Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Neuroscience: Exploring the...

Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Neuroscience: Exploring the Brain, 3e

Chapter 23: Wiring the Brain


IntroductionIntroduction

• Operation of the brain

– Precise interconnections among 100 billion neurons

• Brain development

– Begins as a tube

– Neurogenesis, synaptogenesis, pathway formation, connections formed and modified

• Wiring in brain

– Establishing correct pathways and targets

– Fine tuning based on experience


The Genesis of NeuronsThe Genesis of Neurons• Example: Mammalian retinogeniculocortical pathway


Activity-dependent SynapticRearrangementActivity-dependent SynapticRearrangement

• Synaptic rearrangement

– Change from one pattern to another

– Consequence of neural activity/synaptic transmission before and after birth

– Critical Period


The Elimination of Cells and SynapsesThe Elimination of Cells and Synapses• Changes in Synaptic Capacity

– Synapse elimination modeled in the neuromuscular junction


The Lateral Geniculate Nucleus (LGN)

The Lateral Geniculate Nucleus (LGN)



• Synaptic segregation

– Refinement of synaptic connections

• Segregation of Retinal Inputs to the LGN

• Retinal waves (in utero) (Carla Shatz)

• Activity of the two eyes not correlated -> segregation in LGN

• Process of synaptic stabilization

• Hebbian modifications (Donald Hebb)



• Segregation of Retinal Inputs to the LGN (Cont’d)

– Plasticity at

‘Hebb’ synapses

– “Winner-takes-

all”



• Segregation of LGN Inputs in the Striate Cortex

– Visual cortex has ocular dominance columns (cat, monkey) - segregated input from each eye

– Synaptic rearrangement is activity-dependent

– Plastic during critical period

– Effects of congenital cataracts (if not removed early)



• Synaptic Convergence

– Anatomical basis of binocular vision and binocular receptive fields

– Monocular deprivation:

• Ocular dominance shift

• Plasticity of binocular connections

• Synaptic competition



• Critical period for plasticity of binocular connections


Activity-dependent SynapticRearrangementActivity-dependent SynapticRearrangement• Effect of strabismus on cortical binocularity



• Modulatory Influences

– Increasing age

– Before and after birth

– Enabling factors


Elementary Mechanisms of CorticalSynaptic PlasticityElementary Mechanisms of CorticalSynaptic Plasticity

• Two rules for synaptic modification

– Wire together fire together (Hebbian modifications)

– Out of sync lose their link

– Correlation: heard and validated


Elementary Mechanisms of CorticalSynaptic PlasticityElementary Mechanisms of CorticalSynaptic Plasticity• Excitatory Synaptic Transmission in the Immature Visual System

– Focus on 2 glutamate receptors (Rs):

• AMPARs: glutamate-gated ion channels

• NMDARs: Unique properties


Elementary Mechanisms of Cortical Synaptic PlasticityElementary Mechanisms of Cortical Synaptic Plasticity

• Excitatory Synaptic Transmission

– NMDA receptors have two unique properties

• Voltage-gated owing to Mg2+

• Conducts Ca2+

• Magnitude of Ca2+ flux signals level of pre- and postsynaptic activation



• Long-Term Synaptic Potentiation

– Monitor synaptic strength before and after episodes of strong NMDA activation

– Accounting for LTP

• AMPA insertion (“AMPAfication”)

• Splitting synapses (doubling)


Elementary Mechanisms of CorticalSynaptic PlasticityElementary Mechanisms of CorticalSynaptic Plasticity• Lasting synaptic effects of strong NMDA receptor activation



• Long-Term Synaptic Depression (LTD)

– Neurons fire out of sync

– Synaptic plasticity mechanism opposite of LTP

• Loss of synaptic AMPARs

• Loss of synapses? (unknown)

– Mechanism for consequences of monocular deprivation


Elementary Mechanisms of CorticalSynaptic PlasticityElementary Mechanisms of CorticalSynaptic Plasticity• Brief monocular deprivation leads to reduced visual

responsiveness

– Depends on retinal activity, NMDA activation, postsynaptic calcium


Why Critical Periods EndWhy Critical Periods End

• Why do critical periods end?

– Plasticity diminishes:

• When axon growth ceases

• When synaptic transmission matures

• When cortical activation is constrained

– Intrinsic inhibitory circuitry late to mature

– Understanding developmental regulation of plasticity may help recovery from CNS damage


Enriched environment: More complex brain structure.Enriched environment: More complex brain structure.

•Increased dendritic branching and synaptic density

•Increased transmitter levels, total protein

•Better at solving maze problems


Concluding Remarks

• Generation of brain development circuitry

– Placement of wires before birth

– Refinement of synaptic infancy

• Developmental critical periods

– Visual system and other sensory and motor systems

• Environment influences brain modification throughout life


End of Presentation


The Genesis of NeuronsThe Genesis of Neurons

• Cell Proliferation

– Neural stem cells give rise to neurons and glia


The Genesis of NeuronsThe Genesis of Neurons• Cell Proliferation (Cont’d)

– Cleavage plane during cell division determines fate of daughter cells



• Cell Migration

– Pyramidal cells and astrocytes migrate vertically from ventricular zone by moving along thin radial glial fibers

– Inhibitory interneurons and oligodendroglia generate from a different site and migrate laterally



• Cell Migration

– First cells to migrate take up residence in “subplate” layer which eventually disappears

– Next cells to divide migrate to the cortical plate

– The first to arrive become layer VI, followed V, IV, and so on: “inside out”



• Cell Differentiation

– Cell takes the appearance and characteristics of a neuron after reaching its destination but programming occurs much earlier



• Differentiation of Cortical Areas

– Adult cortical sheet is a “patchwork quilt

– Cortical “protomap” in the ventricular zone replicated by radial glial guides

– But some neurons migrate laterally

– Thalamic input contributes to cortical differentiation


The Genesis of ConnectionsThe Genesis of Connections• The three phases of pathway formation:

– (1) pathway, (2) target, (3) address


The Genesis of ConnectionsThe Genesis of Connections• The Growing Axon

– Growth cone: Growing tip of a neurite


The Genesis of ConnectionsThe Genesis of Connections

• Axon Guidance

– Challenge in wiring the brain

• Distances between connected structures

• But in early stages nervous system is a few centimeters long

– Pioneer axons stretch as nervous system expands

• Guide neighbor axons to same targets

– Pioneer neurons grow in the correct direction by “connecting the dots”



• Axon Guidance

– Guidance Cues: Chemoattractant (e.g., netrin), Chemorepellent (e.g., slit)



• Axon Guidance

– Establishing Topographic Maps

• Choice point; Retinal axons innervate targets of LGN and superior colliculus

• Sperry (1940s): Chemoaffinity hypothesis

• CNS axons regenerate in amphibians, not in mammals

• Factors guiding retinal axons to tectum

• Ephrins/eph (repulsive signal)



• Axon Guidance

– Establishing Topographic Maps



• Synapse Formation

– Modeled in the neuromuscular junction



• Synapse Formation

– Steps in the formation of a CNS synapse:

– Dendritic filopodium contacts axon

– Synaptic vesicles and active zone proteins recruited to presynaptic membrane

– Receptors accumulate on postsynaptic membrane


The Elimination of Cells and SynapsesThe Elimination of Cells and Synapses

• The mechanisms of pathway formation– Large-scale reduction in neurons

and synapses

• Development of brain function

– Balance between genesis & elimination of cells and synapses

• Apoptosis: Programmed Cell Death

– Importance of trophic factors, e.g., nerve growth factor

Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Neuroscience: Exploring the...

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