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WIREs Mechanisms of Disease Jan 2022The lateral hypothalamus is critical for the control of ingestive behavior and spontaneous physical activity (SPA), as lesion or stimulation of this region alters these... (Review)
Review
The lateral hypothalamus is critical for the control of ingestive behavior and spontaneous physical activity (SPA), as lesion or stimulation of this region alters these behaviors. Evidence points to lateral hypothalamic orexin neurons as modulators of feeding and SPA. These neurons affect a broad range of systems, and project to multiple brain regions such as the dorsal raphe nucleus, which contains serotoninergic neurons (DRN) important to energy homeostasis. Physical activity is comprised of intentional exercise and SPA. These are opposite ends of a continuum of physical activity intensity and structure. Non-goal-oriented behaviors, such as fidgeting, standing, and ambulating, constitute SPA in humans, and reflect a propensity for activity separate from intentional activity, such as high-intensity voluntary exercise. In animals, SPA is activity not influenced by rewards such as food or a running wheel. Spontaneous physical activity in humans and animals burns calories and could theoretically be manipulated pharmacologically to expend calories and protect against obesity. The DRN neurons receive orexin inputs, and project heavily onto cortical and subcortical areas involved in movement, feeding and energy expenditure (EE). This review discusses the function of hypothalamic orexin in energy-homeostasis, the interaction with DRN serotonin neurons, and the role of this orexin-serotonin axis in regulating food intake, SPA, and EE. In addition, we discuss possible brain areas involved in orexin-serotonin cross-talk; the role of serotonin receptors, transporters and uptake-inhibitors in the pathogenesis and treatment of obesity; animal models of obesity with impaired serotonin-function; single-nucleotide polymorphisms in the serotonin system and obesity; and future directions in the orexin-serotonin field. This article is categorized under: Metabolic Diseases > Molecular and Cellular Physiology.
Topics: Animals; Energy Metabolism; Humans; Hypothalamic Area, Lateral; Hypothalamus; Orexins; Serotonin
PubMed: 35023323
DOI: 10.1002/wsbm.1536 -
Frontiers in Endocrinology 2023Histamine is a biogenic amine that acts as a neuromodulator within the brain. In the hypothalamus, histaminergic signaling contributes to the regulation of numerous... (Review)
Review
Histamine is a biogenic amine that acts as a neuromodulator within the brain. In the hypothalamus, histaminergic signaling contributes to the regulation of numerous physiological and homeostatic processes, including the regulation of energy balance. Histaminergic neurons project extensively throughout the hypothalamus and two histamine receptors (H1R, H3R) are strongly expressed in key hypothalamic nuclei known to regulate energy homeostasis, including the paraventricular (PVH), ventromedial (VMH), dorsomedial (DMH), and arcuate (ARC) nuclei. The activation of different histamine receptors is associated with differential effects on neuronal activity, mediated by their different G protein-coupling. Consequently, activation of H1R has opposing effects on food intake to that of H3R: H1R activation suppresses food intake, while H3R activation mediates an orexigenic response. The central histaminergic system has been implicated in atypical antipsychotic-induced weight gain and has been proposed as a potential therapeutic target for the treatment of obesity. It has also been demonstrated to interact with other major regulators of energy homeostasis, including the central melanocortin system and the adipose-derived hormone leptin. However, the exact mechanisms by which the histaminergic system contributes to the modification of these satiety signals remain underexplored. The present review focuses on recent advances in our understanding of the central histaminergic system's role in regulating feeding and highlights unanswered questions remaining in our knowledge of the functionality of this system.
Topics: Humans; Hypothalamus; Obesity; Arcuate Nucleus of Hypothalamus; Brain; Eating
PubMed: 37448468
DOI: 10.3389/fendo.2023.1202089 -
Brain Structure & Function Jul 2023The mammillary body (MB) is a component of the extended hippocampal system and many studies have shown that its functions are vital for mnemonic processes. Together with... (Review)
Review
The mammillary body (MB) is a component of the extended hippocampal system and many studies have shown that its functions are vital for mnemonic processes. Together with other subcortical structures, such as the anterior thalamic nuclei and tegmental nuclei of Gudden, the MB plays a crucial role in the processing of spatial and working memory, as well as navigation in rats. The aim of this paper is to review the distribution of various substances in the MB of the rat, with a description of their possible physiological roles. The following groups of substances are reviewed: (1) classical neurotransmitters (glutamate and other excitatory transmitters, gamma-aminobutyric acid, acetylcholine, serotonin, and dopamine), (2) neuropeptides (enkephalins, substance P, cocaine- and amphetamine-regulated transcript, neurotensin, neuropeptide Y, somatostatin, orexins, and galanin), and (3) other substances (calcium-binding proteins and calcium sensor proteins). This detailed description of the chemical parcellation may facilitate a better understanding of the MB functions and its complex relations with other structures of the extended hippocampal system.
Topics: Rats; Animals; Mammillary Bodies; Neurochemistry; Anterior Thalamic Nuclei; Amino Acids; Memory, Short-Term
PubMed: 37378855
DOI: 10.1007/s00429-023-02673-4 -
Frontiers in Endocrinology 2020The pituitary is a master endocrine gland that developed early in vertebrate evolution and therefore exists in all modern vertebrate classes. The last decade has... (Review)
Review
The pituitary is a master endocrine gland that developed early in vertebrate evolution and therefore exists in all modern vertebrate classes. The last decade has transformed our view of this key organ. Traditionally, the pituitary has been viewed as a randomly organized collection of cells that respond to hypothalamic stimuli by secreting their content. However, recent studies have established that pituitary cells are organized in tightly wired large-scale networks that communicate with each other in both homo and heterotypic manners, allowing the gland to quickly adapt to changing physiological demands. These networks functionally decode and integrate the hypothalamic and systemic stimuli and serve to optimize the pituitary output into the generation of physiologically meaningful hormone pulses. The development of 3D imaging methods and transgenic models have allowed us to expand the research of functional pituitary networks into several vertebrate classes. Here we review the establishment of pituitary cell networks throughout vertebrate evolution and highlight the main perspectives and future directions needed to decipher the way by which pituitary networks serve to generate hormone pulses in vertebrates.
Topics: Animals; Endocrine Cells; Gonadotrophs; Humans; Hypothalamo-Hypophyseal System; Hypothalamus; Metabolic Networks and Pathways; Phylogeny; Pituitary Gland; Vertebrates
PubMed: 33584547
DOI: 10.3389/fendo.2020.619352 -
International Journal of Molecular... Dec 2021Obesity has now reached pandemic proportions and represents a major socioeconomic and health problem in our societies [...].
Obesity has now reached pandemic proportions and represents a major socioeconomic and health problem in our societies [...].
Topics: Energy Metabolism; Humans; Hypothalamus; Obesity
PubMed: 34948254
DOI: 10.3390/ijms222413459 -
Current Biology : CB Dec 2023Endotherms can survive low temperatures and food shortage by actively entering a hypometabolic state known as torpor. Although the decrease in metabolic rate and body...
Endotherms can survive low temperatures and food shortage by actively entering a hypometabolic state known as torpor. Although the decrease in metabolic rate and body temperature (Tb) during torpor is controlled by the brain, the specific neural circuits underlying these processes have not been comprehensively elucidated. In this study, we identify the neural circuits involved in torpor regulation by combining whole-brain mapping of torpor-activated neurons, cell-type-specific manipulation of neural activity, and viral tracing-based circuit mapping. We find that Trpm2-positive neurons in the preoptic area and Vgat-positive neurons in the dorsal medial hypothalamus are activated during torpor. Genetic silencing shows that the activity of either cell type is necessary to enter the torpor state. Finally, we show that these cells receive projections from the arcuate and suprachiasmatic nucleus and send projections to brain regions involved in thermoregulation. Our results demonstrate an essential role of hypothalamic neurons in the regulation of Tb and metabolic rate during torpor and identify critical nodes of the torpor regulatory network.
Topics: Hypothalamus; Torpor; Preoptic Area; Suprachiasmatic Nucleus; Brain
PubMed: 37992720
DOI: 10.1016/j.cub.2023.10.076 -
Hormone Research in Paediatrics 2023The infantile, childhood, and adolescent periods of growth and development also represent times of increased vulnerability to stressors. Growth velocity in each period... (Review)
Review
The infantile, childhood, and adolescent periods of growth and development also represent times of increased vulnerability to stressors. Growth velocity in each period is dependent on the interplay of genetic, environmental, dietary, socioeconomic, developmental, behavioral, nutritional, metabolic, biochemical, and hormonal factors. A stressor may impact growth directly through modulation of the growth hormone axis or indirectly through other factors. The adaptive response to stressors culminates in behavioral, physiological, and biochemical responses which together support survival and conservation of energy. The immediate response involves activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. The time-limited stress response is at once antigrowth, antireproductive, and catabolic with no lasting adverse consequences. However, chronic activation of the stress system and hypercortisolism have consequential negative impacts on growth, thyroid function, reproduction-puberty, and metabolism. High cortisol suppresses growth hormone-insulin-like growth factor 1, hypothalamic-pituitary-gonadal, and thyroid axes and has been reported to be responsible for an increase in visceral adiposity, a decrease in lean mass, suppression of osteoblastic activity with risk of osteoporosis, and induction of insulin resistance. Early-life adversities, emotional or physical, have been associated with long-term negative physical and mental health outcomes. Existing models of chronic stress corroborate that early-life adversities can affect growth and have consequences in other aspects of well-being throughout the lifespan. Targeted interventions to reduce stress during infancy, childhood, and adolescence can have far-reaching benefits to long-term health as well as attaining adequate growth. In this review, we describe the neuroendocrinology of the stress response, the factors influencing growth, and the impact of chronic stress on growth during critical periods of infancy, childhood, and puberty with particular reference to growth, thyroid, and gonadal axis.
Topics: Humans; Child; Adolescent; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Pituitary Gland; Puberty; Growth Hormone; Stress, Physiological; Stress, Psychological
PubMed: 34814153
DOI: 10.1159/000521074 -
CNS Neuroscience & Therapeutics Dec 2023The lateral periaqueductal gray (LPAG), which mainly contains glutamatergic neurons, plays an important role in social responses, pain, and offensive and defensive...
OBJECTIVE
The lateral periaqueductal gray (LPAG), which mainly contains glutamatergic neurons, plays an important role in social responses, pain, and offensive and defensive behaviors. Currently, the whole-brain monosynaptic inputs to LPAG glutamatergic neurons are unknown. This study aims to explore the structural framework of the underlying neural mechanisms of LPAG glutamatergic neurons.
METHODS
This study used retrograde tracing systems based on the rabies virus, Cre-LoxP technology, and immunofluorescence analysis.
RESULTS
We found that 59 nuclei projected monosynaptic inputs to the LPAG glutamatergic neurons. In addition, seven hypothalamic nuclei, namely the lateral hypothalamic area (LH), lateral preoptic area (LPO), substantia innominata (SI), medial preoptic area, ventral pallidum, posterior hypothalamic area, and lateral globus pallidus, projected most densely to the LPAG glutamatergic neurons. Notably, we discovered through further immunofluorescence analysis that the inputs to the LPAG glutamatergic neurons were colocalized with several markers related to important neurological functions associated with physiological behaviors.
CONCLUSION
The LPAG glutamatergic neurons received dense projections from the hypothalamus, especially nuclei such as LH, LPO, and SI. The input neurons were colocalized with several markers of physiological behaviors, which show the pivotal role of glutamatergic neurons in the physiological behaviors regulation by LPAG.
Topics: Mice; Animals; Periaqueductal Gray; Brain; Neurons; Hypothalamus; Preoptic Area
PubMed: 37424163
DOI: 10.1111/cns.14338 -
Current Biology : CB May 2021How many thalamic neurons converge onto a cortical cell? This is an important question, because the organization of thalamocortical projections can influence the...
How many thalamic neurons converge onto a cortical cell? This is an important question, because the organization of thalamocortical projections can influence the cortical architecture. Here, we estimate the degree of thalamocortical convergence in primary visual cortex by taking advantage of the cortical expansion-neurons within a restricted volume in primary visual cortex have overlapping receptive fields driven by a smaller set of inputs from the lateral geniculate nucleus. Under these conditions, the measurements of cortical receptive fields in a population can be used to infer the receptive fields of their geniculate inputs and the weights of their projections using non-negative matrix factorization. The analysis reveals sparse connectivity, where a handful (~2-6) of thalamic inputs account for 90% of the total synaptic weight to a cortical neuron. Together with previous findings, these results paint a picture consistent with the idea that convergence of a few inputs partly determine the retinotopy and tuning properties of cortical cells..
Topics: Animals; Geniculate Bodies; Neurons; Primary Visual Cortex; Thalamus
PubMed: 33705713
DOI: 10.1016/j.cub.2021.02.032 -
Brain Structure & Function Sep 2023The Subthalamic Nucleus (STh) is a lens-shaped subcortical structure located ventrally to the thalamus, that despite being embryologically derived from the diencephalon,... (Review)
Review
The Subthalamic Nucleus (STh) is a lens-shaped subcortical structure located ventrally to the thalamus, that despite being embryologically derived from the diencephalon, is functionally implicated in the basal ganglia circuits. Because of this strict structural and functional relationship with the circuits of the basal ganglia, the STh is a current target for deep brain stimulation, a neurosurgical procedure employed to alleviate symptoms in movement disorders, such as Parkinson's disease and dystonia. However, despite the great relevance of this structure for both basal ganglia physiology and pathology, the neurochemical and molecular anatomy of the STh remains largely unknown. Few studies have specifically addressed the detection of neurotransmitter systems and their receptors within the structure, and even fewer have investigated their topographical distribution. Here, we have reviewed the scientific literature on neurotransmitters relevant in the STh function of rodents, non-human primates and humans including glutamate, GABA, dopamine, serotonin, noradrenaline with particular focus on their subcellular, cellular and topographical distribution. Inter-species differences were highlighted to provide a framework for further research priorities, particularly in humans.
Topics: Animals; Humans; Subthalamic Nucleus; Basal Ganglia; Thalamus; Dopamine; Parkinson Disease
PubMed: 37479801
DOI: 10.1007/s00429-023-02678-z