Hypothalamus location

CRH (Corticotropin releasing hormone) is expressed in the nucleus paraventricularis of the hypothalamus and drives the stress hormone system by activating synthesis and release of corticotropin at the pituitary and in turn corticosteroid from the adrenal cortex. CRH is also expressed at many other brain locations not involved in neuroendocrine regulation, e.g. the prefrontal cortex and the amygdala. Preclinical studies have shown that CRH also coordinates the behavioral adaptation to stress (e.g. anxiety, loss of appetite, decreased sleepiness, autonomic changes, loss of libido). 

In the mammalian brain orexins are almost exclusively expressed in a small group of neurons located in the lateral hypothalamus (LH) andperifornical area (PEA)... 

The paraventricular nucleus in the hypothalamus is located adjacent to the third ventricle and has been identified as a satiety center. Neurons in the paraventricular nucleus produce neuropeptides which inhibit feeding when injected into the brain (thyrotropinreleasing hormone (TRH), corticotropin-releasing hormone (CRH), oxytocin). 

Autoradiography and receptor mRNA studies have shown Hi receptors to be located in most of the brain areas innervated by the ascending histaminergic axons, e.g. cerebral cortex, hippocampus, limbic areas and hypothalamus. Their presence in the cerebellum is not accompanied by appropriate histaminergic innervation. Very few are found in the striatum but this region does show a high density of H2 receptors. H2 receptors are also found with Hi in the cortex, hippocampus and limbic areas, but not in the hypothalamus. Although basically presynaptic the H3 receptor is also found postsynaptically in the striatum and cerebral cortex (Pollard et al. 1993). 

Prolactin is an essential hormone for normal production of breast milk following childbirth. It also plays a pivotal role in a variety of reproductive functions. Prolactin is regulated primarily by the hypothalamus-pituitary axis and secreted solely by the lactotroph cells of the anterior pituitary gland. Under normal conditions, secretion of prolactin is predominantly under inhibitory control by dopamine and acts on the D2 receptors located on the lactotroph cells. Increase of hypothalamic thyrotropin-releasing hormone (TRH) in primary hypothyroidism can stimulate the release of prolactin. 

The pituitary gland, or hypophysis, is located at the base of the brain just below the hypothalamus. It is composed of two functionally and anatomically distinct lobes (see Figure 10.2) ... 

The adenohypophysis does not have a direct anatomical connection with the hypothalamus therefore, regulation of hormone secretion by way of neuronal signals is not possible. Instead, these two structures are associated by a specialized circulatory system and the secretion of hormones from the adenohypophysis is regulated by hormonal signals from the hypothalamus (see Figure 10.2). Systemic arterial blood is directed first to the hypothalamus. The exchange of materials between the blood and the interstitial fluid of the hypothalamus takes place at the primary capillary plexus. The blood then flows to the adenohypophysis through the hypothalamic-hypophyseal portal veins. Portal veins are blood vessels that connect two capillary beds. The second capillary bed in this system is the secondary capillary plexus located in the adenohypophysis. 

Located in close proximity to the primary capillary plexus in the hypothalamus are specialized neurosecretory cells. In fact, the axons of these cells terminate on the capillaries. The neurosecretory cells synthesize two types of hormones releasing hormones and inhibiting hormones (see Table 10.2). Each of these hormones helps to regulate the release of a particular hormone from the adenohypophysis. For example, thyrotropin-releasing hormone produced by the neurosecretory cells of the hypothalamus stimulates secretion of thyrotropin from the thyrotrope cells of the adenohypophysis. The hypo-thalamic-releasing hormone is picked up by the primary capillary plexus travels through the hypothalamic-hypophyseal portal veins to the anterior pituitary leaves the blood by way of the secondary capillary plexus and exerts its effect on the appropriate cells of the adenohypophysis. The hypophyseal hormone, in this case, thyrotropin, is then picked up by the secondary capillary plexus, removed from the pituitary by the venous blood, and delivered to its target tissue. 

The primary factor that influences ADH secretion is a change in plasma osmolarity. Osmoreceptors in the hypothalamus are located in close proximity to the ADH-producing neurosecretory cells. Stimulation of these osmoreceptors by an increase in plasma osmolarity results in stimulation of the neurosecretory cells an increase in the frequency of action potentials in these cells and the release of ADH from their axon terminals in the neurohypo-... 

Figure 2.1 Schematic of the rat brain (sagittal section) showing the approximate location of important brain structures controlling wakefulness and REM sleep. Abbreviations AH, anterior hypothalamus BF, basal forebrain DL pons, dorsolateral pons (rapid eye movement sleep control area) M-RA, Magoun/Rhines inhibitory area in the ventral medulla PH, posterior hypothalamus.

Histamine-containing neurons, located in the tuberomammillary nuclei (TMN) of the posterior hypothalamus, stimulate cortical activation through... 

Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy, may be caused by the lack of hypocretin mRNA and peptides in humans (Peyron et al., 2000) or a disruption of the hypocretin receptor 2 or its ligand in dogs and mice (Lin et al., 1999 Chemelli et al., 1999). Hypocretin-containing neurons are located exclusively in the dorsomedial, lateral, and perifornical hypothalamic areas (Peyron et al., 1998). Two hypocretin sequences, Hcrt-1 (orexin-A) and Hcrt-2 (orexin-B), are generated from a single preprohypocretin (De Lecea et al., 1998 Peyron et al, 1998 Sakurai et al, 1998). Axons from these neurons are found in the hypothalamus, locus coeruleus (LC), raphe nuclei, tuberomamillary nucleus, midline thalamus, all levels of spinal cord, sympathetic and parasympathetic centers, and many other brain regions... 

Figure 6.2 The location and distribution of the histamine-containing neurons in the brain. These neurons are localized in the tuberomammiUaiy nucleus within the posterior hypothalamus and send projections throughout the brain. Abbreviations Hi, hippocampus Hy, hypothalamus IC, inferior colliculus OB, olfactory bulb SC, superior colliculus SI, substantia innominata St, striatum TH, thalamus TMN, tuberomammillary nucleus. Adapted from Watanabe Yanai (2001).

The neural structures involved in the promotion of the waking (W) state are located in the (1) brainstem [dorsal raphe nucleus (DRN), median raphe nucleus (MRN), locus coeruleus (LC), laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT), and medial-pontine reticular formation (mPRF)] (2) hypothalamus [tuberomammillary nucleus (TMN) and lateral hypothalamus (LH)[ (3) basal forebrain (BFB) (medial septal area, nucleus basalis of Meynert) and (4) midbrain ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) (Pace-Schott Hobson, 2002 Jones, 2003). The following neurotransmitters function to promote W (1) acetylcholine (ACh LDT/PPT, BFB) (2) noradrenaline (NA LC) (3) serotonin (5-HT DRN, MRN) (4) histamine (HA TMN) (5) glutamate (GLU mPRF, BFB, thalamus) (6) orexin (OX LH) and (7) dopamine (DA VTA, SNc) (Zoltoski et al, 1999 Monti, 2004). 

Neuropeptide S (NPS) is a recently discovered bioactive peptide that has emerged as a new signaling molecule in the complex circuitry that modulates sleep-wakefulness and anxiety-like behavior. The peptide precursor is expressed most prominently in a novel nucleus located in the perilocus coeruleus, a brain structure with well-defined functions in arousal, stress, and anxiety. NPS was also found to induce anxiolytic-like behavior in a battery of four different tests of innate responses to stress. Infusion of NPS potently increases wakefulness and suppresses non-REM (NREM) and REM sleep (Xu et al, 2004). NPS binds to a G-protein-coupled receptor, the NPS receptor, with nanomolar affinity activation of the receptor mobilizes intracellular calcium. The NPS receptor is expressed throughout the brain, particularly in regions relevant to the modulation of sleep and waking, in the tuberomammillary region, lateral hypothalamus, and medial thalamic nuclei. 

FIGURE 14-2 The histaminergic system of the rat brain. (A) Frontal sections through the posterior hypothalamus showing the location of histaminergic neurons. Arc, arcuate nucleus DM, dorsomedial nucleus LM, lateral mammillary nucleus MM, medial mammillary nucleus MR, mammillary recess PM, premammillary nucleus 3V, third ventricle VMH, ventromedial hypothalamic nucleus. (Modified with permission from reference [5].)... 

In clinical settings core temperature measurements, including pulmonary artery and esophagus measurements, are often required. In 1959 Benzinger [1] first proposed the human tympanic membrane as the ideal site for core temperature measurements. The tympanic membrane is ideal, because it is located near the carotid artery and shares its blood supply with the hypothalamus, which controls body temperature. First temperature measurements in the ear were performed with thermistor sensors in direct contact with the tympanic membrane. The invasiveness of this method limited its use mainly to anaesthetized patients. 

By contrast, the accessory olfactory system is thought to be involved in the detection of odors that influence a variety of reproductive and aggressive behaviors (Keverne 1999). Sensory neurons are located in the vomeronasal organ (VNO) and detect pheromones which gain access to the VNO by a pumping mechanism (Meredith and O Connell, 1979). VNO neurons send projections to the accessory olfactory bulb (AOB). Mitral cells of the AOB project in turn to the medial nucleus of the amygdala olfactory information is then dispatched to several hypothalamic regions such as the bed nucleus of the stria terminalis, the medial preoptic area and the ventromedial hypothalamus (Scalia and Winans 1975). 

Leptin signalling is via monomeric receptors in the brain. A short-form of the leptin receptor (Lep-R) is required to transport the hormone across the blood-brain barrier and a long-form Lep-R is located in the hypothalamus. The long-form is functionally linked with a particular type of receptor-associated tyrosine kinase called Janus kinase (JAK, see Section 4.7) whose function is to phosphorylate a STAT (signal transducer and activator of transcription) protein a similar mechanism to that often associated with signalling by inflammatory cytokines. 

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