Editing Hypothalamus (section)

==Function==

===Hormone release===
[[File:Endocrine central nervous en.svg|thumbnail|[[Endocrine gland]]s in the human head and neck and their hormones]]
The hypothalamus has a central [[neuroendocrine]] function, most notably by its control of the [[anterior pituitary]], which in turn regulates various endocrine glands and organs. [[Releasing hormone]]s (also called releasing factors) are produced in hypothalamic nuclei then transported along [[axons]] to either the [[median eminence]] or the [[posterior pituitary]], where they are stored and released as needed.<ref>{{cite web|vauthors=Bowen R|title=Overview of Hypothalamic and Pituitary Hormones|url=http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/overview.html|access-date=5 October 2014|archive-date=1 March 2019|archive-url=https://web.archive.org/web/20190301174400/http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/overview.html|url-status=dead}}</ref>

;Anterior pituitary
In the hypothalamic–adenohypophyseal axis, releasing hormones, also known as hypophysiotropic or hypothalamic hormones, are released from the median eminence, a prolongation of the hypothalamus, into the [[hypophyseal portal system]], which carries them to the anterior pituitary where they exert their regulatory functions on the secretion of adenohypophyseal hormones.<ref name=MelmedJameson>{{cite book |vauthors=Melmed S, Jameson JL |veditors=Kasper DL, Braunwald E, Fauci AS |title=Harrison's Principles of Internal Medicine|url=https://archive.org/details/harrisonsprincip00kasp |url-access=limited |edition=16th |year=2005 |publisher=McGraw-Hill |location=New York, NY |isbn=978-0-07-139140-5 |pages=[https://archive.org/details/harrisonsprincip00kasp/page/n2104 2076]–97 |chapter=Disorders of the anterior pituitary and hypothalamus|display-editors=etal}}</ref> These hypophysiotropic hormones are stimulated by parvocellular neurosecretory cells located in the periventricular area of the hypothalamus. After their release into the capillaries of the third ventricle, the hypophysiotropic hormones travel through what is known as the hypothalamo-pituitary portal circulation. Once they reach their destination in the anterior pituitary, these hormones bind to specific receptors located on the surface of pituitary cells. Depending on which cells are activated through this binding, the pituitary will either begin secreting or stop secreting hormones into the rest of the bloodstream.<ref>{{cite book | vauthors = Bear MF, Connors BW, Paradiso MA | chapter = Hypothalamic Control of the Anterior Pituitary | title = Neuroscience: Exploring the Brain |edition=4th|location=Philadelphia| publisher=Wolters Kluwer|year=2016|page=528|isbn=978-0-7817-7817-6}}</ref>

{| class="wikitable" width=100%
! width=25% | Secreted hormone !! width=6% | Abbreviation !! width=17% | Produced by !! Effect
|-
! [[Thyrotropin-releasing hormone]] <br>(Prolactin-releasing hormone)
| TRH, TRF, or PRH || [[Parvocellular neurosecretory cell]]s of the [[paraventricular nucleus]] || Stimulate [[Thyroid-stimulating hormone|thyroid-stimulating hormone (TSH)]] release from [[anterior pituitary]] (primarily) <br>Stimulate [[prolactin]] release from [[anterior pituitary]]
|-
! [[Corticotropin-releasing hormone]]
| CRH or CRF || Parvocellular neurosecretory cells of the paraventricular nucleus || Stimulate [[Adrenocorticotropic hormone|adrenocorticotropic hormone (ACTH)]] release from [[anterior pituitary]]
|-
! [[Dopamine]] <br>(Prolactin-inhibiting hormone)
| DA or PIH || [[Arcuate nucleus|Dopamine neurons of the arcuate nucleus]] || Inhibit [[prolactin]] release from [[anterior pituitary]]
|-
! [[Growth-hormone-releasing hormone]]
| GHRH || [[Neuroendocrine]] neurons of the [[Arcuate nucleus]] || Stimulate [[Growth hormone|growth-hormone (GH)]] release from [[anterior pituitary]]
|-
! [[Gonadotropin-releasing hormone]]
| GnRH or LHRH || [[Neuroendocrine]] cells of the [[Preoptic area]] || Stimulate [[Follicle-stimulating hormone|follicle-stimulating hormone (FSH)]] release from [[anterior pituitary]] <br>Stimulate [[Luteinizing hormone|luteinizing hormone (LH)]] release from [[anterior pituitary]]
|-
! [[Somatostatin]]<ref>{{cite journal | vauthors = Ben-Shlomo A, Melmed S | title = Pituitary somatostatin receptor signaling | journal = Trends in Endocrinology and Metabolism | volume = 21 | issue = 3 | pages = 123–33 | date = March 2010 | pmid = 20149677 | pmc = 2834886 | doi = 10.1016/j.tem.2009.12.003 }}</ref> <br>(growth-hormone-inhibiting hormone)
| SS, GHIH, or SRIF || [[Neuroendocrine]] cells of the [[Periventricular nucleus]] || Inhibit [[Growth hormone|growth-hormone (GH)]] release from [[anterior pituitary]] <br>Inhibit (moderately) [[Thyroid-stimulating hormone|thyroid-stimulating hormone (TSH)]] release from [[anterior pituitary]]
|}

Other hormones secreted from the median eminence include [[vasopressin]], [[oxytocin]], and [[neurotensin]].<ref name=horn>{{cite journal | vauthors = Horn AM, Robinson IC, Fink G | title = Oxytocin and vasopressin in rat hypophysial portal blood: experimental studies in normal and Brattleboro rats | journal = The Journal of Endocrinology | volume = 104 | issue = 2 | pages = 211–24 | date = February 1985 | pmid = 3968510 | doi = 10.1677/joe.0.1040211 }}</ref><ref>{{cite journal | vauthors = Date Y, Mondal MS, Matsukura S, Ueta Y, Yamashita H, Kaiya H, Kangawa K, Nakazato M | title = Distribution of orexin/hypocretin in the rat median eminence and pituitary | journal = Brain Research. Molecular Brain Research | volume = 76 | issue = 1 | pages = 1–6 | date = March 2000 | pmid = 10719209 | doi = 10.1016/s0169-328x(99)00317-4 }}</ref><ref>{{cite journal | vauthors = Watanobe H, Takebe K | title = In vivo release of neurotensin from the median eminence of ovariectomized estrogen-primed rats as estimated by push-pull perfusion: correlation with luteinizing hormone and prolactin surges | journal = Neuroendocrinology | volume = 57 | issue = 4 | pages = 760–4 | date = April 1993 | pmid = 8367038 | doi = 10.1159/000126434 }}</ref><ref>{{cite journal | vauthors = Spinazzi R, Andreis PG, Rossi GP, Nussdorfer GG | title = Orexins in the regulation of the hypothalamic–pituitary–adrenal axis | journal = Pharmacological Reviews | volume = 58 | issue = 1 | pages = 46–57 | date = March 2006 | pmid = 16507882 | doi = 10.1124/pr.58.1.4 | s2cid = 17941978 }}</ref>

;Posterior pituitary
In the hypothalamic–pituitary–adrenal axis, [[neurohypophysial hormone]]s are released from the posterior pituitary, which is actually a prolongation of the hypothalamus, into the circulation.

{| class="wikitable" width=100%
! width=25% | Secreted hormone !! width=6% | Abbreviation !! width=17% | Produced by !! Effect
|-
! [[Oxytocin]]
| OXY or OXT || [[Magnocellular neurosecretory cell]]s of the paraventricular nucleus and [[supraoptic nucleus]] || [[Uterine contraction]] <br>[[Letdown reflex|Lactation (letdown reflex)]] <!--Not effects from hypothalamus: sexual arousal, bonding, trust, material behavior-->
|-
! [[Vasopressin]] <br>(antidiuretic hormone)
| ADH or AVP || Magnocellular and parvocellular neurosecretory cells of the paraventricular nucleus, magnocellular cells in supraoptic nucleus || Increase in the permeability to water of the cells of [[distal tubule]] and [[collecting duct]] in the kidney and thus allows water reabsorption and excretion of concentrated urine
|}

It is also known that [[hypothalamic–pituitary–adrenal axis]] (HPA) hormones are related to certain skin diseases and skin homeostasis. There is evidence linking hyperactivity of HPA hormones to stress-related skin diseases and skin tumors.<ref>{{cite web|title=Expression of Hypothalamic–Pituitary–Adrenal Axis in Common Skin Diseases: Evidence of its Association with Stress-related Disease Activity|url=http://web.b.ebscohost.com/ehost/pdfviewer/pdfviewer?sid=8239d5d4-8cd4-48b0-b25c-e1218229f462%40sessionmgr115&vid=11&hid=122|publisher=National Research Foundation of Korea|access-date=4 March 2014|author1=Jung Eun Kim |author2=Baik Kee Cho |author3=Dae Ho Cho |author4=Hyun Jeong Park |year=2013}}</ref>

===Stimulation===
The hypothalamus coordinates many hormonal and behavioural circadian rhythms, complex patterns of [[neuroendocrine]] outputs, complex [[homeostasis|homeostatic]] mechanisms, and important behaviours. The hypothalamus must, therefore, respond to many different signals, some of which are generated externally and some internally. [[Delta wave]] signalling arising either in the thalamus or in the cortex influences the secretion of releasing hormones; [[GHRH]] and [[prolactin]] are stimulated whilst [[TRH]] is inhibited. {{cn|date=March 2025}}

The hypothalamus is responsive to:
* Light: daylength and [[photoperiod]] for regulating [[circadian]] and seasonal rhythms
* [[Olfactory]] stimuli, including [[pheromones]]
* [[Steroids]], including [[gonadal steroids]] and [[corticosteroids]]
* Neurally transmitted information arising in particular from the heart, [[enteric nervous system]] (of the [[gastrointestinal tract]]),<ref>{{cite journal | vauthors = Mayer EA | title = Gut feelings: the emerging biology of gut-brain communication | journal = Nature Reviews. Neuroscience | volume = 12 | issue = 8 | pages = 453–66 | date = July 2011 | pmid = 21750565 | pmc = 3845678 | doi = 10.1038/nrn3071 }}</ref> and the reproductive tract.{{citation needed|reason=Your explanation here|date=April 2016}}
* [[Autonomic Nervous System|Autonomic]] inputs
* Blood-borne stimuli, including [[leptin]], [[ghrelin]], [[angiotensin]], [[insulin]], [[pituitary hormones]], [[cytokines]], plasma concentrations of glucose and osmolarity etc.
* [[Stress (medicine)|Stress]]
* Invading microorganisms by increasing body temperature, resetting the body's thermostat upward.

====Olfactory stimuli====
Olfactory stimuli are important for [[sexual reproduction]] and [[neuroendocrine]] function in many species. For instance, if a pregnant mouse is exposed to the urine of a 'strange' male during a critical period after coitus then the pregnancy fails (the [[Bruce effect]]). Thus, during coitus, a female mouse forms a precise 'olfactory memory' of her partner that persists for several days. Pheromonal cues aid synchronization of [[oestrus]] in many species; in women, synchronized [[menstruation]] may also arise from pheromonal cues, although the role of pheromones in humans is disputed. {{cn|date=March 2025}}

====Blood-borne stimuli====
[[Peptide]] hormones have important influences upon the hypothalamus, and to do so they must pass through the [[blood–brain barrier]]. The hypothalamus is bounded in part by specialized brain regions that lack an effective blood–brain barrier; the [[Capillary#Types|capillary]] [[endothelium]] at these sites is fenestrated to allow free passage of even large proteins and other molecules. Some of these sites are the sites of neurosecretion - the [[neurohypophysis]] and the [[median eminence]]. However, others are sites at which the brain samples the composition of the blood. Two of these sites, the SFO ([[subfornical organ]]) and the OVLT ([[organum vasculosum of the lamina terminalis]]) are so-called [[circumventricular organs]], where neurons are in intimate contact with both blood and [[Cerebrospinal fluid|CSF]]. These structures are densely vascularized, and contain osmoreceptive and sodium-receptive neurons that control [[drinking]], [[vasopressin]] release, sodium excretion, and sodium appetite. They also contain neurons with receptors for [[angiotensin]], [[atrial natriuretic factor]], [[endothelin]] and [[relaxin]], each of which important in the regulation of fluid and electrolyte balance. Neurons in the OVLT and SFO project to the [[supraoptic nucleus]] and [[paraventricular nucleus]], and also to preoptic hypothalamic areas. The circumventricular organs may also be the site of action of [[interleukins]] to elicit both fever and ACTH secretion, via effects on paraventricular neurons.{{citation needed|date=February 2013}}

It is not clear how all peptides that influence hypothalamic activity gain the necessary access. In the case of [[prolactin]] and [[leptin]], there is evidence of active uptake at the [[choroid plexus]] from the blood into the [[cerebrospinal fluid]] (CSF). Some pituitary hormones have a negative feedback influence upon hypothalamic secretion; for example, [[growth hormone]] feeds back on the hypothalamus, but how it enters the brain is not clear. There is also evidence for central actions of [[prolactin]].{{citation needed|date=February 2013}}

Findings have suggested that [[thyroid hormone]] (T4) is taken up by the hypothalamic [[glial cells]] in the [[infundibular nucleus]]/ [[median eminence]], and that it is here converted into [[Triiodothyronine|T3]] by the type 2 deiodinase (D2). Subsequent to this, T3 is transported into the [[thyrotropin-releasing hormone]] ([[TRH]])-producing [[neurons]] in the [[paraventricular nucleus]]. [[Thyroid hormone receptor]]s have been found in these [[neurons]], indicating that they are indeed sensitive to T3 stimuli. In addition, these neurons expressed [[SLC16A2|MCT8]], a [[thyroid hormone]] transporter, supporting the theory that T3 is transported into them. T3 could then bind to the thyroid hormone receptor in these neurons and affect the production of thyrotropin-releasing hormone, thereby regulating thyroid hormone production.<ref>{{cite journal|vauthors=Fliers E, Unmehopa UA, Alkemade A|date=June 2006|title=Functional neuroanatomy of thyroid hormone feedback in the human hypothalamus and pituitary gland|journal=Molecular and Cellular Endocrinology|volume=251|issue=1–2|pages=1–8|doi=10.1016/j.mce.2006.03.042|pmid=16707210|s2cid=33268046}}<!--|access-date=7 July 2011--></ref>

The hypothalamus functions as a type of [[thermostat]] for the body.<ref name=Harrisons>{{cite book | author-link = Anthony Fauci | author = Fauci, Anthony | title = Harrison's Principles of Internal Medicine | url = https://archive.org/details/harrisonsprincip00asfa | url-access = limited | edition = 17 | publisher = McGraw-Hill Professional | year = 2008 | isbn = 978-0-07-146633-2 | pages = [https://archive.org/details/harrisonsprincip00asfa/page/n155 117]–121 | display-authors = etal }}</ref> It sets a desired body temperature, and stimulates either heat production and retention to raise the blood temperature to a higher setting or sweating and [[vasodilation]] to cool the blood to a lower temperature. All [[fever]]s result from a raised setting in the hypothalamus; elevated body temperatures due to any other cause are classified as [[hyperthermia]].<ref name=Harrisons /> Rarely, direct damage to the hypothalamus, such as from a [[stroke]], will cause a fever; this is sometimes called a ''hypothalamic fever''. However, it is more common for such damage to cause abnormally low body temperatures.<ref name=Harrisons />

====Steroids====
The hypothalamus contains neurons that react strongly to steroids and [[glucocorticoids]] (the steroid hormones of the [[adrenal gland]], released in response to [[ACTH]]). It also contains specialized glucose-sensitive neurons (in the [[arcuate nucleus]] and [[ventromedial hypothalamus]]), which are important for [[appetite]]. The preoptic area contains thermosensitive neurons; these are important for [[TRH]] secretion. {{cn|date=March 2025}}

====Neural====
[[Oxytocin]] secretion in response to suckling or vagino-cervical stimulation is mediated by some of these pathways; [[vasopressin]] secretion in response to cardiovascular stimuli arising from chemoreceptors in the [[carotid body]] and [[aortic arch]], and from low-pressure [[atrial volume receptors]], is mediated by others. In the rat, stimulation of the [[vagina]] also causes [[prolactin]] secretion, and this results in [[pseudo-pregnancy]] following an infertile mating. In the rabbit, coitus elicits [[Induced ovulation (animals)|reflex ovulation]]. In the sheep, [[cervix|cervical]] stimulation in the presence of high levels of estrogen can induce [[maternal bond|maternal behavior]] in a virgin ewe. These effects are all mediated by the hypothalamus, and the information is carried mainly by spinal pathways that relay in the brainstem. Stimulation of the nipples stimulates release of oxytocin and prolactin and suppresses the release of [[Luteinizing hormone|LH]] and [[Follicle-stimulating hormone|FSH]]. {{cn|date=March 2025}}

Cardiovascular stimuli are carried by the [[vagus nerve]]. The vagus also conveys a variety of visceral information, including for instance signals arising from gastric distension or emptying, to suppress or promote feeding, by signalling the release of [[leptin]] or [[gastrin]], respectively. Again, this information reaches the hypothalamus via relays in the brainstem. {{cn|date=March 2025}}

In addition, hypothalamic function is responsive to—and regulated by—levels of all three classical [[monoamine neurotransmitter]]s, [[noradrenaline]], [[dopamine]], and [[serotonin]] (5-hydroxytryptamine), in those tracts from which it receives innervation. For example, noradrenergic inputs arising from the locus coeruleus have important regulatory effects upon [[corticotropin-releasing hormone]] (CRH) levels. {{cn|date=March 2025}}

===Control of food intake===
{| class="wikitable sortable" style="width:40%; float:right; margin-left:15px"
|+ Peptide hormones and neuropeptides that regulate feeding<ref name="Feeding peptides table">{{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 | page = 263 | edition = 2nd | chapter = Chapter 10: Neural and Neuroendocrine Control of the Internal Milieu – Table 10:3 }}</ref>
! scope="col" style="width:50%"| Peptides that increase<br />feeding behavior
! scope="col" style="width:50%"| Peptides that decrease<br />feeding behavior
|-
| [[Ghrelin]] || [[Leptin]]
|-
| [[Neuropeptide Y]] || (α,β,γ)-[[Melanocyte-stimulating hormone]]s
|-
| [[Agouti-related peptide]] || [[Cocaine and amphetamine regulated transcript|Cocaine- and amphetamine-regulated transcript peptides]]
|-
| [[Orexin]]s (A,B) || [[Corticotropin-releasing hormone]]
|-
| [[Melanin-concentrating hormone]] || [[Cholecystokinin]]
|-
| [[Galanin]] || [[Insulin]]
|-
| || [[Glucagon-like peptide 1]]
|-
|}
The extreme [[anatomical terms of location|lateral]] part of the [[ventromedial nucleus]] of the hypothalamus is responsible for the control of [[food]] intake. Stimulation of this area causes increased food intake. Bilateral [[lesion]] of this area causes complete cessation of food intake. Medial parts of the nucleus have a controlling effect on the lateral part. Bilateral lesion of the medial part of the ventromedial nucleus causes [[hyperphagia]] and obesity of the animal. Further lesion of the lateral part of the ventromedial nucleus in the same animal produces complete cessation of food intake.

There are different hypotheses related to this regulation:<ref>{{cite journal | vauthors = Theologides A | title = Anorexia-producing intermediary metabolites | journal = The American Journal of Clinical Nutrition | volume = 29 | issue = 5 | pages = 552–8 | date = May 1976 | pmid = 178168 | doi = 10.1093/ajcn/29.5.552 | doi-access = free }}</ref>

# Lipostatic hypothesis: This hypothesis holds that [[adipose]] [[biological tissue|tissue]] produces a [[humoral immunity|humoral]] signal that is proportionate to the amount of fat and acts on the hypothalamus to decrease food intake and increase energy output. It has been evident that a [[hormone]] [[leptin]] acts on the hypothalamus to decrease food intake and increase energy output.
# Gutpeptide hypothesis: [[gastrointestinal tract|gastrointestinal]] hormones like Grp, [[glucagon]]s, [[cholecystokinin|CCK]] and others claimed to inhibit food intake. The food entering the gastrointestinal tract triggers the release of these hormones, which act on the brain to produce satiety. The brain contains both CCK-A and CCK-B receptors.
# Glucostatic hypothesis: The activity of the satiety center in the ventromedial nuclei is probably governed by the [[glucose]] utilization in the neurons. It has been postulated that when their glucose utilization is low and consequently when the arteriovenous blood glucose difference across them is low, the activity across the neurons decrease. Under these conditions, the activity of the feeding center is unchecked and the individual feels hungry. Food intake is rapidly increased by intraventricular administration of [[2-deoxy-D-glucose|2-deoxyglucose]] therefore decreasing glucose utilization in cells.
# Thermostatic hypothesis: According to this hypothesis, a decrease in body temperature below a given set-point stimulates appetite, whereas an increase above the set-point inhibits appetite.

===Fear processing===
The medial zone of hypothalamus is part of a circuitry that controls motivated behaviors, like defensive behaviors.<ref name="swanson2000">{{cite journal | vauthors = Swanson LW | title = Cerebral hemisphere regulation of motivated behavior | journal = Brain Research | volume = 886 | issue = 1–2 | pages = 113–164 | date = December 2000 | pmid = 11119693 | doi = 10.1016/S0006-8993(00)02905-X | s2cid = 10167219 }}</ref> Analyses of [[c-Fos|Fos]]-labeling showed that a series of nuclei in the "behavioral control column" is important in regulating the expression of innate and conditioned defensive behaviors.<ref name="canteras2002">{{cite journal|author=Canteras, N.S.| title=The medial hypothalamic defensive system:Hodological organization and functional implications| journal=Pharmacology Biochemistry and Behavior|volume=71| issue=3|pages=481–491|year=2002|doi=10.1016/S0091-3057(01)00685-2| pmid=11830182| s2cid=12303256}}</ref>

;Antipredatory defensive behavior

Exposure to a predator (such as a cat) elicits defensive behaviors in laboratory rodents, even when the animal has never been exposed to a cat.<ref name="ribeiro2005">{{cite journal | vauthors = Ribeiro-Barbosa ER, Canteras NS, Cezário AF, Blanchard RJ, Blanchard DC | title = An alternative experimental procedure for studying predator-related defensive responses | journal = Neuroscience and Biobehavioral Reviews | volume = 29 | issue = 8 | pages = 1255–63 | year = 2005 | pmid = 16120464 | doi = 10.1016/j.neubiorev.2005.04.006 | s2cid = 8063630 }}</ref> In the hypothalamus, this exposure causes an increase in [[c-Fos#Applications|Fos-labeled]] cells in the anterior hypothalamic nucleus, the dorsomedial part of the ventromedial nucleus, and in the ventrolateral part of the premammillary nucleus (PMDvl).<ref name="cezario2008">{{cite journal | vauthors = Cezario AF, Ribeiro-Barbosa ER, Baldo MV, Canteras NS | title = Hypothalamic sites responding to predator threats--the role of the dorsal premammillary nucleus in unconditioned and conditioned antipredatory defensive behavior | journal = The European Journal of Neuroscience | volume = 28 | issue = 5 | pages = 1003–15 | date = September 2008 | pmid = 18691328 | doi = 10.1111/j.1460-9568.2008.06392.x | s2cid = 10073236 | doi-access = free }}</ref> The premammillary nucleus has an important role in expression of defensive behaviors towards a predator, since lesions in this nucleus abolish defensive behaviors, like freezing and flight.<ref name="cezario2008"/><ref name="blanchardpmd"/> The PMD does not modulate defensive behavior in other situations, as lesions of this nucleus had minimal effects on post-shock freezing scores.<ref name="blanchardpmd">{{cite journal|author=Blanchard, D.C.|title=Dorsal premammillary nucleus differentially modulates defensive behaviors induced by different threat stimuli in rats|journal=Neuroscience Letters|volume=345|issue=3|pages=145–148|year=2003|doi=10.1016/S0304-3940(03)00415-4|pmid=12842277|s2cid=16406187}}</ref> The PMD has important connections to the dorsal [[periaqueductal gray]], an important structure in fear expression.<ref name="canteras1992">{{cite journal | vauthors = Canteras NS, Swanson LW | title = The dorsal premammillary nucleus: an unusual component of the mammillary body | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 21 | pages = 10089–93 | date = November 1992 | pmid = 1279669 | pmc = 50283 | doi = 10.1073/pnas.89.21.10089 | bibcode = 1992PNAS...8910089C | doi-access = free }}</ref><ref name="behbehani1995">{{cite journal | vauthors = Behbehani MM | title = Functional characteristics of the midbrain periaqueductal gray | journal = Progress in Neurobiology | volume = 46 | issue = 6 | pages = 575–605 | date = August 1995 | pmid = 8545545 | doi = 10.1016/0301-0082(95)00009-K | s2cid = 24690642 }}</ref> In addition, animals display risk assessment behaviors to the environment previously associated with the cat. Fos-labeled cell analysis showed that the PMDvl is the most activated structure in the hypothalamus, and inactivation with [[muscimol]] prior to exposure to the context abolishes the defensive behavior.<ref name="cezario2008"/> Therefore, the hypothalamus, mainly the PMDvl, has an important role in expression of innate and conditioned defensive behaviors to a predator.

;Social defeat

Likewise, the hypothalamus has a role in [[social defeat]]: nuclei in medial zone are also mobilized during an encounter with an aggressive conspecific. The defeated animal has an increase in Fos levels in sexually dimorphic structures, such as the medial pre-optic nucleus, the ventrolateral part of ventromedial nucleus, and the ventral premammilary nucleus.<ref name="motta2009">{{cite journal | vauthors = Motta SC, Goto M, Gouveia FV, Baldo MV, Canteras NS, Swanson LW | title = Dissecting the brain's fear system reveals the hypothalamus is critical for responding in subordinate conspecific intruders | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 12 | pages = 4870–5 | date = March 2009 | pmid = 19273843 | pmc = 2660765 | doi = 10.1073/pnas.0900939106 | bibcode = 2009PNAS..106.4870M | doi-access = free }}</ref> Such structures are important in other social behaviors, such as sexual and aggressive behaviors. Moreover, the premammillary nucleus also is mobilized, the dorsomedial part but not the ventrolateral part.<ref name="motta2009"/> Lesions in this nucleus abolish passive defensive behavior, like freezing and the "on-the-back" posture.<ref name="motta2009"/>

=== Learning arbitrator ===
Recent research has questioned whether the lateral hypothalamus's role is only restricted to initiating and stopping innate behaviors and argued it learns about food-related cues. Specifically, that it opposes learning about information what is neutral or distant to food. According this view, the lateral hypothalamus is "a unique arbitrator of learning capable of shifting behavior toward or away from important events".<ref name="h081">{{cite journal | vauthors = Sharpe MJ | title = The cognitive (lateral) hypothalamus | journal = Trends in Cognitive Sciences | volume = 28 | issue = 1 | pages = 18–29 | date = January 2024 | pmid = 37758590 | pmc = 10841673 | doi = 10.1016/j.tics.2023.08.019 }}</ref>