-
Frontiers in Neural Circuits 2023Parental care plays a crucial role in the physical and mental well-being of mammalian offspring. Although sexually naïve male mice, as well as certain strains of female... (Review)
Review
Parental care plays a crucial role in the physical and mental well-being of mammalian offspring. Although sexually naïve male mice, as well as certain strains of female mice, display aggression toward pups, they exhibit heightened parental caregiving behaviors as they approach the time of anticipating their offspring. In this Mini Review, I provide a concise overview of the current understanding of distinct limbic neural types and their circuits governing both aggressive and caregiving behaviors toward infant mice. Subsequently, I delve into recent advancements in the understanding of the molecular, cellular, and neural circuit mechanisms that regulate behavioral plasticity during the transition to parenthood, with a specific focus on the sex steroid hormone estrogen and neural hormone oxytocin. Additionally, I explore potential sex-related differences and highlight some critical unanswered questions that warrant further investigation.
Topics: Humans; Mice; Male; Animals; Female; Paternal Behavior; Aggression; Oxytocin; Mammals
PubMed: 38298741
DOI: 10.3389/fncir.2023.1340497 -
Molecular Metabolism Jun 2024Hypothalamic signals potently stimulate energy expenditure by engaging peripheral mechanisms to restore energy homeostasis. Previous studies have identified several...
OBJECTIVE
Hypothalamic signals potently stimulate energy expenditure by engaging peripheral mechanisms to restore energy homeostasis. Previous studies have identified several critical hypothalamic sites (e.g. preoptic area (POA) and ventromedial hypothalamic nucleus (VMN)) that could be part of an interconnected neurocircuit that controls tissue thermogenesis and essential for body weight control. However, the key neurocircuit that can stimulate energy expenditure has not yet been established.
METHODS
Here, we investigated the downstream mechanisms by which VMN neurons stimulate adipose tissue thermogenesis. We manipulated subsets of VMN neurons acutely as well as chronically and studied its effect on tissue thermogenesis and body weight control, using Sf1 and Adcyap1 mice and measured physiological parameters under both high-fat diet and standard chow diet conditions. To determine the node efferent to these VMN neurons, that is involved in modulating energy expenditure, we employed electrophysiology and optogenetics experiments combined with measurements using tissue-implantable temperature microchips.
RESULTS
Activation of the VMN neurons that express the steroidogenic factor 1 (Sf1; VMN neurons) reduced body weight, adiposity and increased energy expenditure in diet-induced obese mice. This function is likely mediated, at least in part, by the release of the pituitary adenylate cyclase-activating polypeptide (PACAP; encoded by the Adcyap1 gene) by the VMN neurons, since we previously demonstrated that PACAP, at the VMN, plays a key role in energy expenditure control. Thus, we then shifted focus to the subpopulation of VMN neurons that contain the neuropeptide PACAP (VMN neurons). Since the VMN neurons do not directly project to the peripheral tissues, we traced the location of the VMN neurons' efferents. We identified that VMN neurons project to and activate neurons in the caudal regions of the POA whereby these projections stimulate tissue thermogenesis in brown and beige adipose tissue. We demonstrated that selective activation of caudal POA projections from VMN neurons induces tissue thermogenesis, most potently in negative energy balance and activating these projections lead to some similar, but mostly unique, patterns of gene expression in brown and beige tissue. Finally, we demonstrated that the activation of the VMN neurons' efferents that lie at the caudal POA are necessary for inducing tissue thermogenesis in brown and beige adipose tissue.
CONCLUSIONS
These data indicate that VMN connections with the caudal POA neurons impact adipose tissue function and are important for induction of tissue thermogenesis. Our data suggests that the VMN → caudal POA neurocircuit and its components are critical for controlling energy balance by activating energy expenditure and body weight control.
Topics: Animals; Ventromedial Hypothalamic Nucleus; Thermogenesis; Preoptic Area; Mice; Neurons; Energy Metabolism; Male; Steroidogenic Factor 1; Pituitary Adenylate Cyclase-Activating Polypeptide; Diet, High-Fat; Mice, Inbred C57BL; Body Weight; Adipose Tissue, Brown
PubMed: 38729241
DOI: 10.1016/j.molmet.2024.101951 -
The Journal of Neuroscience : the... Nov 2023The medial preoptic area (MPOA) is a sexually dimorphic region of the brain that regulates social behaviors. The sexually dimorphic nucleus (SDN) of the MPOA has been...
Two-Step Actions of Testicular Androgens in the Organization of a Male-Specific Neural Pathway from the Medial Preoptic Area to the Ventral Tegmental Area for Modulating Sexually Motivated Behavior.
The medial preoptic area (MPOA) is a sexually dimorphic region of the brain that regulates social behaviors. The sexually dimorphic nucleus (SDN) of the MPOA has been studied to understand sexual dimorphism, although the anatomy and physiology of the SDN is not fully understood. Here, we characterized SDN neurons that contribute to sexual dimorphism and investigated the mechanisms underlying the emergence of such neurons and their roles in social behaviors. A target-specific neuroanatomical study using transgenic mice expressing Cre recombinase under the control of , a gene expressed abundantly in the SDN, revealed that SDN neurons are divided into two subpopulations, GABA neurons projecting to the ventral tegmental area (VTA), where they link to the dopamine system (Calb neurons), and GABA neurons that extend axons in the MPOA or project to neighboring regions (Calb neurons). Calb neurons were abundant in males, but were scarce or absent in females. There was no difference in the number of Calb neurons between sexes. Additionally, we found that emergence of Calb neurons requires two testicular androgen actions that occur first in the postnatal period and second in the peripubertal period. Chemogenetic analyses of Calb neurons indicated a role in modulating sexual motivation in males. Knockdown of in the MPOA reduced the intromission required for males to complete copulation. These findings provide strong evidence that a male-specific neural pathway from the MPOA to the VTA is organized by the two-step actions of testicular androgens for the modulation of sexually motivated behavior. The MPOA is a sexually dimorphic region of the brain that regulates social behaviors, although its sexual dimorphism is not fully understood. Here, we describe a population of MPOA neurons that contribute to the sexual dimorphism. These neurons only exist in masculinized brains, and they project their axons to the ventral tegmental area, where they link to the dopamine system. Emergence of such neurons requires two testicular androgen actions that occur first in the postnatal period and second in the peripubertal period. These MPOA neurons endow masculinized brains with a neural pathway from the MPOA to the ventral tegmental area and modulate sexually motivated behavior in males.
Topics: Animals; Mice; Female; Male; Preoptic Area; Androgens; Ventral Tegmental Area; Dopamine; Neural Pathways; Mice, Transgenic
PubMed: 37722849
DOI: 10.1523/JNEUROSCI.0361-23.2023 -
Psychological Review Jul 2023Maternal behavior is a highly motivated and adaptive social behavior. Its frequency and pattern change across the postpartum period in response to the changing... (Review)
Review
Maternal behavior is a highly motivated and adaptive social behavior. Its frequency and pattern change across the postpartum period in response to the changing characteristics of the young and psychophysiological state of the mother. In rodents, maternal behavior peaks shortly after parturition, remains stable for a certain period of time, and then declines gradually until weaning. These dramatic behavioral changes all happen within a 3- to 4-week period. This article reviews evidence on the role of the medial prefrontal cortex (mPFC) in the regulation of the postpartum maternal behavior cycle in rats. Based on this review, a triadic model is proposed to explain how the mPFC, functioning as an executive control system, organizes different patterned maternal responses in different stages of postpartum via its interactions with the maternal excitatory system (centered around the medial preoptic area, the mesolimbic dopamine [DA] system) and the maternal inhibitory system (centered around the olfactory bulb-medial amygdala-ventromedial hypothalamus system). Dopamine and serotonin are hypothesized to operate in all three neural systems to regulate maternal behavior by influencing the motivational, executive control, and memory processes. This triadic model provides a useful framework for understanding dynamic changes of postpartum maternal behavior, as it integrates the evidence-supported approach-withdrawal model with the new prefrontal regulatory model of maternal behavior. Future research aimed at delineating the exact maternal neurocircuits and their interactions could benefit from the ideas derived from this model. Given that human maternal behavior is mainly cortical-driven, this model has significant implications for constructing neural models of human parental behavior. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Topics: Female; Rats; Animals; Humans; Dopamine; Postpartum Period; Maternal Behavior; Brain; Amygdala; Prefrontal Cortex
PubMed: 35679205
DOI: 10.1037/rev0000374 -
Current Biology : CB Jan 2024Sleep disturbances are detrimental to our behavioral and emotional well-being. Stressful events disrupt sleep, in particular by inducing brief awakenings (microarousals,...
Sleep disturbances are detrimental to our behavioral and emotional well-being. Stressful events disrupt sleep, in particular by inducing brief awakenings (microarousals, MAs), resulting in sleep fragmentation. The preoptic area of the hypothalamus (POA) is crucial for sleep control. However, how POA neurons contribute to the regulation of MAs and thereby impact sleep quality is unknown. Using fiber photometry in mice, we examine the activity of genetically defined POA subpopulations during sleep. We find that POA glutamatergic neurons are rhythmically activated in synchrony with an infraslow rhythm in the spindle band of the electroencephalogram during non-rapid eye movement sleep (NREMs) and are transiently activated during MAs. Optogenetic stimulation of these neurons promotes MAs and wakefulness. Exposure to acute social defeat stress fragments NREMs and significantly increases the number of transients in the calcium activity of POA glutamatergic neurons during NREMs. By reducing MAs, optogenetic inhibition during spontaneous sleep and after stress consolidates NREMs. Monosynaptically restricted rabies tracing reveals that POA glutamatergic neurons are innervated by brain regions regulating stress and sleep. In particular, presynaptic glutamatergic neurons in the lateral hypothalamus become activated after stress, and stimulating their projections to the POA promotes MAs and wakefulness. Our findings uncover a novel circuit mechanism by which POA excitatory neurons regulate sleep quality after stress.
Topics: Mice; Animals; Sleep Deprivation; Sleep; Hypothalamus; Preoptic Area; Neurons; Wakefulness
PubMed: 38096820
DOI: 10.1016/j.cub.2023.11.035 -
Neuroscience Letters Sep 2023Transient receptor potential melastatin 8 (TRPM8) is a menthol receptor that detects cold temperatures and influences behaviors and autonomic functions under cold...
Transient receptor potential melastatin 8 (TRPM8) is a menthol receptor that detects cold temperatures and influences behaviors and autonomic functions under cold stimuli. Despite the well-documented peripheral roles of TRPM8, the evaluation of its central functions is still of great interest. The present study clarifies the nature of a subpopulation of TRPM8-expressing neurons in the adult mice. Combined in situ hybridization and immunohistochemistry revealed that TRPM8-expressing neurons are exclusively positive for glutamate decarboxylase 67 mRNA signals in the lateral septal nucleus (LS) and preoptic area (POA) but produced no positive signal for vesicular glutamate transporter 2. Double labeling immunohistochemistry showed the colocalization of TRPM8 with vesicular GABA transporter at axonal terminals. Immunohistochemistry further revealed that TRPM8-expressing neurons frequently expressed calbindin and calretinin in the LS, but not in the POA. TRPM8-expressing neurons in the POA expressed a prostaglandin E2 receptor, EP3, and neurotensin, whereas expression in the LS was minimal. These results indicate that hypothalamic TRPM8-expressing neurons are inhibitory GABAergic, while the expression profile of calcium-binding proteins, neurotensin, and EP3 differs between the POA and LS.
Topics: Animals; Mice; Neurotensin; Calcium-Binding Proteins; Calbindins; Cold Temperature; Neurons; TRPM Cation Channels
PubMed: 37640249
DOI: 10.1016/j.neulet.2023.137463 -
ELife Dec 2023Evidence suggests that estradiol-sensing preoptic area GABA neurons are involved in the preovulatory surge mechanism necessary for ovulation. In vivo CRISPR-Cas9 editing...
Evidence suggests that estradiol-sensing preoptic area GABA neurons are involved in the preovulatory surge mechanism necessary for ovulation. In vivo CRISPR-Cas9 editing was used to achieve a 60-70% knockdown in estrogen receptor alpha (ESR1) expression by GABA neurons located within the regions of the rostral periventricular area of the third ventricle (RP3V) and medial preoptic nuclei (MPN) in adult female mice. Mice exhibited variable reproductive phenotypes with the only significant finding being mice with bilateral ESR1 deletion in RP3V GABA neurons having reduced cFos expression in gonadotropin-releasing hormone (GnRH) neurons at the time of the surge. One sub-population of RP3V GABA neurons expresses kisspeptin. Re-grouping ESR1-edited mice on the basis of their RP3V kisspeptin expression revealed a highly consistent phenotype; mice with a near-complete loss of kisspeptin immunoreactivity displayed constant estrus and failed to exhibit surge activation but retained pulsatile luteinizing hormone (LH) secretion. These observations demonstrate that ESR1-expressing GABA-kisspeptin neurons in the RP3V are essential for the murine preovulatory LH surge mechanism.
Topics: Mice; Female; Animals; Kisspeptins; CRISPR-Cas Systems; Gonadotropin-Releasing Hormone; GABAergic Neurons; Estrous Cycle; gamma-Aminobutyric Acid
PubMed: 38126277
DOI: 10.7554/eLife.90959 -
Hormones and Behavior Sep 2023Social relationships, affiliative social attachments, are important for many species. The best studied types of relationships are monogamous pair bonds. However, it...
Social relationships, affiliative social attachments, are important for many species. The best studied types of relationships are monogamous pair bonds. However, it remains unclear how generalizable models of pair bonding are across types of social attachments. Zebra finches are a fascinating system to explore the neurobiology of social relationships because they form various adult bonds with both same- and opposite-sex partners. To test whether different bonds are supported by a single brain network, we quantified individuals' neuroendocrine state after either 24 h or 2 weeks of co-housing with a novel same- or opposite-sex partner. We defined neuroendocrine state by the expression of 22 genes related to 4 major signaling pathways (dopamine, steroid, nonapeptide, and opioid) in six brain regions associated with affiliation or communication [nucleus accumbens (NAc), nucleus taeniae of the amygdala (TnA), medial preoptic area (POM), and periaqueductal gray (PAG), ventral tegmental area, and auditory cortex]. Overall, we found dissociable effects of social contexts (same- or opposite-sex partnerships) and duration of co-housing. Social bonding impacted the neuroendocrine state of four regions in males (NAc, TnA, POM, and PAG) and three regions in females (NAc, TnA, and POM). Monogamous pair bonding specifically appeared to impact male NAc. However, the patterns of gene expression in zebra finches were different than has previously been reported in mammals. Together, our results support the view that there are numerous mechanisms regulating social relationships and highlight the need to further our understanding of how social interactions shape social bonds.
PubMed: 37678093
DOI: 10.1016/j.yhbeh.2023.105403 -
Nature Metabolism Sep 2023
Topics: Humans; Hypothalamus
PubMed: 37524786
DOI: 10.1038/s42255-023-00858-z -
Annals of the New York Academy of... Apr 2024This review consolidates current knowledge on mammalian parental care, focusing on its neural mechanisms, evolutionary origins, and derivatives. Neurobiological studies... (Review)
Review
This review consolidates current knowledge on mammalian parental care, focusing on its neural mechanisms, evolutionary origins, and derivatives. Neurobiological studies have identified specific neurons in the medial preoptic area as crucial for parental care. Unexpectedly, these neurons are characterized by the expression of molecules signaling satiety, such as calcitonin receptor and BRS3, and overlap with neurons involved in the reproductive behaviors of males but not females. A synthesis of comparative ecology and paleontology suggests an evolutionary scenario for mammalian parental care, possibly stemming from male-biased guarding of offspring in basal vertebrates. The terrestrial transition of tetrapods led to prolonged egg retention in females and the emergence of amniotes, skewing care toward females. The nocturnal adaptation of Mesozoic mammalian ancestors reinforced maternal care for lactation and thermal regulation via endothermy, potentially introducing metabolic gate control in parenting neurons. The established maternal care may have served as the precursor for paternal and cooperative care in mammals and also fostered the development of group living, which may have further contributed to the emergence of empathy and altruism. These evolution-informed working hypotheses require empirical validation, yet they offer promising avenues to investigate the neural underpinnings of mammalian social behaviors.
Topics: Humans; Animals; Female; Male; Parenting; Brain; Mammals; Social Behavior; Neurons; Maternal Behavior
PubMed: 38426943
DOI: 10.1111/nyas.15111