Editing Hypothalamus (section)

==Structure==
The hypothalamus is divided into four regions (preoptic, supraoptic, tuberal, mammillary) in a parasagittal plane, indicating location anterior-posterior; and three zones (periventricular, intermediate, lateral) in the coronal plane, indicating location medial-lateral.<ref>{{Cite book | vauthors = Singh V |title=Textbook of Clinical Neuroanatomy |publisher=Elsevier Health Sciences |year=2014 |isbn=9788131229811 |edition=2nd |pages=134|url=https://books.google.com/books?id=LdCGBAAAQBAJ&dq=hypothalamus+regions++supraoptic%2C+tuberal%2C+mammillary&pg=PA134}}</ref> Hypothalamic nuclei are located within these specific regions and zones.<ref name="Singh2011">{{cite book|author=Inderbir Singh|title=Textbook of Anatomy: Volume 3: Head and Neck, Central Nervous System|url=https://books.google.com/books?id=8NJYL4ixFZQC&pg=PA1101|date=September 2011|publisher=JP Medical Ltd|isbn=978-93-5025-383-0|pages=1101–}}</ref> It is found in all vertebrate nervous systems. In mammals, [[magnocellular neurosecretory cell]]s in the [[paraventricular nucleus]] and the [[supraoptic nucleus]] of the hypothalamus produce [[neurohypophysial hormone]]s, [[oxytocin]] and [[vasopressin]].<ref name="Sukhov 1993">{{cite journal | vauthors = Sukhov RR, Walker LC, Rance NE, Price DL, Young WS | title = Vasopressin and oxytocin gene expression in the human hypothalamus | journal = The Journal of Comparative Neurology | volume = 337 | issue = 2 | pages = 295–306 | date = November 1993 | pmid = 8277003 | pmc = 9883978 | doi = 10.1002/cne.903370210 }}</ref> These hormones are released into the blood in the [[posterior pituitary]].<ref name=williams>{{cite book| vauthors = Melmed S, Polonsky KS, Larsen PR, Kronenberg HM |title=Williams Textbook of Endocrinology|date=2011|url=https://www.elsevier.com/books/williams-textbook-of-endocrinology/melmed/978-1-4377-0324-5|publisher=Saunders|pages=107|isbn=978-1437703245|edition=12th}}</ref> Much smaller [[parvocellular neurosecretory cell]]s, neurons of the paraventricular nucleus, release [[corticotropin-releasing hormone]] and other hormones into the [[hypophyseal portal system]], where these hormones diffuse to the [[anterior pituitary]].{{cn|date=September 2023}}

===Nuclei===
The hypothalamic nuclei include the following:<ref>{{cite web| website= psycheducation.org| url= http://www.psycheducation.org/emotion/pics/big%20hypothalamus.htm| title= Enlarged view of the hypothalamus |archive-url= https://web.archive.org/web/20051215094638/http://psycheducation.org/emotion/pics/big%20hypothalamus.htm |archive-date=15 December 2005| publisher= Jim Phelps |access-date= 2020-02-07}}</ref><ref>{{cite web| url= http://www.utdallas.edu/~tres/integ/hom3/display13_04.html |title= Emotion and the limbic system | website= utdallas.edu | publisher= Lucien T. "Tres" Thompson, [[The University of Texas at Dallas]] | access-date= 2020-02-07}}</ref>

{| class="wikitable"
|+ List of nuclei, their functions, and the neurotransmitters, neuropeptides, or hormones that they utilize
<!--This table needs to be restructured so as to separate the functions of a nucleus from the neurochemicals and hormones that mediate them; the compounds released by a particular nucleus should probably go into another column and it should be made clear whether a compound is released onto another neuron (i.e., a neuropeptide/neurotransmitter) or into the blood stream (i.e., a hormone)-->
|-
|'''Region'''
|'''Area'''
|'''Nucleus'''
|'''Function'''<ref>{{cite book| title= Guyton and Hall Textbook of Medical Physiology| vauthors = Hall JE, Guyton AC | isbn= 978-1416045748| year= 2011| publisher= Saunders/Elsevier | edition= 12th}}</ref>
|-
|rowspan=8|Anterior (supraoptic)
| rowspan="2" | Preoptic<!--Per neurolex--> || [[Preoptic area|Preoptic nucleus]] ||
* [[Thermoregulation]]
|-
|[[Ventrolateral preoptic nucleus]]
|[[Sleep]]
|-
|rowspan=5|Medial
| [[Medial preoptic nucleus]] ||
* Regulates the release of gonadotropic hormones from the adenohypophysis
* Contains the [[sexually dimorphic nucleus]], which releases GnRH, differential development between sexes is based upon in utero testosterone levels
* Thermoregulation<ref>{{cite journal | vauthors = Yoshida K, Li X, Cano G, Lazarus M, Saper CB | title = Parallel preoptic pathways for thermoregulation | journal = The Journal of Neuroscience | volume = 29 | issue = 38 | pages = 11954–64 | date = September 2009 | pmid = 19776281 | pmc = 2782675 | doi = 10.1523/JNEUROSCI.2643-09.2009 }}</ref>
|-
| [[Supraoptic nucleus]] ||
* [[Vasopressin]] release
* [[Oxytocin]] release

|-
| [[Paraventricular nucleus]] ||
* [[thyrotropin-releasing hormone]] release
* [[corticotropin-releasing hormone]] release
* [[oxytocin]] release
* [[vasopressin]] release
* [[somatostatin]] round
* [[arousal]] (wakefulness and attention)<ref>{{cite journal | vauthors = Chen CR, Zhong YH, Jiang S, Xu W, Xiao L, Wang Z, Qu WM, Huang ZL | title = Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice | journal = eLife | volume = 10 | pages = e69909 | date = November 2021 | pmid = 34787078 | pmc = 8631797 | doi = 10.7554/eLife.69909 | doi-access = free | veditors  = Elmquist JK, Wong ML, Lazarus M }}</ref><ref>{{cite journal | vauthors = Wang Z, Zhong YH, Jiang S, Qu WM, Huang ZL, Chen CR | title = Case Report: Dysfunction of the Paraventricular Hypothalamic Nucleus Area Induces Hypersomnia in Patients | language = English | journal = Frontiers in Neuroscience | volume = 16 | pages = 830474 | date = 2022-03-14 | pmid = 35360167 | doi = 10.3389/fnins.2022.830474 | doi-access = free | pmc = 8964012 }}</ref>
* [[appetite]]

|-
| [[Anterior hypothalamic nucleus]] ||
* [[thermoregulation]]
* [[Thermoregulation|panting]]
* [[sweating]]
* [[thyrotropin]] inhibition
|-
| [[Suprachiasmatic nucleus]] ||
* [[Circadian rhythms]]
|-
|Lateral
| [[Lateral hypothalamic nucleus|Lateral nucleus]]|| See {{Section link|Lateral hypothalamus|Function}}&nbsp;– primary source of [[orexin]] neurons that project throughout the brain and spinal cord
|-
|rowspan=5|Middle (tuberal)
|rowspan=3|Medial
| [[Dorsomedial hypothalamic nucleus]] ||
* [[blood pressure]]
* [[heart rate]]
* [[gastrointestinal tract|GI]] stimulation
|-
| [[Ventromedial nucleus]] ||
* [[satiety]]
* [[neuroendocrine]] control
|-
| [[Arcuate nucleus]] ||
* [[Growth hormone-releasing hormone]] (GHRH)
* [[feeding]]
* [[Dopamine]]-mediated [[prolactin]] inhibition
|-
|rowspan=2| Lateral || [[Lateral hypothalamic nucleus|Lateral nucleus]] || See {{Section link|Lateral hypothalamus|Function}}&nbsp;– primary source of [[orexin]] neurons that project throughout the brain and spinal cord
|-
| [[Lateral tuberal nuclei]] ||
|-
|rowspan=4|Posterior (mammillary)
|rowspan=2|Medial
|Mammillary nuclei (part of [[mammillary body|mammillary bodies]]) ||
* [[memory]]
|-
| [[Posterior nucleus (hypothalamus)|Posterior nucleus]] ||
* Increase [[blood pressure]]
* [[pupil]]lary dilation
* [[shivering]]
* [[vasopressin]] release
|-
| rowspan=2 | Lateral
| [[Lateral hypothalamic nucleus|Lateral nucleus]] || See {{Section link|Lateral hypothalamus|Function}}&nbsp;– primary source of [[orexin]] neurons that project throughout the brain and spinal cord
|-
| [[Tuberomammillary nucleus]]<ref name="Histamine pathways">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors= Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher= McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 175–176 | edition = 2nd | chapter = Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin | quote = Within the brain, histamine is synthesized exclusively by neurons with their cell bodies in the tuberomammillary nucleus (TMN) that lies within the posterior hypothalamus. There are approximately 64000 histaminergic neurons per side in humans. These cells project throughout the brain and spinal cord. Areas that receive especially dense projections include the cerebral cortex, hippocampus, neostriatum, nucleus accumbens, amygdala, and hypothalamus. &nbsp;... While the best characterized function of the histamine system in the brain is regulation of sleep and arousal, histamine is also involved in learning and memory&nbsp;... It also appears that histamine is involved in the regulation of feeding and energy balance.}}</ref> <!--Per neurolex and ref for this entry-->||
* [[arousal]] (wakefulness and attention)
* feeding and [[energy balance (biology)|energy balance]]
* learning
* memory
* [[sleep]]
|}

<gallery>
File:HIGHPVN.jpg|Cross-section of the monkey hypothalamus displays two of the major hypothalamic nuclei on either side of the fluid-filled third ventricle.
File:HypothalamicNuclei.PNG|Hypothalamic nuclei <!--Symbols: AC: anterior commissure PO: preoptic nucleus SC: suprachiasmatic nucleus OC: optic chiasma TC: tuber cinereum AP: anterior pituitary IN: infundibulum PP: posterior pituitary ME: median eminence AH: anterior hypothalamic nucleus SO: supraoptic nucleus TH: thalamus PV: paraventricular nucleus (not to be confused with periventricular nucleus, which is not shown) DM: dorsomedial nucleus VM: ventromedial nucleus AR: arcuate nucleus (associated with periventricular nucleus, which is not shown) LT: lateral nucleus PN: posterior nucleus MB: mamillary body-->
File:3D-Hypothalamus.JPG|Hypothalamic nuclei on one side of the hypothalamus, shown in a 3-D computer reconstruction<ref>Brain Research Bulletin 35:323–327, 1994</ref>
</gallery>

===Connections===
{{Further|Lateral hypothalamus#Orexinergic projection system|Tuberomammillary nucleus#Histaminergic outputs}}
The hypothalamus is highly interconnected with other parts of the [[central nervous system]], in particular the brainstem and its [[reticular formation]]. As part of the [[limbic system]], it has connections to other limbic structures including the [[amygdala]] and [[septum]], and is also connected with areas of the [[autonomous nervous system]]. {{cn|date=March 2025}}

The hypothalamus receives many inputs from the [[brainstem]], the most notable from the [[nucleus of the solitary tract]], the [[locus coeruleus]], and the [[ventrolateral medulla]]. {{cn|date=March 2025}}

'''Most''' nerve fibres within the hypothalamus run in two ways (bidirectional).
* Projections to areas [[Anatomical terms of location|caudal]] to the hypothalamus go through the [[medial forebrain bundle]], the [[mammillotegmental fasciculus|mammillotegmental tract]] and the [[dorsal longitudinal fasciculus]].
* Projections to areas rostral to the hypothalamus are carried by the [[mammillothalamic tract]], the [[Fornix of brain|fornix]] and [[terminal stria]].
* Projections to areas of the [[sympathetic nervous system|sympathetic motor system]] ([[lateral horn of spinal cord|lateral horn]] spinal segments T1–L2/L3) are carried by the [[hypothalamospinal tract]] and they activate the sympathetic motor pathway.

===Sexual dimorphism===
Several hypothalamic nuclei are [[sexually dimorphic]]; i.e., there are clear differences in both structure and function between males and females.<ref name="ReferenceA">{{cite journal | vauthors = Hofman MA, Swaab DF | title = The sexually dimorphic nucleus of the preoptic area in the human brain: a comparative morphometric study | journal = Journal of Anatomy | volume = 164 | pages = 55–72 | date = June 1989 | pmid = 2606795 | pmc = 1256598 }}</ref> Some differences are apparent even in gross neuroanatomy: most notable is the [[sexually dimorphic nucleus]] within the [[preoptic area]],<ref name="ReferenceA"/> in which the differences are subtle changes in the connectivity and chemical sensitivity of particular sets of neurons. The importance of these changes can be recognized by functional differences between males and females. For instance, males of most species prefer the odor and appearance of females over males, which is instrumental in stimulating male sexual behavior. If the sexually dimorphic nucleus is lesioned, this preference for females by males diminishes. Also, the pattern of secretion of [[growth hormone]] is sexually dimorphic;<ref>{{cite journal | vauthors = Quinnies KM, Bonthuis PJ, Harris EP, Shetty SR, Rissman EF | title = Neural growth hormone: Regional regulation by estradiol and / or sex chromosome complement in male and female mice | journal = Biology of Sex Differences | volume = 6 | pages = 8 | year = 2015 | pmid = 25987976 | pmc = 4434521 | doi = 10.1186/s13293-015-0026-x | doi-access = free }}</ref> this is why in many species, adult males are visibly distinct sizes from females.

====Responsiveness to ovarian steroids====
Other striking functional dimorphisms are in the behavioral responses to [[ovarian steroids]] of the adult. Males and females respond to ovarian steroids in different ways, partly because the expression of [[estrogen]]-sensitive neurons in the hypothalamus is sexually dimorphic; i.e., estrogen receptors are expressed in different sets of neurons.{{cn|date=May 2022}}

[[Estrogen]] and [[progesterone]] can influence gene expression in particular neurons or induce changes in [[cell membrane]] potential and [[kinase]] activation, leading to diverse non-genomic cellular functions. Estrogen and [[progesterone]] bind to their cognate [[nuclear hormone receptor]]s, which translocate to the cell nucleus and interact with regions of DNA known as [[hormone response element]]s (HREs) or get tethered to another [[transcription factor]]'s binding site. [[Estrogen receptor]] (ER) has been shown to transactivate other transcription factors in this manner, despite the absence of an [[estrogen response element]] (ERE) in the proximal promoter region of the gene. In general, ERs and [[progesterone receptor]]s (PRs) are gene activators, with increased mRNA and subsequent protein synthesis following hormone exposure.{{citation needed|date=February 2013}}

Male and female brains differ in the distribution of estrogen receptors, and this difference is an irreversible consequence of neonatal steroid exposure.{{citation needed|date=December 2021}} Estrogen receptors (and progesterone receptors) are found mainly in neurons in the anterior and mediobasal hypothalamus, notably:
* the [[preoptic area]] (where [[LHRH]] neurons are located, regulating dopamine responses and maternal behavior;<ref>{{cite journal | vauthors = Castañeyra-Ruiz L, González-Marrero I, Castañeyra-Ruiz A, González-Toledo JM, Castañeyra-Ruiz M, de Paz-Carmona H, Castañeyra-Perdomo A, Carmona-Calero EM | title = Luteinizing hormone-releasing hormone distribution in the anterior hypothalamus of the female rats | journal = ISRN Anatomy | volume = 2013 | pages = 1–6 | year = 2013 | pmid = 25938107 | pmc = 4392965 | doi = 10.5402/2013/870721 | doi-access = free }}</ref>
* the [[periventricular nucleus]] where [[somatostatin]] neurons are located, regulating stress levels;<ref>{{cite journal | vauthors = Isgor C, Cecchi M, Kabbaj M, Akil H, Watson SJ | title = Estrogen receptor beta in the paraventricular nucleus of hypothalamus regulates the neuroendocrine response to stress and is regulated by corticosterone |journal=Neuroscience|volume=121|issue=4|pages= 837–45 | year = 2003|pmid=14580933|doi=10.1016/S0306-4522(03)00561-X | s2cid = 31026141 }}</ref>
* the [[ventromedial hypothalamus]] which regulates hunger and sexual arousal.

===Development===
[[File:Gray654.png|thumbnail|Median sagittal section of brain of human embryo of three months]]
In neonatal life, gonadal steroids influence the development of the neuroendocrine hypothalamus. For instance, they determine the ability of females to exhibit a normal reproductive cycle, and of males and females to display appropriate reproductive behaviors in adult life.
* If a ''female rat'' is injected once with testosterone in the first few days of postnatal life (during the "critical period" of sex-steroid influence), the hypothalamus is irreversibly masculinized; the adult rat will be incapable of generating an [[LH surge]] in response to estrogen (a characteristic of females), but will be capable of exhibiting ''male'' sexual behaviors (mounting a sexually receptive female).<ref name="jneuro">{{cite journal|vauthors= McCarthy MM, Arnold AP, Ball GF, Blaustein JD, De Vries GJ|title=Sex differences in the brain: the not so inconvenient truth|journal=The Journal of Neuroscience |volume=32|issue=7|pages=2241–7|date = February 2012|pmid =22396398|pmc=3295598|doi=10.1523/JNEUROSCI.5372-11.2012 }}</ref>
* By contrast, a ''male rat'' castrated just after birth will be ''feminized'', and the adult will show ''female'' sexual behavior in response to estrogen (sexual receptivity, [[lordosis behavior]]).<ref name=jneuro/>

In primates, the developmental influence of [[androgens]] is less clear, and the consequences are less understood. Within the brain, testosterone is aromatized (to [[estradiol]]), which is the principal active hormone for developmental influences. The human [[testis]] secretes high levels of testosterone from about week eight of fetal life until five to six months after birth (a similar perinatal surge in testosterone is observed in many species), a process that appears to underlie the male phenotype. Estrogen from the maternal circulation is relatively ineffective, partly because of the high circulating levels of steroid-binding proteins in pregnancy.<ref name=jneuro/>

[[Sex steroid]]s are not the only important influences upon hypothalamic development; in particular, [[Puberty|pre-pubertal]] stress in early life (of rats) determines the capacity of the adult hypothalamus to respond to an acute stressor.<ref>{{cite journal | vauthors = Romeo RD, Bellani R, Karatsoreos IN, Chhua N, Vernov M, Conrad CD, McEwen BS | title = Stress history and pubertal development interact to shape hypothalamic–pituitary–adrenal axis plasticity | journal = Endocrinology | volume = 147 | issue = 4 | pages = 1664–74 | date = April 2006 | pmid = 16410296 | doi = 10.1210/en.2005-1432 | doi-access = free }}</ref> Unlike gonadal steroid receptors, [[glucocorticoid]] receptors are very widespread throughout the brain; in the [[paraventricular nucleus]], they mediate negative feedback control of [[Corticotropin-releasing hormone|CRF]] synthesis and secretion, but elsewhere their role is not well understood.