Diencephalon By Rashid Alshahoumi Outline Overview n Development

Diencephalon By Rashid Alshahoumi

Outline: Overview n Development of Diencephalon n Basic Organization n Dorsal Thalamus (Thalamus) n Hypothalamus n Ventral Thalamus ( Subthalamus) n Epithalamus n Vasculature of the Diencephalon n

Diencephalon p The diencephalon includes - Dorsal thalamus - Hypothalamus - Ventral thalamus - Epithalamus q Situated between telencephalon & brainstem. p Main processing center for information

p Rt & Lt halves of the diencephalon, contain symmetrically distributed cell groups separated by the space of the 3 rd ventricle

Development of the Diencephalon n n The cell groups that give rise to the diencephalon form in the caudomedial portion of the prosencephalon, bordering on the space that will become the 3 rd ventricle. The developing brain at this level consists initially of a roof plate and the two alar plates; it lacks a well-defined floor plate and basal plates.

n - Ø Ø n The hypothalamic sulcus A shallow groove appears in the wall of the 3 rd ventricle & extends rostrally from the developing cerebral aqueduct to the ventral edge of the interventricular foramen Divides the alar plate into : Superior (dorsal) area : future dorsal thalamus Inferior (ventral) portion : future hypothalamus The dorsal thalamus - On each side of the 3 rd ventricle increases rapidly in size & will partially fuse across the space of the 3 rd ventricle to form : - massa intermedia, or interthalamic adhesion. (present in about 80% of the general population)

n The epithalamus - Develops from the caudal portion of the roof plate. - By 7 th week, a small thickening of the roof plate forms. It gradually increases in size & evaginates to form the epiphysis, which develops into the pineal gland of the adult. - The portion of the roof plate immediately rostral to the epiphysis gives rise to the habenula, a small thickening in which the habenular nuclei will develop n Just anterior to the habenular region, the roof plate epithelium & adjacent pia mater give rise to the choroid plexus of the third ventricle, This choroid plexus is continuous through the interventricular foramina with that of the lateral ventricles.

n n Ø Ø In locations around the perimeter of the 3 rd ventricle, specialized patches of ependyma lie on the midline & form unpaired structures called the circumventricular organs These structures include : Subfornical organ Organum vasculosum of the lamina terminalis Subcommissural organ, Pineal gland.

n The development of the pituitary gland during the 3 rd week is linked to that of the diencephalon. n A downward extension of the floor of the 3 rd ventricle, the infundibulum, meets the Rathke pouch, an upward outpocketing of the stomodeum, the primitive oral cavity.

n By the end of the 2 nd month, the Rathke pouch loses its connection with the developing oral cavity but maintains its attachment to the infundibulum. n As development continues, the Rathke pouch gives rise to the anterior lobe (adenohypophysis) and pars intermedia of the pituitary gland Infundibulum differentiates into the posterior lobe of the pituitary gland, or neurohypophysis n

n n A craniopharyngioma (Rathke pouch tumor) can arise from a portion of the Rathke pouch that fails to undergo proper migration & apposition to the infundibulum. These tumors mimic lesions of the pituitary & may cause visual problems, diabetes insipidus, & ↑ ICP

Basic Organization l The junction between the diencephalon & midbrain lies along a line extending from the posterior commissure to the caudal edge of the mammillary body on the medial aspect of the hemisphere. l On the surface of the hemisphere, this interface is represented by a line starting at the caudal aspect of the mammillary body, extending anterolaterally over the edge of the crus cerebri & following the caudal edge of the optic tract. l The boundary between the diencephalon & surrounding telencephalon is less distinct & represented : - laterally by the internal capsule - rostrally by the interventricular foramen, lamina terminalis & optic chiasm.

l - - - The 3 rd third ventricle has small evaginations or recesses associated with Optic chiasm (supraoptic recess) Infundibulum (infundibular recess) Pineal gland (pineal& suprapineal recesses)

n Ø Ø The dorsal thalamus Located superior to the hypothalamic sulcus Extends from the interventricular foramen caudally to the level of the splenium of the corpus callosum. The hypothalamus Located inferior to the hypothalamic sulcus Bordered : - Rostrally by the lamina terminalis - Caudally by a line that extends from the posterior aspect of the mammillary body - Superiorly to intersect with the hypothalamic sulcus.

n Ø - n Ø Ø The ventral thalamus (subthalamus) Located : Caudal to the hypothalamus Rostral to the diencephalon-midbrain junction Lateral to the midline Epithalamic structures Located posteriorly & caudally in close apposition to the posterior commissure Include : - pineal gland - habenular nuclei - main afferent bundle of these nuclei - stria medullaris thalami.

Dorsal Thalamus (Thalamus) ¢ The dorsal thalamus (or thalamus) is a massive collection of neuronal cell groups that participate in a widely diverse array of functions involving motor, sensory & limbic systems. ¢ Typically, thalamic output neurons project to the cerebral cortex → !! very little information reaches the cerebral cortex without first being processed by thalamic neurons→ the thalamus is functional "gateway" to the cerebral cortex

¢ In turn, nearly all regions of the cerebral cortex give rise to reciprocal projections that return to the thalamic region from which they originally received input.

¢ The thalamus is covered on its lateral aspect by a layer of myelinated axons, the external medullary lamina ( includes fibers that enter or leave the subcortical white matter) ¢ Within the external medullary lamina are clusters of neurons that form the thalamic reticular nucleus.

An internal medullary lamina: - Consisting of myelinated fibers - Extends into the substance of the thalamus, where it forms partitions or boundaries that divide thalamus into its principal cell groups : - anterior, medial, lateral & intraluminar nuclear groups. ¢ There are midline thalamic nuclei located just superior to the hypothalamic sulcus. ¢ Finally, attached to the caudolateral portion of the thalamus are the medial and lateral geniculate bodies (and their nuclei). ¢

Anterior Thalamic Nuclei ¡ This group of cells consists of a large principal nucleus & two smaller nuclei → form the anterior nucleus of the thalamus ¡ The anterior nucleus forms a prominent wedge on the rostral aspect of the dorsal thalamus just caudolateral to the interventricular foramen → this wedge is the anterior thalamic tubercle. ¡ Rostrally, the internal medullary lamina divides to partially encapsulate the anterior nucleus.

Anterior Thalamic Nuclei ¡ The cells of this nucleus receive dense limbic-related projections from (1) the mammillary nuclei via the mammillothalamic tract and (2) the medial temporal lobe (hippocampus) via the fornix. ¡ The output of this nucleus is primarily directed to the cingulate gyrus through the anterior limb of the internal capsule.

Medial Thalamic Nuclei Comprises the dorsomedial nucleus ¡ Composed of : -Large parvicellular (located caudally) -Magnocellular (located rostrally) -Small paralaminar adjacent to the internal medullary lamina ¡ 2 larger portions are linked to parts of the frontal & temporal lobes & to the amygdaloid complex. ¡ Cells of the paralaminar subdivision receive input from the frontal lobe & substantia nigra (may play a role in the control of eye movement) ¡

Lateral Thalamic Nuclei 2 subdivisions o Dorsal subdivision Ø Lateral dorsal - Functionally part of anterior group (limbic system) Ø Lateral posterior

Ø Pulvinar § Border with lateral posterior is vague Inputs �� Pretectal area �� Superior colliculus § Roles: �� Visual relay center �� Selective attention �� Speech § § Reciprocal connections: �� Lateral geniculate nucleus �� Parietal lobe �� Temporal lobe �� Occipital lobe

o Ventral subdivision - Ventral anterior - Ventral lateral - Ventral posterior Ø Receive direct input from long ascending tracts Ø Reprocal connections with cortex Ø Retrograde degeneration on cortical lesions

Ventral Anterior o Input o Roles: �� Globus pallidus �� Substantia nigra �� Intralaminar nucleus (thalamus) �� Premotor/prefrontal cortex �� Motor relay station - Regulate movement (Control of voluntary movement) �� Medial part - Eye, head, neck �� Lateral part - Body, limb o Output (reciprocal connections) : �� Premotor cortex �� Prefrontal cortex �� Intralaminar nucleus

Ventral Lateral Nucleus o Input �� Deep cerebellar nuclei �� Globus pallidus �� Primary motor cortex o Output �� Primary motor cortex (reciprocal) �� Parietal lobe -Somatosensory areas �� Premotor/Supplementary motor areas q Role: �� Motor relay station - Cerebellum/basal ganglia/cortex

Ventral Posterior Nucleus o 2 Divisions Ø Ventral posterior medial (VPM) Ø Ventral posterior lateral (VPL) o Inputs �� Medial lemniscus - VPL �� Spinothalamic -VPL �� Trigeminal lemniscus (taste) - VPM �� Primary somatosensory cortex - VPM & VPL o Output �� Primary somatosensory cortex (reciprocal) �� Parietal operculum (taste)

n The lateral (LGB) and medial (MGB) geniculate nuclei are considered parts of the lateral thalamic nuclear group. n MGB receives ascending auditory input via the brachium of the inferior colliculus → projects to the primary auditory cortex in the temporal lobe. n LGB receives visual input from the retina via the optic tract → projects to the primary visual cortex on the medial surface of the occipital lobe.

q Located in the posterior thalamus at about the level of the pulvinar and geniculate nuclei is a cluster of cell groups collectively called the posterior nuclear complex. This complex consists of : - Suprageniculate nucleus - Nucleus limitans - Posterior nucleus Ø These nuclei are positioned superior to the medial geniculate and medial to the rostral pulvinar. q q The posterior nuclear complex receives& sends to the cortex nociceptive cutaneous input that is transmitted over somatosensory pathways

Intralaminar Nuclei Ø Embedded within the internal medullary lamina are the discontinuous groups of neurons that form the intralaminar nuclei. Ø Projections to the neostriatum & to other thalamic nuclei, along with diffuse projections to the cerebral cortex. 2 of the most prominent cell groups are : Centromedian : projects to the neostriatum & to motor areas of the cerebral cortex - Parafascicular nuclei : projects to rostral & lateral areas of the frontal lobe. Ø - Ø Other intralaminar nuclei receive input from ascending pain pathways and project to somatosensory and parietal cortex.

Midline Nuclei Ø The midline nuclei are the least understood components of the thalamus? ? Ø The largest is the paratenial nucleus, which is located just ventral to the rostral portion of the stria medullaris thalami; other cells are associated with the interthalamic adhesion (massa intermedia). Ø Ø Inputs are poorly defined Efferent fibers reach the amygdaloid complex &the anterior cingulate cortex, suggesting a role in the limbic system.

Thalamic Reticular Nucleus Ø The cells are situated within the external medullary lamina & between this lamina and the internal capsule. Ø Axons of these cells project medially into the nuclei of the dorsal thalamus or to other parts of the reticular nucleus, but not into the cerebral cortex. Ø Afferents are received from the cortex and from nuclei of the dorsal thalamus via collaterals of thalamocortical & corticothalamic axons. Ø Thalamic reticular neurons modulate, or gate, the responses of thalamic neurons to incoming cerebral cortical input.

Thalamic nucleus : efferent projections (thalamocortical axons) → corterx Ø Cortex → reciprocal projection (corticothalamic axons) → thalamic nucleus Ø VL/motor/precentral gyrus and anterior paracentral gyrus Ø VPL/sensory for the body/postcentral gyrus and posterior paracentral gyrus Ø VPM/sensory for the face/postcentral gyrus Ø MGB/auditory/transverse temporal gyrus Ø LGB/vision/cortex on the calcarine sulcus Ø The anterior nucleus projects primarily to the cingulate gyrus and functions in the broad area of behavior Ø

Ø Thalamic nuclei : relay nuclei or association nuclei Ø Thalamic nuclei : specific or nonspecific

Hypothalamus The hypothalamus is mainly involved in visceromotor, viscerosensory & endocrine activities. The hypothalamus & related limbic structures receive sensory input regarding the internal environment & in turn, regulate through four mechanisms the motor systems that modify the internal environment.

Hypothalamus Is a principal modulator of autonomic nervous system function. Is a viscerosensory transducer, containing neurons with specialized receptors capable of responding to changes in the temperature or osmolality of blood, as well as to specific hormonal levels in the general circulation. It regulates the activity of the anterior pituitary through the production of releasing factors (hormone-releasing hormones) It performs an endocrine function by producing & releasing oxytocin &vasopressin into the general circulation within the posterior pituitary.

• The hypothalamus can be divided into lateral, medial & periventricular zones :

Lateral Hypothalamic Zone Composed of diffuse clusters of neurons intermingled with longitudinally oriented axon bundles Cells are involved in cardiovascular function & in the regulation of food & water intake.

Medial Hypothalamic Zone - In contrast to the lateral zone, it contains discrete groups of neurons whose function & connections are established. Within the chiasmatic (anterior) region are 5 nuclei: Preoptic supraoptic paraventricular Anterior Suprachiasmatic

(Preoptic, supraoptic, periventricular) → are generally involved in regulating hormone release Anterior → cardiovascular function Suprachiasmatic → circadian rhythms Preoptic → body temperature & heat loss mechanisms

- In the tuberal region : Dorsomedial Ventromedial Arcuate nuclei The ventromedial nucleus - Food intake (satiety) center. - Bilateral lesions produce hyperphagia, a greatly increased food intake with resultant obesity. Cells of the arcuate nucleus deliver peptides to the portal vessels & through these channels, to the anterior pituitary.

Peptides Releasing factors that ↑ secretion of specific hormones by the anterior pituitary Inhibiting factors that ↓ secretion of specific hormones by the anterior pituitary.

At caudal levels, the mammillary region - Posterior nucleus - Mammillary nuclei The mammillary nuclei consist of a large medial & a small lateral nucleus. Although both of these nuclei receive input via the fornix, only the medial nucleus projects to the anterior thalamic nucleus through the mammillothalamic tract.

- The neurons of the posterior nucleus are involved in : ↑ BP Pupillary dilation Shivering or body heat conservation. The mammillary nuclei are involved in Control of various reflexes associated with feeding Mechanisms relating to memory formation.

Afferent Fiber Systems l The fornix & stria terminalis are 2 major afferent fiber bundles that reach the hypothalamus l The fornix consists of axons that largely originate in the hippocampus, and the stria terminalis arises from neurons in the amygdaloid complex. l Fibers composing the ventral amygdalofugal bundle exit the amygdala and course through the substantia innominata to enter the hypothalamus and thalamus. l The medial forebrain bundle passes bidirectionally through the lateral hypothalamic region. Ascending axons → forebrain & brainstem. l

Efferent Fibers l Several nuclei give rise to descending fibers that contribute to the dorsal longitudinal fasciculus and the medial forebrain bundle and to diffuse projections that pass into the tegmentum. l These fiber systems project directly to numerous brainstem nuclei, as well as to preganglionic sympathetic and parasympathetic neurons in the spinal cord. l Other projections reach the thalamus and frontal cortex, and still others extend to the posterior pituitary or to the tuberohypophysial portal system for delivery of substances to the anterior pituitary.

Ventral Thalamus (Subthalamus) l 3 main structures �� Subthalamic nuclei Inputs: �� Globus pallidus �� Cerebral cortex �� Thalamus �� Reticular formation �� Contralateral subthalamic nucleus �� supramamillary commisure Outputs: �� Globus pallidus �� Substantia nigra Hemiballismus �� Damage �� Involuntary violent hyperkinesia of contralateral upper & lower extremities

Ventral Thalamus (Subthalamus) 3 main structures �� Fields of Forel l H field of Forel �� Prerubral H 1 field of Forel �� Thalamic fasciculus H 2 field of Forel �� Lenticular fasciculus

Ventral Thalamus (Subthalamus) 3 main structures �� Zona incerta �� Implicated in many functions : l Locomotion, l Oculomotor, arousal, l Attention, feeding, l Sociosexual, l Somatosensory

Epithalamus u - Principal components : Pineal gland Habenular nuclei Stria medullaris thalami u The pineal gland consists of richly vascularized connective tissue containing glial cells & pinealocytes but no true neurons. u Pinealocytes are cells that synthesize melatonin from serotonin via enzymes that are sensitive to diurnal fluctuations in light. u Production of melatonin by pinealocytes is rhythmic & calibrated to the 24 -hour cycle of photic input to the retina = circadian rhythm.

Epithalamus u u The habenular nuclei consist of a large lateral nucleus and a small medial nucleus. Both nuclei contribute axons to the habenulointerpeduncular tract (fasciculus retroflexus), which terminates in the midbrain interpeduncular nucleus. The stria medullaris thalami, conveys input to both habenular nuclei. The habenular commissure, a small bundle of fibers riding on the upper edge of the posterior commissure, connects the habenular regions of the two sides.

Vasculature of the Diencephalon n The diencephalon is supplied by Smaller vessels that branch from the various arteries making up the cerebral arterial circle (circle of Willis) - Larger arteries that originate from the proximal parts of the posterior cerebral artery -

n The hypothalamus & subthalamus are supplied by central branches of the circle (perforating or ganglionic)

Ø Anterior parts of the hypothalamus are served by central branches Ø Caudal hypothalamic regions and the ventral thalamus are supplied by branches of the (posteromedial group) Ø arising from the posterior communicating artery and the P 1 segment of the posterior cerebral artery. (anteromedial group) Ø arising from the anterior communicating artery and the A 1 segment of the anterior cerebral artery and from branches of the proximal part of the posterior communicating artery.

n n Some of the branches of the posteromedial group that arise from the P 1 segment near the basilar bifurcation are called the thalamoperforating arteries. Supply → rostral areas of the thalamus

n n Slightly more distal branches, which usually arise from the P 2 segment, are the posterior choroidal and thalamogeniculate arteries. Supply → portions of the diencephalon A narrow portion of the caudal and medial thalamus bordering on the 3 rd ventricle is supplied by the medial posterior choroidal artery, whereas the thalamogeniculate branches irrigate the caudal thalamus, including the pulvinar & geniculate nuclei Branches of the medial posterior choroidal artery also serve the choroid plexus of the 3 rd ventricle.

n The anterior choroidal artery originates from Ø Cerebral portion of the internal carotid artery penetrating branches into the genu & posterior limb of the internal capsule Ø Serves the optic tract, inferior portions of the lenticular nucleus, the choroid plexus of the inferior horn of the lateral ventricle, and large parts of the hippocampal formation. Ø Sends

n Although the thalamus receives a blood supply largely separate from that of the internal capsule , vascular lesions in the thalamus may extend into the internal capsule or vice versa.

n Ischemic or hemorrhagic strokes in the hemisphere may result in contralateral hemiparesis in combination with hemianesthesia. n These losses correlate with damage to corticospinal and thalamocortical fibers in the internal capsule.

n Strokes involving the larger thalamic arteries, such as the thalamogeniculate artery, may result in total or dissociated sensory losses. n These patients may subsequently experience persistent, intense pain (thalamic pain, Dejerine-Roussy syndrome).

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