5.3.2015
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Kaan Yücel M.D., Ph.D. http://drkaanyucel.org
[email protected] SOURCES USED
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1. Editör: Doğan Taner. Fonksiyonel Nöroanatomi 13. Baskı, ODTÜ Geliştirme Vakfı Yayıncılık ve İletişim A.Ş. Yayınları, Ankara, 2014. ISBN: 978-975-7064-05-3 2. Richard S. Snell. Clinical Neuroanatomy 7th Edition, Lippincott Williams & Wilkins, Philadelphia, USA, 2010. ISBN: 978-0-7817-9427-5 3. Maria Patestas & Leslie P. Gartner. A textbook of Neuroanatomy 1st Edition, Blackwell Publishing, 2006. ISBN: 978-1405103404 4. Kaplan Arıncı, Alaittin Elhan. Anatomi I. Cilt., 5. Baskı, Güneş Kitabevi, Ankara, 2014. ISBN: 978975-277-513-8 5. Mehmet Yıldırım. Resimli Sistematik Anatomi 2. Baskı, Nobel Tıp Kitabevleri. 2013. ISBN: 978975-420-949-5 6. Warwick R& Williams PL. Gray's Anatomy 36th Edition, Churchill Livingstone, London, 1980.
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1. Diencephalon (Interbrain; Ara beyin) Prosencephalon is the largest part of the brain. We use it in our anatomy textbooks mostly. The term “forebrain” is used more commonly instead. Forebrain has two parts. They are 1) Telencephalon and 2) Diencephalon. The diencephalon forms only 1/40 of the prosencephalon (Source #5). On the other hand, the significant functions of the diencephalic structures are incomparable with its relatively small size. The diencephalon means the “within, or through the brain”. It actually deserves this name. Diencephalon is formed by two halves of structures under the cerebral hemispheres. Between these two halves lies the narrow vertical third ventricle. The diencephalon is located at the dorsal end of the brain stem surrounded by the internal capsule laterally and the lateral ventricles and corpus callosum superiorly. It is divided into symmetrical halves separated by the narrow third ventricle but connected by the massa intermedia. The superior part of the diencephalon is mainly formed by the thalamus, where the part under (-hypo) is the hypothalamus. As you will see the structures of the diencephalon are named according to their position to the thalamus. See yourself below: The diencephalon has four structures (Sources # 1-3 ). Some textbooks counts metathalamus as the fifth structure in the diencephalon (Sources #4,5 ). We will consider “metathalamus” as a part of thalamus. (1) Thalamus (2) Hypothalamus [-hypo: “under” ] (3) Subthalamus [-sub: 'inferior to”] (4) Epithalamus [-epi: “superior to”] The diencephalon extends posteriorly to the point where the third ventricle becomes continuous with the cerebral aqueduct (aqueduct of Slyvius). It extends anteriorly as far as the interventricular foramina (of Monro). Anterior to posterior, we can easily say our diencephalon lies between the two openings of the CSF (CerebroSpinal Fluid) system. A line drawn between the posterior commissure and mammillary bodies separates the diencephalon from the mesencephalon (midbrain). A line connecting foramen of Monro with the optic chiasma separates it from the telencephalon (Source #4).
1. 1. Surfaces of the diencephalon The inferior surface of the diencephalon is the only area exposed to the surface in the intact brain. It is formed by hypothalamic and other structures, which include, from anterior to posterior: •optic chiasma, with the optic tract on either side •infundibulum, with the tuber cinereum •mammillary bodies. The superior surface of the diencephalon is concealed by the fornix. The actual superior wall of the diencephalon is formed by the roof of the third ventricle. From the roof of the third ventricle, a pair of vascular processes, the choroid plexuses of the third ventricle, project downward from the midline into the cavity of the third ventricle. The choroid plexus is the place where the CSF is produced. The lateral surface of the diencephalon is bounded by the internal capsule. The medial surface of the diencephalon (i.e., the lateral wall of the third ventricle) is formed in its superior part by the medial surface of the thalamus and in its inferior part by the hypothalamus. These two areas are separated from one another by a shallow sulcus, the hypothalamic sulcus. A bundle of nerve fibers are afferent fibers to the habenular nucleus. It forms a ridge along the superior margin of the medial surface of the diencephalon. This bundle is called the stria medullaris thalami.
2.Thalamus
Gr. Inner chamber, bedroom The thalamus is a subcortical relay station. Any sensory information, except the sense of olfaction/smell, is relayed to the primary sensory areas in the cerebral cortex by the thalamus. Impulses (information) on movement from basal ganglia and cerebellum is relayed to motor areas in the cerebral cortex by the thalamus. 1
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The information is processed and integrated here. It is then sent to specific areas of the ipsilateral cerebral cortex. These cortical areas are also connected to thalamic nuclei with reciprocal connections. The cerebral cortex is the most prominent input source to the thalamus. The thalamus not only functions in the further processing and integration of sensory and motor information but also serves as the main entrance. It also controls the cerebral activity. The thalamus mainly projects to the cerebral cortex. Additionally, it provides input to the basal ganglia and hypothalamus.
2.1. GROSS ANATOMY The thalamus is an egg-shaped mass of gray matter. It is embedded in the depths of the cerebral white matter (substantia alba). It forms the major part of the diencephalon. It forms 3/5 of the diencephalon (Source #4). The thalamus has an anterior and posterior pole. It has four surfaces. Anterior tubercle of thalamus is an elavation on the anterior pole of thalamus. Superiorly it is covered by a layer of white substance: stratum zonale. Anterior border Interventricular foramen (of Monro) (the narrow anterior end of thalamus forms the posterior border of the foramen) Posterior border Posterior extent of the pulvinar Dorsal (Superior) border Its free surface. It contributes to the floor of the lateral ventricle. Ventral (Inferior) border Hypothalamic sulcus Medial border Third ventricle (Medial surface of thalamus forms the superior part of lateral wall of 3rd ventricle) Lateral border Posterior limb of internal capsule (lies between thalamus and lentiform nucleus-basal ganglia nuclei) Head of caudate and genu of internal capsule are located anterior to thalamus. The right and left thalami (plural for thalamus) are separeted from each other along most of their medial surfaces by the third ventricle. The interthalamic adhesion (massa intermedia) transverses the vertically oriented narrow third ventricle. It forms a bridge between the two thalami. It is not considered as a commissural pathway. It means no information is carried between right and left thalamus. The interthalamic adhesion is found in 70-80% of humans. The stria medullaris thalami and stria terminalis are two thin bands of white matter. They lie on the superior surface of thalamus. The stria medullaris thalami courses on the superomedial margin of thalamus. It separates superior surface from the medial surface of thalamus. Although, there is the word “thalami” in it, this slender bundle with two-way fibers connect the septal nuclei and hypothalamus with the habenular nucleus of epithalamus. The stria terminalis carries fibers mainly from the amygdala. It ends in the hypothalamus, septal area, and bed nucleus of stria terminalis. It courses on the superolateral margin of thalamus. Stria terminalis along with the terminal vein (superior thalamostriate vein) lies in the sulcus terminalis. The sulcus terminalis is between thalamus and caudate nucleus. The caudate nucleus lies over the superior surface of thalamus and in a lateral position. The caudate nucleus is a component of the basal ganglia. Pulvinar (thalami) is an almond-shaped small elevation. It is located on the posterior pole and projects laterally. Sulcus choroideus lies in the midline of the superior surface of thalamus. Sulcus choroideus contains a part of the choroid plexus of lateral ventricle. Medial to the sulcus choroideus, the superior surface of thalamus is covered by the tela choroidea of third ventricle. Lateral to this sulcus, the superior surface is covered by lamina affixa. The lamina affixa is formed by the ependymal cells. The thalamus rests on the midbrain. Its inferior surface forms a ceiling over the mesencephalic tectum. Numerous tracts ascend through the brainstem and pass into the thalamus from its inferior surface. The brainstem reticular formation extends superiorly into the thalamus through this surface. 2.2. INTERNAL & EXTERNAL MEDULLARY LAMINAE The gray matter of thalamus is divided by laminae of white matter tracts. The internal medullary lamina is a Y-shaped layer of white matter. It divides the thalamus into three groups of nuclei. They are 1) Anterior 2) Lateral, and 3) Medial groups of nuclei. The anterior portion is divided into two limbs. These limbs of the internal medullary lamina surrounds the anterior thalamic nuclei. They separate the anterior nuclei from the medial and lateral thalamic nuclei. The posterior portion of this lamina, the leg of the Y, separates the medial and lateral nuclear group. The internal medullary lamina contains afferent and efferent thalamic fibers which enter or leave the thalamic subnuclei. 2
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The external medullary lamina is a curved layer of white matter. It is on the lateral surface of the thalamus close to internal capsule. It contains thalamocortical and corticothalamic fibers. Both thalamocortical and corticothalamic fibers course through the corona radiata and internal capsule. This lamina is covered by a thin layer of gray matter; thalamic reticular nucleus. The thalamic reticular nucleus is the most lateral (outermost) nucleus of the thalamus.
2.3. THALAMIC NUCLEI Each thalamic nuclear group functions as an independent unit with its afferent and efferent connections. The nuclear groups are further divided into subnuclei. The role of each thalamic subnucleus is associated with the source of incoming afferents and the cortical target areas of its efferents. Except the thalamic reticular nucleus, all thalamic subnuclei send the processed information to the cerebral cortex. The anterior and medial nuclear groups are called paleothalamus. They are phylogenetically older. The lateral group subnuclei are relatively newer. They are called as neothalamus. (Source # 3) The intralaminar and reticular nuclei are listed separately from the anterior, medial and lateral nuclear groups. 2.3.1. Anterior thalamic nuclei (nuclear group) 1) Anteroventral 2) Anteromedial, 3) Anterodorsal subnuclei The anterior thalamic nuclei are located in the anterior tubercle of thalamus. This is the smallest thalamic nuclear group. The anterior thalamic nuclei are actually relay nuclei of the Papez circuit. We will cover that in the Limbic System lecture. With its limbic connections, the anterior thalamic nuclei function in the expression of emotions. With its connections with the hippocampal formation, they are also believed to play a role in learnng and memory processes. 2.3.2. Medial thalamic nuclei (nuclear group) The medial thalamic nuclei are located medial to the internal medullary lamina. The medial thalamic nuclear group contains 1) the more prominent dorsomedial nucleus, 2) midline nuclei (median or periventricular nuclei). The midline nuclei are diffuse. They are located on the most medial surface of the third ventricle and within the interthalamic adhesion. The midline nuclei function in the modulation of cortical excitability. They have connections with the striatum, limbic cortex and hippocampal formation. The dorsomedial nucleus is an important group of nuclei for the limbic system. This limbic structure functions in the processing of information related to emotion. It also acts in learning and recent memory. 2.3.3. Lateral thalamic nuclei (nuclear group) The lateral thalamic nuclear group is located between the internal and external medullary laminae. It is the largest nuclear group in thalamus. The subnuclei of this group are arranged in two step-like rows. They are 1) Dorsal, 2) Ventral tiers of nuclei (subnuclei). Dorsal tier of the thalamic nuclei The dorsal tier of the thalamic nuclei are composed of 1) Lateral dorsal nucleus 2) Lateral posterior nucleus 3) Pulvinar nucleus. Except the lateral dorsal nucleus, these nuclei are connected with the association areas of the cerebral cortex. They function in the integration of sensory input. The lateral dorsal nucleus is believed to play a role in expression of emotions. The lateral posterior nucleus is believed to play a role in sensory integration. The pulvinar nucleus (L. cushion) is the most prominent nucleus of thalamus. The pulvinar nucleus functions in the integration of visual, auditory and somatosensory information. It has reciprocal connections with the association areas of the parietal, temporal and occipital lobes. It also receives sensory information from the components of the visual system the medial geniculate nucleus and cerebellum. Ventral tier of the thalamic nuclei The ventral tier of the thalamic nuclei contain the 1) Ventral anterior nucleus (VA), 2) Ventral lateral nucleus (VL) , and 3) Ventral posterior nucleus (ventrobasal complex). The ventral posterior nucleus is further subdivided into the ventral posteromedial nucleus (VPM), ventral posterolateral nucleus (VPL), and ventral posteroinferior nucleus (VPI). The ventral tier also includes the metathalamic nuclei.
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The nuclei in the anterior aspect of the ventral tier of the thalamic nuclei are ventral anterior and ventral lateral (sub)nuclei. They serve as relay stations for the somatic motor system including the basal ganglia and cerebellum. They also process information from the brainstem reticular formation. The nuclei in the posterior aspect of the ventral tier of the thalamic nuclei are VPM, VPL, medial and lateral geniculate nuclei. They serve as relay stations for all of the sensory systems (somatosensory, visual, auditory, and gustatory systems, excluding the olfactory system). VA nucleus: plays a role in the control of the movement of the eyes, face, head, and limbs. Nigrothalamic and pallidothalamic patways terminate here. Afferent fibers also come from the brainstem reticular formation. This nucleus is interconnected with the premotor cortex and supplementary motor area (Brodmann’s area 6). VL nucleus: exerts its influence on somatic motor activity via the basal ganglia and the cerebellum. It projects to the premotor and primary motor cortices. Ventral posterior nucleus VP nucleus (Ventrobasal complex) The VP nucleus relays processed sensory information to the primary somesthetic cortex located in the postcentral gyrus of the parietal lobe (Brodmann’s areas 3, 1, and 2). These cortical areas send corticothalamic fibers back to the VP nucleus. The VPM nucleus receives the terminals of the trigeminothalmic tracts (the ventral and dorsal trigeminal lemnisci) relaying general somatic afferent information (touch, pressure, pain and temperature sensation, and proprioception) from the orofacial region, and special visceral afferent sensation (taste) from the solitary nucleus. The VPL and VPI nuclei receive terminals of: lateral spinothalamic tract relaying pain and temperature sensation from the body medial lemniscus bringing discriminatory (fine) touch, pressure, joint movement, and vibratory sensation anterior spinothalamic tract relaying light (crude) touch sensation from the body. Additionally, the VPI nucleus receives fibers from the vestibular nuclei (vestibulothalamic fibers) and projects to the vestibular area of the somatosensory cortex.
2.3.4. Metathalamic nuclei The medial and lateral geniculate nuclei are two oval-shaped elevations inferior to the pulvinar. The medial geniculate nucleus (body) is located on the posterior aspect of thalamus. It is inferior to the pulvinar and lateral to the superior colliculus. The medial geniculate nucleus receives auditory input from the inferior colliculus (İ, işitme. Mİ?:medial işitme). The auditory input comes from both ears. The medial geniculate nucleus also receives some projections from other nuclei of the auditory system via the brachium of the colliculus inferior. The medial geniculate nucleus gives rise to the auditory radiation. The auditory radiation terminates in the primary auditory cortex. The primary auditory cortex is in the superior temporal gyrus, gyrus of Heschl (Brodmann areas 41 and 42). These areas are reciprocally connected with the medial geniculate nucleus. The lateral geniculate nucleus (body) is a thalamic relay nucleus for vision. It is larger than the medial geniculate nucleus. The majority fibers of the optic tract bring information from both eyes and end here. Via the geniculocalcarine tract (optic radiation), the lateral geniculate nucleus projects to the primary visual cortex (Brodmann area 17). The primary visual cortex is on the banks of the calcarine sulcus (fissure) of the occipital lobe. In addition to its reciprocal connections with the primary visual cortex, the lateral geniculate nucleus is interconnected with the pulvinar and other subnuclei of the thalamus. 2.3.5. Intralaminar nuclei The intralaminar nuclei are the rostral continuation of the ascending reticular activating system (ARAS) into the thalamus. They contain diffuse group of nuclei embedded in the internal medullary lamina and interthalamic adhesion. These nuclei receive sensory information from the spinothalamic tract, ventral trigeminal lemniscus (ventral trigeminothalamic tract), multisynaptic ascending pathways of the reticular formation that relay pain sensation, pain perception and arousal of the organism. The centromedian and the parafascicular nuclei are the prominent nuclei of this group. 4
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2.3.5. Thalamic reticular nucleus It is named for is reticular (mesh-like) apperance. It is not considered as a part of the reticular formation system of the brainstem. It consists of a thin layer of nerve cell bodies. This layer covers the external medullary lamina on the lateral surface of thalamus. It is the most lateral nucleus of thalamus. It is in direct contact with the posterior limb of the internal capsule, laterally. The thalamic reticular nucleus receives collaterals of the thalamocortical, corticothalamic, thalamostriatal, and pallidothalamic fibers. It is in a position where it gets a copy of thalamic projections, and monitors these projections. It relays sensory input to other thalamic nuclei and reticular formation. It has no cerebral projections.
3.Hypothalamus The hypothalamus is only 4-5 gr. But it is one of the parts of the body with a long list of different functions. The hypothalamus functions in the regulation of the body temperature, food intake, fluid intake, and control of the autonomic nervous system. It plays a role in emotional expression, memory and agression. Hypothalamus is considered as the major primary ganglion of the autonomic nervous ssytem. Hypothalamus is considered as the output center (window) of the limbic system. The functions of the hypothalamus are vital for the survival of the organism. Control of apetitte Fluid balance Electrolyte balance Glucose concentration Metabolism Sleeping Body temperature regulation Plus: Reproduction, sexual behaviour. The hypothalamus mediates all these functions by integrating the functions of the endocrine, autonomic (visceral motor), somatic motor and limbic systems. 3.1. BORDERS Anterior border from superior to inferior: Anterior commissure, lamina terminalis, and optic chiasma Posterior border Interpeduncular fossa Superior border Hypothalamic sulcus Inferior border Tuber cinereum (L. gray swelling) Medial border Third ventricle Lateral border Subthalamic nucleus, and internal capsule 3.2 GROSS ANATOMY The part of the hypothalamus between chiasma opticum anteriorly and mammillary bodies posteriorly is called tuber cinereum (Sources #1,6). The tuber cinereum is a convex mass of grey matter. It forms an elevation at the base of the infundibulum; eminentia mediana(Source #6). It projects inferiorly. The infundibulum (infundibular stalk or pituitary stalk) goes down from the eminentia mediana. The infundibular stalk continues with neurohypophysis (posterior lobe of pituitary gland) inferiorly. Area preoptica is the area just posterior to lamina terminalis. Developmentally, it is a part of telencephalon. The hypothalamic sulcus is the border between thalamus and hypothalamus. 3.3. HYPOTHALAMIC ZONES & NUCLEI There are many nuclei in hypothalamus. They have different functions. The hypothalamus is divided into zones and regions. Generally two bundles are used to divide the hypothalamus into different zones. One is the mammillothalamic tract (bundle of Vicq d'Azyr). The other one is fornix. The mammillothalamic tract is the heavily myelinated bundle of axons between the thalamus and mammillary bodies. Fornix is the bundle originating from hippocampus. We will cover these in the “Limbic System” lecture. Periventricular zone is located next to the midline. The nuclei here line the 3rd ventricle wall from anterior to posterior. Medial zone is the intermediate zone. Lateral zone contains nuclei which receive informaiton from 5
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the limbic system and mammillary bodies. Then they relay this information to other hypothalamic nuclei and the brainstem. The lateral zone plays an important role in the behavioral expression of emotions. Additionally, the lateral zone also contains the longitudinally oriented fibers of the medial forebrain bundle. 3.4. HYPOTHALAMIC REGIONS As the hypothalamus is divided into three zones from medial to lateral sagittaly. There is also another way of dividing the hypothalamus into different regions. The reason why we are doing all this is that it is difficult to identify the hypothalmic nuclei. The nuclei located in each region might extend into the adjacent zones and regions. The hypothalamus is divided into four regions anterior to posterior (rostocaudally) coronally. These four regions are located near the three prominent structures. 1) Tuber cinereum 2) Optic chiasma and 3) Mammillary bodies. Lateral hypothalamic region: is lateral to fornix and mammillothalamic tract. Lateral hypothalamic nucleus in the lateral zone The lateral hypothalamic nucleus is related to the control of appetite. The stimulation of the lateral hypothalamic nucleus nucleus induces eating. “Açlık merkezi”. Lesions will result in anorexia nervosa and loss of liquid intake. Lateral preoptic nucleus in the lateral zone: acts in the sleepwake cycle; biorhythm. Medial hypothalamic region 1. Preoptic region
2. Supraoptic (Chiasmatic or Anterior) region 3. Tuberal (Infundibular or Middle) region 4. Mammillary (Posterior) region 1. Preoptic region is located partly anterior to lamina terminalis. So, some of it is in the telencephalon. It is the anterior telencephalic portion of the hypothalamus. It has been considered part of the diencephalon for so long. It consists of gray matter located in the anteriormost extent of the 3 rd ventricle. It is located both in the anterior and posterior plane of lamina terminalis. The preoptic region extends into all three zones. Periventricular nuclei in the periventricular zone Medial preoptic nucleus in the medial zone The preoptic region controls the release of reproductive hormones from the anterior lobe of the pituitary gland. 2. Supraoptic region is located posterior to the optic chiasma. It is continuous rostrally with the preoptic area (region). The suprachiasmatic nucleus is a small nucleus. It is located next to the midline dorsal to the optic chiasma. It receives visual information from the retina via retinahypothalamic fibers. The paraventricular and the supraoptic nuclei have the most abundant blood supply in the brain. The neurons of these two nuclei synthesize the neurophysieal hormones: Anti-diuretic hormone (ADH) and oxyctosin. ADH and oxytosin are transported via axons of the neurons in these nuclei to the posterior lobe of the pituitary gland. The unmyelinated axons gather to form the supraopticohypophyseal (hypothalamohypophyseal) tract. This tract lies in the infundibular stalk. It ends in the neurohypophysis. The supraoptic nuclei mainly releases ADH. Lesions result diabetes insipidus. The paraventricular nucleus releases mainly oxytocin. Anterior hypothalamic nuclei act in thermoregulation by starting the mechanisms for heat loss. It does this by stimulating the parasympathetic system (peripheric vasodilatation, sweating, increase in breathing, decrease in somatomotor activities). 3. Tuberal region is dorsal to the tuber cinereum. Arcuate nucleus in the periventricular zone Dorsomedial and ventromedial nuclei in the medial zone The arcuate nucleus is in the tuber cinerum. It arches under the ventral aspect of the 3rd ventricle. The neurons of the arcuate nucleus produce hypothalamic-releasing hormones. Their axons form the tuberohypophyseal tract. This tract carries the releasing hormones of the hypothalamus to the hypophyseal portal system. The 6
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dorsomedial nucleus produces aggressive behaviour in animals when stimulated. The ventromedial nucleus is a “satiety” center [Tokluk merkezi]. The stimulation of the ventromedial nucleus results in satiety. Bilateral lesions of the nucleus results in obesity and hyperphagia. 4. Mammillary region includes the mammillary nuclei and the posterior hypothalamic nucleus. Three to four mammillary nuclei collectively form each mammillary body. The two mammillary bodies are seen as two elevations on the ventral (inferior) surface of the hypothalamus. The other hypothalamic nuclei are related to endocrine and/or autonomic system. The mammillary nuclei are the major targets of the fornix. Fornix brings information from (and carries to) the hippocampal formation. This information is about emotions. The hippocampal formation inhibits hypothalamus. In addition, information is relayed to the mammillary nuclei via the mammillary peduncle from the dorsal and ventral tegmental nuclei as well as the raphe nuclei. The mammillary nuclei carries information to the anterior thalamic nuclei via the prominent mammillothalamic tract. (We are going to repeat that in the “Limbic System” lecture!) The posterior hypothalamic nucleus contains neurons sensitive to decrease in the blood temperature. The posterior hypothalamic nucleus serves as the “thermostat”. It regulates body temperature by conserving heat and stimulating heat production via sympathetic system. Heat is conserved by vasoconstriction of cutaneous vessels. Heat is produced by an increase in thyroid activity. 3.5. CONNECTIONS OF THE HYPOTHALAMUS The hypothalamus is connected to widespread regions of the nervous system. The hypothalamus receives different types of input. Input on emotions from the limbic system Input from sensory & motor nuclei in the brainstem and spinal cord. The hypothalamus exerts its influence via its outputs on the endocrine and autonomic nervous systems. 3.5.1. AFFERENT CONNECTIONS OF THE HYPOTHALAMUS INPUT TO THE HYPOTHALAMUS Most neural input to the hypothalamus comes from the limbic system. Other neural input comes from the visceral structures and brainstem. Non-neural input is carried to the hypothalamus via the vascular system.
Sources of neural input to the hypothalamus Orbitofrontal cortex Basal forebrain Septal area and septal nuclei Ventral striatum Midline nuclei of thalamus Medial dorsal nucleus of thalamus Hippocampus (Hippocampal formation) Amygdala (Amygdaloid complex) Dorsal and ventral tegmental nuclei Raphe nuclei Locus ceruleus Spinal cord Reticular formation
3.5.1.1. NON-NEURAL INPUT TO THE HYPOTHALAMUS See the pituitary gland. 3.5.2. EFFERENT CONNECTIONS OF THE HYPOTHALAMUS OUTPUT FROM THE HYPOTHALAMUS Most hypothalamic output projections end in the sources of the hypothalamic input. We call this kind of projections as “reciprocal” projections. Additionally, hypothalamus (mammillary nuclei) Project to the anterior thalamic nuclei. Also hypothalamic output ends in the midbrain reticular formation, brainstem and spinal cord autonomic nuclei. In addition to the neural output, the hypothalamus provides output to the adenohypophysis and neurohypophysis.
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3.6. PATHWAYS OF THE HYPOTHALAMUS Although we classifiy the pathways of the hypothalamus as “afferent” and “efferent” depending on the direction of the most of the information carried, no pathway carries exclusively afferent or efferent fibers. They all carry bidirectional information. 3.6.1. Afferent pathways of the hypothalamus 1. Fornix Fornix is the most prominent pathway carrying neural input to the hypothalamus. The fornix originates from the hippocampal formation (hippocampus) of the limbic system. It distributes fibers to the preoptic and anterior areas of the hypothalamus. It finally ends mostly on the medial nucleus of the mammillary body. 2. Mammillary peduncle The mammillary peduncle carries sensory input from the dorsal and ventral tegmental nuclei of the midbrain. It also carries information from the raphe nuclei. 3. Stria terminalis The stria terminalis (amygdalohypothalamic fibers) brings information from the amygdaloid nuclear complex (amygdala in short) to the medial preoptic area and anterior nucleus of the hypothalamus. It brings olfactory information. It is important in reproductive behaviour, particularly in animals. 4. Thalamohypothalamic tract The thalamohypothalamic tract carries fibers from the mediodorsal nucleus and midline nuclei of the thalamus to the lateral preoptic area of the hypothalamus. 5. Ventral amygdalohypothalamic (Amygadalofugal) tract The ventral amygdalaohypothalamic tract relays signals from the amygdala to the lateral hypothalamic nucleus. It influences autonomic nervous system activities. 6. Retinosuprachiasmatic tract The retinosuprachiasmatic tract consists of a bundle of fibers. They originate from the retina. They end in the suprachiasmatic nucleus of the hypothalamus. It is involved in the control of circadian rhytms. 7. Spinohypothalamic fibers The spinohypothalamic fibers relay nociceptive input from the spinal cord to the autonomic control centers of the hypothalamus. These fibers synapse with the neurons which give rise to the hypothalamospinal tract. This tract is associated with the autonomic and reflex responses (i.e. endocrine and cardiovascular responses) to nociception. 8. Fibers from the reticular formation Most of the nociceptive fibers from the spinal cord ascending in the anterolateral system of the ascending sensory pathway and fibers from the trigeminothalamic tract send collateral branches to the reticular formation as they ascend in the brainstem. These collateral branches activate the ascending reticular activating system (ARAS). ARAS brings information to the cerebral cortex alerting the individual. ARAS also relays information to the hypothalamus, limbic system, and serotonergic raphe nucleus magnus. 3.6.2. Efferent pathways of the hypothalamus 1. Fasciculus mammillaris princeps The fasciculus mammillaris princeps arises from the mammillary body. It then quickly bifurcates into two tracts. 1. 1. Mammillothalamic tract (Mammillary fasciculus, tract of Vicqd’ Azyr): arises from the medial and lateral mammillary nuclei. It ends in the anterior thalamic nucleus. 1.2. Mammillotegmental tract (fasciculus): is a component of the medial forebrain bundle (MFB). It carries mammillothalamic tract axon collaterals from the lateral mammillary nuclei to the dorsal and ventral tegmental nuclei in the reticular formation located in the mibdrain. 2. Mammillointerpeduncular tract The mammillointerpeduncular tract carries fibers from the mammillary nucleus. This tract ends in the interpeduncular nucleus. The interpeduncular nucleus plays a role in the sleep-wake cycle. 8
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3. Supraopticohypophyesal tract The supraopticohypophyesal tract is also known as the hypothalamohypophyseal tract. It carries oxytocin or vasopressin (ADH) to the posterior lobe of the pituitary gland. These two hormones are synthyesized in the hypothalamic neurons in the supraoptic and paraventricular nuclei. 4. Periventricular bundle The periventricular bundle connects the nuclei of the periventricular zone with the frontal cortex, dorsal motor nucleus of vagus in the medulla, lateral cell column at T1 to L2 and sacral parasympathetic nucleus of the spinal cord (S2-S4). It acts in autonomic system responses. 5. Tuberohypophyesal tract The tuberohypophyesal tract also is known as tuberoinfundibular or infundibular tract. It carries information from the arcuate and periventricular nuclei to the infundibular stalk and anterior lobe of pituitary gland. The axon terminals of the tract release “releasing hormones” or “release-inhibiting hormones” into the hypophyseal portal system. Here these hormones regulate the synthtesis and release of anterior pituitary hormones. The tuberohypophyesal tract and the hypophyseal portal system are the connections between the hypothalamus and anterior lobe of the pituitary gland. 6. Dorsal longitudinal fasciculus The dorsal longitudinal fasciculus carries fibers that connect various parts of the central nervous system. Some of them start from the hypothalamus, descend and end in the brainstem and spinal cord autonomic nuclei. It also carries information from the hypothalamus to the reticular formation. These signals are then relayed to the brainstem lower motor nuclei via reticulobulbar tract. Via reticulospinal tract the signals are relayed to the spinal cord lower motor neurons. The hypothalamus, by the dorsal longitudinal fasciculus, influences chewing, swallowing and shivering. 7. Hypothalamospinal tract The hypothalamospinal tract is a direct route of hypothalamus influencing the autonomic nervous system neurons in the spinal cord. The fibers of the hypothalamospinal tract mainly arise from the paraventricular nucleus of the hypothalamus. Additional fibers originate from the dorsomedial, ventromedial and posterior nuclei. These fibers descend to end in the brainstem and spinal cord. They synapse directly with the neurons of the presynaptic pre-ganglionic sympathetic (lateral cell column) and parasympathetic (sacral) nuclei. 3.6.3. Bidirectional pathways of the hypothalamus 1. Medial forebrain bundle (MFB) The medial forebrain bundle (MFB) contains fibers which are believed to be important in motivation and sense of smell. The MFB rather than being a bundle, is actually a vast arrays of axons with different origins and terminations. It includes both afferent and efferent fibers to and from the hypothalamus. The afferent ones primarily arise from the septal nuclei (area). Others arise from the basal forebrain and primary olfactory cortex. They also originate from the raphe nuclei in the brainstem, VTA (Ventral tegmental area), and locus ceruleus. Efferent fibers terminate in the septal nuclei and brainstem reticular formation, autonomic nuclei, and autonomic nuclei of the spinal cord. MFB is blamed to play a role in the pathophysiology of addiction. 2. Stria medullaris thalami The stria medullaris thalami also carries both afferent and efferent fibers to and from the hypothalamus. It connects supraoptic nucleus and preoptic area with the habenula (again another place for addiction; such as smoking).
4.Pituitary gland (Hypophysis) When you count the structures in the diencephalon, you DO NOT count the pituitary gland. On the other hand, with its intense relation with the hypothalamus the anatomy of the pituitary gland is covered under the title “Diencephalon”. The pituitary gland is located in the hypophysial fossa. The hypophysial fossa is a part of the sella turcicae of the sphenoid bone. It is oval-shaped. It has gray-reddish colour. It weighs 0.5 gr (Source #1). The superior part 9
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of the gland is covered by diaphragma sellae. This diaphragma sellae is formed by dura mater. The infundibulum (pituitary stalk) passes through the opening at the centre of diapraghma sellae. It connects tuber cinerum of hypothalamus with hypophysis. In the diaphragma sellae, anterior to infundibulum is anterior intercavernous sinus. Posterior to the infundibulum is posterior intercavernous sinus. The right and left cavernous sinuses are interconnected with these sinuses. The pituitary gland neighbours with chiasma opticum superiorly and cavernous sinuses on its sides. Anteroinferiorly it is related to a paranasal sinus; sphenoid sinus. The pituitary gland has two parts. 1) Adenohypophysis (Anterior lobe), 2) Neurohypophysis (Posterior lobe). These lobes have been developed from different embriyological sources. The adenohypophysis has tuberal part, intermediate part and distal part. The neurohypophysis has infundibulum and neural lobe. 4.1. HYPOPHYSEAL PORTAL SYSTEM The arterial supply of the pituitary gland has two sources. They are 1) Superior hypophysial artery and 2) Inferior hypophysial artery. There is one inferior hypophysial artery on each side. They originate from internal carotid artery (cavernous part). The superior hypophysial arteries are usually more than one on each side. They originate from the internal carotid artery (cerebral part), anterior and posterior cerebral arteries (#Sources 1 & 5). The superior hypophysial arteries form an arterial network around the infundibulum. The inferior hypophysial arteries form a similar network around the neurohypophysis. The branches of the superior hypophysial artery end in the sinusoids located in the eminen mediana and superior part of infundibulum. The branches of the inferior hypophysial artery end in the sinusoids located in the inferior part of infundibulum and neurohypophysis. The sinusoids in the infundibulum open into the sinusoids in the adenohyposis via portal hypophysial veins. Almost all of the arterial supply of the adenohypophysis comes from these portal veins. Portal System of the Hypophysis Sinusoids in the infundibulum+Portal hypophysial veins+Sinusoids in the adenohyposis All the sinusoids in the adenohypopyhsis and neurohypophysis drain into dural venous sinuses. Hypothalamus regulates the release of hormones from anterior and posterior lobes differently. Anterior lobe regulation: Releasing factors (hormones) secreted from the hypothalamus reaches the sinusoids in the infundibulum via axons carried in the tuberoinfundibular tract. These releasing hormones are carried to anterior lobe of the pituitary gland via the portal ssytem of hypophysis. Posterior lobe regulation: Hormones secreted from the neurohypophysis are actually synthesized in the supraoptic and paraventricular nuclei of the hypothalamus. These hormones are carried to the posterior lobe via supraopticohypophysial tract (hypothalamohypophysial tract) to the sinusoids in the neurohypohysis. From there they are sent to the bloodstream.
5. Epithalamus (Dorsal thalamus) The epithalamus forms the dorsal surface of the diencephalon. The epithalamus contains 1) Pineal body, 2) Stria medullaris, 3) Habenular trigone. 5.1. Pineal gland The pineal gland is a small, conical structure that is attached by the pineal stalk to the diencephalon. The superior part of the base of the stalk (superior lamina) contains the habenular commissure. The inferior part of the base of the stalk (inferior lamina) contains the posterior commissure. The pineal gland possesses no nerve cells, but adrenergic sympathetic fibers derived from the superior cervical sympathetic ganglia. They enter the gland and run in association with the blood vessels and the pinealocytes. Functions of the Pineal Gland The pineal gland is recognized as an important endocrine gland capable of influencing the activities of the pituitary gland, the islets of Langerhans of the pancreas, the parathyroids, the adrenal cortex and the adrenal medulla, and the gonads. The pineal secretions, produced by the pinealocytes, reach their target organs via the bloodstream or through the cerebrospinal fluid. Their actions are mainly inhibitory and either directly inhibit the production of hormones or indirectly inhibit the secretion of releasing factors by the hypothalamus. Animal experiments have shown that pineal activity exhibits a circadian rhythm that is influenced by light. The gland has 10
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been found to be most active during darkness. Melatonin and the enzymes needed for its production are present in high concentrations within the pineal gland. 5.2. Habenula The limbic system projects to midbrain reticular formation via a relay in the habenular nuclei. Habenula is seen as a small swelling rostral to the pineal gland above the posterior commissure. It contains the habenular nuclei. It is separated from the pulvinar thalami by the habenular sulcus. Habenular trigone is the part of habenula medial to habenular sulcus. The habenular trigone contains the medial and lateral habenular nuclei. These nuclei connect with the habenular nuclei on the other side by the habenular commissure. The afferent fibers to these nuclei are carried via stria medullaris thalami. The axons in the stria medullaris thalami also originate from the lateral parts of the area preoptica, anterior thalamic nuclei, hippocampus and amygdala along with septal nuclei. The stria medullaris thalami basically connects the habenular nucleus with the septal nuclei and anterior hypothalamus. The efferent fibers starting from the habenular nuclei form the fasciculus retroflexus (habenulointerpeduncular tract). The habenular nuclei project to the interpeduncular and raphe nuclei of the midbrain via the fasciculus retroflexus. Other habenular efferent fibers terminate in the hypothalamus, VTA (Ventral Tegmental Area), and substantia nigra. The dorsal diencephalic conduction (DDC) system is a highly conserved pathway found in all vertebrates The DDC comprises three core components: the habenular nuclei; the stria medullaris (SM) and the fasciculus retroflexus (of Meynert). For more info see the “Not Included in the Exam Zone” if you wish.
6. Subthalamus The subthalamus lies inferior to the thalamus and, therefore, is situated between the thalamus and the tegmentum of the midbrain; craniomedially, it is related to the hypothalamus. The nucleus has important connections with the corpus striatum; as a result, it is involved in the control of muscle activity. We are going to talk more about it in the “Basal ganglia” lecture.
7. Third ventricle The third ventricle is quadrilateral and slit-like. It is vertically placed between the walls of the right and left thalami. The third ventricle has the following outpocketings (recesses). 1. Infundibular recess: Part of the 3rd ventricle projecting to the infundibulum. 2. Optic (Supraoptic) recess: Part of the 3rd ventricle projecting to the the superior part of optic chiasma 3. Pineal recess: Part of the 3rd ventricle projecting the area between the two laminae of the pineal gland. The cerebral aqueduct (of Sylvius) conveys CSF from the third ventricle into the fourth ventricle. 7.1. Borders of the third ventricle Anterior wall: Lamina terminalis & Anterior commissure (AC) Posterior wall: Cerebral aqueduct, superior and inferior laminae of pineal gland Lateral wall: Superiorly: Medial surface of thalamus Inferiorly: Hypothalamus Superior surface: Fornix (body) and stria medullaris thalami Inferior surface: Optic chiasma, infundibulum, tuber cinereum, mamillary bodies, posterior perforated substance, tegmentum of mesencephalon
8. Anterior commissure & Posterior commissure The anterior commissure (AC) is a tract of axons that primarily connects the right and left neocortex of the middle and inferior temporal lobes. It connects the right and left amygdalae and olfacory bulb. It is located at the anterior part of diencephalon. The septal nuclei are located rostral to the AC. The posterior commissure (PC) bridges the upper part of the midbrain. It is located in the midline rostral to superior colliculus. It lies adjacent to the posterior end of the third ventricle. The posterior commissure interconnects the pretectal nuclei, mediating the consensual pupillary light reflex. It is also related to superior colluculi related to light reflex. The fibers passing from the posterior commissure come from pretectal nuclei, interstitial nuclei (Cajal’s intertitial nucleus), superior colliculus and dorsal thalamic nuclei. 11
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Vascular infarction in thalamus & Persistent Personality Changes _____ There are 4 major thalamic vascular territories, each supplying particular groups of nuclei (1). The branches supplying these vascular territories originate from the posterior communicating artery and posterior cerebral artery. Pulvinar, subthalamic nuclei and medial half of the medial geniculate nucleus are supplied by the posterior choroideal artery. The tuberothalamic artery originates from the middle third of the posterior communicating artery. Within thalamus it follows the course of the mamillothalamic tract. The clinical syndrome resulting from infarction in the territory of the tuberothalamic artery is characteristic, with the principal manifestation being severe and wide-ranging neuropsychological deficits. Infarction of this artery is accompanied with personality changes such as disorientation in time and place, euphoria, lack of insight, apathy, and lack of spontaneity. Emotional unconcern may be prominent. It is not surprising, as this artery supplies a list of structures including the anterior thalamic nuclei and mammillothalamic tract.
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Interthalamic adhesion & Schizophrenia
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The adhesio interthalamica (AI) is a diencephalic midline structure formed by fusion of medial borders of both thalami (1). The interthalamic adhesion is found in 70-80% of humans. Patients with schizophrenia or with a subtype of schizophrenia showed more common absence of interthalamic adhesion (2). This type of midline abnormalites are critical in schizophrenia research as they present indirect evidence of neuro-developmental abnormality in the pathophsiology of schizophrenia.
________________________Drug addiction & Smoking & Habenula ________________ The habenula is a small brain structure located posterior to the thalamus and adjacent to the third ventricle. Despite its small size, the habenula can be divided into medial habenula (MHb) and lateral habenula (LHb) nuclei that are anatomically and transcriptionally distinct. The habenula receives inputs from the limbic system and basal ganglia primarily via the stria medullaris. The fasciculus retroflexus is the primary habenular output from the habenula to the midbrain and governs release of glutamate onto gabaergic cells in the rostromedial tegmental nucleus (RMTg) and onto the interpeduncular nucleus. The resulting GABA released from RMTg neurons inactivates dopaminergic cells in the ventral tegmental area/substantia nigra compacta. Through this process, the habenula controls dopamine levels in the striatum. Thus, the habenula plays a critical role in reward and rewardassociated learning (3). This reward system is linked to drug addiction. The habenula is an epithalamic nucleus involved in the mechanisms of fear, anxiety, depression, and stress (4) Nicotine dependence is accompanied by neuroadaptive changes that occur especially in the circuits underlying emotion and motivation (4). The dorsal diencephalon, or epithalamus, contains the bilaterally paired habenular nuclei and the pineal complex. The habenulae form part of the dorsal diencephalic conduction (DDC) system, a highly conserved pathway found in all vertebrates (5). The DDC comprises three core components: the habenular nuclei; the stria medullaris (SM), which is the main fibre tract through which inputs from the forebrainarrive at the habenulae; and the fasciculus retroflexus (FR), a prominent fibre tract that predominantly carries efferent axons from the habenula towards the targets in the midbrain/hindbrain (5). In accordance with the diversity of its afferent inputs and efferent targets, the DDC is involved in a diverse range of cerebral functions: (a) Control of dopaminergic circuitry: motor activity and reward prediction (b) Cognition The DDC has been implicated in cognitive processes, in particular relating to spatial learning and attention. (c ) Aversive responses 12
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Several studies indicate that the DDC is involved in learning conditional avoidance responses (behavioural responses to avoid aversive stimuli). Habenular lesions appear to inhibit learning by reducing behavioural flexibility, especially under stressful conditions. (d) Circadian rhythms The nuclei comprising the dorsal diencephalon are involved in regulating circadian rhythms. In addition to the habenulae, the epithalamus contains the pineal complex, and the pineal has a conserved role in the generation and/or regulation of circadian rhythms. DDC circuitry is implicated in various psychological conditions including depression, anxiety, schizophrenia and neuropathological responses to addictive drugs.
__________________Medial Forebrain Bundle & Drug Addiction ________________ The most extensively studied substrate of reward function is embedded among the dozens of fiber systems that comprise the hypothalamic portion of the medial forebrain bundle (MFB). Electrical stimulation of the medial forebrain bundle can reward arbitrary acts or motivate biologically primitive, species-typical behaviors like feeding or copulation. The sub-systems involved in these behaviors are only partially characterized, but they appear to trans-synaptically activate the mesocorticolimbic dopamine system. Basal function of the dopamine system is essential for arousal and motor function; phasic activation of this system is rewarding and can potentiate the effectiveness of reward-predictors that guide learned behaviors. This system is phasically activated by most drugs of abuse and such activation contributes to the habit-forming actions of these drugs (6).
__________________ Mediodorsal thalamic nucleus & Schizophrenia ________________ The mediodorsal nucleus (MD) is also one of the principal sites where selective serotonin reuptake inhibitors (SSRIs) accumulate. Moreover, numerous reports have described maniac conditions of patients with damage around and within the MD, suggesting that the neuronal activity of this nucleus is involved in affective behaviour. Overall, these data suggest that the MD is implicated in the pathophysiology of affective disorders and in the therapeutic actions of SSRIs. Mediodorsal nucleus and cognitive functions In the performance of tasks in which short-term memory is evaluated, there is an increase in the glucose metabolism in the MD, which suggests that this thalamic structure could be involved in the first phases of information processing for memory and learning. Studies of lesions in the MD in nonhuman primates have evaluated the involvement of this nucleus in different cognitive processes or domains and in behaviour. For instance, lesions in the MD produced a deficit in association and visual object recognition as well as in processes associating stimulus and reward (7).
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Anterior commissure & Schizophrenia ________________
Alterations in white matter connections in schizophrenia have been investigated using diffusion tensor imaging (DTI). There is also evidence from post-mortem studies as well as from magnetic resonance imaging morphometry studies that the anterior commissure (AC) might be implicated in schizophrenia (8). The idea that connections between brain regions are disrupted in schizophrenia goes back at least as far as Kraepelin (1911/1917), who speculated that schizophrenia was caused by a disruption of connectivity between the frontal and temporal lobes (8). In a recent DTI study by the Shenton’s group in Boston, the researchers found that patients with schizophrenia reveal a significant decrease in FA and an increase in trace in the AC compared with healthy controls. To the extent that FA is related to axonal integrity, density, caliber and myelination. References 1. Schmahmann JD. Vascular syndromes of the thalamus. Stroke. 2003;34(9):2264-2278. 2. Haghir H1, Mokhber N, Azarpazhooh MR, Haghighi MB, Radmard M. A magnetic resonance imaging study of adhesio interthalamica in clinical subtypes of schizophrenia. Indian J Psychiatry. 2013;55(2):135-139. 3. Velasquez KM, Molfese DL, Salas R. The role of the habenula in drug addiction. Front Hum Neurosci. 2014;8:174. 4. Paolini M, De Biasi M.Mechanistic insights into nicotine withdrawal. Biochem Pharmacol. 2011;82(8):996-1007. 5. Bianco IH, Wilson SW. The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain. Philos Trans R Soc Lond B Biol Sci. 2009;364(1519):1005-1020. 6. Wise RA. Forebrain substrates of reward and motivation. J Comp Neurol.;493(1):115-121. 7. Alelú-Paz R1 Giménez-Amaya JM.The mediodorsal thalamic nucleus and schizophrenia. J Psychiatry Neurosci. 2008;33(6):489-498.
8. Choi H, Kubicki M, Whitford TJ, Alvarado JL, Terry DP, Niznikiewicz M, McCarley RW, Kwon JS, Shenton ME. Diffusion tensor imaging of anterior commissural fibers in patients with schizophrenia. Schizophr Res. 2011;130(1-3):78-85.
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