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Frontiers in Physiology 2014The lateral parabrachial nucleus (LPBN) is located in an anatomical position that enables it to perform a critical role in relaying signals related to the regulation of... (Review)
Review
The lateral parabrachial nucleus (LPBN) is located in an anatomical position that enables it to perform a critical role in relaying signals related to the regulation of fluid and electrolyte intake and cardiovascular function from the brainstem to the forebrain. Early neuroanatomical studies have described the topographic organization of blood pressure sensitive neurons and functional studies have demonstrated a major role for the LPBN in regulating cardiovascular function, including blood pressure, in response to hemorrhages, and hypovolemia. In addition, inactivation of the LPBN induces overdrinking of water in response to a range of dipsogenic treatments primarily, but not exclusively, those associated with endogenous centrally acting angiotensin II. Moreover, treatments that typically cause water intake stimulate salt intake under some circumstances particularly when serotonin receptors in the LPBN are blocked. This review explores the expanding body of evidence that underlies the complex neural network within the LPBN influencing salt appetite, thirst and the regulation of blood pressure. Importantly understanding the interactions among neurons in the LPBN that affect fluid balance and cardiovascular control may be critical to unraveling the mechanisms responsible for hypertension.
PubMed: 25477821
DOI: 10.3389/fphys.2014.00436 -
Scientific Reports Jul 2020Anorexia nervosa is a complex eating disorder with genetic, metabolic, and psychosocial underpinnings. Using genome-wide methods, recent studies have associated many...
Anorexia nervosa is a complex eating disorder with genetic, metabolic, and psychosocial underpinnings. Using genome-wide methods, recent studies have associated many genes with the disorder. We characterized these genes by projecting them into reference transcriptomic atlases of the prenatal and adult human brain to determine where these genes are expressed in fine detail. We found that genes from an induced stem cell study of anorexia nervosa cases are expressed at higher levels in the lateral parabrachial nucleus. Although weaker, expression enrichment of the adult lateral parabrachial is also found with genes from independent genetic studies. Candidate causal genes from the largest genetic study of anorexia nervosa to date were enriched for expression in the arcuate nucleus of the hypothalamus. We also found an enrichment of anorexia nervosa associated genes in the adult and fetal raphe and ventral tegmental areas. Motivated by enrichment of these feeding circuits, we tested if these genes respond to fasting in mice hypothalami, which highlighted the differential expression of Rps26 and Dalrd3. This work improves our understanding of the neurobiology of anorexia nervosa by suggesting disturbances in subcortical appetitive circuits.
Topics: Adult; Animals; Anorexia Nervosa; Brain; Exome; Female; Gene Expression Profiling; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Hypothalamus; Induced Pluripotent Stem Cells; Male; Mice; Microglia; Oligonucleotide Array Sequence Analysis; Ribosomal Proteins; Transcriptome; tRNA Methyltransferases
PubMed: 32651428
DOI: 10.1038/s41598-020-67692-1 -
Handbook of Clinical Neurology 2018Body core temperature of mammals is regulated by the central nervous system, in which the preoptic area (POA) of the hypothalamus plays a pivotal role. The POA receives... (Review)
Review
Body core temperature of mammals is regulated by the central nervous system, in which the preoptic area (POA) of the hypothalamus plays a pivotal role. The POA receives peripheral and central thermosensory neural information and provides command signals to effector organs to elicit involuntary thermoregulatory responses, including shivering thermogenesis, nonshivering brown adipose tissue thermogenesis, and cutaneous vasoconstriction. Cool-sensory and warm-sensory signals from cutaneous thermoreceptors, monitoring environmental temperature, are separately transmitted through the spinal-parabrachial-POA neural pathways, distinct from the spinothalamocortical pathway for perception of skin temperature. These cutaneous thermosensory inputs to the POA likely impinge on warm-sensitive POA neurons, which monitor body core (brain) temperature, to alter thermoregulatory command outflows from the POA. The cutaneous thermosensory afferents elicit rapid thermoregulatory responses to environmental thermal challenges before they impact body core temperature. Peripheral humoral signals also act on neurons in the POA to transmit afferent information of systemic infection and energy storage to induce fever and to regulate energy balance, respectively. This chapter describes the thermoregulatory afferent mechanisms that convey cutaneous thermosensory signals to the POA and that integrate the neural and humoral afferent inputs to the POA to provide descending command signals to thermoregulatory effectors.
Topics: Afferent Pathways; Animals; Autonomic Nervous System; Body Temperature Regulation; Humans; Neurons; Preoptic Area; Shivering; Skin
PubMed: 30454594
DOI: 10.1016/B978-0-444-63912-7.00016-3 -
Brain and Nerve = Shinkei Kenkyu No... Mar 2022Epileptic activity that involves the central autonomic system, including the insular lobe, medial prefrontal cortex, amygdala, hypothalamus, periaqueductal gray,...
Epileptic activity that involves the central autonomic system, including the insular lobe, medial prefrontal cortex, amygdala, hypothalamus, periaqueductal gray, parabrachial complex, nucleus tractus solitarius, and ventrolateral medulla results in seizures with various autonomic manifestations. Some autonomic manifestations suggest localization and lateralization of epileptic foci. The autonomic nervous system modulates cerebral activity under physiological and pathological conditions. Vagus nerve stimulation (VNS) has attracted much attention for treatment of various neurological and psychiatric disorders and is an established palliative care strategy for patients with medically intractable epilepsy. Clinical and experimental studies suggest that VNS stabilizes cerebral cortical activity and inhibits abnormal excitability via pathways including upward vagus nerve conduction, nucleus tractus solitarius, and the thalamus, which consequently produces an anti-epileptic effect.
Topics: Autonomic Nervous System; Cerebral Cortex; Epilepsy; Humans; Medulla Oblongata; Thalamus; Vagus Nerve
PubMed: 35260526
DOI: 10.11477/mf.1416202023 -
Neurochemical Research Jan 2018Due to the biological importance of sodium and its relative scarcity within many natural environments, 'salt appetite' has evolved whereby dietary salt is highly sought... (Review)
Review
Due to the biological importance of sodium and its relative scarcity within many natural environments, 'salt appetite' has evolved whereby dietary salt is highly sought after and palatable when tasted. In addition to peripheral responses, salt depletion is detected within the brain via circumventricular organs and 11β-hydroxysteroid dehydrogenase type 2 (HSD2) neurons to increase salt appetite. Salt appetite is comprised of two main components. One component is the incentive salience or motivation for salt (i.e. how much salt is 'wanted'). Incentive salience is dynamic and largely depends on internal homeostatic conditions in combination with the detection of relevant cues. It involves the mesolimbic system and structures such as the central amygdala, and opioid signalling within these regions can increase salt intake in rodents. A second key feature is the hedonic palatability of salt (i.e. how much it is 'liked') when it is tasted. After detection on the tongue, gustatory information passes through the brainstem nucleus of the solitary tract and thalamus, before being consciously detected within the gustatory cerebral cortex. The positive or negative hedonic value of this stimulus is also dynamic, and is encoded by a network including the nucleus accumbens, ventral pallidum, and lateral parabrachial nucleus. Opioid signalling within these areas can alter salt intake, and 'liking'. The overconsumption of dietary salt likely contributes to hypertension and associated diseases, and hence further characterising the role played by opioid signalling has important implications for human health.
Topics: Analgesics, Opioid; Animals; Appetite; Brain; Humans; Motivation; Neurons; Sodium Chloride, Dietary
PubMed: 28646260
DOI: 10.1007/s11064-017-2336-3 -
Neuron Jan 2022Thermoregulatory behavior is a basic motivated behavior for body temperature homeostasis. Despite its fundamental importance, a forebrain region or defined neural...
Thermoregulatory behavior is a basic motivated behavior for body temperature homeostasis. Despite its fundamental importance, a forebrain region or defined neural population required for this process has yet to be established. Here, we show that Vgat-expressing neurons in the lateral hypothalamus (LH neurons) are required for diverse thermoregulatory behaviors. The population activity of LH neurons is increased during thermoregulatory behavior and bidirectionally encodes thermal punishment and reward (P&R). Although this population also regulates feeding and caloric reward, inhibition of parabrachial inputs selectively impaired thermoregulatory behaviors and encoding of thermal stimulus by LH neurons. Furthermore, two-photon calcium imaging revealed a subpopulation of LH neurons bidirectionally encoding thermal P&R, which is engaged during thermoregulatory behavior, but is largely distinct from caloric reward-encoding LH neurons. Our data establish LH neurons as a required neural substrate for behavioral thermoregulation and point to the key role of the thermal P&R-encoding LH subpopulation in thermoregulatory behavior.
Topics: Body Temperature Regulation; Hypothalamic Area, Lateral; Neurons; Prosencephalon; Reward
PubMed: 34687664
DOI: 10.1016/j.neuron.2021.09.039 -
ELife Mar 2022A new brain circuit that contributes to aversive states, such as fear or anxiety, has been characterized in mice.
A new brain circuit that contributes to aversive states, such as fear or anxiety, has been characterized in mice.
Topics: Affect; Animals; Anxiety; Brain; Emotions; Fear; Mice
PubMed: 35297762
DOI: 10.7554/eLife.77550 -
Peptides Aug 2021Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic polypeptide that can activate G protein-coupled PAC1, VPAC1, and VPAC2 receptors, and has... (Review)
Review
Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic polypeptide that can activate G protein-coupled PAC1, VPAC1, and VPAC2 receptors, and has been implicated in stress signaling. PACAP and its receptors are widely distributed throughout the nervous system and other tissues and can have a multitude of effects. Human and animal studies suggest that PACAP plays a role responding to a variety of threats and stressors. Here we review the roles of PACAP in several regions of the central nervous system (CNS) as they relate to several behavioral functions. For example, in the bed nucleus of the stria terminalis (BNST), PACAP is upregulated following chronic stress and may drive anxiety-like behavior. PACAP can also influence both the consolidation and expression of fear memories, as demonstrated by studies in several fear-related areas, such as the amygdala, hippocampus, and prefrontal cortex. PACAP can also mediate the emotional component of pain, as PACAP in the central nucleus of the amygdala (CeA) is able to decrease pain sensitivity thresholds. Outside of the central nervous system, PACAP may drive glucocorticoid release via enhanced hypothalamic-pituitary-adrenal axis activity and may participate in infection-induced stress responses. Together, this suggests that PACAP exerts effects on many stress-related systems and may be an important driver of emotional behavior.
Topics: Animals; Humans; Mental Disorders; Pituitary Adenylate Cyclase-Activating Polypeptide; Stress, Psychological
PubMed: 33865930
DOI: 10.1016/j.peptides.2021.170554 -
Seminars in Neurology Aug 2023Nervous system disorders may be accompanied by gastrointestinal (GI) dysfunction. Brain lesions may be responsible for GI problems such as decreased peristalsis (e.g.,... (Review)
Review
Nervous system disorders may be accompanied by gastrointestinal (GI) dysfunction. Brain lesions may be responsible for GI problems such as decreased peristalsis (e.g., lesions in the basal ganglia, pontine defecation center/Barrington's nucleus), decreased abdominal strain (e.g., lesions in the parabrachial nucleus), hiccupping and vomiting (e.g., lesions in the area postrema), and appetite loss (e.g., lesions in the hypothalamus). Decreased peristalsis also may be caused by lesions of the spinal long tracts or the intermediolateral nucleus projecting to the myenteric plexus. This review addresses GI dysfunction caused by multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein-associated disorder. Neuro-associated GI dysfunction may develop concurrently with brain or spinal cord dysfunction or may predate it. Collaboration between gastroenterologists and neurologists is highly desirable when caring for patients with GI dysfunction related to nervous system disorders, particularly since patients with these symptoms may visit a gastroenterologist prior to the establishment of a neurological diagnosis.
Topics: Humans; Multiple Sclerosis; Gastrointestinal Diseases; Myelin-Oligodendrocyte Glycoprotein; Basal Ganglia; Brain
PubMed: 37703888
DOI: 10.1055/s-0043-1771462 -
The Journal of Pain Aug 2022The lateral parabrachial nucleus (LPBN) plays an important role in the processing and establishment of pain aversion. It receives direct input from the superficial...
The lateral parabrachial nucleus (LPBN) plays an important role in the processing and establishment of pain aversion. It receives direct input from the superficial dorsal horn and forms reciprocal connections with the periaqueductal grey matter (PAG), which is critical for adaptive behaviour and the modulation of pain processing. Here, using in situ hybridization and optogenetics combined with in vitro electrophysiology, we characterized the spinal- and PAG-LPBN circuits of rats. We found spinoparabrachial projections to be strictly glutamatergic, while PAG neurons send glutamatergic and GABAergic projections to the LPBN. We next investigated the effects of drugs with anti-aversive and/or anti-nociceptive properties on these synapses: The µ-opioid receptor agonist DAMGO (10 µM) reduced spinal and PAG synaptic inputs onto LPBN neurons, and the excitability of LPBN neurons receiving these inputs. The benzodiazepine receptor agonist diazepam (5 µM) strongly enhanced GABAergic action at inhibitory PAG-LPBN synapses. The cannabinoid receptor agonist WIN 55,212-2 (5 µM) led to a reduction in inhibitory and excitatory PAG-LPBN synaptic transmission, without affecting excitatory spinoparabrachial synaptic transmission. Our study reveals that opioid, cannabinoid and benzodiazepine receptor agonists differentially affect distinct LPBN synapses. These findings may support the efforts to develop pinpointed therapies for pain patients. PERSPECTIVE: The LPBN is an important brain region for the control of pain aversion versus recuperation, and as such constitutes a promising target for developing new strategies for pain management. We show that clinically-relevant drugs have complex and pathway-specific effects on LPBN processing of putative nociceptive and aversive inputs.
Topics: Analgesics, Opioid; Animals; Pain; Parabrachial Nucleus; Periaqueductal Gray; Rats; Rats, Sprague-Dawley; Receptors, GABA-A
PubMed: 35339662
DOI: 10.1016/j.jpain.2022.03.234