The Hypothalamus Contains Neuronal Bodies With Axons That Continue Into the

Hypothalamic Sulcus

The Peripheral and Central Nervous System

S. Franklin , in Conn's Translational Neuroscience, 2017

Hypothalamus

The hypothalamus lies below the hypothalamic sulcus separating it from the thalamus above. Like the thalamus, a thin vertical space filled with CSF called the 3rd ventricle is positioned midline between the two halves of the hypothalamus thalamus. The hypothalamus extends anteriorly to the optic chiasm and posteriorly to include the mammillary bodies on the ventral surface of the brain. The hypothalamus is continuous with the pituitary gland via the pituitary stalk (infundibulum). While not apparent in gross specimens, the hypothalamus is divided into nuclear regions that are related to monitoring and controlling homeostatic function.

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Endocrinology

Mark Johnson , in Basic Science in Obstetrics and Gynaecology (Fourth Edition), 2010

Boundaries

The thalamus lies superior to the hypothalamus, separated from it by the hypothalamic sulcus. Medially the third ventricle, superiorly the thalamus and inferiorly the pituitary stalk provide anatomical limits for the hypothalamus; anteriorly, posteriorly and laterally the hypothalamus is without distinct boundaries.

The pituitary lies within the sella turcica (the Turkish saddle); anteriorly and inferiorly lies the sphenoid sinus, laterally the cavernous sinus (containing internal carotid arteries, and sixth cranial nerve), posteriorly the clinoid processes of the sphenoid bone (often eroded on skull X-rays in the presence of a pituitary tumour), and superiorly the pituitary stalk which merges into the hypothalamus (Fig. 11.12). Anterior to the pituitary stalk lies the optic chiasma, which may be compressed by an expanding pituitary tumour, giving the typical presentation of bi-temporal hemianopia.

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The Hypothalamus

A.D. Parent , E. Perkins , in Fundamental Neuroscience for Basic and Clinical Applications (Fifth Edition), 2018

Abstract

The hypothalamus is a small, anatomical region of the diencephalon that is separated superiorly from the dorsal thalamus by the hypothalamic sulcus. The rostral boundary of the hypothalamus is the lamina terminalis. The lateral boundary of the hypothalamus is formed rostrally by the substantia innominata and caudally by the medial edge of the posterior limb of the internal capsule. Medially, the hypothalamus is bordered by the inferior portion of the third ventricle. Caudally, the hypothalamus is not sharply demarcated, merging instead into the midbrain tegmentum and the periaqueductal gray. Externally, the boundary between the hypothalamus and the midbrain is represented by the caudal edge of the mammillary body. The hypothalamus is involved in the control of visceral functions and emotional behavior. Through influences on the visceromotor center, endocrine system, and limbic system, the hypothalamus partially regulates water and electrolyte balance, food intake, temperature, blood pressure, sleep-waking mechanism, circadian rhythmicity, emergency responses to stressors in the environment, and reproduction through mating and pregnancy.

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Hypothalamic Regulation of Anterior Pituitary Function

Anat Ben-Shlomo , Shlomo Melmed , in The Pituitary (Fourth Edition), 2017

The Hypothalamus

The hypothalamus comprises less than 1% of brain volume and weighs approximately 5 grams [11,12] . The hypothalamic sulcus defines the upper border and extends from the interventricular foramen to the cerebral aqueduct, above which lies the thalamus. The anterior border is roughly defined as a line through the anterior commissure, lamina terminalis, and optic chiasm. The posterior border is adjacent to the midbrain tegmentum superiorly and the mammillary bodies inferiorly. Lateral borders are defined by the substantia innominata, the internal capsule, the subthalamic nucleus, and the cerebral peduncle.

Hypothalamic neuronal bodies producing factors controlling the pituitary are clustered in different nuclei. Each hypothalamic hormone may be produced in more than one nucleus, and a single nucleus may express several hormones. Nuclei predominantly involved in pituitary regulation are mostly located in the medial hypothalamus.

The median eminence is the major functional link between the hypothalamus and the pituitary and lies outside the blood–brain barrier [13]. Its blood supply is separate from the rest of the hypothalamus and is largely shared with the pituitary [14–16]. The median eminence is composed of ependymal, internal, and external zones [17]. The innermost ependymal zone resides on the floor of the third ventricle; tight junctions and tanycytes prevent exchange of large molecules between the cerebrospinal fluid (CSF) and the extracellular median eminence spaces, as well as back-trafficking of releasing factors into the hypothalamus [18]. The internal zone consists of axons arising from the supraoptic and paraventricular nuclei to the posterior pituitary, and axons from the hypophysiotropic neurons to the external zone of the median eminence. The external zone of the median eminence contains axons from periventricular hypophysiotropic neurons, including the periventricular hypothalamic nucleus, and paraventricular and arcuate nuclei. This zone is the primary source for transfer of releasing factors into the hypophyseal–portal circulation, eventually reaching anterior pituitary trophic hormone-secreting cells [17]. Axons from peptidergic neurons release peptides including TRH, GnRH, corticotrophin-releasing hormone (CRH), growth hormone–releasing hormone (GHRH), and somatostatin. Axons from monoamine-secreting neurons release dopamine and serotonin. Some releasing factors reaching the median eminence do not enter the hypophyseal–portal circulation, but are released locally to regulate secretion by other nerve terminals [19].

The hypophyseal–portal circulation derives from the superior hypophyseal artery, a branch of the internal carotid artery, forming a capillary loop network that penetrates and surrounds the internal and external median eminence zones. Arterial blood in this network receives releasing factors secreted upon depolarization of hypothalamic neurons, and transports these peptides to a large network of sinusoids surrounding the pituitary stalk, supplying the entire anterior pituitary [17,20]. Utilizing plasmalemmal vesicle-associated protein 1 (PV1) staining, extensive fenestrations were demonstrated at the median eminence, at the arcuate nucleus, and proximal to the pituitary stalk [21]. Estrous cycle-dependent PV1 expression and glycosylation levels in this area suggest that time-dependent enhanced permeability controls exposure to feedback regulators between the mediobasal hypothalamus, the pituitary, and the periphery [21]. The large surface area of this vascular network [22,23] and its fenestrations [21] facilitate efficient diffusion of hypothalamic releasing factors to pituitary cells. Hypophyseal–portal circulation blood likely flows predominantly, if not exclusively, from the hypothalamus to the pituitary [20], but humoral feedback regulation on hypothalamic neurons controlling the pituitary likely also occurs. Potential routes for peripheral humoral factors regulating the hypothalamus include transcytosis through glial and endothelial cells in the blood–brain barrier, permeable capillaries that allow access of peripheral factors to the CSF, and bidirectional fenestrated capillaries.

Non-neuroendocrine supporting cell types including pituicytes and tanycytes also contribute to hypothalamic–pituitary regulation. Pituicytes are glial-like cells that engulf axon terminals of vasopressin neurons when the hormone is not required, but retract when vasopressin secretion is increased, such as during dehydration [24]. Tanycytes, activated by growth factors and adhesion molecules, operate similarly on axon terminals of GnRH neurons [18,25].

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Hypothalamic Regulation of Anterior Pituitary Function

Anat Ben-Shlomo , Shlomo Melmed , in The Pituitary (Third Edition), 2011

The Hypothalamus

The hypothalamus constitutes less than 1% of brain volume and weighs approximately 5 g [10,11] . The hypothalamic sulcus defines the upper border and extends from the interventricular foramen to the cerebral aqueduct, above which lies the thalamus. The anterior delineation is roughly defined as a line through the anterior commissure, lamina terminalis and optic chiasm. The posterior border is adjacent to the midbrain tegmentum superiorly and the mammillary bodies inferiorly. The lateral borders are defined by the substantia innominata, the internal capsule, the subthalamic nucleus, and the cerebral peduncle.

Hypothalamic neuronal bodies that produce factors controlling the pituitary are clustered in different nuclei, and any given hypothalamic hormone is often produced in more than one nucleus, and often a single nucleus may express several hormones. Nuclei predominantly involved in pituitary regulation are mostly located in the medial hypothalamus.

The median eminence is the major functional link between the hypothalamus and the pituitary, and lies outside the blood–brain barrier, receiving blood supply separately from the rest of the hypothalamus, and largely shared with the pituitary [12–14]. The median eminence is composed of ependymal, internal and external zones [15]. The innermost ependymal layer in the floor of the third ventricle contains tight junctions to prevent exchange of large molecules between the cerebrospinal fluid (CSF) and extracellular median eminence spaces. Other cells in this zone termed tanycytes send processes to other median eminence zones [16]. Tight junctions and tanycytes likely prevent back-trafficking of releasing factors into the hypothalamus. The internal zone consists of axons arising from the supraoptic and paraventricular nuclei to the posterior pituitary, and axons from the hypophyseotropic neurons to the external zone of the median eminence. The external zone of the median eminence contains axons from periventricular hypophyseotropic neurons, including the periventricular hypothalamic nucleus, paraventricular and arcuate nucleus. Axons from peptidergic neurons release peptides including TRH, GnRH, corticotropin-releasing hormone (CRH), growth-hormone-releasing hormone (GHRH) and somatostatin. Axons from monoamine-secreting neurons release dopamine and serotonin. Releasing factors are transferred into the hypophyseal–portal circulation in the external zone of the median eminence, and from there, they eventually reach anterior pituitary trophic hormone-secreting cells [15]. There is an intimate anatomic connection between the axon termini and the fenestrated capillary endothelium of the hypothalamic–pituitary circulation in both the anterior and posterior pituitary.

However, many releasing factors do not reach the hypophyseal–portal circulation, but are released locally to regulate secretion by other nerve terminals in the zone [17]. The hypophyseal–portal circulation originates from the superior hypophyseal artery, a branch of the internal carotid artery, forming a capillary loop network that penetrates and surrounds the internal and external median eminence zones. Arterial blood in this network receives releasing factors secreted upon depolarization of hypothalamic neurons, and transports these peptides to a large network of sinusoids surrounding the pituitary stalk and supplying the entire anterior pituitary [15,18]. The large surface area of this fenestrated vascular network [19,20] facilitates diffusion of hypothalamic releasing factors to pituitary cells. Recently, staining with plasmalemmal vesicle-associated protein 1 (PV1), which constitutes individual radial fibrils in the fenestrated diaphragm, demonstrated the hypothalamic–pituitary vascular unit to be fenestrated, especially at the median eminence, arcuate nucleus and proximal to the pituitary stalk [21]. Moreover, PV1 in this area was not glycosylated, suggesting greater permeability to vascular fenestrations which are estrous-cycle dependent. During the pre-ovulatory LH surge, PV1 expression increased, coinciding with increased fenestrations, suggesting anticipation of the mediobasal hypothalamus to feedback regulators from the pituitary/periphery [21]. Hypophyseal–portal circulation blood likely flows predominantly, if not exclusively, from the hypothalamus to the pituitary [18], however humoral feedback regulation on hypothalamic neurons controlling the pituitary likely also occurs. Potential routes for peripheral humoral factors regulating the hypothalamus include transcytosis through glial and endothelial cells in the blood–brain barrier, permeable capillaries that allow access of peripheral factors to the CSF and the presence of bidirectional fenestrated capillaries.

Non-neuroendocrine supporting cell types including pituicytes and tanycytes also contribute to hypothalamic–pituitary regulation. Pituicytes engulf axon terminals of vasopressin neurons when the hormone is not required, but retract when vasopressin secretion is increased, for example during dehydration [22]. Tanycytes, activated by growth factors and adhesion molecules, operate similarly on axon terminals of GnRH neurons [16,23].

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The Neuroendocrine Immune Network in Ageing

Michel A. Hofman , Dick F. Swaab , in NeuroImmune Biology, 2004

1 INTRODUCTION

The human hypothalamus, which measures only 4 cm³ , is confined anteriorly by the lamina terminalis, posteriorly by the midbrain tegmentum, and superiorly by the hypothalamic sulcus [1, 2]. Although the complex cellular arrangement and multitude of afferent and efferent projections have made analysis of hypothalamic organization difficult, most authors distinguish three major regions: (i) the preoptic or chiasmatic region – containing the suprachiasmatic nucleus, sexually dimorphic nucleus, supraoptic nucleus and paraventricular nucleus. In addition, the nucleus basalis of Meynert, the diagonal band of Broca and the bed nucleus of the stria terminalis are considered in connection with the preoptic region; (ii) the tuberal region – containing the ventromedial and dorsomedial hypothalamic nuclei, along with the arcuate (or tubero-infundibular) nucleus, lateral tuberal nucleus and tubero-mamillary nucleus, and (iii) the posterior or mamillary region, which is dominated by the mamillary bodies that abut the midbrain tegmentum (Figure 1) [for reviews, see 1–5].

Before 1900 there were only vague intimations of the function of the brain surrounding the third ventricle and these were based primarily on various pathological and assorted clinical observations [6]. Since then a large body of experimental evidence has been derived implicating that this part of the brain contains the control systems which are critically involved in a wide range of homeostatic and rheostatic regulatory processes [see e.g., 4,7,8]. Among these are the control of water balance, food ingestion and energy metabolism, sleep, body temperature and neuroendocrine secretion and the regulation of reproduction and various emotional-affective states. Increasing age and a variety of diseases may impair many of these functions and may have deleterious effects on the morphology of hypothalamic structures [see, e.g., 2,5,9–11]. Some hypothalamic cell groups, on the other hand, remain functionally intact or even show clear signs of neuroplasticity by becoming more active later in life. In the present review, recent data on a number of prominent hypothalamic nuclei in the preoptic and tuberal regions are discussed in relation to sexual differentiation, ageing and some neuropathological conditions.

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Morphology of the human hypothalamus

Bertalan Dudás M.D., Ph.D. , in Atlas of the Human Hypothalamus, 2021

Paraventricular and supraoptic nuclei

According to this compartmentalized view, paraventricular nucleus occupies primarily the preoptic region extending into the tuberal zone where it tapers off (Figs. 12 and 13 ). The superior border of the nucleus is the hypothalamic sulcus that also marks the border between the thalamus and the hypothalamus. Mediolaterally the paraventricular nucleus is located in the medial hypothalamic area and the periventricular zone. In human, the former region is filled mostly by darkly stained magnocellular neurons that are easily detectable with Nissl staining, while the latter area is populated primarily with smaller, less intensely stained parvocellular cells. Magnocellular neurosecretory system is responsible for the production of oxytocin and vasopressin; the axons of these neurons form the hypothalamo-hypophyseal tract running through the hypophyseal stalk and projecting to the neurohypophysis where oxytocin and vasopressin are eventually stored in nerve terminals (Herring bodies). The neurons that secrete oxytocin and vasopressin inhabit different zones in the magnocellular system; vasopressin-secreting perikarya form a dense cluster populating the ventrolateral zone of the paraventricular nucleus, while oxytocin-producing cells tend to avoid this zone and instead they are more scattered throughout the nucleus ( Saper, 2004).

Neurons composing the supraoptic nucleus have similar morphology to the cells populating the magnocellular part of the paraventricular nucleus; they have large, intensely stained perikarya populating the corner of lateral hypothalamus between the basal surface and the optic tract (Figs. 11–13). Magnocellular neurons also form additional cell clusters scattered along an arched line between the supraoptic and paraventricular nuclei as well as along the medial edge of the optic tract. Similar to the rest of the magnocellular cells, these perikarya are oxytocin- or vasopressin-immunoreactive and project to the neurohypophysis. Both supraoptic and paraventricular nuclei are densely vascularized, and magnocellular neurons are often associated with blood vessels.

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Neurobiology of Cytokines

Ashley Grossman , ... Alfredo Costa , in Methods in Neurosciences, 1993

Hypothalamic Dissection

The brain is placed with its ventral surface upward, and the well-demarcated hypothalamic area is dissected within the following limits: the posterior border of the optic chiasm, the anterior border of the mamillary bodies, and the lateral hypothalamic sulci. The depth of the fragment is chosen according to the peptide whose secretion is to be investigated. Thus, in the case of CRH-41, the depth of the fragments is approximately 2 mm, in order to include the paraventricular nucleus (PVN), the principal source of hypothalamic CRH-41, which is located close to the third ventricle. For SRIF, GnRH, and GHRH, a depth of approximately 1 mm allows the inclusion of the relevant cell nuclei, which have a more anterior and inferior position than in the PVN. A depth of 3 mm is chosen for studies on AVP and oxytocin, for which the high posterior hypothalamic nuclei are to be included. The hypothalamic blocks obtained are then entirely bisected by a longitudinal incision through the midsagittal plane, using a surgical blade. The total dissection time is usually less than 2 min from decapitation; and approximately 30 min elapse between sacrificing the first animal and the completion of this stage (using 8–16 animals), during which time the tissue is placed in vials containing ice-cold incubation medium.

Some experiments are performed on the isolated median eminence, in which the hypophysiotropic hormones have their highest concentration. The median eminence contains a large number of nerve terminals in close proximity to the primary capillary bed of the portal system, from which they are released (17). In experiments on the median eminence, a dissecting microscope is required, through which the area of interest is easily recognized and then cut and removed.

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Pulsatility in Neuroendocrine Systems

Stanko S. Stojilkovic , ... Kevin J. Catt , in Methods in Neurosciences, 1994

Primary Culture of Hypothalamic Cells

Hypothalamic tissue is removed from fetuses of 17-day pregnant Sprague–Dawley rats. The borders of the excised hypothalami are delineated by the anterior margin of the optic chiasm, by the posterior margin of the mammilary bodies, and laterally by the hypothalamic sulci. After dissection, hypothalami are placed into ice-cold dissociation buffer consisting of 137 mM NaCl, 5 mM KC1, 0.7 mM Na₂HP0₄, 25 mM HEPES, 100 mg/liter gentamicin, pH 7.4. The preparation of hypothalamic cells is performed by minor modifications of the method described by Peterfreund and Vale (11). The tissues are washed and then incubated in a sterile flask with dissociation buffer supplemented with 0.2% collagenase (activity 149 U/mg; Worthington, Freehold, NJ), 0.4% bovine serum albumin, 0.2% glucose, and a pinch of DNase I (Sigma, St. Louis, MO). After 60 min of incubation in a 37°C water bath with shaking at 60 cycles min⁻¹, the tissue is gently triturated by repeated aspiration into a smooth-tipped Pasteur pipette. Incubation is continued for another 30 min, after which the tissue is finally dispersed. The dispersed cells are passed through sterile mesh (200 µm) into a 50-ml tube, pelleted by centrifugation for 10 min at 200 g, and then washed once in dissociation buffer and once in culture medium consisting of 500 ml Dulbecco's modified Eagle's medium (DMEM) containing 0.584 g/liter l-glutamine and 4.5 g/liter glucose (Sigma), mixed with 500 ml F-12 medium containing 0.146 g/liter l-glutamine, 1.802 g/liter glucose (Sigma), 100 µg/ml gentamicin, 2.438 g/liter sodium bicarbonate, and 10% heat-inactivated fetal calf serum (Gibco). Each fetal hypothalamus yields about 1.5 × 10⁶ cells.

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Homeostatic Mechanisms

Pierre-Marie Lledo , in Encyclopedia of the Human Brain, 2002

II.B Structure of the Hypothalamus

The hypothalamus in the mammalian brain encompasses the most ventral part of the diencephalon, where it forms the floor and, in parts, the walls of the third ventricle. Its upper boundary is marked by a sulcus in the ventricular wall, the ventral diencephalic or hypothalamic sulcus, which separates the hypothalamus from the dorsally located thalamus ( Fig. 2). Caudally, the hypothalamus merges without any clear limits with the periventricular gray and the tegmentum of the mesencephalon. However, it is customary to define the caudal boundary of the hypothalamus as represented by a plane extending from the caudal limit of the mammilary nuclei ventrally and from the posterior commissure dorsally. Rostrally, the hypothalamus is continuous with the preoptic area, which lies partly forward to and above the optic chiasm.

By means of the previously mentioned external landmarks at the ventral surface of the brain, the hypothalamus can be subdivided in the anterior–posterior direction into an anterior part that includes the preoptic area, a middle part, and a posterior part. Another subdivision in the lateral–medial direction consists of three longitudinal zones recognized as the periventricular, the medial, and the lateral zones. The periventricular zone consists mostly of small cells that, in general, are oriented along fibers parallel with the wall of the third ventricle. The medial zone is cell rich, containing most of the well-delineated nuclei of the hypothalamus that include the preoptic and suprachiasmatic nuclei in the anterior region; the dorsomedial, ventromedial, and paraventricular nuclei in the middle region; and the posterior nucleus and mammillary bodies in the posterior region (Fig. 2). The lateral zone contains only a small number of cells interposed between the longitudinal fiber system of the medial forebrain bundle. This region possesses long fibers that project to the spinal cord and cortex as well as extensive short-fiber, multisynaptic ascending and descending pathways. The basal portion of the medial region and the periventricular region contain many of the small hypothalamic neurons that secrete the substances that control the release of anterior pituitary hormones. Most fiber systems of the hypothalamus are bidirectional. Projections to and from areas caudal to the hypothalamus are carried in the medial forebrain bundle, the mammillo-tegmental tract, and the dorsal longitudinal fasciculus. Rostral structures are interconnected with the hypothalamus by means of the mammillo-thalamic tracts, fornix, and stria terminalis. However, there are two important exceptions to the rule that fibers are bidirectional in the hypothalamus. First, the hypothalamo-hypophyseal tract contains only descending axons of paraventricular and supraoptic neurons, which terminate primarily in the posterior pituitary (Fig. 3). Second, the hypothalamus receives one-way afferent connections directly from the retina. These fibers terminate in the suprachiasmatic nucleus, which is involved in generating light–dark cycles. The role of these rhythms in the control of motivated behaviors is discussed later.

The following section describes the interrelated functions of the hypothalamus and the pituitary gland as well as some of the major functions of the limbic system.

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Source: https://www.sciencedirect.com/topics/neuroscience/hypothalamic-sulcus

The Hypothalamus Contains Neuronal Bodies With Axons That Continue Into the

Hypothalamic Sulcus

The Peripheral and Central Nervous System

Hypothalamus

Endocrinology

Boundaries

The Hypothalamus

Abstract

Hypothalamic Regulation of Anterior Pituitary Function

The Hypothalamus

Hypothalamic Regulation of Anterior Pituitary Function

The Hypothalamus

The Neuroendocrine Immune Network in Ageing

1 INTRODUCTION

Morphology of the human hypothalamus

Paraventricular and supraoptic nuclei

Neurobiology of Cytokines

Hypothalamic Dissection

Pulsatility in Neuroendocrine Systems

Primary Culture of Hypothalamic Cells

Homeostatic Mechanisms

II.B Structure of the Hypothalamus

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