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Acta Pharmacologica Sinica May 2024It has been shown that prostaglandin (PG) E synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural...
It has been shown that prostaglandin (PG) E synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE in male rats. The core temperature (T) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE. We demonstrated that EP3 receptor was a pivotal receptor for PGE-induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE, respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (I) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE; however, the I current density was significantly increased by PGE perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of I currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.
PubMed: 38702500
DOI: 10.1038/s41401-024-01289-6 -
The Journal of Experimental Biology May 2024Hibernation is an extreme state of seasonal energy conservation, reducing metabolic rate to as little as 1% of the active state. During the hibernation season, many...
Hibernation is an extreme state of seasonal energy conservation, reducing metabolic rate to as little as 1% of the active state. During the hibernation season, many species of hibernating mammals cycle repeatedly between the active (aroused) and hibernating (torpid) states (T-A cycling), using brown adipose tissue (BAT) to drive cyclical rewarming. The regulatory mechanisms controlling this process remain undefined but are presumed to involve thermoregulatory centres in the hypothalamus. Here, we used the golden hamster (Mesocricetus auratus), and high-resolution monitoring of BAT, core body temperature and ventilation rate, to sample at precisely defined phases of the T-A cycle. Using c-fos as a marker of cellular activity, we show that although the dorsomedial hypothalamus is active during torpor entry, neither it nor the pre-optic area shows any significant changes during the earliest stages of spontaneous arousal. Contrastingly, in three non-neuronal sites previously linked to control of metabolic physiology over seasonal and daily time scales - the choroid plexus, pars tuberalis and third ventricle tanycytes - peak c-fos expression is seen at arousal initiation. We suggest that through their sensitivity to factors in the blood or cerebrospinal fluid, these sites may mediate metabolic feedback-based initiation of the spontaneous arousal process.
Topics: Animals; Proto-Oncogene Proteins c-fos; Arousal; Torpor; Hibernation; Ependymoglial Cells; Choroid Plexus; Mesocricetus; Male; Adipose Tissue, Brown; Cricetinae
PubMed: 38690647
DOI: 10.1242/jeb.247224 -
BioRxiv : the Preprint Server For... Apr 2024Neurotensin (Nts) is a neuropeptide acting as a neuromodulator in the brain. Pharmacological studies have identified Nts as a potent hypothermic agent. The medial...
Neurotensin (Nts) is a neuropeptide acting as a neuromodulator in the brain. Pharmacological studies have identified Nts as a potent hypothermic agent. The medial preoptic area, a region that plays an important role in the control of thermoregulation, contains a high density of neurotensinergic neurons and Nts receptors. The conditions in which neurotensinergic neurons play a role in thermoregulation are not known. In this study optogenetic stimulation of preoptic Nts neurons induced a small hyperthermia. , optogenetic stimulation of preoptic Nts neurons resulted in synaptic release of GABA and net inhibition of the preoptic pituitary adenylate cyclase-activating polypeptide (PACAP) neurons firing activity. GABA-A receptor antagonist or genetic deletion of VGAT in Nts neurons unmasked also an excitatory effect that was blocked by a Nts receptor 1 antagonist. Stimulation of preoptic Nts neurons lacking VGAT resulted in excitation of PACAP neurons and hypothermia. Mice lacking VGAT expression in Nts neurons presented changes in the fever response and in the responses to heat or cold exposure as well as an altered circadian rhythm of body temperature. Chemogenetic activation of all Nts neurons in the brain induced a 4-5 °C hypothermia, which could be blocked by Nts receptor antagonists in the preoptic area. Chemogenetic activation of preoptic neurotensinergic projections resulted in robust excitation of preoptic PACAP neurons. Taken together our data demonstrate that endogenously released Nts can induce potent hypothermia and that excitation of preoptic PACAP neurons is the cellular mechanism that triggers this response.
PubMed: 38659782
DOI: 10.1101/2024.04.15.589556 -
The Journal of Neuroscience : the... Jun 2024Aggression is a crucial behavior that impacts access to limited resources in different environmental contexts. Androgens synthesized by the gonads promote aggression...
Aggression is a crucial behavior that impacts access to limited resources in different environmental contexts. Androgens synthesized by the gonads promote aggression during the breeding season. However, aggression can be expressed during the non-breeding season, despite low androgen synthesis by the gonads. The brain can also synthesize steroids ("neurosteroids"), including androgens, which might promote aggression during the non-breeding season. Male song sparrows, , are territorial year-round and allow the study of seasonal changes in the steroid modulation of aggression. Here, we quantified steroids following a simulated territorial intrusion (STI) for 10 min in wild adult male song sparrows during the breeding and non-breeding seasons. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we examined 11 steroids: pregnenolone, progesterone, corticosterone, dehydroepiandrosterone, androstenedione, testosterone, 5α-dihydrotestosterone, 17β-estradiol, 17α-estradiol, estriol, and estrone. Steroids were measured in blood and 10 microdissected brain regions that regulate social behavior. In both seasons, STI increased corticosterone in the blood and brain. In the breeding season, STI had no rapid effects on androgens or estrogens. Intriguingly, in the non-breeding season, STI increased testosterone and androstenedione in several behaviorally relevant regions, but not in the blood, where androgens remained non-detectable. Also in the non-breeding season, STI increased progesterone in the blood and specific brain regions. Overall, rapid socially modulated changes in brain steroid levels are more prominent during the non-breeding season. Brain steroid levels vary with season and social context in a region-specific manner and suggest a role for neuroandrogens in aggression during the non-breeding season.
Topics: Animals; Male; Seasons; Aggression; Androgens; Brain; Sparrows; Territoriality; Songbirds
PubMed: 38658166
DOI: 10.1523/JNEUROSCI.1095-23.2024 -
Peptides Jul 2024Close contact between lactating rodent mothers and their infants is essential for effective nursing. Whether the mother's effort to retrieve the infants to their nest...
Close contact between lactating rodent mothers and their infants is essential for effective nursing. Whether the mother's effort to retrieve the infants to their nest requires the vasopressin-signaling via V1b receptor has not been fully defined. To address this question, V1b receptor knockout (V1bKO) and control mice were analyzed in pup retrieval test. Because an exploring mother in a new test cage randomly accessed to multiple infants in changing backgrounds over time, a computer vision-based deep learning analysis was applied to continuously calculate the distances between the mother and the infants as a parameter of their relationship. In an open-field, a virgin female V1bKO mice entered fewer times into the center area and moved shorter distances than wild-type (WT). While this behavioral pattern persisted in V1bKO mother, the pup retrieval test demonstrated that total distances between a V1bKO mother and infants came closer in a shorter time than with a WT mother. Moreover, in the medial preoptic area, parts of the V1b receptor transcripts were detected in galanin- and c-fos-positive neurons following maternal stimulation by infants. This research highlights the effectiveness of deep learning analysis in evaluating the mother-infant relationship and the critical role of V1b receptor in pup retrieval during the early lactation phase.
Topics: Animals; Female; Mice; Animals, Newborn; Deep Learning; Lactation; Maternal Behavior; Mice, Knockout; Preoptic Area; Receptors, Vasopressin
PubMed: 38649033
DOI: 10.1016/j.peptides.2024.171226 -
Annals of Anatomy = Anatomischer... Jun 2024Short- or mid-term fasting, full or partial, triggers metabolic response known to have in turn health effects in an organism. At central level, the metabolic stimulus...
BACKGROUND
Short- or mid-term fasting, full or partial, triggers metabolic response known to have in turn health effects in an organism. At central level, the metabolic stimulus triggered by fasting is known to be perceived firstly by hypothalamic neurons. In the field of neuroscience, ribosomal protein S6 (S6) phosphorylation is commonly used as a readout of the mammalian target of rapamycin complex 1 signalling activation or as a marker for neuronal activity. The aim of this study is addressed to evaluate whether the phosphorylation of S6 occurs in the central neurons of zebrafish exposed to four (short-term) and seven (mid-term) days of complete fasting.
METHODS
Group-housed adult zebrafish were exposed to four and seven days of complete food withdrawal. At the end of the experimental period, Western blotting analyses were carried out to measure the expression levels of the phosphorylated S6 (pS6) by comparing the two experimental conditions versus the control group. The same antibody was then used to identify the distribution pattern of pS6 immunoreactive neurons in the whole brain and in the taste buds.
RESULTS
We did not observe increased pS6 levels expression in the brain of animals exposed to short-term fasting compared to the control, whereas the expression increased in brain homogenates of animals exposed to mid-term fasting. pS6 immunoreactivity was reported in some hypothalamic neurons, as well as in the dorsal area of telencephalon and preoptic area, a neurosecretory region homolog to the mammalian paraventricular nucleus. Remarkably, we observed pS6 immunostaining in the sensory cells of taste buds lining the oral epithelium.
CONCLUSIONS
Taken together, our data show that in zebrafish, differently from other fish species, seven days of fasting triggers neuronal activity. Furthermore, the immunostaining on sensory cells of taste buds suggests that metabolic changes may modulate also peripheral sensory cells. This event may have valuable implications when using zebrafish to design metabolic studies involving fasting as well as practical consequences on the animal welfare, in particularly stressful conditions, such as transportation.
Topics: Animals; Zebrafish; Phosphorylation; Fasting; Brain; Ribosomal Protein S6; Neurons; Animal Welfare
PubMed: 38642855
DOI: 10.1016/j.aanat.2024.152266 -
Neuroscience and Biobehavioral Reviews Jun 2024Understanding how social and affective behavioral states are controlled by neural circuits is a fundamental challenge in neurobiology. Despite increasing understanding... (Review)
Review
Understanding how social and affective behavioral states are controlled by neural circuits is a fundamental challenge in neurobiology. Despite increasing understanding of central circuits governing prosocial and agonistic interactions, how bodily autonomic processes regulate these behaviors is less resolved. Thermoregulation is vital for maintaining homeostasis, but also associated with cognitive, physical, affective, and behavioral states. Here, we posit that adjusting body temperature may be integral to the appropriate expression of social behavior and argue that understanding neural links between behavior and thermoregulation is timely. First, changes in behavioral states-including social interaction-often accompany changes in body temperature. Second, recent work has uncovered neural populations controlling both thermoregulatory and social behavioral pathways. We identify additional neural populations that, in separate studies, control social behavior and thermoregulation, and highlight their relevance to human and animal studies. Third, dysregulation of body temperature is linked to human neuropsychiatric disorders. Although body temperature is a "hidden state" in many neurobiological studies, it likely plays an underappreciated role in regulating social and affective states.
Topics: Body Temperature Regulation; Humans; Social Behavior; Animals; Brain; Neurons; Neural Pathways
PubMed: 38599356
DOI: 10.1016/j.neubiorev.2024.105667 -
Scientific Reports Apr 2024Nest-building behavior is a widely observed innate behavior. A nest provides animals with a secure environment for parenting, sleep, feeding, reproduction, and...
Nest-building behavior is a widely observed innate behavior. A nest provides animals with a secure environment for parenting, sleep, feeding, reproduction, and temperature maintenance. Since animal infants spend their time in a nest, nest-building behavior has been generally studied as parental behaviors, and the medial preoptic area (MPOA) neurons are known to be involved in parental nest-building. However, nest-building of singly housed male mice has been less examined. Here we show that male mice spent longer time in nest-building at the early to middle dark phase and at the end of the dark phase. These two periods are followed by sleep-rich periods. When a nest was removed and fresh nest material was introduced, both male and female mice built nests at Zeitgeber time (ZT) 6, but not at ZT12. Using Fos-immunostaining combined with double in situ hybridization of Vgat and Vglut2, we found that Vgat- and Vglut2-positive cells of the lateral preoptic area (LPOA) were the only hypothalamic neuron population that exhibited a greater number of activated cells in response to fresh nest material at ZT6, compared to being naturally awake at ZT12. Fos-positive LPOA neurons were negative for estrogen receptor 1 (Esr1). Both Vgat-positive and Vglut2-positive neurons in both the LPOA and MPOA were activated at pup retrieval by male mice. Our findings suggest the possibility that GABAergic and glutamatergic neurons in the LPOA are associated with nest-building behavior in male mice.
Topics: Humans; Mice; Male; Female; Animals; Hypothalamus; Preoptic Area; Neurons
PubMed: 38594484
DOI: 10.1038/s41598-024-59061-z -
Frontiers in Neural Circuits 2024Animals need sleep, and the suprachiasmatic nucleus, the center of the circadian rhythm, plays an important role in determining the timing of sleep. The main input to... (Review)
Review
Animals need sleep, and the suprachiasmatic nucleus, the center of the circadian rhythm, plays an important role in determining the timing of sleep. The main input to the suprachiasmatic nucleus is the retinohypothalamic tract, with additional inputs from the intergeniculate leaflet pathway, the serotonergic afferent from the raphe, and other hypothalamic regions. Within the suprachiasmatic nucleus, two of the major subtypes are vasoactive intestinal polypeptide (VIP)-positive neurons and arginine-vasopressin (AVP)-positive neurons. VIP neurons are important for light entrainment and synchronization of suprachiasmatic nucleus neurons, whereas AVP neurons are important for circadian period determination. Output targets of the suprachiasmatic nucleus include the hypothalamus (subparaventricular zone, paraventricular hypothalamic nucleus, preoptic area, and medial hypothalamus), the thalamus (paraventricular thalamic nuclei), and lateral septum. The suprachiasmatic nucleus also sends information through several brain regions to the pineal gland. The olfactory bulb is thought to be able to generate a circadian rhythm without the suprachiasmatic nucleus. Some reports indicate that circadian rhythms of the olfactory bulb and olfactory cortex exist in the absence of the suprachiasmatic nucleus, but another report claims the influence of the suprachiasmatic nucleus. The regulation of circadian rhythms by sensory inputs other than light stimuli, including olfaction, has not been well studied and further progress is expected.
Topics: Animals; Suprachiasmatic Nucleus; Hypothalamus; Circadian Rhythm; Vasoactive Intestinal Peptide; Sleep; Arginine Vasopressin
PubMed: 38590628
DOI: 10.3389/fncir.2024.1385908 -
Behavioural Brain Research May 2024Brain areas important for social perception, social reward, and social behavior - collectively referred to as the social-decision-making network (SDN) - appear to be...
Brain areas important for social perception, social reward, and social behavior - collectively referred to as the social-decision-making network (SDN) - appear to be highly conserved across taxa. These brain areas facilitate a variety of social behaviors such as conspecific approach/avoidance, aggression, mating, parental care, and recognition. Although the SDN has been investigated across taxa, little is known about its functioning in reptiles. Research on the snake SDN may provide important new insights, as snakes have a keen social perceptual system and express a relatively reduced repertoire of social behaviors. Here, we present the results of an experiment in which ball pythons (Python regius) interacted with a same-sex conspecific for one hour and neural activation was investigated through Fos immunoreactivity. Compared to controls, snakes that interacted socially had higher Fos counts in brain areas implicated in social behavior across taxa, such as the medial amygdala, preoptic area, nucleus accumbens, and basolateral amygdala. Additionally, we found differential Fos immunoreactivity in the ventral amygdala, which facilitates communication between social brain areas. In many of these areas, Fos counts differed by sex, which may be due to increased competition between males. Fos counts did not differ in early sensory (i.e., vomeronasal) processing structures. As ball python social systems lack parental care, cooperation, or long-term group living, these results provide valuable insight into the basal functions of the vertebrate social decision-making network.
Topics: Male; Animals; Proto-Oncogene Proteins c-fos; Brain; Preoptic Area; Nucleus Accumbens; Snakes
PubMed: 38522595
DOI: 10.1016/j.bbr.2024.114965