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Current Opinion in Pharmacology Aug 2023Gonadotropin-releasing hormone (GnRH) neurons are the final output pathway for the brain control of reproduction. The activity of this neuronal population, mainly... (Review)
Review
Gonadotropin-releasing hormone (GnRH) neurons are the final output pathway for the brain control of reproduction. The activity of this neuronal population, mainly located at the preoptic area of the hypothalamus, is controlled by a plethora of metabolic signals. However, it has been documented that most of these signal impact on GnRH neurons through indirect neuronal circuits, Kiss1, proopiomelanocortin, and neuropeptide Y/agouti-related peptide neurons being some of the most prominent mediators. In this context, compelling evidence has been gathered in recent years on the role of a large range of neuropeptides and energy sensors in the regulation of GnRH neuronal activity through both direct and indirect mechanisms. The present review summarizes some of the most prominent recent advances in our understanding of the peripheral factors and central mechanisms involved in the metabolic control of GnRH neurons.
Topics: Humans; Gonadotropin-Releasing Hormone; Reproduction; Hypothalamus; Neuropeptides; Neurons
PubMed: 37307655
DOI: 10.1016/j.coph.2023.102382 -
Journal of Experimental Zoology. Part... Apr 2024This review article includes a literature review of synteny analysis of the amphibian gonadotropin-releasing hormone (GnRH) genes, the distribution of GnRH 1 and GnRH2... (Review)
Review
This review article includes a literature review of synteny analysis of the amphibian gonadotropin-releasing hormone (GnRH) genes, the distribution of GnRH 1 and GnRH2 neurons in the central nervous system of amphibians, the function and regulation of hypophysiotropic GnRH1, and the function of GnRH1 in amphibian reproductive behaviors. It is generally accepted that GnRH is the key regulator of the hypothalamic-pituitary-gonadal axis. Three independent GnRH genes, GnRH1, GnRH2, and GnRH3, have been identified in vertebrates. Previous genome synteny analyses suggest that there are likely just two genes, gnrh1 and gnrh2, in amphibians. In three groups of amphibians: Anura, Urodela, and Gymnophiona, the distributions of GnRH1 and GnRH2 neurons in the central nervous system have also been previously reported. Moreover, these neuronal networks were determined to be structurally independent in all species examined. The somata of GnRH1 neurons are located in the terminal nerve, medial septum (MS), and preoptic area (POA), and some GnRH1 neurons in the MS and POA project into the median eminence. In contrast, the somata of GnRH2 neurons are located in the midbrain tegmentum. In amphibians, GnRH1 neurons originate from the embryonic olfactory placode, while GnRH2 neurons originate from the midbrain. The characterization and feedback regulation mechanisms of hypophysiotropic GnRH1 neurons in amphibians, the involvement of GnRH1 in amphibian reproductive behavior, and its possible mechanism of action should be elucidated in future.
Topics: Animals; Gonadotropin-Releasing Hormone; Reproduction; Vertebrates; Amphibians
PubMed: 38084833
DOI: 10.1002/jez.2769 -
Nature Neuroscience Oct 2023The prefrontal cortex (PFC) enables mammals to respond to situations, including internal states, with appropriate actions. One such internal state could be 'tiredness'....
The prefrontal cortex (PFC) enables mammals to respond to situations, including internal states, with appropriate actions. One such internal state could be 'tiredness'. Here, using activity tagging in the mouse PFC, we identified particularly excitable, fast-spiking, somatostatin-expressing, γ-aminobutyric acid (GABA) (PFC) cells that responded to sleep deprivation. These cells projected to the lateral preoptic (LPO) hypothalamus and the lateral hypothalamus (LH). Stimulating PFC terminals in the LPO hypothalamus caused sleep-preparatory behavior (nesting, elevated theta power and elevated temperature), and stimulating PFC terminals in the LH mimicked recovery sleep (non-rapid eye-movement sleep with higher delta power and lower body temperature). PFC terminals had enhanced activity during nesting and sleep, inducing inhibitory postsynaptic currents on diverse cells in the LPO hypothalamus and the LH. The PFC also might feature in deciding sleep location in the absence of excessive fatigue. These findings suggest that the PFC instructs the hypothalamus to ensure that optimal sleep takes place in a suitable place.
Topics: Mice; Animals; Hypothalamic Area, Lateral; Neurons; Somatostatin; Sleep; Hypothalamus; gamma-Aminobutyric Acid; Prefrontal Cortex; Mammals
PubMed: 37735497
DOI: 10.1038/s41593-023-01430-4 -
The Journal of Physiological Sciences :... Jun 2024Hibernation and torpor are not passive responses caused by external temperature drops and fasting but are active brain functions that lower body temperature. A...
Hibernation and torpor are not passive responses caused by external temperature drops and fasting but are active brain functions that lower body temperature. A population of neurons in the preoptic area was recently identified as such active torpor-regulating neurons. We hypothesized that the other hypothermia-inducing maneuvers would also activate these neurons. To test our hypothesis, we first refined the previous observations, examined the brain regions explicitly activated during the falling phase of body temperature using c-Fos expression, and confirmed the preoptic area. Next, we observed long-lasting hypothermia by reactivating torpor-tagged Gq-expressing neurons using the activity tagging and DREADD systems. Finally, we found that about 40-60% of torpor-tagged neurons were activated by succeeding isoflurane anesthesia and by icv administration of an adenosine A1 agonist. Isoflurane-induced and central adenosine-induced hypothermia is, at least in part, an active process mediated by the torpor-regulating neurons in the preoptic area.
Topics: Animals; Preoptic Area; Isoflurane; Adenosine; Neurons; Male; Anesthetics, Inhalation; Body Temperature; Hypothermia; Torpor; Mice; Proto-Oncogene Proteins c-fos
PubMed: 38867187
DOI: 10.1186/s12576-024-00927-2 -
Behavioral Neuroscience Aug 2023The medial preoptic area (MPOA) is well known for its role in sexual and maternal behaviors. This region also plays an important role in affiliative social behaviors...
The medial preoptic area (MPOA) is well known for its role in sexual and maternal behaviors. This region also plays an important role in affiliative social behaviors outside reproductive contexts. We recently demonstrated that the MPOA is a central nucleus in which opioids govern highly rewarding social play behavior in adolescent rats. However, the neural circuit mechanisms underlying MPOA-mediated social play remain largely unresolved. We hypothesized that the MPOA unites a complementary neural system through which social play induces reward via a projection to the ventral tegmental area (VTA) and reduces a negative affective state through a projection to the periaqueductal gray (PAG). To test whether the two projection pathways are activated in response to social play behavior, we combined retrograde tract tracing with immediate early gene (IEG) expression and immunofluorescent labeling to identify opioid-sensitive projection pathways from the MPOA to VTA and PAG that are activated after performance of social play. Retrograde tracer, fluoro-gold (FG), was microinjected into the VTA or PAG. IEG expression (i.e., Egr1) was assessed and triple immunofluorescent labeling for mu opioid receptor (MOR), Egr1, and FG in the MPOA was performed after social play. We revealed that play animals displayed an increase in neurons double labeled for Egr1 + FG and triple labeled for MOR + Egr1 + FG in the MPOA projecting to both the VTA and PAG when compared to no-play rats. The increased activation of projection neurons that express MORs from MPOA to VTA or PAG after social play suggests that opioids may act through these projection pathways to govern social play. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Topics: Female; Rats; Animals; Preoptic Area; Periaqueductal Gray; Neural Pathways; Ventral Tegmental Area; Analgesics, Opioid
PubMed: 36877484
DOI: 10.1037/bne0000555 -
The European Journal of Neuroscience Aug 2023The bed nucleus of the stria terminalis (BNST) is a neuropeptide-enriched brain region that modulates a wide variety of emotional behaviours and states, including...
The bed nucleus of the stria terminalis (BNST) is a neuropeptide-enriched brain region that modulates a wide variety of emotional behaviours and states, including stress, anxiety, reward and social interaction. The BNST consists of diverse subregions and neuronal ensembles; however, because of the high molecular heterogeneity within BNST neurons, the mechanisms through which the BNST regulates distinct emotional behaviours remain largely unclear. Prior studies have identified BNST calretinin (CR)-expressing neurons, which lack neuropeptides. Here, employing virus-based cell-type-specific retrograde and anterograde tracing systems, we mapped the whole-brain monosynaptic inputs and axonal projections of BNST CR-expressing neurons in male mice. We found that BNST CR-expressing neurons received inputs mainly from the amygdalopiriform transition area, central amygdala and hippocampus and moderately from the medial preoptic area, basolateral amygdala, paraventricular thalamus and lateral hypothalamus. Within the BNST, plenty of input neurons were primarily located in the oval and interfascicular subregions. Furthermore, numerous BNST CR-expressing neuronal boutons were observed within the BNST but not in other brain regions, thus suggesting that these neurons are a type of interneuron. These results will help further elucidate the neuronal circuits underlying the elaborate and distinct functions of the BNST.
Topics: Mice; Male; Animals; Septal Nuclei; Calbindin 2; Brain; Neuropeptides; Interneurons
PubMed: 37452644
DOI: 10.1111/ejn.16068 -
CNS Neuroscience & Therapeutics May 2024The preoptic area (POA) of the hypothalamus, crucial in thermoregulation, has long been implicated in the pain process. However, whether nociceptive stimulation affects...
AIMS
The preoptic area (POA) of the hypothalamus, crucial in thermoregulation, has long been implicated in the pain process. However, whether nociceptive stimulation affects body temperature and its mechanism remains poorly studied.
METHODS
We used capsaicin, formalin, and surgery to induce acute nociceptive stimulation and monitored rectal temperature. Optical fiber recording, chemical genetics, confocal imaging, and pharmacology assays were employed to confirm the role and interaction of POA astrocytes and extracellular adenosine. Immunofluorescence was utilized for further validation.
RESULTS
Acute nociception could activate POA astrocytes and induce a decrease in body temperature. Manipulation of astrocytes allowed bidirectional control of body temperature. Furthermore, acute nociception and astrocyte activation led to increased extracellular adenosine concentration within the POA. Activation of adenosine A1 or A2A receptors contributed to decreased body temperature, while inhibition of these receptors mitigated the thermo-lowering effect of astrocytes.
CONCLUSION
Our results elucidate the interplay between acute nociception and thermoregulation, specifically highlighting POA astrocyte activation. This enriches our understanding of physiological responses to painful stimuli and contributes to the analysis of the anatomical basis involved in the process.
Topics: Animals; Preoptic Area; Astrocytes; Nociception; Hypothermia; Male; Mice; Receptors, Purinergic P1; Mice, Inbred C57BL; Adenosine; Capsaicin; Formaldehyde
PubMed: 38715251
DOI: 10.1111/cns.14726 -
Frontiers in Physiology 2023The medial preoptic area (mPOA) participates in thermoregulatory control and blood pressure modulation as shown by studies with electrical stimulation of this area or...
The medial preoptic area (mPOA) participates in thermoregulatory control and blood pressure modulation as shown by studies with electrical stimulation of this area or cobalt chloride injection, a non-selective synapse inhibitor. This study aimed to investigate whether angiotensin II (Ang II) and GABA could act or not in the mPOA to mediate the cardiovascular and micturition control pathways. Female Wistar rats were submitted to stereotaxic surgery for implantation of a guide cannula into the mPOA 7 days prior to the experiments. Afterwards, the animals were isoflurane- anesthetized and submitted to the catheterization of the femoral artery and vein and urinary bladder cannulation for mean arterial pressure (MAP), heart rate (HR), and intravesical pressure (IP) recordings, respectively. After the baseline MAP, HR, and IP recordings for 15 min, Ang II (0.1 nM, 1 μL), losartan (AT-1 receptor antagonist, 100 nM, 1 μL), GABA (50 mM, 1 μL) or saline (1 μL) were injected into the mPOA, and the variables were measured for additional 30 min. In a different group of rats, the AT-1 receptor, angiotensin II converting enzyme (ACE), and GABAa receptor gene expression was evaluated in mPOA samples by qPCR. The data are as mean ± SEM and submitted to One-way ANOVA (Tukey posttest) or paired Student t-test (P <0.05). The injection of Ang II into the mPOA evoked a significant hypotension (-37±10 mmHg, n = 6, = 0.024) and bradycardia (-47 ± 20 bpm, = 0.030) compared to saline (+1 ± 1 mmHg and +6 ± 2 bpm, n = 6). A significant increase in IP was observed after Ang II injection into the mPOA (+72.25 ± 17.91%, = 0.015 vs. -1.80 ± 2.98%, n = 6, saline). No significant changes were observed in MAP, HR and IP after the losartan injection in the mPOA compared to saline injection. Injection of GABA into the mPOA evoked a significant fall in MAP and HR (-68 ± 2 mmHg, n = 6, < 0.0001 and -115 ± 14 bpm, n = 6, = 0.0002 vs. -1 ± 1 mmHg and +4 ± 2 bpm, n = 6, saline), but no significant changes were observed in IP. The AT-1 receptor, ACE and GABAa receptor mRNA expression was observed in all mPOA samples. Therefore, in female rats, Ang II mediated transmission in the mPOA is involved in the cardiovascular regulation and in the control of central micturition pathways. A phasic control dependent on AT-1 receptors in the mPOA seems to be involved in the regulation of those cardiovascular and intravesical 3 parameters. In contrast, GABAergic transmission in the mPOA participates in the pathways of cardiovascular control in anesthetized female rats, nevertheless, this neurotransmission is not involved in the micturition control.
PubMed: 37772054
DOI: 10.3389/fphys.2023.1224505 -
Annals of Anatomy = Anatomischer... Oct 2023Decreased estrogen levels can cause abnormal thermosensitivity of the preoptic area (POA) in the hypothalamus during menopause, which may cause hot flashes....
BACKGROUND
Decreased estrogen levels can cause abnormal thermosensitivity of the preoptic area (POA) in the hypothalamus during menopause, which may cause hot flashes. Thermosensitive transient receptors (ThermoTRPs) affect the thermosensitivity of neurons. It is worth exploring whether ThermoTRPs change under low estrogen state and participate in the abnormal thermoregulation of POA.
METHODS
Adult female Sprague-Dawley rats were randomly divided into sham operation (SHAM), ovariectomy (OVX) and estrogen treatment after ovariectomy (OVX+E) groups. Under 10 ℃, 18 ℃, 25 ℃, 37 ℃ and 45 ℃ incubations, their skin temperature was monitored and the expression of TRPA1, TRPM8, TRPM2, and TRPV1 in POA were investigated.
RESULTS
The skin temperature of ovariectomized rats changed faster and more dramatically under different incubation temperatures. The results at mRNA level show that only the expression of TRPM2 decreased in POA of OVX group compared with the other two groups at 25 ℃, TRPA1 expression in POA of the three groups increased at 10 ℃, TRPM8 increased at 10 ℃ and 18 ℃, TRPV1 increased at 10 ℃ and 45 ℃, while the expression of TRPM2 decreased at 10 ℃ and 18 ℃ and increased at 37 ℃ and 45 ℃. In all these cases, the magnitudes of the changes were less in the OVX group relative to the other two groups. The further immunohistochemical and Western blot results of TRPM2 and the activated TRPM2 positive cells labeled by c-Fos were consistent with the results of mRNA level.
CONCLUSIONS
The expression and thermosensitivity of TRPM2 in POA changed greatly under different incubation temperatures, but the changes in ovariectomized rats were less. This may be the key factor triggering thermoregulation dysfunction under low estrogen and may cause hot flashes.
Topics: Rats; Female; Animals; Humans; Preoptic Area; Hot Flashes; Rats, Sprague-Dawley; Transient Receptor Potential Channels; TRPM Cation Channels; Estradiol; Hypothalamus; Menopause; Estrogens; Body Temperature Regulation; RNA, Messenger; Ovariectomy
PubMed: 37454827
DOI: 10.1016/j.aanat.2023.152132 -
Neuropeptides Aug 2023Arginine vasopressin (AVP) plays a hypothermic regulatory role in thermoregulation and is an important endogenous mediator in this mechanism. In the preoptic area (POA),...
Arginine vasopressin (AVP) plays a hypothermic regulatory role in thermoregulation and is an important endogenous mediator in this mechanism. In the preoptic area (POA), AVP increases the spontaneous firing and thermosensitivity of warm-sensitive neurons and decreases those of cold-sensitive and temperature-insensitive neurons. Because POA neurons play a crucial role in precise thermoregulatory responses, these findings indicate that there is an association between the hypothermia and changes in the firing activity of AVP-induced POA neurons. However, the electrophysiological mechanisms by which AVP controls this firing activity remain unclear. Therefore, in the present study, using in vitro hypothalamic brain slices and whole-cell recordings, we elucidated the membrane potential responses of temperature-sensitive and -insensitive POA neurons to identify the applications of AVP or V vasopressin receptor antagonists. By monitoring changes in the resting potential and membrane potential thermosensitivity of the neurons before and during experimental perfusion, we observed that AVP increased the changes in the resting potential of 50% of temperature-insensitive neurons but reduced them in others. These changes are because AVP enhances the membrane potential thermosensitivity of nearly 50% of the temperature-insensitive neurons. On the other hand, AVP changes both the resting potential and membrane potential thermosensitivity of temperature-sensitive neurons, with no differences between the warm- and cold-sensitive neurons. Before and during AVP or V vasopressin receptor antagonist perfusion, no correlation was observed between changes in the thermosensitivity and membrane potential of all neurons. Furthermore, no correlation was observed between the thermosensitivity and membrane potential thermosensitivity of the neurons during experimental perfusion. In the present study, we found that AVP induction did not result in any changes in resting potential, which is unique to temperature-sensitive neurons. The study results suggest that AVP-induced changes in the firing activity and firing rate thermosensitivity of POA neurons are not controlled by resting potentials.
Topics: Rats; Animals; Preoptic Area; Membrane Potentials; Temperature; Arginine Vasopressin; Rats, Sprague-Dawley; Neurons
PubMed: 37148733
DOI: 10.1016/j.npep.2023.102344