Median preoptic nucleus

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Median preoptic nucleus
Identifiers
NeuroNames 378
NeuroLex ID birnlex_1208
TA98 A14.1.08.908
TA2 5711
FMA 62323
Anatomical terms of neuroanatomy
Location of the hypothalamus. Hypothalamus.jpg
Location of the hypothalamus.
Nuclei of the Hypothalamus: The preoptic area is located in the anterior portion of the hypothalamus, superior to the optic chiasm. HypothalamicNuclei.PNG
Nuclei of the Hypothalamus: The preoptic area is located in the anterior portion of the hypothalamus, superior to the optic chiasm.

The median preoptic nucleus is located dorsal to the other three nuclei of the preoptic area of the anterior hypothalamus. The hypothalamus is located just beneath the thalamus, the main sensory relay station of the nervous system, and is considered part of the limbic system, which also includes structures such as the hippocampus and the amygdala. The hypothalamus is highly involved in maintaining homeostasis of the body, and the median preoptic nucleus is no exception, contributing to regulation of blood composition, body temperature, and non-REM sleep.

Contents

The median preoptic nucleus is highly involved in three main areas. These include osmoregulation, thermoregulation, and sleep homeostasis. Within each area are many functions. The role that the median preoptic nucleus plays in osmoregulation is in blood composition and volume, including fluid and salt balance, and produces responses ranging from behavioral to endocrine. Thermoregulation includes both responses to infection and to decreased core temperature upon cutaneous exposure to cold, both of which involve the median preoptic nucleus as an important mediator of sensory input and regulatory output. Sleep homeostasis is involved in both the onset and maintenance of sleep.

The median preoptic nucleus has excitatory and inhibitory projections to many areas of the brain. It has inhibitory influences through GABAergic projections to the areas of the brain involved in the stimulation of thermogenesis, as well as on wake-active areas of the brain to induce sleep. Microinjection of ethanol, triazolam, and propofol into this area induces sleep in rodents, suggesting that it is involved in their pharmacologic effects on sleep. Glutamatergic and noradrenergic, as well as other neurotransmitters, have excitatory influences on other areas of the brain. The median preoptic nucleus is highly involved in cardiovascular regulation, including the release of atrial natriuretic peptide by the heart in response to high blood volume. It also is involved in controlling febrile response to infection and stimulation of thirst, among other functions. Both the connectivity and anatomical position of the median preoptic nucleus allow it to be both a relay station and mediator for sensory and regulatory information, and produce neural, endocrine and behavioral responses to maintain homeostasis.

Location

The median preoptic nucleus is located in the preoptic area of the hypothalamus. Forming a critical part of the anteroventral third ventricle and the midline of the lamina terminalis, the median preoptic nucleus occupies an anatomical position that allows it to play an important role in many aspects of homeostatic regulation. This region is important in cardiovascular, blood pressure, and blood composition regulation, and receives inputs from the subfornical organ (SFO) and the vascular organ of lamina terminalis (VOLT), which lie outside the blood brain barrier and relay information concerning blood osmolality and levels of endocrine signals such as atrial natriuretic peptide (ANP). [1]

Connectivity

Connectivity with other regions of the hypothalamus, such as the ventrolateral preoptic area (VLPO) and with regions of the brain stem also allow the median preoptic nucleus to be involved in other aspects of homeostasis. These include sleep-waking behaviors as well as thirst and drinking behavior, as well as thermoregulation. Parallel pathways in the preoptic area are involved in regulation of body temperature and fever response. One pathway originates in the median preoptic nucleus while the other originates in the dorsolateral preoptic area (DLPO). Both are inhibitory to areas in the brainstem which activate non-shivering thermogenesis via brown adipose tissue (BAT) in response to cutaneous cold or prostaglandin E2. [2]

Role in thermoregulation

It's known that mammals have a circadian rhythm in body temperature (Tb) that depend on the integrity of the suprachiasmatic nucleus (SCN), However, fasting also influences the Tb in the resting period and the presence of the SCN is essential for this process. Although not only the SCN but also the arcuate nucleus (ARC), are involved in the Tb setting through afferents to the thermoregulatory median preoptic nucleus (MnPO). After studies performed by Guzmán-Ruiz et al. it's known that the vasopressin release from the SCN decreases the temperature just before light onset, whereas a-melanocyte stimulating hormone release, especially at the end of the dark period, maintains high temperature. Both peptides have opposite effects on the brown adipose tissue activity through thermoregulatory nuclei such as the dorsomedial nucleus of the hypothalamus and the dorsal raphe nucleus. Coordination between circadian and metabolic signaling within the hypothalamus is essential for an adequate temperature control. The balance between the releases of neuropeptides derived from the biological clock and from a metabolic sensory organ as the arcuate nucleus, are essential for an adequate temperature control. These observations show that brain areas involved in circadian and metabolic functions of the body need to interact to produce a coherent arrangement of physiological processes associated with temperature control.[11]

The neural activation mechanisms involved in the regulation of body temperature are largely undefined. It is known that sympathetic pathways are involved in increasing heat production and reducing heat loss and are activated by neurons in the rostral medullary raphe (RMR). [2] These neurons were identified as playing an important role in the elevation of body temperature during both cold exposure and induced fever by observation that hyperpolarization prior to exposure to these conditions inhibits the elevation of body temperature in response.

Febrile response

Inputs to the RMR from the median preoptic nucleus are GABAergic, and therefore inhibitory in nature. Lesions on the median preoptic nucleus produce diminished fever responses, as the projections from the MnPn to the RMR contain prostaglandin EP3 receptors, which are essential for fever response. Prostaglandin E2 binds to E3 receptors in the median preoptic nucleus to inhibit their activity and cause fever. This means that the median preoptic nucleus is responsible for inhibiting mechanisms which elevate body temperature. This is not the only area of the hypothalamus involved, and elimination of the activity of the median preoptic nucleus will not in and of itself cause elevated body temperature. When combined with lesions on other preoptic hypothalamic nuclei, however, damage to the median preoptic nucleus causes an elevated baseline body temperature. [2]

Menopause

Other receptors, neurokinin 3 receptors, which are expressed in the median preoptic nucleus, are also involved in thermoregulation. Activation of these receptors in rats causes decrease in core temperature. These receptors are highly expressed in the median preoptic area in response to decreased estrogen levels in menopausal women, and are thought to play a role in the generation of hot flashes during menopause. [3]

Environmental cold exposure

Responses to cold are produced by cutaneous cold sensitive pathways through the Parabrachial area. Thermoreceptors in the skin detect temperature in the environment relative to body temperature. These afferent neurons project up the spinal cord to the parabrachial area, which innervates several areas of the preoptic area, including the median preoptic nucleus. Exposure to cold leads to disinhibition of the RMR and other regions, which leads to brown adipose thermogenesis. This is also known as non-shivering thermogenesis, which metabolizes fat but dissipates heat from the proton motive force in mitochondria rather than using oxidative phosphorylation to produce ATP. [4]

Role in osmoregulation

The region of the brain which includes the ventral portion of the median preoptic nucleus, the anteroventral third ventricle (AV3V), is highly involved in the maintenance of fluid, electrolyte, and cardiovascular homeostasis. [5] The median preoptic nucleus, along with the vascular organ of lamina terminalis (VOLT) and the subfornical organ (SFO) respond to changes in blood composition as well as neural input from receptors in blood vessels. Stretch receptors in the aorta and other vessels send sensory input to this region, relaying information about blood volume and blood pressure.

Response to changes in blood osmolality

The importance of the median preoptic nucleus in fluid composition and homeostasis can be seen anatomically, as it contains connections between several regions highly involved in body fluid balance and cardiovascular function, such as the paraventricular nucleus and the supraoptic nucleus.

Functionally, its importance can be understood because lesions to the median preoptic nucleus generally cause inappropriate fluid composition, water intake and release of atrial natriuretic peptide (ANP). [5] The responses to the changes in fluid composition mediated by the median preoptic nucleus result from noradrenergic innervation from regions of the caudal ventrolateral medulla. Responses can be endocrine, autonomic or behavioral, and responses to spikes in blood sodium levels include the release of atrial natriuretic peptide and oxytocin. Atrial natriuretic peptide is released by the heart in response to high blood pressure and high salinity of the blood. It is an important and potent vasodilator, and also reduces the reuptake of sodium in the kidneys. In addition, it inhibits pathways such as the renin-aldostrone-angiotensin pathway which raise blood pressure. [5]

Activation of the median preoptic nucleus leads to stimulation of the paraventricular nucleus (PVN). The afferents to this area are glutamatergic, or use glutamate as their primary neurotransmitter, although angiotensin II produces a similar response, and result in sympathoexcitation of the PVN. [6] This was confirmed by the use of a glutamate receptor antagonist in the PVN, which inhibited this response as a result of the activation of the MnPn. Thus, glutamate bound to receptors is necessary for the activation of these neurons in the median preoptic nucleus and the activation of the paraventricular nucleus. The activation of the PVN via this glutamatergic mechanism results in increased activity of renal sympathetic nerve pathways as well as heart rate and mean arterial pressure. [7]

Role in homeostatic regulation of sleep

Anatomical and electrophysiological experiments on adult rats show an important role is for the median preoptic nucleus in the production of sleep. The first evidence of this was an observation that damage to this area caused insomnia in human patients. [8] Current experiments using c-Fos expression as a marker for activation of neurons during sleep shows a dichotomy of function in sleep promotion and maintenance between the ventrolateral preoptic nucleus and the median preoptic nucleus. Evidence suggests that GABAergic neurons in the median preoptic nucleus play a role in the promotion of the onset of sleep, while neurons in the ventrolateral preoptic nucleus play a role in the maintenance of sleep. [9] While the idea of a complete separation of function between these two nuclei is an attractive one, it is more likely a question of degree of involvement of these two nuclei in the onset and maintenance of sleep, rather than playing completely separate roles. It is likely that the MnPn plays an important, but not exclusive, role in the onset of sleep, while the VLPO plays a more important role in the maintenance of sleep. Both areas project to wake-active areas of the brain. There is also a dense, bidirectional neuronal projection between the median preoptic nucleus and the ventrolateral preoptic nucleus. These existence of inhibitory projections between the ventrolaternal preoptic nucleus and the median preoptic nucleus suggests shared function and a regulatory relationship between the two nuclei. [9]

Non-REM sleep

The promotion of sleep by GABAergic neurons in the median preoptic area is most closely associated with NREM, or quiet sleep. [10] The amount of time spent in NREM sleep increases with the number of activated GABA receptors in the median preoptic area, as demonstrated by increased time in NREM sleep in response to microinjections of GABA agonists into the median preoptic area of cats. Time spent in REM sleep did not increase, and control injections decreased time spent in both NREM and REM sleep. [10]

Relationship with the VLPO

The ventrolateral (VLPO) and median preoptic (MnPn) nuclei promote sleep through GABAergic neuronal projections to wake-active areas of the brain. Activation of the neurons in the VLPO and MnPn leads to increased concentrations of the primary inhibitory neurotransmitter, GABA, in wakefulness areas of the brain, such as the tuberomammillary nucleus and the locus coeruleus. This leads to the inhibition of cholinergic, noradrenergic and serotonergic activity in these areas. Noradrenergic projections from wake-promoting areas inhibit sleep-promoting areas, establishing a "reciprocal inhibitory interaction" between sleep and wakefulness areas which leads to the regulation of sleep patterns. The mechanism for the activation of the sleep-promoting neurons in the VLPO and MnPn has not been well defined, however, it has been suggested that the suprachiasmic nucleus may play a role, as well as simply decreased sensory input at the onset of sleepiness. [8]

Related Research Articles

<span class="mw-page-title-main">Neurotransmitter</span> Chemical substance that enables neurotransmission

A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.

<span class="mw-page-title-main">Hypothalamus</span> Area of the brain below the thalamus

The hypothalamus is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus is located below the thalamus and is part of the limbic system. In the terminology of neuroanatomy, it forms the ventral part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is the size of an almond.

<span class="mw-page-title-main">Thirst</span> Craving for potable fluids experienced by animals

Thirst is the craving for potable fluids, resulting in the basic instinct of animals to drink. It is an essential mechanism involved in fluid balance. It arises from a lack of fluids or an increase in the concentration of certain osmolites, such as sodium. If the water volume of the body falls below a certain threshold or the osmolite concentration becomes too high, structures in the brain detect changes in blood constituents and signal thirst.

<span class="mw-page-title-main">Suprachiasmatic nucleus</span> Part of the brains hypothalamus

The suprachiasmatic nucleus or nuclei (SCN) is a tiny region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regulate many different body functions in a 24-hour cycle. The mouse SCN contains approximately 20,000 neurons.

<span class="mw-page-title-main">Dopaminergic pathways</span> Projection neurons in the brain that synthesize and release dopamine

Dopaminergic pathways in the human brain are involved in both physiological and behavioral processes including movement, cognition, executive functions, reward, motivation, and neuroendocrine control. Each pathway is a set of projection neurons, consisting of individual dopaminergic neurons.

<span class="mw-page-title-main">Ventral tegmental area</span> Group of neurons on the floor of the midbrain

The ventral tegmental area (VTA), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is the origin of the dopaminergic cell bodies of the mesocorticolimbic dopamine system and other dopamine pathways; it is widely implicated in the drug and natural reward circuitry of the brain. The VTA plays an important role in a number of processes, including reward cognition and orgasm, among others, as well as several psychiatric disorders. Neurons in the VTA project to numerous areas of the brain, ranging from the prefrontal cortex to the caudal brainstem and several regions in between.

<span class="mw-page-title-main">Arcuate nucleus</span>

The arcuate nucleus of the hypothalamus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. The arcuate nucleus includes several important and diverse populations of neurons that help mediate different neuroendocrine and physiological functions, including neuroendocrine neurons, centrally projecting neurons, and astrocytes. The populations of neurons found in the arcuate nucleus are based on the hormones they secrete or interact with and are responsible for hypothalamic function, such as regulating hormones released from the pituitary gland or secreting their own hormones. Neurons in this region are also responsible for integrating information and providing inputs to other nuclei in the hypothalamus or inputs to areas outside this region of the brain. These neurons, generated from the ventral part of the periventricular epithelium during embryonic development, locate dorsally in the hypothalamus, becoming part of the ventromedial hypothalamic region. The function of the arcuate nucleus relies on its diversity of neurons, but its central role is involved in homeostasis. The arcuate nucleus provides many physiological roles involved in feeding, metabolism, fertility, and cardiovascular regulation.

The baroreflex or baroreceptor reflex is one of the body's homeostatic mechanisms that helps to maintain blood pressure at nearly constant levels. The baroreflex provides a rapid negative feedback loop in which an elevated blood pressure causes the heart rate to decrease. Decreased blood pressure decreases baroreflex activation and causes heart rate to increase and to restore blood pressure levels. Their function is to sense pressure changes by responding to change in the tension of the arterial wall The baroreflex can begin to act in less than the duration of a cardiac cycle and thus baroreflex adjustments are key factors in dealing with postural hypotension, the tendency for blood pressure to decrease on standing due to gravity.

<span class="mw-page-title-main">Reticular formation</span> Spinal trigeminal nucleus

The reticular formation is a set of interconnected nuclei that are located throughout the brainstem. It is not anatomically well defined, because it includes neurons located in different parts of the brain. The neurons of the reticular formation make up a complex set of networks in the core of the brainstem that extend from the upper part of the midbrain to the lower part of the medulla oblongata. The reticular formation includes ascending pathways to the cortex in the ascending reticular activating system (ARAS) and descending pathways to the spinal cord via the reticulospinal tracts.

<span class="mw-page-title-main">Ventrolateral preoptic nucleus</span> Nucleus of the anterior hypothalamus

The ventrolateral preoptic nucleus (VLPO), also known as the intermediate nucleus of the preoptic area (IPA), is a small cluster of neurons situated in the anterior hypothalamus, sitting just above and to the side of the optic chiasm in the brain of humans and other animals. The brain's sleep-promoting nuclei, together with the ascending arousal system which includes components in the brainstem, hypothalamus and basal forebrain, are the interconnected neural systems which control states of arousal, sleep, and transitions between these two states. The VLPO is active during sleep, particularly during non-rapid eye movement sleep, and releases inhibitory neurotransmitters, mainly GABA and galanin, which inhibit neurons of the ascending arousal system that are involved in wakefulness and arousal. The VLPO is in turn innervated by neurons from several components of the ascending arousal system. The VLPO is activated by the endogenous sleep-promoting substances adenosine and prostaglandin D2. The VLPO is inhibited during wakefulness by the arousal-inducing neurotransmitters norepinephrine and acetylcholine. The role of the VLPO in sleep and wakefulness, and its association with sleep disorders – particularly insomnia and narcolepsy – is a growing area of neuroscience research.

<span class="mw-page-title-main">Subfornical organ</span>

The subfornical organ (SFO) is one of the circumventricular organs of the brain. Its name comes from its location on the ventral surface of the fornix near the interventricular foramina, which interconnect the lateral ventricles and the third ventricle. Like all circumventricular organs, the subfornical organ is well-vascularized, and like all circumventricular organs except the subcommissural organ, some SFO capillaries have fenestrations, which increase capillary permeability. The SFO is considered a sensory circumventricular organ because it is responsive to a wide variety of hormones and neurotransmitters, as opposed to secretory circumventricular organs, which are specialized in the release of certain substances.

<span class="mw-page-title-main">Slow-wave sleep</span> Period of sleep in humans and other animals

Slow-wave sleep (SWS), often referred to as deep sleep, consists of stage three of non-rapid eye movement sleep. It usually lasts between 70 and 90 minutes and takes place during the first hours of the night. Initially, SWS consisted of both Stage 3, which has 20–50 percent delta wave activity, and Stage 4, which has more than 50 percent delta wave activity.

The zona incerta (ZI) is a horizontally elongated region of gray matter in the subthalamus below the thalamus. Its connections project extensively over the brain from the cerebral cortex down into the spinal cord.

The amygdalofugal pathway is one of the three major efferent pathways of the amygdala, meaning that it is one of the three principal pathways by which fibers leave the amygdala. It leads from the basolateral nucleus and central nucleus of the amygdala. The amygdala is a limbic structure in the medial temporal lobe of the brain. The other main efferent pathways from the amygdala are the stria terminalis and anterior commissure.

<span class="mw-page-title-main">Dorsomedial hypothalamic nucleus</span>

The dorsomedial hypothalamic nucleus is a nucleus of the hypothalamus. It is involved in feeding, drinking, body-weight regulation and circadian activity. More specifically, it is a necessary component for the expression of numerous behavioral and physiological circadian rhythms. The dorsomedial hypothalamic nucleus receives information from neurons and humors involved in feeding regulation, body weight and energy consumption, and then passes this information on to brain regions involved in sleep and wakefulness regulation, body temperature and corticosteroid secretion.

<span class="mw-page-title-main">Lateral hypothalamus</span>

The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cognitive and physical processes, such as promoting feeding behavior and arousal, reducing pain perception, and regulating body temperature, digestive functions, and blood pressure, among many others. Clinically significant disorders that involve dysfunctions of the orexinergic projection system include narcolepsy, motility disorders or functional gastrointestinal disorders involving visceral hypersensitivity, and eating disorders.

Sleep onset is the transition from wakefulness into sleep. Sleep onset usually transmits into non-rapid eye movement sleep but under certain circumstances it is possible to transit from wakefulness directly into rapid eye movement sleep.

The parabrachial nuclei, also known as the parabrachial complex, are a group of nuclei in the dorsolateral pons that surrounds the superior cerebellar peduncle as it enters the brainstem from the cerebellum. They are named from the Latin term for the superior cerebellar peduncle, the brachium conjunctivum. In the human brain, the expansion of the superior cerebellar peduncle expands the parabrachial nuclei, which form a thin strip of grey matter over most of the peduncle. The parabrachial nuclei are typically divided along the lines suggested by Baxter and Olszewski in humans, into a medial parabrachial nucleus and lateral parabrachial nucleus. These have in turn been subdivided into a dozen subnuclei: the superior, dorsal, ventral, internal, external and extreme lateral subnuclei; the lateral crescent and subparabrachial nucleus along the ventrolateral margin of the lateral parabrachial complex; and the medial and external medial subnuclei

The rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral tegmental area (tVTA), is a GABAergic nucleus which functions as a "master brake" for the midbrain dopamine system. It is poorly differentiated from the rest of the ventral tegmental area (VTA) and possesses robust functional and structural links to the dopamine pathways. Notably, both acute and chronic exposure to psychostimulants have been shown to induce FosB and ΔFosB expression in the RMTg; no other drug type has been shown to induce these proteins in the RMTg.

The parafacial zone (PZ) is a brain structure located in the brainstem within the medulla oblongata believed to be heavily responsible for non-rapid eye movement (non-REM) sleep regulation, specifically for inducing slow-wave sleep.

References

  1. ↑ Kolaj, M., & Renaud, L. P. (2010). Metabotropic Glutamate Receptors in Median Preoptic Neurons modulate Neuronal Excitability and Glutamatergic and GAGAergic Inputs From the Subfornical Organ (vol 103, pg 1104, 2010). Journal of Neurophysiology, 104(1), 579-579
  2. 1 2 3 Yoshida, K., Li, X. D., Cano, G., Lazarus, M., & Saper, C. B. (2009). Parallel Preoptic Pathways for Thermoregulation. Journal of Neuroscience, 29(38)
  3. ↑ Dacks, P. A., Krajewski, S. J., & Rance, N. E. (2011). Activation of Neurokinin 3 Receptors in the Median Preoptic Nucleus Decreases Core Temperature in the Rat. Endocrinology, 152(12), 4894-4905.
  4. ↑ Nakamura, K. (2011). Central circuitries for body temperature regulation and fever. American Journal of Physiology. Regulatory Integrative and Comparative Physiology, 301(5), R1207-R1228.
  5. 1 2 3 Pedrino, G. R., Monaco, L. R., & Cravo, S. L. (2009). Renal vasodilation induced by hypernatraemia Role of alpha-adrenoceptors in the median preoptic nucleus. Clinical and Experimental Pharmacology and Physiology, 36(12)
  6. ↑ Henry, M., Grob, M., & Mouginot, D. (2009). Endogenous angiotensin II facilitates GABAergicneurotransmission afferent to the Na+-responsive neurons of the rat median preoptic nucleus. American Journal of Physiology. Regulatory Integrative and Comparative Physiology, 297(3), R783-R792.
  7. ↑ Llewellyn, T., Zheng, H., Liu, X. F., Xu, B., & Patel, K. P. (2012). Median preoptic nucleus and subfornical organ drive renal sympathetic nerve activity via a glutamatergic mechanism within the paraventricular nucleus. American Journal of Physiology. Regulatory Integrative and Comparative Physiology, 302(4), R424-R432.
  8. 1 2 Luppi, P. H., & Fort, P. (2011). What are the mechanisms activating the sleep-active neurons located in the preoptic area? Sleep and Biological Rhythms, 9, 59-64.
  9. 1 2 Gvilia, I., Suntsova, N., Angara, B., McGinty, D., & Szymusiak, R. (2011). Maturation of sleep homeostasis in developing rats: a role for preoptic area neurons. American Journal of Physiology. Regulatory Integrative and Comparative Physiology, 300(4), R885-R894
  10. 1 2 Benedetto, L., Chase, M. H., & Torterolo, P. (2012). GABAergic processes within the median preoptic nucleus promote NREM sleep. Behavioural Brain Research, 232(1), 60-65.

[11]Guzmán-Ruiz, M. A., Ramirez-Corona, A., Guerrero-Vargas, N. N., Sabath, E., Ramirez-Plascencia, O. D., Fuentes-Romero, R., ... & Buijs, R. M. (2015). Role of the suprachiasmatic and arcuate nuclei in diurnal temperature regulation in the rat. The Journal of Neuroscience, 35(46), 15419-15429.

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