PRE LECTURE QUIZ WILL BE PRE LECTURE QUIZ WILL BE GIVEN ON:GIVEN ON:

BRAIN DEVELOPMENTBRAIN DEVELOPMENT CRANIAL NERVESCRANIAL NERVES

The Human EmbryoThe Human Embryo

ZygoteZygote EmbryoEmbryo (first 8 weeks) (first 8 weeks)

– endoderm (bodily linings)endoderm (bodily linings)

– mesodermmesoderm (connective tissues)(connective tissues)

– ectoderm (nervous system)ectoderm (nervous system) FetusFetus (after 8 weeks) (after 8 weeks)

Emergence of the Nervous SystemEmergence of the Nervous System

Neural plate becomes neural tubeNeural plate becomes neural tube

……Emergence of the Nervous SystemEmergence of the Nervous System

Walls of neural tube Walls of neural tube become neurons and become neurons and glial cellsglial cells

Cavity of neural tube Cavity of neural tube becomes ventricular becomes ventricular systemsystem

……Emergence of the Nervous SystemEmergence of the Nervous System

Neural tube defectsNeural tube defects

– anencephalyanencephaly

– spina bifidaspina bifida

AnencephalyAnencephaly

cephalic disorder cephalic disorder that results from a that results from a neural tube defectneural tube defect

occurs when the cephalic (head) end of the neural tube fails to close usually between the 23rd and 26th day of pregnancy, resulting in the absence of a major portion of the brain, skull, and scalp.

Children with this disorder are born without Children with this disorder are born without a forebrain, the largest part of the brain a forebrain, the largest part of the brain consisting mainly of the cerebral consisting mainly of the cerebral hemispheres (which include the neocortex, hemispheres (which include the neocortex, which is responsible for higher-level which is responsible for higher-level cognition, i.e., thinking). cognition, i.e., thinking).

The remaining brain tissue is often exposedThe remaining brain tissue is often exposed—not covered by bone or skin.—not covered by bone or skin.

AnencephalyAnencephaly

A baby born with anencephaly is usually blind, A baby born with anencephaly is usually blind, deaf, unconscious, and unable to feel pain. deaf, unconscious, and unable to feel pain.

Although some individuals with anencephaly Although some individuals with anencephaly may be born with a main brain stem, the lack of may be born with a main brain stem, the lack of a functioning cerebrum permanently rules out a functioning cerebrum permanently rules out the possibility of ever gaining consciousness. the possibility of ever gaining consciousness.

Reflex actions such as breathing and responses Reflex actions such as breathing and responses to sound or touch occur.to sound or touch occur.

Spina bifidaSpina bifida developmental birth defect caused by the developmental birth defect caused by the

incomplete closure of the embryonic neural incomplete closure of the embryonic neural tubetube

cleft spine, which is an incomplete closure cleft spine, which is an incomplete closure in the spinal column.in the spinal column.

Some vertebrae overlying the spinal cord are not Some vertebrae overlying the spinal cord are not fully formed and remain unfused and open. fully formed and remain unfused and open.

If the opening is large enough, this allows a If the opening is large enough, this allows a portion of the spinal cord to protrude through the portion of the spinal cord to protrude through the opening in the bones. opening in the bones.

There may or may not be a fluid-filled sac There may or may not be a fluid-filled sac surrounding the spinal cord. surrounding the spinal cord.

Other neural tube defects include Other neural tube defects include anencephalanencephaly y encephalocele, which results when other parts of , which results when other parts of the brain remain unfused.the brain remain unfused.

The Developing BrainThe Developing Brain

Rostral part of neural tube becomes brainRostral part of neural tube becomes brain Caudal part of neural tube becomes spinal Caudal part of neural tube becomes spinal

cordcord Differentiation of brain into 3 parts:Differentiation of brain into 3 parts:

– prosencephalon (forebrain)prosencephalon (forebrain)– mesencephalon (midbrain)mesencephalon (midbrain)– rhombencephalon (hindbrain)rhombencephalon (hindbrain)

Further differentiation of these 3 partsFurther differentiation of these 3 parts

The Developing Spinal CordThe Developing Spinal Cord

2 major zones of cells:2 major zones of cells:– alar platealar plate (dorsal) (dorsal)

» sends sensory projections to brainsends sensory projections to brain

– basal platebasal plate (ventral) (ventral)» motor neuron developmentmotor neuron development

Formation of Neurons and Glial CellsFormation of Neurons and Glial Cells

Single layer of cells within Single layer of cells within neural tube…ventricular layerneural tube…ventricular layer

Daughter cellsDaughter cells

– Migration first to marginal Migration first to marginal (outer) layer(outer) layer

– Migration then to Migration then to intermediate layerintermediate layer

– Migration to cortical plate & Migration to cortical plate & subventricular layersubventricular layer

– Some remain in ventricular Some remain in ventricular layer (ependymal cells)layer (ependymal cells)

Cell Formation and MigrationCell Formation and Migration

NeurogenesisNeurogenesis: formation of : formation of new neuronsnew neurons

Neural migration guided by:Neural migration guided by:

– radial glial cellsradial glial cells

– glycoproteinsglycoproteins

Cell DifferentiationCell Differentiation

Creation of different cell Creation of different cell typestypes

2 types:2 types:– cell-autonomous cell-autonomous

differentiation (genetic)differentiation (genetic)– induction (dependent upon induction (dependent upon

influence of other cells)influence of other cells)

Glial Cell DevelopmentGlial Cell Development Begins in embryonic Begins in embryonic

periodperiod Most intense glial Most intense glial

production after birthproduction after birth Myelination (wrapping Myelination (wrapping

axon in myelin sheath)axon in myelin sheath)– spinal cord then spinal cord then

hindbrain then hindbrain then midbrain then forebrainmidbrain then forebrain

– sensory then motorsensory then motor

Formation of Neural ConnectionsFormation of Neural Connections

Axons grow towards target cellsAxons grow towards target cells Axon emerges from growth cone (containing Axon emerges from growth cone (containing

filopodia)filopodia) Filopodia are attracted to target cell through Filopodia are attracted to target cell through

chemical signalchemical signal– neurotrophinsneurotrophins

Abrupt changes in direction of growth due to Abrupt changes in direction of growth due to guidepost cellsguidepost cells

Importance of Neural ActivityImportance of Neural Activity

Axonal remolding (Shatz, 1992) Axonal remolding (Shatz, 1992)

– neurons grow to many neurons grow to many addressesaddresses

» correct address...remaincorrect address...remain

» incorrect incorrect address...eliminatedaddress...eliminated

Neurons that fire together wire Neurons that fire together wire togethertogether

Neuron Cell DeathNeuron Cell Death

Theories:Theories:– Competition to attain connections with target Competition to attain connections with target

cellscells– Need to receive certain qualitity of Need to receive certain qualitity of

neurotrophins for survivalneurotrophins for survival Examples:Examples:

– Motor neuron-muscle fiber connections (PNS)Motor neuron-muscle fiber connections (PNS)– Purkinje cells of cerebellum (CNS)Purkinje cells of cerebellum (CNS)

Failures of Neural DevelopmentFailures of Neural Development

Genetic defectsGenetic defects– Down Syndrome Down Syndrome - trisomy 21, is a chromosomal condition - trisomy 21, is a chromosomal condition

caused by the presence of all or part of an extra 21st chromosome.caused by the presence of all or part of an extra 21st chromosome.

– Phenylketonuria (PKU) - Phenylketonuria (PKU) - autosomal recessive metabolic autosomal recessive metabolic genetic disorder characterized by a deficiency in the hepatic enzyme genetic disorder characterized by a deficiency in the hepatic enzyme phenylalanine hydroxylase (PAH)phenylalanine hydroxylase (PAH)

» PAH : converts phenylalanine ('Phe') to the amino acid tyrosine.PAH : converts phenylalanine ('Phe') to the amino acid tyrosine.

» hyperphenylalaninemia (HPA) was associated with mental retardationhyperphenylalaninemia (HPA) was associated with mental retardation ..

– Fragile X Syndrome Fragile X Syndrome

Fragile X Syndrome Fragile X Syndrome genetic syndrome which results in a genetic syndrome which results in a

spectrum of characteristic physical and spectrum of characteristic physical and intellectual limitations and emotional and intellectual limitations and emotional and behavioral features which range from behavioral features which range from severe to mild in manifestation.severe to mild in manifestation.

expansion of a single trinucleotide gene expansion of a single trinucleotide gene sequence (sequence (CGG) CGG) on the on the X chromosome, and chromosome, and results in a failure to express the protein results in a failure to express the protein coded by the coded by the FMR1 gene, which is required ne, which is required for normal neural development.for normal neural development.

External factorsExternal factors– MalnutritionMalnutrition– Fetal Alcohol Syndrome - next slideFetal Alcohol Syndrome - next slide

Failures of Neural DevelopmentFailures of Neural Development

(Andrew Syndrome) is a pattern of mental (Andrew Syndrome) is a pattern of mental and physical defects that can develop in a and physical defects that can develop in a fetus when a woman drinks alcohol during fetus when a woman drinks alcohol during pregnancy. pregnancy.

Redevelopment of the Nervous SystemRedevelopment of the Nervous System

Damage to cell body of nerve...death; damage to axon...degenerative changes, Damage to cell body of nerve...death; damage to axon...degenerative changes, sometimes deathsometimes death

anterograde degeneration (from point of injury to axon terminals)anterograde degeneration (from point of injury to axon terminals) retrograde degeneration (between point of injury and cell body)retrograde degeneration (between point of injury and cell body) chromatolysis (degeneration of cell body)chromatolysis (degeneration of cell body) transneuronal degeneration (damage to connecting neurons)transneuronal degeneration (damage to connecting neurons)

...Redevelopment of the Nervous System...Redevelopment of the Nervous System

Regeneration occurs within PNS onlyRegeneration occurs within PNS only Collateral sprouting within CNSCollateral sprouting within CNS Research on recovery of CNS functioningResearch on recovery of CNS functioning

– collateral sproutingcollateral sprouting– suppression of growth-inhibiting chemicalssuppression of growth-inhibiting chemicals– fetal tissue transplantationfetal tissue transplantation

Compensatory strategies after CNS damageCompensatory strategies after CNS damage– rehabilitationrehabilitation