PSYC 2012: Biological Psychology I

Week 5: Developmental Neurogenesis, and Brain

Development and Environment

Goals of This Week’s Lectures:

To learn how a structure as complex and incredible as our brain is formed

and how brain development is affected by postnatal influences

The Human Brain• Has ~100 billion

neurons

• It has even more glial cells

• All of these cells have specialized structure and function

Where do all these cells come from, and how do they become specialized during

development?

Developmental Neurogenesis

Developmental Neurogenesis

The process by which neurons are formed and specialize during

development

Gross Development of the Human Nervous System

Early Stages of Human Development

• Zygote---from fertilization to 4 days old

• Blastula or Blastocyst—hollow ball of cells forms around 4-5 days

• Gastrula—3-layered ball of cells, forms 7-10 days

3 layers of the gastrula will eventually form different tissues

1) Ectoderm—outer layer, forms skin and nervous system

2) Mesoderm—middle layer, forms muscle, blood and bone

3) Endoderm—inner layer, forms internal organs—lungs, liver, intestines, etc.

Ectoderm then forms other neural structures

• Neural plate— part of the back ectoderm that forms the neural tube and neural crest by folding in on itself

• Neural tube—hollow tube of cells that eventually forms the spinal cord and brain

• Neural crest—these cells eventually migrate out and form the peripheral nerves

• Incomplete folding of the neural tube can result in anencephaly (lack of brain formation) or spina bifida

Formation of the Nervous System

6 Main Processes That Form the Nervous System

• Cell proliferation

• Cell migration

• Cell differentiation & maturation

• Synaptogenesis

• Cell death and synaptic pruning

• Myelination

Cell Proliferation:

The formation of two new cells from one cell

Neural Stem Cell Proliferation

• Starts shortly after conception and is mostly complete 4-5 months post-conception

• Forms >100 billion neuronal precursor cells

• More neurons are actually formed than are needed

PNET—Primitive Neuroectodermal Tumor

• A rare but dangerous tumor found in children

• Forms because rarely neural stem cells may refuse to stop proliferating like normal

• 5-year survival rate is usually around 50%

Cell Migration:

The movement of cells from one place to another

Neural Cell Migration• Starts around 8-9

weeks post-conception and is complete 2-3 months before birth

• Two main types of migration:1) Tangential—moving

up/down or around2) Radial—moving out

from center

2 Main Migration Events in Neural Development:

• Tangential migration of neural crest cells to form Schwann cells and neurons in peripheral nerves

• Radial migration of cerebral cortical neurons to form the layers of the cerebral cortex—defects in radial migration of cortical neurons can cause lissencephaly, formation of a brain without folds and cortical layers

Differentiation:

The process by which unspecialized stem cells or precursor cells take on

their final specialized state

2 Types of Differentiation• Chemical differentiation:

hormones and other chemical signals activate master regulatory genes—genes that produce a protein that then turns on neuron-specific proteins—what are some examples of neuron-specific proteins?

• Morphological differentiation: cell taking on its adult form—dendrites & axons begin to form—continues into childhood

2 Types of Differentiation• Chemical differentiation:

hormones and other chemical signals activate master regulatory genes—genes that produce a protein that then turns on neuron-specific proteins—voltage-gated ion channels, neurotransmitter receptors, neurotransmitter synthesis enzymes, etc.—done by birth

• Morphological differentiation: cell taking on its adult form—dendrites & axons begin to form—continues into childhood

2 Main Processes of Morphological Differentiation:

• Grow dendrites

• Extend axons

Growing Dendrites

Increase in the length and branching of dendrites

•Larger, more complex dendrites increases the surface area for synapse formation

Extending Axons•May need to extend millimeters

•Requires 2 cues:

1)Secretion of chemoattractants from the target cell that guide the axon to them

2)Cell adhesion molecules that then grasp the axon and adhere it to the target cell

Synaptogenesis:

The formation of a functional synapse between an axon from a presynaptic

neuron and the dendrites of a postsynaptic neuron

Synaptogenesis• Starts during prenatal development

and continues into late childhood

• Creation of proper synaptic structure by cellular activities in both neurons:1)Pre-synaptic neuron needs to synthesize and store neurotransmitter vesicles

2)Post-synaptic neuron needs to form and insert neurotransmitter

receptors into membrane

• Number of synapses in the human brain exceeds 100 quadrillion

Cell Death and Synaptic Pruning

Key Point:

More neurons, and more synapses, are formed during development than

are actually needed

Neuronal Cell Death & Neurotrophins

• Neurotrophins—special hormone-like chemicals secreted by postysnaptic neurons in response to electrical activation by presynaptic neurons

• Neurotrophins are NOT neurotransmitters but instead promote neuronal growth & survival of presynaptic neurons and maintenance of their synapses

Neurotophins & Neuronal Cell Death

• Post-synaptic cells secrete neurotrophins

• Neurotrophins promote the survival of neurons

• Neurons with a stronger connection get more neurotrophic support; those with weaker connections don’t and eventually die

• This “sculpts” away neurons with weaker connections, leaving only ones with strong, functional connections

(1)Strong SynapticConnection

(1) Weak SynapticConnection

Target cell

(2)StrongNeurotrophin Support

(2)WeakNeurotrophin Support

(3) Continued Survival (3) Cell Death

Target cell

Neurotrophins & Synaptic Pruning

Target cell (2)StrongNeurotrophin Support

(3) SynapseMaintenance

Target cell (2) WeakNeurotrophin Support

(3) SynapseElimination

Myelination:

The formation of myelin sheaths around neurons

Myelination

•Myelination begins just after birth and continues into young adulthood (mid 20’s)

•Does not progress evenly throughout the brain—which brain regions do you think myelinate first? Which myelinate last?

•Myelination allows neurons to fire more rapidly so greatly improves neural communication

•Defects in myelination lead to leukodystrophies

Myelination

•Myelination begins just after birth and continues into young adulthood (mid 20’s)

•Does not progress evenly throughout the brain--regions controlling basic sensory analysis and simple movement myelinate first, regions involved with decision-making and impulse control like the prefrontal cortex myelinate last

•Myelination allows neurons to fire more rapidly so greatly improves neural communication

•Defects in myelination lead to leukodystrophies

Correlating Behavior with Nervous System Development

Motor Behaviors, Language Development, and Problem Solving

Grasping Motor Behaviors• ~2 months—hand orients

toward object and gropes to hold it

• ~4 months—grasps with entire hand

• ~6-8 months—”mature” grasp using fingers individually

• ~10 months—fine pincer grasp for holding small objects

Neural Changes and Grasping Motor Behaviors

• Increased dendritic maturation in motor cortex neurons

• Increased myelination of motor cortex neurons at both later stages of grasp development

• Decreases in cortical thickness in the hand region of the motor cortex—may reflect pruning of less effective motor neurons and synapses and selection of the strongest connections

Language Development• 12 months—vocabulary

starts to form, 5-10 words

• 24 months—200-300 words

• 36 months—500-1000 words, now using them in sentences

• 72 months—2500 words

Language acquisition depends on childhood environment

Major Neural Changes and Language Development

1) Increased cortical thickness in speech areas of cortex for the language the child is hearing and speaking—may represent

1) increase in glial cells & myelination

2) Increased dendritic branching and synaptogenesis

2) Pruning of neurons and

synapses in speech areas of other languages the child is not hearing or speaking—children who are raised bilingual will keep around more speech sound synapses

Loss of speech sound synapses duringdevelopment makes it harder butnot impossible to learn new languagesIn adulthood—it will just require theformation of new synapses, which is obviously more difficult than keeping or strengthening existing ones

Problem Solving—Piagetian Stages of Development

• Sensorimotor stage—birth-2 years old: object permanence, cause-and-effect

• Preoperational stage-2-6 years old: form mental, word, and drawing representations of things

• Concrete operations-7 to 11 years old: mentally manipulate dimensions, mathematics, conservation of mass

• Formal operations—abstract reasoning

Neural Changes & Piagetian Stages

• Spurts of brain growth accompany or precede the changes in Piagetian development

• Neuronal number doesn’t change but glial cell number, myelination, and dendritic branching and synaptic density all increase in the cerebral cortex

Brain Development & the Postnatal Environment

Cerebral cortex

Hippocampus

Enriched Environments & Neural Development in Animals

• Rats raised in an enriched environment perform better on cognitive tasks like solving mazes than rats raised in standard cages

• The brains of these animals had thicker cerebral cortex and larger structures involved in memory and emotion regulation like the hippocampus

Enriched Environments & Neural Development in Humans

• Children in poor environments show severe cognitive, language, social, and motor defects

• Conversely, children who are bilingual or who learn to play music early in life have better emotional and impulse control, decision-making, and academic performance

• The brains of these children also show enlargements of the cerebral cortex and hippocampus compared to children who are not bilingual and don’t play an instrument

Environmental enrichment may reflect the influence of our experiences on the formation and/or pruning of synapses

Neural Changes to Enriched Environments

• Increased dendritic branching in neurons in the cortex

• Increased dendritic branching in neurons of the hippocampus

• Postnatal Neurogenesis—new neuron formation in the hippocampus only—is also increased in rats raised in an enriched environment and in humans too!

Exercise also increases postnatal hippocampal neurogenesis

• Rats given a cage wheel to run on had equal or greater neuronal proliferation as rats raised in an enriched environment

• This may explain some of the well-established cognitive benefits of regular exercise

What are Some Other Factors Negatively Influencing Postnatal Hippocampal

Neurogenesis?

Developmental Disorder:

Autism Spectrum Disorder

What are Some Symptoms of Autism Spectrum Disorder?

Autism now affects 1 in 68 male live births in the U.S.

Key Neural Changes in Autism—Under-Connectivity Hypothesis

•Undergrowth/under-connectivity: some brain regions are smaller or less well connected in autistic brains:

1) the hippocampus & amygdala—emotion processing 2) the insular cortex—social processing 3) some brainstem nuclei—hearing and facial expressions

Undergrowth may reflect defective proliferation of neurons, defects in dendritic branching and synapse formation, or excessive pruning

Non-autistic brain

Autistic brain

Key Neural Changes in Autism—the Over-Connectivity Hypothesis

•Overgrowth/over-connectivity: some brain regions are larger or overly connected in autistic brains:

1) basal ganglia &motor cortex —repetitive movements 2) sensory cortex—fixation with certain sensory stimuli 3) prefrontal cortex—immersion in own thoughts

Overgrowth may reflect excessive neuron or synapse formation and/or defective pruning of cells or synapses

How do any of us develop a normal brain?