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Cited by 59Neuroendocrine regulation and behaviorNeuropeptides and Animal PhysiologyRegulation of Appetite and Obesity

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Neural Functions of Hypothalamic Oxytocin and its Regulation

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Wang, Ping, Wang, Stephani C., Liu, Xiaoyu, Jia, Shuwei, Wang, Xiaoran, Li, Tong, Yu, Jiawei, Parpura, Vladimir, Wang, Yu-Feng·2022·ASN Neuro
DOI 10.1177/17590914221100706PMC PMC9125079
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Abstract

Oxytocin (OT), a nonapeptide, has a variety of functions. Despite extensive studies on OT over past decades, our understanding of its neural functions and their regulation remains incomplete. OT is mainly produced in OT neurons in the supraoptic nucleus (SON), paraventricular nucleus (PVN) and accessory nuclei between the SON and PVN. OT exerts neuromodulatory effects in the brain and spinal cord. While magnocellular OT neurons in the SON and PVN mainly innervate the pituitary and forebrain regions, and parvocellular OT neurons in the PVN innervate brainstem and spinal cord, the two sets of OT neurons have close interactions histologically and functionally. OT expression occurs at early life to promote mental and physical development, while its subsequent decrease in expression in later life stage accompanies aging and diseases. Adaptive changes in this OT system, however, take place under different conditions and upon the maturation of OT release machinery. OT can modulate social recognition and behaviors, learning and memory, emotion, reward, and other higher brain functions. OT also regulates eating and drinking, sleep and wakefulness, nociception and analgesia, sexual behavior, parturition, lactation and other instinctive behaviors. OT regulates the autonomic nervous system, and somatic and specialized senses. Notably, OT can have different modulatory effects on the same function under different conditions. Such divergence may derive from different neural connections, OT receptor gene dimorphism and methylation, and complex interactions with other hormones. In this review, brain functions of OT and their underlying neural mechanisms as well as the perspectives of their clinical usage are presented.

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Crossref · 10.1177/17590914221100706

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Figures

Figure 1. Summary of hormonal functions of oxytocin (OT). Abbreviations: Adrenaline (Adr), Atrial natriuretic peptide (ANP), Corticosteroids (CorT), Free fatty acids (FFA), Gonadotropin-releasing hormone (GnRH), Hypothalamic-pituitary-adrenal (HPA) axis, Hypothalamic pituitary gonad (HPG) axis, Hypothalamic pituitary thyroid (HPT) axis, Interleukin (IL), and Tumor necrosis factor (TNF)-α.
Figure 1. Summary of hormonal functions of oxytocin (OT). Abbreviations: Adrenaline (Adr), Atrial natriuretic peptide (ANP), Corticosteroids (CorT), Free fatty acids (FFA), Gonadotropin-releasing hormone (GnRH), Hypothalamic-pituitary-adrenal (HPA) axis, Hypothalamic pituitary gonad (HPG) axis, Hypothalamic pituitary thyroid (HPT) axis, Interleukin (IL), and Tumor necrosis factor (TNF)-α.CC BY-NC · PubMed Central
Figure 2. Outline of neural innervations of OT neurons in the central nervous system. A-C. Magnocellular OT neurons (A), parvocellular OT neurons (B) and their interconnections (C). Note that: Oxytocin (OT, green triangles) neurons in the parvocellular division (smaller triangles) of the paraventricular nucleus (pPVN) likely belong to different functional groups; OT neurons in the supraoptic nucleus (SON) and PVN connect mutually through axon/axon collaterals (dashed blue arrows) or dendrites (red dashed arrows); the downward arrows indicate inhibition evoked by OT activation of GABAergic interneurons. Abbreviations of neural structures: The third ventricle (3rdV), Accessory magnocellular nuclei (AMN), Anterior cingulate cortex (ACC), Amygdala (Amy), Arcuate nucleus (Arc), Anteroventral third ventricle region (AV3 V), Barrington's nucleus (BAR), Bed nuclei of the stria terminalis (BNST), Bulbospinal system (BSS), Caudate putamen (CPu), Dorsal vagal complex (DVC), Hippocampus (Hipp), Hypophyseal portal system (HPS), Inferior colliculus (IC), Insular cortex (InsC), Intermediate lobe of the pituitary (IPit), Lateral hypothalamus area (LHA), Lateral septum (LS), Left auditory cortex (LAC), Locus coeruleus (LC), Mammillary body complex (MB), Median eminence (ME), Medial prefrontal cortex (mPFC), Medial preoptic area (MPOA), Nucleus accumbens (NAc), Nucleus tractus solitarius (NTS), Olfactory bulb (OB), Parabrachial nucleus (PBN), Phrenic motor nucleus (PMN), Periaqueductal gray (PAG), Piriform cortex (Pir), Posterior pituitary (PPit), Raphe nucleus (RN), Spinal dorsal horn (SDH), Spinal ejaculation generator (SEG). Substantia nigra compact part (SNc), Superior cervical ganglion (SCG), Sympathetic excitatory neuron (SEN), Ventromedial hypothalamic nucleus (VMH), Ventral tegmental area (VTA). Neural connections of OT neurons refer to (Knobloch & Grinevich, 2014; Liao et al., 2020; Zhang et al., 2021).
Figure 2. Outline of neural innervations of OT neurons in the central nervous system. A-C. Magnocellular OT neurons (A), parvocellular OT neurons (B) and their interconnections (C). Note that: Oxytocin (OT, green triangles) neurons in the parvocellular division (smaller triangles) of the paraventricular nucleus (pPVN) likely belong to different functional groups; OT neurons in the supraoptic nucleus (SON) and PVN connect mutually through axon/axon collaterals (dashed blue arrows) or dendrites (red dashed arrows); the downward arrows indicate inhibition evoked by OT activation of GABAergic interneurons. Abbreviations of neural structures: The third ventricle (3rdV), Accessory magnocellular nuclei (AMN), Anterior cingulate cortex (ACC), Amygdala (Amy), Arcuate nucleus (Arc), Anteroventral third ventricle region (AV3 V), Barrington's nucleus (BAR), Bed nuclei of the stria terminalis (BNST), Bulbospinal system (BSS), Caudate putamen (CPu), Dorsal vagal complex (DVC), Hippocampus (Hipp), Hypophyseal portal system (HPS), Inferior colliculus (IC), Insular cortex (InsC), Intermediate lobe of the pituitary (IPit), Lateral hypothalamus area (LHA), Lateral septum (LS), Left auditory cortex (LAC), Locus coeruleus (LC), Mammillary body complex (MB), Median eminence (ME), Medial prefrontal cortex (mPFC), Medial preoptic area (MPOA), Nucleus accumbens (NAc), Nucleus tractus solitarius (NTS), Olfactory bulb (OB), Parabrachial nucleus (PBN), Phrenic motor nucleus (PMN), Periaqueductal gray (PAG), Piriform cortex (Pir), Posterior pituitary (PPit), Raphe nucleus (RN), Spinal dorsal horn (SDH), Spinal ejaculation generator (SEG). Substantia nigra compact part (SNc), Superior cervical ganglion (SCG), Sympathetic excitatory neuron (SEN), Ventromedial hypothalamic nucleus (VMH), Ventral tegmental area (VTA). Neural connections of OT neurons refer to (Knobloch & Grinevich, 2014; Liao et al., 2020; Zhang et al., 2021).CC BY-NC · PubMed Central
Figure 3. Approaches of OT modulation of the higher brain functions. A-B. Magnocellular OT neurons (A) and parvocellular OT neurons (B). The red font indicates a variety of OT effects (please refer to the text for details). Signs and abbreviations are the same as Figure 2.
Figure 3. Approaches of OT modulation of the higher brain functions. A-B. Magnocellular OT neurons (A) and parvocellular OT neurons (B). The red font indicates a variety of OT effects (please refer to the text for details). Signs and abbreviations are the same as Figure 2.CC BY-NC · PubMed Central
Figure 4. Approaches mediating OT effects on the instinctive behaviors and somatosensory processes. A-B. Magnocellular OT neurons (A) and parvocellular OT neurons (B). The red font indicates a variety of targets of OT actions (please refer to the text for details). Abbreviations: Adrenocorticotropic hormone (ACTH), Anterior pituitary (APit), Corticotrophin-releasing hormone (CRH), Follicle-stimulating hormone (FSH), Gonadotropin-releasing hormone (GnRH), Luteinizing hormone (LH), Proopiomelanocortin (POMC), Prolactin (PRL), Thoracic sympathetic preganglionic neurons (TSPN), Thyroid-stimulating hormone (TSH) and Vasopressin (VP). Signs and other abbreviations are the same as Figure 2.
Figure 4. Approaches mediating OT effects on the instinctive behaviors and somatosensory processes. A-B. Magnocellular OT neurons (A) and parvocellular OT neurons (B). The red font indicates a variety of targets of OT actions (please refer to the text for details). Abbreviations: Adrenocorticotropic hormone (ACTH), Anterior pituitary (APit), Corticotrophin-releasing hormone (CRH), Follicle-stimulating hormone (FSH), Gonadotropin-releasing hormone (GnRH), Luteinizing hormone (LH), Proopiomelanocortin (POMC), Prolactin (PRL), Thoracic sympathetic preganglionic neurons (TSPN), Thyroid-stimulating hormone (TSH) and Vasopressin (VP). Signs and other abbreviations are the same as Figure 2.CC BY-NC · PubMed Central

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  1. 10.1093/scan/nsab072 · DOI
  2. 10.1155/2013/179 · DOI

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Metadata

Authors
Wang, P., Wang, S. C., Liu, X., Jia, S., Wang, X., Li, T., Yu, J., Parpura, V., & Wang, Y.-F.
Affiliations
  • Harbin Medical University (CN)
  • University of California, Irvine (US)
  • University of Alabama at Birmingham (US)
Corresponding author
  • Parpura, Vladimir
  • Wang, Yu-Feng
ORCID
Venue
ASN Neuro
Publisher
Informa UK Limited
Published
2022-01
Volume
14
Issue
1
Pages
17590914221100706-17590914221100706
ISSN
1759-0914 (ISSN-L)
DOI
10.1177/17590914221100706
PMC
PMC9125079
OpenAlex
W4281254264
Cited by
59
References
311
Citations by year
2026: 13 · 2025: 11 · 2024: 14 · 2023: 17 · 2022: 4
FWCI
1.72
Type
journal article
Language
en
Open access
Licence
Locations
  • ASN NEURO (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Fund of the Ministry of Science and Technology of China (G2021011014L)
  • National Institute of General Medical Sciences of the National Institutes of Health (R01GM123971)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
oxytocin, hypothalamus, supraoptic nucleus, paraventricular nucleus, magnocellular neurons, parvocellular neurons, neuromodulation, social behavior, learning and memory, emotions, reward, sleep and wakefulness, sexual behavior, autonomic nervous system, DNA methylation, hormone crosstalk, aging
MeSH terms
Female, Humans, Hypothalamus, Neurons, Oxytocin, Paraventricular Hypothalamic Nucleus, Supraoptic Nucleus

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