Pinel basics ch07

Copyright © 2007 by Allyn and Bacon

Chapter 7Development of the Nervous System

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Neurodevelopment

Neural development – an ongoing process, the nervous system is plastic

Complex Experience plays a key role Dire consequences when something

goes wrong


The Case of Genie

What impact does severe deprivation have on development?

At age 13, Genie weighed 62 pounds and could not chew solid food

Beaten, starved, restrained, kept in a dark room, denied normal human interactions

Can the damage be undone?


The Case of Genie

Genie’s story is often cited for what it told us about language development (she only uses short utterances), but it also illustrates the impact of abuse on all aspects of behavior No response to temperature extremes Unable to chew Extremely inappropriate reactions (‘silent tantrums’) Easily terrified

How can neurodevelopment explain this?


Phases of Development

Ovum + sperm = zygote Cells then multiply and

DifferentiateMove and take their appropriate positionsMake the needed functional relations with

other cells Developing neurons accomplish these

things in 5 phases


Induction of the Neural Plate

A patch of tissue on the dorsal surface of the embryo

Development induced by chemical signals from the mesoderm (the “organizer”)

Visible 3 weeks after conception 3 layers of embryonic cells

Ectoderm – outermost, mesoderm – middle, endoderm - innermost


Induction of the Neural Plate

Part of induction is inhibition of bone morphogenetic proteins that suppress neurodevelopment

Totipotent – earliest cells have the ability to become any type of body cell

With the development of the neural plate cell destinies become specified – cells are multipotent – able to develop into any type of mature nervous system cell


Stem cells

Neural plate cells are often referred to as stem cells. Stem cells: seem to have an unlimited capacity for

self-renewal can develop into different mature cell

types (totipotent) As the neural tube develops

specificity increases, resulting in glial and neural stem cells (multipotent)



Neural Proliferation

Neural plate folds to form the neural groove which then fuses to form the neural tube

Inside will be the cerebral ventricles and neural tube

Neural tube cells proliferate in species-specific ways – 3 swellings at the anterior end in humans will become the forebrain, midbrain, and hindbrain


Migration

Once cells have been created through cell division in the ventricular zone of the neural tube they migrate

Migrating cells are immature, lacking axons and dendrites

Radial migration – towards the outer wall of the tube

Tangential migration – at a right angle to radial migration, parallel to the tube walls

Most cells engage in both types of migration


Migration

Two types of neural tube migrationRadial migration – moving out – usually by

moving along radial glial cellsTangential migration – moving up

Two methods of migrationSomal – an extension develops that leads

migration, cell body followsGlial-mediated migration – cell moves along a

radial glial network




Aggregation

the process of cells that are done migrating aligning themselves with others cells and forming structures.

Cell-adhesion molecules (CAMs) – aid both migration and aggregation

CAMs found on cell surfaces, recognize and adhere to molecules


Axon Growth and Synapse Formation Once migration is complete and structures have

formed (aggregation), axons and dendrites begin to grow

Growth cone – at the growing tip of each extension, extends and retracts filopidia as if finding its way

Chemoaffinity hypothesis – postsynaptic targets release a chemical that guides axonal growth – but this does not explain the often circuitous routes often observed


Axon growth

Mechanisms underlying axonal growth are the same across species

A series of chemical signals exist along the way Such guidance molecules are often released

by glia chemoattractants attract growing axons chemorepellants repel them

Adjacent growing axons also provide signals


Axon growth

Pioneer growth cones – the 1st to travel a route – follow guidance molecules

Fasciculation – the tendency of developing axons to grow along the paths established by preceding axons

Topographic gradient hypothesis – seeks to explain topographic maps


Synaptogenesis

Formation of new synapses Depends on the presence of glial cells –

especially astrocytes High levels of cholesterol are needed – supplied

by astrocytes Chemical signal exchange between pre and

postsynaptic neurons is needed A variety of signals act on developing neurons


Neuron Death and Synapse Rearrangement ~50% more neurons than are needed are

produced – death is normal Neurons die due to failure to compete for

chemicals provided by targets Increase targets > decreased deathDestroy some cells > increased survival of

remaining cells Increase number of innervating axons >

decreased proportion survive


Life-preserving chemicals

Neurotrophins – promote growth and survival, guide axons, stimulate synaptogenesis Nerve growth factor (NGF)

Both passive cell death (necrosis) and active cell death (apoptosis)

Apoptosis is safer than necrosis – “cleaner”


Postnatal Cerebral Development in Human Infants Postnatal growth is a consequence of

SynaptogenesisMyelination – sensory areas and then motor

areas. Myelination of prefrontal cortex continues into adolescence

Increased dendritic branches Overproduction of synapses may underlie

the greater plasticity of the young brain


Development of the Prefrontal Cortex Believed to underlie age-related

changes in cognitive function No single theory explains the

function of this area Prefrontal cortex plays a role in

working memory, planning and carrying out sequences of actions, and inhibiting inappropriate responses



Effects of Experience on Neural Circuits Neurons and synapses that are not

activated by experience usually do not survive – “use it or lose it”

Humans are uniquely slow in neurodevelopment – allows for fine-tuning

How do nature and nurture interact to modify the early development, maintenance, and reorganization of neural circuits?


Early Studies of Experience and Neurodevelopment Early visual deprivation:

fewer synapses and dendritic spines in 1° visual cortex

deficits in depth and pattern vision Enriched environment:

thicker corticesgreater dendritic developmentmore synapses per neuron


Competitive Nature of Experience and Neurodevelopment Monocular deprivation changes the

pattern of synaptic input into layer IV of V1

Altered exposure during a sensitive period leads to reorganization

Active motor neurons take precedence over inactive ones


Effects of Experience on Topographic Sensory Cortex Maps Cross-modal (involving at least 2

different senses) rewiring experiments demonstrate sensory cortex plasticity – with visual input, auditory cortex can see

Change input, change cortical topography - shifted auditory map in prism-exposed owls


Effects of Experience on Topographic Sensory Cortex Maps Neural activity prior to sensory input

plays a role in development – ferret visual development disrupted by interference with neuronal activity prior to eye opening

Early music training influences the organization of human auditory cortex – fMRI studies


Neuroplasticity in Adults

Mature brain changes and adapts Neurogenesis (growth of new

neurons) seen in olfactory bulbs and hippocampi of adult mammals

Researchers still looking to see if there is neurogenesis in other adult brain structures


Effects of Experience on the Reorganization of the Adult Cortex Tinnitus (ringing in the ears) – produces

major reorganization of 1° auditory cortex Adult musicians who play instruments

fingered by hand have an enlarged representation of the hand in right somatosensory cortex

Skill training leads to reorganization of motor cortex


Autism

4 of every 10,000 individuals – 3 core symptoms: Reduced ability to interpret emotions and intentions Reduced capacity for social interaction Preoccupation with a single subject or activity

Intensive behavioral therapy may improve function

Heterogenous – level of brain damage and dysfunction varies


Autism

Most have some abilities preserved – rote memory, ability to complete jigsaw puzzles, musical ability, artistic ability

Savants – intellectually handicapped individuals who display specific cognitive or artistic abilities

~1/10 autistic individuals display savant abilities Perhaps a consequence of compensatory

functional improvement in the right hemisphere following damage to the left


Neural Basis of Autism

Genetic basisSiblings of the autistic have a 5% chance of

being autistic60% concordance rate for monozygotic twins

Several genes interacting with the environment

Brain damage tends to be widespread, but is most commonly seen in the cerebellum


Neural Basis for Autism

Thalidomide – given early in pregnancy – increases chance of autism Indicates neurodevelopmental error occurs within 1st

few weeks of pregnancy when motor neurons of the cranial nerves are developing

Consistent with observed deficits in face, mouth, and eye control

Anomalies in ear structure indicate damage occurs between 20 and 24 days after conception

Evidence for a role of a gene on chromosome 7



Williams Syndrome

~ 1 of every 20,000 births Mental retardation and an uneven pattern of abilities and

disabilities Sociable, empathetic, and talkative – exhibit language

skills, music skills and an enhanced ability to recognize faces

Profound impairments in spatial cognition Usually have heart disorders associated with a mutation

in a gene on chromosome 7 – the gene (and others) are absent in 95% of those with Williams


Williams Syndrome

Variety of abilities – like autistics Evidence for a role of chromosome 7 – as

in autism Underdeveloped occipital and parietal

cortex, normal frontal and temporal “elfin” appearance – short, small upturned

noses, oval ears, broad mouths


Think About It

Compare and contrast autism and Williams syndrome

What do these disorders demonstrated about neurodevelopment?

How are such developmental disorders studied?

Pinel basics ch07

Technology

stem cells neural plate

process of cells

migrating cells

specified cells

asstem cells

zygote cells

neural stem cells multipotent

presence of glial cells