1. Neuroscience: Exploring the Brain, 3e
Chapter 23: Wiring the Brain

2. Introduction 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

3. The Genesis of Neurons
Example: Mammalian retinogeniculocortical pathway

4. Activity-dependent Synaptic Rearrangement
Change from one pattern to another
Consequence of neural activity/synaptic transmission before and after birth
Critical Period

5. The Elimination of Cells and Synapses
Changes in Synaptic Capacity
Synapse elimination modeled in the neuromuscular junction

6. The Lateral Geniculate Nucleus (LGN)

7. Activity-dependent Synaptic Rearrangement
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)

8. Activity-dependent Synaptic Rearrangement
Segregation of Retinal Inputs to the LGN (Cont’d)
Plasticity at
‘Hebb’ synapses
“Winner-takes-
all”

9. Activity-dependent Synaptic Rearrangement
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)

10. Activity-dependent Synaptic Rearrangement
Synaptic Convergence
Anatomical basis of binocular vision and binocular receptive fields
Monocular deprivation:
Ocular dominance shift
Plasticity of binocular connections
Synaptic competition

13. Activity-dependent Synaptic Rearrangement
Critical period for plasticity of binocular connections

14. Activity-dependent Synaptic Rearrangement
Effect of strabismus on cortical binocularity

15. Activity-dependent Synaptic Rearrangement
Modulatory Influences
Increasing age
Before and after birth
Enabling factors
Basal forebrain & LC must be intact for plasticity

16. Elementary Mechanisms of Cortical Synaptic Plasticity
Two rules for synaptic modification
Wire together fire together (Hebbian modifications)
Out of sync lose their link
Correlation: heard and validated

17. Elementary Mechanisms of Cortical Synaptic Plasticity
Excitatory Synaptic Transmission in the Immature Visual System
Focus on 2 glutamate receptors (Rs):
AMPARs: glutamate-gated ion channels
NMDARs: Unique properties

18. Elementary 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

19. Elementary Mechanisms of Cortical Synaptic Plasticity
Long-Term Synaptic Potentiation
Monitor synaptic strength before and after episodes of strong NMDA activation
Accounting for LTP
AMPA insertion (“AMPAfication”)
Splitting synapses (doubling)

20. Elementary Mechanisms of Cortical Synaptic Plasticity
Lasting synaptic effects of strong NMDA receptor activation

21. Elementary Mechanisms of Cortical Synaptic Plasticity
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

22. Elementary Mechanisms of Cortical Synaptic Plasticity
Brief monocular deprivation leads to reduced visual responsiveness
Depends on retinal activity, NMDA activation, postsynaptic calcium

23. Why 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

24. Enriched environment: More complex brain structure.
Increased dendritic branching and synaptic density
Increased transmitter levels, total protein
Better at solving maze problems

25. 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

26. Barn Owl : Space Map in Inf. Colliculus
This is a computational map!

27. ‘Supervised’ learning / plasticity
Prism goggles experiment: ‘eye instructs the ear’ A V
After 8 weeks w/ Prism goggles A V

28. End of Presentation

29. The Genesis of Neurons Cell Proliferation
Neural stem cells give rise to neurons and glia

30. The Genesis of Neurons Cell Proliferation (Cont’d)
Cleavage plane during cell division determines fate of daughter cells

31. The Genesis of Neurons 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

32. The Genesis of Neurons 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”

33. The Genesis of Neurons Cell Differentiation
Cell takes the appearance and characteristics of a neuron after reaching its destination but programming occurs much earlier

34. The Genesis of Neurons 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

35. The Genesis of Connections
The three phases of pathway formation:
(1) pathway, (2) target, (3) address

36. The Genesis of Connections
The Growing Axon
Growth cone: Growing tip of a neurite

37. The 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”

38. The Genesis of Connections
Axon Guidance
Guidance Cues: Chemoattractant (e.g., netrin), Chemorepellent (e.g., slit)

39. The Genesis of Connections
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)

40. The Genesis of Connections
Axon Guidance
Establishing Topographic Maps

41. The Genesis of Connections
Synapse Formation
Modeled in the neuromuscular junction

42. The Genesis of Connections
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

43. The 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