1. Chapter 23: Wiring the Brain
Neuroscience: Exploring the Brain, 4e
Chapter 23: Wiring the Brain

2. Introduction Operation of the brain
Precise interconnections among 85 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. Mammalian Retinogeniculocortical Pathway

4. The Genesis of Neurons Cell proliferation
Radial glial cells give rise to neurons and astrocytes.

5. Cell Proliferation
Transcription factors and cleavage plane during cell division determine fate of daughter cells.

6. 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.

7. Cell Migration—(cont.)
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.”

8. Cell Differentiation
Cell takes the appearance and characteristics of a neuron after reaching its destination, but programming occurs much earlier.

9. Differentiation of Cortical Areas
Adult cortical sheet like a “patchwork quilt”
Cortical protomap in the ventricular zone replicated by radial glial guides
Radial unit hypothesis
Some neurons migrate laterally.
Thalamic input contributes to cortical differentiation.

10. Differentiation of Cortical Areas—(cont.)
Differentiation of monkey striate cortex requires LGN input during fetal development.

11. The Three Phases of Pathway Formation
(1) Pathway selection, (2) target selection, (3) address selection

12. The Growing Axon
Growth cone: growing tip of a neurite

13. Axon Guidance Challenge in wiring the brain
Distances between connected structures
In early stages, nervous system is only 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.”

14. Axon Guidance—(cont.)
Growth guidance cues: chemoattractant (e.g., netrin), chemorepellent (e.g., slit)

15. Establishing Topographic Maps
“Choice point” at optic chiasm: to innervate targets such as LGN and superior colliculus
Sperry (1940s): chemoaffinity hypothesis
CNS axons regenerate in amphibians (useful for study), not in mammals.
Factors guiding retinal axons to tectum
Ephrins/eph (repulsive signal)

16. Establishing Retinotopy in Frog Retinotectal Projection

17. Steps in Formation of Neuromuscular Synapse

18. Steps in Formation of CNS Synapse
(1) Dendritic filopodium contacts axon
(2) Synaptic vesicles and active zone proteins recruited to presynaptic membrane
(3) Receptors accumulate on postsynaptic membrane

19. The Elimination of Cells and Synapses
Large-scale reduction in neurons
and synapses
Development of brain function
Balance between genesis and elimination of cells and synapses
Apoptosis: programmed cell death
Importance of trophic factors, for example, nerve growth factor

20. Changes in Synaptic Capacity
Synapse elimination in the neuromuscular junction

21. Activity-Dependent Synaptic Rearrangement
Change from one pattern to another
Consequence of neural activity and synaptic transmission before and after birth
Critical period

22. Synaptic Segregation Final 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)

23. Segregation of Retinal Inputs to the LGN
Plasticity at Hebb synapses
“Winner-takes- all”

24. Segregation of LGN Inputs in the Striate Cortex
Visual cortex has ocular dominance columns (cat, monkey)—segregated input from each eye
Synaptic rearrangement
Activity-dependent
Experience-dependent
Plasticity during critical period

25. Synaptic Convergence
Anatomical basis of binocular vision and binocular receptive fields
Monocular deprivation experiments
Ocular dominance shift
Plasticity of binocular connections
Synaptic competition

26. Ocular Dominance Shift

27. Critical Period for Plasticity of Binocular Connections

28. Effects of Strabismus on Cortical Binocularity

29. Modulatory Influences on Cortical Circuits
Retinal activity before birth
Visual environment after birth
Enabling factors

30. Elementary Mechanisms of Cortical Synaptic Plasticity
Two rules for synaptic modification
Fire together, wire together (Hebbian modifications)
Fire out of sync, lose their link
A single synapse has little influence on firing rate of postsynaptic neuron.
Activity of a synapse must be correlated with activity of many other inputs converging on the same postsynaptic neuron.

31. Excitatory Synaptic Transmission in the Immature Visual System
Focus on two glutamate receptors
AMPA receptors: glutamate-gated ion channels
NMDA receptors: unique properties

32. Excitatory Synaptic Transmission
NMDA receptors have two unique properties.
Voltage-gated owing to action of Mg2+
Conducts Ca2+
Magnitude of Ca2+ flux signals level of pre- and postsynaptic coactivation.

33. Long-Term Synaptic Potentiation (LTP)
Hypothesis
NMDA receptors serve as Hebbian detectors of simultaneous presynaptic and postsynaptic activity.
Ca2+ entry through the NMDA receptor channel triggers the biochemical mechanisms that modify synaptic effectiveness.
Testing: Monitor synaptic strength before and after episodes of strong NMDA activation.
Strong NMDA receptor activation  strengthening of synaptic transmission (LTP)

34. Lasting Synaptic Effects of Strong NMDA Receptor Activation

35. Long-Term Synaptic Depression (LTD)
Neurons fire out of sync.
Synaptic plasticity mechanism opposite of LTP
Loss of synaptic AMPA receptors
Loss of synapses?
Mechanism for consequences of monocular deprivation
With fewer AMPA receptors, synapses lose influence over responses of cortical neurons.

36. Brief Monocular Deprivation Leads to Reduced Visual Responsiveness

37. Why Critical Periods End
Three hypotheses why 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.

38. Concluding Remarks Generation of brain development circuitry
Placement of wires before birth
Refinement of synaptic connections in infancy
Developmental critical periods
Visual system and other sensory and motor systems
Environment influences brain modification throughout life.