Diencephalon (“in-between brain”) 3rd Ventricle CNS divisions Directional terms – forebrain level dorsal superior caudal posterior rostral anterior ventral inferior Diencephalon – regional organization Thalamus (dorsalis) – topographic and nuclear organization (Gr. thalamos, “inner chamber”) Metathalamus – the geniculate bodies Epithalamus – pineal gland and habenula Subthalamus (thalamus ventralis) Hypothalamus – divisions, nuclei and connections The Diencephalon The Diencephalon THALAMUS EPITHALAMUS SUBTHALAMUS HYPOTHALAMUS The Diencephalon Fornix Adhesio Interthalamica Posterior commissure Pineal Gland Hypothal Sulcus Anterior Commissure Lamina Terminalis Mammillary Body Optic Chiasm Infundibulum Diencephalon dorsal surface Diencephalon – superior dorsal view anterior tubercle 3rd ventricle Diencephalon – lateral dorsal view Diencephalon ventral surface Metathalamus Pulvinar Lateral Geniculate Medial Geniculate Borders of thalamus Lat. ventricle Int.capsule 3rd Ventricle Borders of thalamus Posterior commissure Fornix Hypothalamic sulcus Lamina terminalis Лимбичен таламус Thalamus Origin of CNS subdivisions Secondary vesicles Diencephalon is larger during brain development than in postnatal brain Neural tube folding (5th -8th wk) Diencephalic development The diencephalon consists of roof and alar plates but lacks the basal and floor plates Lateral ventricle Alar plate → thalamus, hypothalamus, neurohypophysis, and infundibulum Roof plate → epiphysis, habenular nuclei and the posterior commissure Alar vs. Basal in forebrain alar basal Diencephalic development Embryonic brain Adult brain Thalamocortical axons pass through the ventral telencephalon (VT) and future basal ganglia (GP/STR) before they reach the cortex Estimated time of development of various brain regions 2 mo 6 mo Modified from Bayer SA et al. Neurotoxicology 14:83–144, 1993 General organization of the thalamus Reticular nucleus Internal medullary lamina Nuclear groups Interthalamic adhesion Internal medullary lamina External medullary lamina External medullary lamina Midline nuclei Thalamic nuclei form nuclear groups I. Lateral Group II. Medial Group III. Anterior Group IV. Posterior Group V. Intralaminar Group VI. Reticular nucleus metathalamus Thalamus – section at anterior level LV LV 3v reticular internal medullary lamina Thalamus – section at mid-level LV LV 3v reticular internal medullary lamina Thalamus – section at posterior level LV LV 3v reticular internal medullary lamina Thalamus is the critical relay for the flow of sensory information to the neocortex Cortex Motor pathway Sensory pathway Thalamus is more than simply a relay! It acts as a gatekeeper for information to the cerebral cortex, preventing or enhancing the passage of specific information depending on the behavioral state Thalamic nuclei – lateral group Ventral nuclear group I. Lateral Group II. Medial Group III. Anterior Group IV. Posterior Group V. Intralaminar Group VI. Reticular nucleus ventral posterolateral nucleus (VPL) ventral posteromedial nucleus (VPM) ventral posteroinferior nucleus (VPI) ventral lateral nucleus (VL) ventral anterior nucleus (VA) Dorsal nuclear group Lateral dorsal nucleus (LD) Lateral posterior nucleus (LP) Pulvinar-lateral posterior complex Connections of the lateral thalamic nuclei Ventral Nuclear Group Cortex Prefrontal SMA MI, PM SI SN pars reticulata Basal Cerebellum ganglia SMA - supplementary motor area MI (M1) – primary motor cortex PM – premotor cortex SI (S1) – primary somatosensory cortex Trigeminal lemniscus Medial lemniscus, Spinothalamic tracts Somatosensory map (somatotopic organization) in VPL & VPM VPL +taste fibers VPM Connections of the lateral thalamic nuclei Dorsal Nuclear Group cingulate gyrus, precuneus Somatosensory Association Area Visual Association area Pulvinar Hippocampal formation Superior colliculus, Pretectal area Thalamic nuclei – medial group Mid Dorsomedial Nucleus (MD) I. Lateral Group II. Medial Group III. Anterior Group IV. Posterior Group V. Intralaminar Group VI. Reticular nucleus pars magnocellularis (MDmc) pars parvocellularis (MDpc) pars paralaminaris (MDpl) Midline Nuclear Group (poorly developed in humans) paratenial nucleus reunience nucleus submedial nucleus rhomboid nucleus Midline thalamic nuclei Interthalamic adhesion Midline nuclei Thalamic nuclei – anterior & posterior groups Mid Anterior Nuclear Group I. Lateral Group II. Medial Group III. Anterior Group IV. Posterior Group V. Intralaminar Group VI. Reticular nucleus anteroventral nucleus (AV) anterodorsal nucleus (AD) anteromedial nucleus (AM) Posterior Nuclear Group (medial to the Pulvinar, merge with MGB) suprageniculate nucleus nucleus limitans posterior nucleus Connections of the thalamic nuclei Medial & Anterior Nuclei Mamillary Prefrontal Frontal bodies, Cortex Eye Field Hippocampus Cingulate gyrus Basal forebrain Medial Frontal Gyrus SN pars reticulata, superior colliculi, reticular formation Thalamic nuclei – intralaminar group Mid Caudal Nuclear Group (most important in humans) centromedian nucleus parafascicular nucleus Rostral Nuclear Group I. Lateral Group II. Medial Group III. Anterior Group IV. Posterior Group V. Intralaminar Group VI. Reticular nucleus paracentral centrolateral centromedial Afferent Efferent Connections of the thalamic intralaminar nuclei Receive from many subcortical and cortical areas Project to other thalamic nuclei cortex striatum (the projection is topographically organized: centromedian nucleus → putamen; parafascicular nucleus → caudate) Intralaminar & midline nuclei are non-specific thalamic nuclei Thalamic nuclei – reticular nucleus I. Lateral Group II. Medial Group III. Anterior Group IV. Posterior Group V. Intralaminar Group VI. Reticular nucleus A continuation of the reticular formation of the brain stem into the diencephalon Unique among thalamic nuclei!!! its axons do not leave the thalamus Receives collaterals of corticothalamic projections and thalamocortical projections Sends to other thalamic nuclei GABAergic (inhibitory) → plays a role in integrating and gating activities of thalamic nuclei Metathalamus Tricorn Shape Pulvinar Medial Geniculate Lateral Geniculate Metathalamic nuclei Medial Geniculate Nucleus (MG) ventral or principal nucleus dorsal nucleus medial nucleus Lateral Geniculate Nucleus (LG) dorsal nucleus (LGd) ventral nucleus (LGv) Lateral Geniculate Nucleus (LGd) → Visual Pathway Dorsal Nucleus (LGd) Magnocellular Part 1, 2 Parvocellular Part 3, 4, 5, 6 dorsolateral contralateral afferents 1, 4, 6 ipsilateral afferents 2, 3, 5 ventromedial Ventral Nucleus (LGv) part of thalamic reticular nucleus Visual Pathway 1. Optic nerve 2. Optic chiasm 3. Optic tract 4. Lateral geniculate body 5. Optic radiation 6. Visual cortex Visual pathway via LGN loops Ocular dominance columns in primary visual cortex (V1) C I I C I = from ipsilateral retina C = from contralateral retina Overview of thalamic connectivity VL VA DM V P L V P M MGB LP Pul AN = Anterior nn. LD = Lateral dorsal n. VA LP = Lateral posterior n. Pul = Pulvinar DM AN DM = Dorsomedial n. Mid = Midline nn. L VA = Ventral anterior n. DM G VL = Ventral lateral n. B VPL = Ventral posterolateral n. VPM = Ventral posteromedial n. LGB = Lateral geniculate body MGB = Medial geniculate body IL = Intralaminar nn. CM = Centromedian n. VL VPL LP Pul LD Pul LGB Summary of the connections of the thalamic nuclei Specific nuclei (sensory or motor) Association nuclei (sensory or motor Non-specific nuclei Overview of major functions thalamic nuclei nonspecific limbic autonomic A motor VA IL VL somatosensory taste visual LP DM R VP Pul LG internal regulator MG higher visual auditory Thalamic radiations = fibers which reciprocally connect the thalamus & cortex via the internal capsule Epithalamus & subthalamus Subthalamus Basal Ganglia Subthalamic Zona nucleus incerta Fields of Forel Subthalamus Subthalamus Red Nucleus Subthalamus • Location: diencephalicmesencephalic border • Abuts the posterior limb of the internal capsule • Shaped like a lens Substantia Nigra Internal Capsule (posterior limb) Connections of subthalamus Afferent Efferent Fields of Forel (fiber bundles containing efferents to the thalamus) H H1 H2 H = “Haube” (German, cap) prerubral field thalamic fasciculus lenticular fasciculus The connections of subthalamic nucleus are connections of the basal ganglia A lesion in the contralateral subthalamic nucleus leads to hemiballismus → violent flinging involuntary movements of one side of the body. Kandel, Schwartz, Jessell; Principles of Neural Science, 4th ed. Zona incerta (zone “in between”) Rostral continuation of the mesencephalic reticular formation that extends laterally into the reticular nucleus of the thalamus Involved in control of movement – its stimulation has been shown to suppress limb tremor (has GABA ergic neurons) Has reciprocal connections with neocortex, thalamus, brain stem, basal ganglia, cerebellum, hypothalamus, basal forebrain, and spinal cord Epithalamus Limbic System Habenular nuclei medial lateral Habenular commissure Pineal gland Epithalamus Habenular commissure (roof of pineal recess) Pineal gland (secretes melatonin) Posterior commissure (eye movements and light reflex) Epithalamus 3rd Ventricle Epiphysis (pineal gland) Pinealocytes – secrete melatonin night↑/day↓ other hormones thyrotropin-releasing hormone (TRH) leuteinizing hormone–releasing hormone (LHRH) somatostatin–release inhibitory factor Interstitial cells – glial-like Blood vessels (SRIF) The pineal gland calcifies after the age of 16 years. This fact is used in the detection of midline shifts in skull x-rays → in case of a space-occupying lesion displacing the pineal. Pineal gland (calcified) Pineal gland neuroglia acervulus (brain sand) pinealocytes Pineal gland saggital section Posterior Commissure cross-section Habenula (Latin diminutive of habena, “a small strap or rein”) Receive the stria medullaris thalami – from septal (medial olfactory) area in frontal lobe Project habenulo-interpeduncular tract (fasciculus retroflexus of Meynert) to the interpeduncular nucleus of the midbrain The two habenular nuclei are connected by the habenular commissure Involved in limbic system – emotions and behavior Connections of habenular nuclei Septal nuclei Blood supply to thalamus medial territory lateral territory Blood supply to thalamus Basilar root of the posterior cerebral a. → paramedian branches (medial territory) Posterior cerebral artery → geniculothalamic branch (posterolateral territory) Posterior communicating artery → tuberothalamic branch (anterolateral territory) Internal carotid artery → anterior choroidal branch (lateral territory) Intracerebral hemorrhage Dejerine-Roussy syndrome Posteior cerebral artery supplies VPL, VPM, MG, LG, pulvinar PCA infarct → Dejerine-Roussy syndrome Pure hemisensory loss + no hemiparesis Venous drainage of thalamus → vv. profundae cerebri Hypothalamus 4 cm3 of neural tissue, 0.3% of the total brain 3rd Ventricle Hypothalamus – ventral view Hypothalamus – ventral view (landmarks) Optic Chiasm Infundibulum Mammillary Bodies Borders of hypothalamus Hypothal Sulcus Midbrain Interpeduncular fossa Lamina Terminalis Optic Chiasm The hypothalamus serves this integrative function by regulation of 5 basic physiological needs It controls blood pressure and electrolyte composition by a set of regulatory mechanisms that range from control of drinking and salt appetite to the maintenance of blood osmolality and vasomotor tone It regulates body temperature by means of activities ranging from control of metabolic thermogenesis to behaviors such as seeking a warmer or cooler environment It controls energy metabolism by regulating feeding, digestion, and metabolic rate It regulates reproduction through hormonal control of mating, pregnancy, and lactation It controls emergency responses to stress, including physical and immunological responses to stress by regulating blood flow to muscle and other tissues and the secretion of adrenal stress hormones Fornix divides the hypothalamus into medial and lateral regions/zones Medial – a cluster of nuclei organized into: preoptic nuclear group suprachiasmatic (supraoptic; anterior) group tuberal (intermediate) nuclear group mamillary (posterior) nuclear group Lateral medial forebrain bundle (axons) lateral hypothalamic area (neurons) Regions of the medial hypothalamus Medial hypothalamus – preoptic region Just caudal to the lamina terminalis Nuclei preoptic nuclei (continuous with one of the circumventricular organs - organum vasculosum laminae terminalis, OVLT; receive hormonal inputs) medial – GnRH → anterior pituitary (reproduction & sexual arousal) lateral – sleep and wakefulness (damage → insomnia) preoptic periventricular nucleus → part of the parvocellular neurosecretory system Medial hypothalamus – suprachiasmatic (supraoptic; anterior) region cross-section 3V Lateral hypothalamus Supraoptic nucleus → ADH secretion into neurophypophysis → retention of water in kidneys (diabetes insipidus; polydipsia, polyuria); (part of magnocellular system) Paraventricular nucleus → oxytocin secretion → contraction of uterine smooth musculature during labour and promotion of milk ejection (part of magnocellular system) Anterior nucleus – thirst center → tumors lead to refusal of patients to drink despite severe dehydration Suprachiasmatic nucleus (poorly developed in humans) - circadian rhythm regulator (sleep-wake/day-night cycles) → receives bilaterally from retina; projects to tuberal hypothalamic nculei (VIP-ergic fibers); influences pineal gland via sympathetic fibers (C8-T1 level of spinal cord) → melatonin secretion The paraventricular nucleus contains 3 distinct cell populations Anterior pituitary Medial hypothalamus – tuberal (intermediate) region Ventromedial nucleus - satiety center (lesions lead to ↑ appetite & obesity); receives from amygdala via stria terminalis Dorsomedial nucleus – TRH release; neuroendocrine control of catecholamines (projects to spinal cord autonomic neurons) Arcuate nucleus Fornix 3V control of anterior pituitary via tuberoinfundibular tract and the hypophyseal portal system (parvocellular system): ACTH, dopamine, β-LPH, βEndorphin major target of leptin actions regulating food intake by acting on food promoting (orexinergic) and food inhibiting (anorexinergic) arcuate neurons Magnocellular vs parvocellular neurosecretory systems tuberoinfundibular tract Hypothalamus → posterior pituitary (neurohypophysis) Hypothalamus → portal blood system → anterior pituitary (adenohypophysis) Information flow between brain and endocrine system parvocellular paraventricular n. periventricular, ventromedial, dorsomedial nuclei periventricular & arcuate nuclei periventricular n. – GIH arcuate n. – GRH arcuate n. – PIH pituitary TSH = PRH Dopamine Medial hypothalamus – mammilary (posterior) region Mamillary nuclei 3V MTT Tuberomammilary n. medial (large) – receives from hippocampus via fornix and sends to anterior thalamus via mamillothalamic tract (MMT) → involved in memory lateral (small) - descending projection to the midbrain and pons, the mammillotegmental tract (reticular formation) tuberomammillary nucleus (histaminergic) – widespread projections to cortex → maintains arousal (antihistamine drugs cause drowsiness) Posterior nucleus - the main source of descending hypothalamic fibers to the brain stem: dorsal longitudinal fasciculus The fornix Hippocampus → mammillary medial nucleus HypothalamusMammillothalamic tract (of Vicq d'Azyr) ANTERIOR NUCLEUS Mamillothalamic tract MAMMILLARY BODY Mammillary medial nucleus → anterior thalamic nuclei Dorsal longitudinal fasciculus – integration of hypothalamic & autonomic function Posterior nucleus Lateral region of hypothalamus Lies lateral to the fornix and mamillothalamic tract The medial forebrain bundle connects the hypothalamus with the septal area, cortex, amygdala rostrally and brain stem reticular formation caudally Lateral hypothalamic area contains orexin (hypocretin)-ergic neurons → stimulate food intake; inhibit anorexigenic neurons in ventromedial nucleus and exite orexigenic neurons in arcuate nucleus controls activities of monoaminergic and cholinergic systems affecting sleep → destruction is associated with the sleep disorder of narcolepsy Medial & lateral hypothalamic nuclear groups Fornix Hypothalamus Limbic System Interthalamic adhesion MTT Tuber cinereum Infundibulum Optic nerve Fornix Afferents to the hypothalamus (amygdala) (amygdala) Afferents to hypothalamus To reticular formation Posterior nucleus Medial forebrain bundle Preoptic area Efferents from hypothalamus Endocrine pathways – posterior pituitary Endocrine pathways – anterior pituitary Functions of hypothalamic nuclei Nucleus Key functions Preoptic nuclei: Medial Parvocellular hormone control Lateral Sleep-wakefulness Paraventricular Magnocellular hormones (oxytocin, vasopressin); parvocellular; direct autonomic control Anterior Thirst Supraoptic Magnocellular hormones (oxytocin, vasopressin) Suprachiasmatic Circadian rhythm Ventromedial Appetitive/consummatory behaviors Dorsomedial Feeding, drinking, and body weight regulation Arcuate Parvocellular hormones; visceral functions Mammillary Memory Tuberomammillary Sleep-wakefulness (histamine) Lateral hypothalamic Various, including arousal, food intake; contain orexin Summary of hypothalamus functions The 3rd Ventricle Narrow vertical cleft between the two halves of the diencephalon Lat. ventricle Fornix 3rd Ventricle Borders thalamus pl. choroideus hypothalamus lamina terminalis Lateral ventricle communicates with the 3rd ventricle via the foramen of Monro Four Parts: • Lateral Ventricle (2) • Third Ventricle The rd 3 ventricle has 4 recesses Foramen of Monro Pineal recess Optic Infundibular Pineal Suprapineal Recesses of the 3rd ventricle Suprapineal Pineal Optic Infundibular