Development of the nervous system

1. Development of the nervous system • Develop from ectoderm • Neural plate – appears at beginning of 3rd week • Thickened ectodermal layer in mid dorsal line • Neural groove • Formed from the folding plate • Neural folds • Elevated sides of neural groove • Neural tube • Fusion of neural folds • Neural Crest cells • Migrate on either side of neural tube • diagram

2. Neural Plate • Originally single layer of columnar cells • Rapidly becomes pseudostratified • Neuroepithelial cells of the pseudostratified layer continue to divide & differentiate into different zones of the neural tube • Neuroblast • Spongioblast

3. Neuroepithelial cells • Neuroblasts • Apolar • Bipolar • Multipolar • Pseudo-unipolar

4. Neuroepithelial cells (cont) • Spongioblasts • Glioblasts • Astroblasts • Astrocytes • Protoplasmic • Fibrous • Oligodendroblast • Oligodendrocytes • Ependymal cells

5. Neural Tube • 6th week -3 concentric zones/layers • Inner ependymal layer • Middle nucleated mantle layer • Future gray matter of CNS • Outer non nucleated marginal layer • Fibrous mesh • Supports axons & dendrites • Contains glial cells that have migrated from mantle layer • White matter of CNS • Central Canal

6. Cephalic end of neural tube • 3 dilatations • Prosencephalon (forebrain) • Mesencephalon (midbrain) • Rhombencephalon (hindbrain) • 2 flexures (ventral bends) • Cervical flexure • At junction of hindbrain & spinal cord • Cephalic flexure • Located in midbrain region

7. 3 dilatations (at 5 weeks) • Prosencephalon  • Anterior portion (telencephalon or endbrain) • Formed by a mid portion and two lateral out pocketings  primative cerbral hemispheres • Posterior portion (diencephalon) • Characterized by outgrowth of the optic vesicles • Mesencephalon  has undergone little  • Rhombencephalon  • Anterior portion (metencephalon) • Later forms the pons and cerebellum • Posterior portion (myelencephalon) • Later become the medulla oblongata

8. Lumen/Central canal • Lumen of spinal cord (central canal) is continuous with brain vesicles • Allowing free circulation of CSF • Cavity of rhombencephalon • 4th ventricle • Cavity of diencephalon • 3rd ventricle • 3rd 4th ventricle (aqueduct of Sylvius) • Becomes very narrow • Lateral ventricle & 3rd ventricle • Communicate via interventricular foramina of Monro

9. Neural tube-spinal cord level • Rhomboid shaped-4 longitudinal grooves • Dorsal sulcus (SD) • Roof plate is above (only ependymal layer) • Ventral sulcus (SV) • Floor plate is below (only ependymal layer) • 2 lateral sulci • Sulcus limitans (SL) • Alar plate between SL & roof plate (all 3 layers) • Sensory neurons & ascending pathways • Basal plate between SL & floor plate (all 3 layers) • Motor neurons & descending pathways • Central canal still lined by neuroepithelium

10. Development of Spinal Cord (SC) • Wall of neural tube thickens quickly • In 4th week typical three layers are present • Continued growth causes narrowing of central canal • Alar plate thickens, roof plate is obliterated • Ependymal layers unite  dorsal median septum • Reduces extent of central canal • Basal plate thickens but do not fuse  ventral median fissure

11. Development of the Spinal Cord • Mantle layer containing neuroblasts  in mass  gray matter • On each side of the midplane the gray substance forms bulky masses • Dorsal, lateral, ventral columns (horns) • Marginal layer • Neuroepithelial cells, glial cells, axons of nerve cells • Thickening of this layer due to nerve fibers & deposition of myelin around these fibers

12. Spinal Ganglia • Pseudo-unipolar neurons in spinal ganglia are derived from the neural crest cells • Each neural crest cell develops two processes  bipolar neuroblast • Two processes grow & fuse at base forming a T shaped structure with a central process (axon) & peripheral process (dendrite) • Central branches enter spinal cord (dorsal roots of spinal N)

13. Positional changes of SC • In 3rd month the SC extends the entire length of the embryo & spinal nerves pass through the IVF at level of origin. • Vertebral column & meninges grow faster than SC, the above relationship does not last • Terminal end of SC gradually shifts to a higher level • At 6th month the end of SC is at level of S1 • At birth the end of SC is at L2-3 • In adult the end of SC is at lower end of L1

14. Myelencephalon • Lies between pontine & cervical flexure • Forms medulla oblongata • Transitions from SC; differences • Lateral walls everted • Loss of serially segmented repetition of cord • Addition of lateral rows of cranial nerves • V, VII, IX, X, XI • Loss of sharp demarcation btw. gray & white • Nerve fibers crossing break up gray matter • This mixture  reticular formation • figure

15. Myelencephalon • Some areas form discrete nuclei • Roof Plate • Stretched into broad thin layer of ependymal cells • Vascular pia + ependymal roof  tela choroidea • Rostrally tela choroidea infolds as vascular tuft • Project into the 4th ventricle  choroid plexus (produces CSF) • 3 foramina formed due to reabsorption • Lateral pair  Luschka • Medial  Madendie • Floor Plate • Ependymal cells elongate  septum-like raphe

16. Myelencephalon (cont) • Alar Plate (sensory) • Sensory nerves enter from CN VII, IX, X • Collect into solitary tract located in marginal layer • Alar plate neuroblasts form 3 sensory nuclei • Somatic afferent (lateral) • Receive input from ear (CN VIII) & head (CN V) • Special visceral afferent (intermediate) • Receive input from taste buds via facial N (CN VII) • General visceral afferent (medial) • Receive input from GI tract, heart via vagus N (CN X) • Olivary n migrate to basal plate area • Receive afferent input from various sources & project output to the cerebellum

17. Myelencephalon (cont) • Basal Plate (motor) Differentiates before alar • Basal plate neuroblasts form 3 motor nuclei • General visceral efferent (lateral) • Parasympathetic • Dorsal motor nucleus of vagus (CN X) • Inferior salvitory nucleus (CN IX) • Special visceral efferent (intermediate) (CN IX, X, XI) • Nucleus Ambiguus • Supply muscles of 3rd & 4th pharyngeal/branchial arches • Somatic efferent (medial) • Hypoglossal Nucleus • Supply muscles of tongue (CN XII) • Decending corticospinal fibers  pyramids

18. Metencephalon • Extends from isthmus  pontine flexure • Similar to Myelencephalon with addition of • Cerebellum dorsally • Chief coordination center of unconscious stimuli related to body position & movement • Pons ventrally • Main conduction pathway between spinal cord & cerebral & cerebellar cortices

19. Metencephalon (cont) • Roof plate • Rostral to cerebellum • Superior medullary velum • Thin sheet of white substance • Caudal to cerebellum • Inferior medullary velum • Ependymal cells • Balance lost in substance of cerebellum • Floor Plate • Ependymal cells elongate  septum-like raphe

20. Metencephalon (cont) • Alar Plates • Become very prominent & forms cerebellum • Somatic afferent (lateral) • Sensory nuclei receive fibers from • Trigeminal (CN V) • Small portion of Vestibulocochlear (CN VIII) • Special visceral afferent (intermediate) • General visceral afferent (medial)

21. Metencephalon (cont) • Basal Plate (motor) • General visceral efferent (lateral) • Axons supply submandibular & sublingual glands • Special visceral efferent (intermediate) • Contain N of trigeminal (CN V) & facial (CN VII) • Supply muscles of 1st & 2nd pharygeal/branchial arches • Somatic efferent (medial) • Gives rise to N of abducens (CN VI) • Marginal layer expands extensively Pons • Many fibers pass uninterrupted through pons • Pyramidal tracts

22. Cerebellum • Formed from thickening of dorsolateral parts of alar plates • Bend medially forming rhombic lips (RL) • Approach each other in midline near mesencephalon • As a result of further deeping of the pontine flexure, RL become compressed in a cephalo-caudal direction  cerebellar plate • Small midline portion  vermis • Two lateral portions  hemispheres • Transverse fissure seperates nodule from vermis & lateral flocculus from the hemispheres

23. Cerebellum (cont) • Cerebellar plate • Initially consists of 3 layers • Neuroepithelial • Number of cells migrate to surface  external granule layer • Retain ability to divide  proliferative zone on surface • Gives rise to granule, basket, cells • Mantle • During 2nd & 3rd month cells migrate into marginal layer organizing cerebellar cortex • Between 3rd & 5th month cortex grows faster than deeper layers forming main lobes & fissures • Many cells of primitive mantle layer  neuroglia & deep nuclei • marginal

24. Mesencephalon • Morphologically the most primitive of the brain vesicles • Least modified from the primitive neural tube • Primarily associated with reflexes of eye & head in response to visual stimuli • Caudal part involved with reflexes of acoustic centers

25. Mesencephalon (cont) • Alar Plate • 2 longitudinal elevations divided by transverse groove • 2 Superior/anterior colliculi (visual reflexes) • 2 Inferior/posterior colliculi (auditory relay) • Colliculi formed by waves of neuroblasts migrating into overlying marginal zone  become stratified

26. Mesencephalon (cont) • Basal Plate (motor nuclei) • Somatic efferent (medial) • Occulomotor (CN III) & Trochlear (CN IV) • General visceral efferent • Edinger-Westphal (parasym)  sphincter pupillary muscle • Marginal layer  crus cerebri (cerebral peduncles) • Neural pathways decending from cerebral cortex  pons & SC • Red nucleus (may have migrated from alar plate) • Substantia Nigra • figure

27. Diencephalon • Caudal portion of prosencephalon (forebrain) • Develops from the primitive roof & alar plates • (no basal plates) • Surrounds third ventricle • Roof plate ( thin plate of ependymal cells) • Ependymal cells + pia mater  choroid plexus • Forms part of epithalamus • Synaptic region for correlation of olfactory impulses • Habenular nuclei • Caudal to choroid plexus evagination (7th week)  epiphysis/pineal body (pineal gland)

28. Diencephalon • Alar Plate • Dorsal part  balance of epithalamus • Contain a group of nuclei  habenular nuclei • Lateral part  Thalamus • Each thalamus contains a # of nuclei • Relay sensory signals to cerebral cortex • Ventral part  hypothalamus • Differentiate into a # of nuclear areas • Visceral functions • Downward extension of hypothalamus (infundibulum) contributes to formation of pituitary gland (neurohypopysis/stalk & posterior lobe) • Neuroglia cells & nerve fibers from hypothalamus

29. Pituitary/Hypophysis • Develops from two different sources • Ectodermal outpocketing of the stomodeum • Rathke’s Pouch • Appears around 3rd week & grows dorsally • By end of 2nd month it loses connection with stomodeum & lies close to the infundibulum • Gives rise primarily to the anterior lobe (adenohypophysis) • Downward extension of the hypothalamus • Indundibulum gives rise to stalk & posterior lobe

30. Telencephalon • Medial portion  Lamina Terminalis • Original rostral end of the neural tube that remains as the medial band • Two lateral outpockets  cerebral hemispheres • Become prominent during the 6th week & expands rapidly until by about 6th month they overgrow the diencephalon & mesencephalon

31. Telencephalon • Divisible into three portions • Corpus Striatum • Continuous with the thalamus • Rhinencephalon • Paleopallium • Archipallium • Hippocampal formation • Neopallium • Largest part & represented primarily by what’s visible externally

32. Corpus Striatum • Appears during the 6th week as a prominent swelling in floor of each hemisphere • Due to proliferating mantle layer cells  caudate & lentiform nuclei • These nuclei are seperated by band like tract of fibers called the internal capsul • Elongates as cerebral hemispheres grow • Caudal portion forms tail of the caudate • Will eventually form the basal ganglia

33. Rhinencephalon • Appears as a swelling on ventral surface of each hemisphere during 6th week • Enlarge into distinct olfactory lobes • Each lobe divided into a rostral bulb & a caudal tract region

34. Neopallium • Predominant part of the forebrain • Comprises almost all of the hemispheres except the hippocampal formation (archipallium) • As each hemisphere expands it is thrown into complex convolutions seperated by numerous fissures

35. Histogenesis of Cortex • In wall of pallium differentiated cells of the following layers typical of the neural tube • Ependymal • Marginal • Mantle • During the third month neuroblasts from this layer start to migrate to the marginal layer  primordial cortex • By the 6th month cortical layers are demarcated (usually 6) • Final differentiation of the outer layers is not completed until mid-childhood

36. Congenital Malformations • Cranium Bifidum • Hydrocephaly • Agenesis of Corpus Callosum • Holoprosencephaly • Macrocephaly • Microcephaly

37. Cranium Bifidum • Open cranium with cyst • Caused by ossification defect in bones of skull (most common is squamous part of occipital bone) • meningocele • Cyst contains meninges • meningoencephalocele • Cyst contains brain & meninges • Meningohydroencephalocele • Cyst contains brain, meninges, ventricular space

38. Hydrocephaly • Abnormal accumulation of cerebralspinal fluid within the ventricular system • Majority of cases is due to obstruction of the aqueduct of Sylvius (aqueductal stenosis) • Fluid buildup in lateral & 3rd ventricles • Reduces volume of brain tissue in anterior & middle fossa

39. Arnold-Chiari malformation • Caudal displacement & herniation of cerebellar structures through the foramen magnum • Defect occurs in virtually every case of spina bifida cystica & is usually accompanied by hydrocephalus