the fundamentals of brain development: integrating nature

The Fundamentals of Brain Development:Integrating Nature and Nurture

Prof. Joan Stiles

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The Fundamentals of Brain Development:

Integrating Nature and Nurture

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Prof. Joan StilesDepartment of Cognitive Science

University of California, San Diego

Why should developmental psychologists care about brain development?

• Alignment of our models of brain and behavioral development is essential

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Cognitive development

• How do children come to know about the world?

• What are the origins of knowledge?

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Prof. Joan Stiles


• Some concepts emerge without experience They are innate

Nativism (nature)

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Constructivism (nurture)

• All concepts are learned

• Capacity to learn is innate

Biological feasibility

Neither side has adequately addressed the question

• How does a biological system support an innate idea?

• What is an innate learning mechanism?

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• Neither side has adequately addressed the question of biological feasibility

• Each side makes assumptions about biology that are under-specified

What is inherited?

• Genes: the nucleotide sequences of DNA

• The Cell: the first environment

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Prof. Joan Stiles


• The essential biological code

• The cellular machinery for generating proteins

Biological inheritance includes:

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• Proteins provide intrinsic signals that influence the development of cells and biological systems

• Both organism intrinsic and extrinsic cues influence the production of proteins

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It is the orchestrated and constrained interaction of intrinsic and extrinsic factors

that defines and drives biological development

It is a mistake to construe:

• Intrinsic factors as “deterministic”

• Extrinsic factors as “modulatory”

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Regardless of their type or source, multiple signaling cues interact in a dynamic way to shape the course

of development


Prof. Joan Stiles


• 100 billion neurons

• At least 60 trillion synapses

• How does this complex system develop?

• With each step, th i ti

10Cowan, W.M. (1979) The development of the brain; Scientific American, 241(3), 113-133

the organization of the neocortex becomes more highly specified

• Intrinsic and extrinsic signaling cues

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Prof. Joan Stiles


Brain development as a dynamic system:the role of intrinsic and extrinsic signaling

Intrinsic signaling

• Specifying the neural progenitor cells and the basic spatial organization of the embryo

• Initial specification of the primary sensorimotor

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Initial specification of the primary sensorimotor areas of the neocortex

Extrinsic signaling

• Input and visual system organization

• Respecifying the function of a cortical sensory area

• Reorganization in the adult neocortex

Differentiation of neural progenitor cells (E13-20)

• Neural progenitor cells differentiate from cells of the upper layer

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• E13: the embryo is a 2-layered structure

Adapted from Stiles, J. (2008) Fundamentals of Brain Development: Integrating Nature and Nurture; Cambridge: Harvard University Press; Figure 3.2

Embryo: Dorsal View (E13)

Differentiation of neural progenitor cells (E13-20) (2)

RostralCaudal Dorsal

Ventral

Rostral (head)

Rostral (head) Cut edge of amnion

Connecting stalk

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Ventral

Ventral

DorsalRostral

Caudal

Caudal (tail)

Adapted from Stiles, J. (2008) Fundamentals of Brain Development: Integrating Nature and Nurture; Cambridge: Harvard University Press Figure 1.1, 4.6


Prof. Joan Stiles


Primitive node

Differentiation of neural stem cells (E13-20)

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Primitivestreak

Once below the upper layer, they migrate

toward the rostral end (head) of the embryo

Adapted from Stiles, J. (2008) Fundamentals of Brain Development: Integrating Nature and Nurture; Cambridge: Harvard University Press; Figure 1.1

They pass the Primitive Node as they migrate down and under the upper layer to form a new middle layer

Host

17Adapted from Stiles, J. (2008) Fundamentals of Brain Development: Integrating Nature and Nurture; Cambridge: Harvard University Press; Figure 3.4


Intrinsic signaling• Specifying the neural progenitor cells and the basic

spatial organization of the embryo


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Extrinsic signaling • Input and visual system organization




Prof. Joan Stiles


Early specification of cortical areas

• Cells in different brain regions express different proteins

• Proteins can be expressed

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Proteins can be expressed in concentration gradients

• Combinations of proteins in varying concentrations signal differentiation of different types of neurons

+Normal(Wild type):

Specific gene mutations alter expression gradients and change the functional

organization of cortex

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Pax6Mutation: + X

+Emx2Mutation: X

Bishop, Goudreau, O’Leary (2000) Science, 288, 344-349

Graded expression of transcription factors

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Loss of function

O’Leary, Chou, Sahara (2007) Neuron, 56, 252-269


Prof. Joan Stiles


22O’Leary, Chou, Sahara (2007) Neuron, 56, 252-269





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What happens to the brain when one eye is deprived of input?

Normal visual experience

24Hubel, Wiesel, LeVay (1977) Philosophical Transactions of Royal Society of London, ser. B, Biological Sciences, 278, 377-409

Monoculardeprivation


Prof. Joan Stiles



Intrinsic signaling

• Specifying the neural progenitor cells and the basic spatial organization of the embryo


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• Initial specification of the primary sensorimotor areas of the neocortex

Extrinsic signaling

• Input and visual system organization



• PVC surgically removed

• Pathway from cochlea to PAC severed

O t

X

Surgical rewiring:

26Sur, Angelucci & Sharma (1999) Neurobiology

Outcome:

• Retina connects with primary auditory cortex (PAC)

• PAC neurons respond to visual input • Visual input to what

would have normallybecome auditory area





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• Initial specification of the primary sensorimotor areas of the neocortex





Prof. Joan Stiles


L H

Pre-treatment tonotopic map of A1

Experience inducedreorganization

in the adult neocortex

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Post-treatment tonotopic map of A1

L MDorsal view of macaque brain with frontal and parietal regions of cortex removed to expose primary auditory cortex (A1)

Schwaber, Garraghty, Kass (1993) Am. J. Otol., 14, 252-8

Brain development is influenced by both:

• Intrinsic factors: molecular cues (proteins) derived from gene expression

• Extrinsic factors: input from sources outside the organism

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• Extrinsic factors: input from sources outside the organism

Neither determines outcome

Intrinsic and Extrinsic factors interact in complex signaling d th t d li d t d l t

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cascades that underlie and support development


Prof. Joan Stiles


How can such a dynamic model of brain development succeed?

• Inherited constraints

E i t l t i t

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• Environmental constraints

• Temporal constraints

• Progressive Differentiation– Increasing complexity of the organism over time

– Specific signaling establishes sub-populations of neuro-progenitors along the emerging neuro-axis of the embryo

• Progressive Commitment

Development is temporally constrained

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• Progressive Commitment– Gradual stabilization of systems and networks

– Declining plasticity– This kind of waning plasticity is also observed much later in development

• Changing sensitivity to developmental signals– Level of development dictates the kinds of signals an organism

can respond to

At any moment in developmental time, the organism has both a history and a state:

• History is the sum of all the events that have contributed to the current state of the organism

• State represented both the current structural

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and functional capacity, as well as the potential for further change

Sensitivity to a specific intrinsic or extrinsic influence depends current developmental state of the organism


Prof. Joan Stiles


• Each step in the developmental process builds upon previous steps

• The developing organism often creates as it goes the tools necessary for each successive step

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in the development

• Development is a self-organizing process

Brain development and the nature-nurture debate

• Everything that develops has an innate aspect

• It must, because all developmental processes rely on: – The information encoded in the genes

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g

– The cellular mechanisms that provide access to that information

• But, genes do not participate directly in developmental processes

• Gene products (proteins) are the active agents in development

• But proteins do not create neural structures or functions

Brain development and the nature-nurture debate (2)

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They participate in complex signaling cascades that over time influence the fate of cells, the organization of systems, and the establishment of functional pathways

But proteins do not create neural structures or functions


Prof. Joan Stiles


Thus, at no point in brain development can the effects of inherited and experiential

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can the effects of inherited and experiential factors be separated

Attempts to categorize neurodevelopmental events as the product of nature or nurture

cannot succeed because:

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The fundamental processes of brain development at every level require the continuousinteraction of nature and nurture

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Prof. Joan Stiles


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the fundamentals of brain development: integrating nature

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