anesthetized rats. Electrical stimulation of the medial preoptic area (mPOA) and the paraventricular nucleus (PVN) revealed a reciprocal neural connection between the AV3V and these hypothalamic nuclei with an ipsilateral preponderance. All the AV3V neurons, which were antidromically activated by the stimulation of the mPOA or the PVN, altered their activity after the systemic injection of interleukin (IL)-1beta. On the other hand, only about 60% of the AV3V neurons that showed orthodromic responses were affected by IL-1beta. In seven of nine AV3V neurons that were electrophysiologically identified to send their axons to the mPOA or the PVN, the recombinant human IL-1beta-induced excitation and inhibition were attenuated by a local application of sodium salicylate through multibarreled micropipettes. These results suggest that the AV3V neurons alter their activity in response to the blood-borne IL-1beta, at least in part, through a local synthesis of prostanoids and then send the information to the mPOA and PVN.

Synaptic Regulation of Proopiomelanocortin Neurons Can Occur Distal to the Arcuate Nucleus

2007 ◽  
Vol 97 (5) ◽  
pp. 3298-3304 ◽  
Author(s):  
Shane T. Hentges
Keyword(s):  
Cell Body ◽  
Energy Homeostasis ◽  
Arcuate Nucleus ◽  
Critical Role ◽  
Brain Slices ◽  
Gaba Release ◽  
Afferent Input ◽  
Inhibitory Synapses ◽  
Body Region ◽  
Neuron Activity

Energy homeostasis is controlled to a large extent by various signals that are integrated in the hypothalamus. It is generally considered that neurons in each of the hypothalamic nuclei are regulated by afferent projections that terminate within the cell body region of the nucleus. However, here it is shown that hypothalamic proopiomelanocortin (POMC) neurons receive synaptic inputs onto distal dendrites that reside outside of the cell body region in the arcuate nucleus. Previous studies using whole cell recordings from identified neurons in brain slices have shown that cannabinoids reduce GABA release from inhibitory synapses onto the POMC cells. Here it was found that endocannabinoids inhibited GABAergic inhibitory postsynaptic currents in POMC neurons only in intact sagittal brain slices, but not coronal, horizontal, or sagittal slices that were truncated rostrally at the level of the optic chiasm. Thus endocannabinoids inhibited presynaptic GABA release only at an anatomically distinct subset of POMC–neuron dendrites that extends rostrally beyond the arcuate nucleus into preoptic hypothalamic regions. There are two key results. First, the activity of POMC neurons can be regulated by afferent input at sites much farther from the soma than previously recognized. Second, endocannabinoids can act to inhibit inputs only at selective dendrites. POMC neurons play a critical role in the maintenance of body weight. Therefore these data suggest that energy balance may be regulated, in part, by modulation of POMC neuron activity at sites outside of the arcuate nucleus.

scholarly journals Firing patterns of gonadotropin-releasing hormone neurons are sculpted by their biologic state

2020 ◽  
Vol 7 (8) ◽  
pp. 201040
Author(s):  
Jonathon Penix ◽  
R. Anthony DeFazio ◽  
Eden A. Dulka ◽  
Santiago Schnell ◽  
Suzanne M. Moenter
Keyword(s):  
Action Potential ◽  
Polycystic Ovary ◽  
Brain Slices ◽  
Gonadotropin Releasing Hormone ◽  
Neuron Activity ◽  
Interval Order ◽  
Short Term ◽  
Firing Patterns ◽  
Releasing Hormone ◽  
Gnrh Neurons

Gonadotropin-releasing hormone (GnRH) neurons form the final pathway for the central neuronal control of fertility. GnRH is released in pulses that vary in frequency in females, helping drive hormonal changes of the reproductive cycle. In the common fertility disorder polycystic ovary syndrome (PCOS), persistent high-frequency hormone release is associated with disrupted cycles. We investigated long- and short-term action potential patterns of GnRH neurons in brain slices before and after puberty in female control and prenatally androgenized (PNA) mice, which mimic aspects of PCOS. A Monte Carlo (MC) approach was used to randomize action potential interval order. Dataset distributions were analysed to assess (i) if organization persists in GnRH neuron activity in vitro , and (ii) to determine if any organization changes with development and/or PNA treatment. GnRH neurons in adult control, but not PNA, mice produce long-term patterns different from MC distributions. Short-term patterns differ from MC distributions before puberty but become absorbed into the distributions with maturation, and the distributions narrow. These maturational changes are blunted by PNA treatment. Firing patterns of GnRH neurons in brain slices thus maintain organization dictated at least in part by the biologic status of the source and are disrupted in models of disease.

scholarly journals Neuropeptide S: a novel regulator of pain-related amygdala plasticity and behaviors

2013 ◽  
Vol 110 (8) ◽  
pp. 1765-1781 ◽  
Author(s):  
Wenjie Ren ◽  
Takaki Kiritoshi ◽  
Stéphanie Grégoire ◽  
Guangchen Ji ◽  
Remo Guerrini ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Direct Action ◽  
Brain Slices ◽  
Inhibitory Effect ◽  
Central Nucleus ◽  
High Frequency Stimulation ◽  
Synaptic Inhibition ◽  
Neuropeptide S ◽  
Cellular Mechanisms ◽  
Postsynaptic Action

Amygdala plasticity is an important contributor to the emotional-affective dimension of pain. Recently discovered neuropeptide S (NPS) has anxiolytic properties through actions in the amygdala. Behavioral data also suggest antinociceptive effects of centrally acting NPS, but site and mechanism of action remain to be determined. This is the first electrophysiological analysis of pain-related NPS effects in the brain. We combined whole cell patch-clamp recordings in brain slices and behavioral assays to test the hypothesis that NPS activates synaptic inhibition of amygdala output to suppress pain behavior in an arthritis pain model. Recordings of neurons in the laterocapsular division of the central nucleus (CeLC), which serves pain-related amygdala output functions, show that NPS inhibited the enhanced excitatory drive [monosynaptic excitatory postsynaptic currents (EPSCs)] from the basolateral amygdala (BLA) in the pain state. As shown by miniature EPSC analysis, the inhibitory effect of NPS did not involve direct postsynaptic action on CeLC neurons but rather a presynaptic, action potential-dependent network mechanism. Indeed, NPS increased external capsule (EC)-driven synaptic inhibition of CeLC neurons through PKA-dependent facilitatory postsynaptic action on a cluster of inhibitory intercalated (ITC) cells. NPS had no effect on BLA neurons. High-frequency stimulation (HFS) of excitatory EC inputs to ITC cells also inhibited synaptic activation of CeLC neurons, providing further evidence that ITC activation can control amygdala output. The cellular mechanisms by which EC-driven synaptic inhibition controls CeLC output remain to be determined. Administration of NPS into ITC, but not CeLC, also inhibited vocalizations and anxiety-like behavior in arthritic rats. A selective NPS receptor antagonist ([d-Cys(tBu)5]NPS) blocked electrophysiological and behavioral effects of NPS. Thus NPS is a novel tool to control amygdala output and pain-related affective behaviors through a direct action on inhibitory ITC cells.

scholarly journals Substance P excites GABAergic neurons in the mouse central amygdala through neurokinin 1 receptor activation

2015 ◽  
Vol 114 (4) ◽  
pp. 2500-2508 ◽  
Author(s):  
L. Sosulina ◽  
C. Strippel ◽  
H. Romo-Parra ◽  
A. L. Walter ◽  
T. Kanyshkova ◽  
...  
Keyword(s):  
Substance P ◽  
Fluorescent Protein ◽  
Input Resistance ◽  
Receptor Activation ◽  
Gabaergic Neurons ◽  
Acid Decarboxylase ◽  
Central Amygdala ◽  
Cellular Mechanisms ◽  
Action Potential Firing

Substance P (SP) is implicated in stress regulation and affective and anxiety-related behavior. Particularly high expression has been found in the main output region of the amygdala complex, the central amygdala (CE). Here we investigated the cellular mechanisms of SP in CE in vitro, taking advantage of glutamic acid decarboxylase-green fluorescent protein (GAD67-GFP) knockin mice that yield a reliable labeling of GABAergic neurons, which comprise 95% of the neuronal population in the lateral section of CE (CEl). In GFP-positive neurons within CEl, SP caused a membrane depolarization and increase in input resistance, associated with an increase in action potential firing frequency. Under voltage-clamp conditions, the SP-specific membrane current reversed at −101.5 ± 2.8 mV and displayed inwardly rectifying properties indicative of a membrane K+ conductance. Moreover, SP responses were blocked by the neurokinin type 1 receptor (NK1R) antagonist L-822429 and mimicked by the NK1R agonist [Sar9,Met(O2)11]-SP. Immunofluorescence staining confirmed localization of NK1R in GFP-positive neurons in CEl, predominantly in PKCδ-negative neurons (80%) and in few PKCδ-positive neurons (17%). Differences in SP responses were not observed between the major types of CEl neurons (late firing, regular spiking, low-threshold bursting). In addition, SP increased the frequency and amplitude of GABAergic synaptic events in CEl neurons depending on upstream spike activity. These data indicate a NK1R-mediated increase in excitability and GABAergic activity in CEl neurons, which seems to mostly involve the PKCδ-negative subpopulation. This influence can be assumed to increase reciprocal interactions between CElon and CEloff pathways, thereby boosting the medial CE (CEm) output pathway and contributing to the anxiogenic-like action of SP in the amygdala.

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