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The Journal of Comparative Neurology Sep 2022The macroscale neuronal connections of the lateral preoptic area (LPO) and the caudally adjacent lateral hypothalamic area anterior region (LHAa) were investigated in...
The macroscale neuronal connections of the lateral preoptic area (LPO) and the caudally adjacent lateral hypothalamic area anterior region (LHAa) were investigated in mice by anterograde and retrograde axonal tracing. Both hypothalamic regions are highly and diversely connected, with connections to >200 gray matter regions spanning the forebrain, midbrain, and rhombicbrain. Intrahypothalamic connections predominate, followed by connections with the cerebral cortex and cerebral nuclei. A similar overall pattern of LPO and LHAa connections contrasts with substantial differences between their input and output connections. Strongest connections include outputs to the lateral habenula, medial septal and diagonal band nuclei, and inputs from rostral and caudal lateral septal nuclei; however, numerous additional robust connections were also observed. The results are discussed in relation to a current model for the mammalian forebrain network that associates LPO and LHAa with a range of functional roles, including reward prediction, innate survival behaviors (including integrated somatomotor and physiological control), and affect. The present data suggest a broad and intricate role for LPO and LHAa in behavioral control, similar in that regard to previously investigated LHA regions, contributing to the finely tuned sensory-motor integration that is necessary for behavioral guidance supporting survival and reproduction.
Topics: Animals; Cerebral Cortex; Hypothalamic Area, Lateral; Hypothalamus; Mammals; Mice; Preoptic Area; Septal Nuclei
PubMed: 35579973
DOI: 10.1002/cne.25331 -
ELife Jun 2023Vocalizations facilitate mating and social affiliation but may also inadvertently alert predators and rivals. Consequently, the decision to vocalize depends on brain...
Vocalizations facilitate mating and social affiliation but may also inadvertently alert predators and rivals. Consequently, the decision to vocalize depends on brain circuits that can weigh and compare these potential benefits and risks. Male mice produce ultrasonic vocalizations (USVs) during courtship to facilitate mating, and previously isolated female mice produce USVs during social encounters with novel females. Earlier we showed that a specialized set of neurons in the midbrain periaqueductal gray (PAG-USV neurons) are an obligatory gate for USV production in both male and female mice, and that both PAG-USV neurons and USVs can be switched on by their inputs from the preoptic area (POA) of the hypothalamus and switched off by their inputs from neurons on the border between the central and medial amygdala (Amg neurons) (Michael et al., 2020). Here, we show that the USV-suppressing Amg neurons are strongly activated by predator cues or during social contexts that suppress USV production in male and female mice. Further, we explored how vocal promoting and vocal suppressing drives are weighed in the brain to influence vocal production in male mice, where the drive and courtship function for USVs are better understood. We found that Amg neurons receive monosynaptic inhibitory input from POA neurons that also project to the PAG, that these inhibitory inputs are active in USV-promoting social contexts, and that optogenetic activation of POA cell bodies that make divergent axonal projections to the amygdala and PAG is sufficient to elicit USV production in socially isolated male mice. Accordingly, Amg neurons, along with POA and PAG-USV neurons, form a nested hierarchical circuit in which environmental and social information converges to influence the decision to vocalize.
Topics: Mice; Male; Female; Animals; Periaqueductal Gray; Amygdala; Neurons; Ultrasonics; Preoptic Area; Vocalization, Animal
PubMed: 37314164
DOI: 10.7554/eLife.85547 -
Hormones and Behavior Feb 2023The medial preoptic area (mPOA) in the hypothalamus is an important integrator of neuroendocrine signaling and a key regulator of both natural and drug-induced reward....
The medial preoptic area (mPOA) in the hypothalamus is an important integrator of neuroendocrine signaling and a key regulator of both natural and drug-induced reward. Although the mPOA modulates sex differences in other behaviors, whether it also modulates sex differences in cocaine response remains unclear. To help us better understand the mPOA's role in sex differences associated with cocaine response, we examined cocaine-induced changes in locomotion and neural activity in the mPOA of male and female rats. In addition, neural activity in the striatum, a brain area known to be involved in cocaine response, was examined for comparison purposes. Fos, the protein product of the immediate early gene c-fos, was used as the marker of neural activity. Locomotion chambers were used to measure behavior, radioimmunoassays and vaginal lavages were used to determine hormonal status, and immunohistochemical assays were used to quantify Fos. To account for the effects of gonadal hormones, rats were left gonadally intact and categorized as either 'low-estradiol' or 'high-estradiol' based on their hormonal status on test day. Results indicate that high-estradiol females experienced greater cocaine-induced mPOA Fos-immunoreactivity (Fos-ir) and displayed greater cocaine-induced locomotion than low estradiol females. Conversely, high-estradiol males experienced less cocaine-induced mPOA Fos-ir and displayed less cocaine-induced locomotion than low-estradiol males. Cocaine-induced Fos-ir in the mPOA also correlated with cocaine-induced Fos-ir in areas of the striatum already associated with cocaine response. These findings further support the mPOA's role in the endocrine-mediated response to cocaine. It also identifies the mPOA as a contributor to sex differences in cocaine response and potential differences in vulnerability to developing cocaine use disorders.
Topics: Rats; Female; Male; Animals; Estradiol; Preoptic Area; Cocaine; Hypothalamus; Proto-Oncogene Proteins c-fos
PubMed: 36528006
DOI: 10.1016/j.yhbeh.2022.105296 -
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 -
Journal of Comparative Physiology. A,... May 2020Establishment of enduring sex differences in brain and behavior occurs during pre- or perinatal development, depending on species. For over 50 years the focus has been... (Review)
Review
Establishment of enduring sex differences in brain and behavior occurs during pre- or perinatal development, depending on species. For over 50 years the focus has been on gonadal steroid production by male fetuses and the impact on developing brain. An increasing awareness of the importance of sex chromosome complement has broadened the focus but identifying specific roles in development has yet to be achieved. Recent emphasis on transcriptomics has revealed myriad and unexpected differences in gene expression in specific regions of male and female brains which may produce sex differences, serve a compensatory role or provide latent sex differences revealed only in response to challenge. More surprising, however, has been the consistent observation of a central role for inflammatory signaling molecules and immune cells in masculinization of brain and behavior. The signal transduction pathways and specific immune cells vary by brain region, as does the neuroanatomical substrate subject to differentiation, reflecting substantial complexity emerging from what may be a common origin, the maternal immune system. A working hypothesis integrating these various ideas is proposed.
Topics: Animals; Behavior, Animal; Brain; Cell Death; Female; Histamine; Humans; Immune System; Inflammation Mediators; Male; Prostaglandins; Sex Characteristics; Sex Chromosomes; Sex Differentiation; Sex Factors; Signal Transduction; Transcriptome
PubMed: 31705197
DOI: 10.1007/s00359-019-01376-8 -
Frontiers in Neuroscience 2020Testicular androgens during the perinatal period play an important role in the sexual differentiation of the brain of rodents. Testicular androgens transported into the... (Review)
Review
Testicular androgens during the perinatal period play an important role in the sexual differentiation of the brain of rodents. Testicular androgens transported into the brain act via androgen receptors or are the substrate of aromatase, which synthesizes neuroestrogens that act via estrogen receptors. The latter that occurs in the perinatal period significantly contributes to the sexual differentiation of the brain. The preoptic area (POA) and the bed nucleus of the stria terminalis (BNST) are sexually dimorphic brain regions that are involved in the regulation of sex-specific social behaviors and the reproductive neuroendocrine system. Here, we discuss how neuroestrogens of testicular origin act in the perinatal period to organize the sexually dimorphic structures of the POA and BNST. Accumulating data from rodent studies suggest that neuroestrogens induce the sex differences in glial and immune cells, which play an important role in the sexually dimorphic formation of the dendritic synapse patterning in the POA, and induce the sex differences in the cell number of specific neuronal cell groups in the POA and BNST, which may be established by controlling the number of cells dying by apoptosis or the phenotypic organization of living cells. Testicular androgens in the peripubertal period also contribute to the sexual differentiation of the POA and BNST, and thus their aromatization to estrogens may be unnecessary. Additionally, we discuss the notion that testicular androgens that do not aromatize to estrogens can also induce significant effects on the sexually dimorphic formation of the POA and BNST.
PubMed: 32848568
DOI: 10.3389/fnins.2020.00797 -
Neuroscience and Biobehavioral Reviews Sep 2020The maternal behavior decline is important for the normal development of the young and the wellbeing of the mother. This paper reviews limited research on the factors... (Review)
Review
The maternal behavior decline is important for the normal development of the young and the wellbeing of the mother. This paper reviews limited research on the factors and mechanisms involved in the rat maternal behavior decline and proposes a multi-level model. Framed in the parent-offspring conflict theory (an ultimate cause) and the approach-withdrawal model (a proximate cause), the maternal behavior decline is viewed as an active and effortful process, reflecting the dynamic interplay between the mother and her offspring. It is instigated by the waning of maternal motivation, coupled with the increased maternal aversion by the mother in responding to the changing sensory and motoric patterns of pup stimuli. In the decline phase, the neural circuit that mediates the inhibitory ("withdrawal") responses starts to increase activity and gain control of behavioral outputs, while the excitatory ("approach") maternal neural circuit is being inhibited or reorganized. Various hormones and certain monoamines may play a critical role in tipping the balance between the excitatory and inhibitory neural circuits to synchronize the mother-infant interaction.
Topics: Animals; Female; Humans; Maternal Behavior; Motivation; Neurobiology; Rats
PubMed: 32569707
DOI: 10.1016/j.neubiorev.2020.06.009 -
Frontiers in Integrative Neuroscience 2022Complex social behaviors are emergent properties of the brain's interconnected and overlapping neural networks. Questions aimed at understanding how brain circuits... (Review)
Review
Complex social behaviors are emergent properties of the brain's interconnected and overlapping neural networks. Questions aimed at understanding how brain circuits produce specific and appropriate behaviors have changed over the past half century, shifting from studies of gross anatomical and behavioral associations, to manipulating and monitoring precisely targeted cell types. This technical progression has enabled increasingly deep insights into the regulation of perception and behavior with remarkable precision. The capacity of reductionist approaches to identify the function of isolated circuits is undeniable but many behaviors require rapid integration of diverse inputs. This review examines progress toward understanding integrative social circuits and focuses on specific nodes of the social behavior network including the medial amygdala, ventromedial hypothalamus (VMH) and medial preoptic area of the hypothalamus (MPOA) as examples of broad integration between multiple interwoven brain circuits. Our understanding of mechanisms for producing social behavior has deepened in conjunction with advances in technologies for visualizing and manipulating specific neurons and, here, we consider emerging strategies to address brain circuit function in the context of integrative anatomy.
PubMed: 35431824
DOI: 10.3389/fnint.2022.862437 -
Handbook of Clinical Neurology 2021In mammals, kisspeptin neurons are the key components of the hypothalamic neuronal networks that regulate the onset of puberty, account for the pulsatile secretion of... (Review)
Review
In mammals, kisspeptin neurons are the key components of the hypothalamic neuronal networks that regulate the onset of puberty, account for the pulsatile secretion of gonadotropin-releasing hormone (GnRH) and mediate negative and positive estrogen feedback signals to GnRH neurons. Being directly connected anatomically and functionally to the hypophysiotropic GnRH system, the major kisspeptin cell groups of the preoptic area/rostral hypothalamus and the arcuate (or infundibular) nucleus, respectively, are ideally positioned to serve as key nodes which integrate various types of environmental, endocrine, and metabolic signals that can influence fertility. This chapter provides an overview of the current state of knowledge on the anatomy, functions, and plasticity of brain kisspeptin systems based on the wide literature available from different laboratory and domestic species. Then, the species-specific features of human hypothalamic kisspeptin neurons are described, covering their topography, morphology, unique neuropeptide content, plasticity, and connectivity to hypophysiotropic GnRH neurons. Some newly emerging roles of central kisspeptin signaling in behavior and finally, clinical perspectives, are discussed.
Topics: Animals; Arcuate Nucleus of Hypothalamus; Gonadotropin-Releasing Hormone; Humans; Hypothalamus; Kisspeptins; Neuroanatomy
PubMed: 34225935
DOI: 10.1016/B978-0-12-820107-7.00017-3 -
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