Deflection of one eye strongly suppresses binocular innervation
*timing of activation must be critical to maintain connectivity
Strabismus also changes intrinsic local cortical projections
Retrograde dye labeling: in strabismic cortex, local
projections to other layers are confined to monocular
columns
Uncorrelated inputs segregate
• Synchronous stimulation of optic nerves
blurs segregation
• Asynchronous stimulation of optic
nerves sharpens segregation
In development of the visual pathway, synaptic refinement occurs
first in the LGN, then in the cortex (IV)
Before light input, RGCs begin firing in waves across retina
Spontaneous waves of RGC activity are lost by P15
Only blockade of neuronal activity ablates formation of columns
Synapses are strengthened by synchronous firing on shared target
Glu & depolarization activates NMDAR & CaMKII
CamKII
NMDAR-mediated Ca2+ signaling increases CaMKII, PKC, &
Fyn to create early-phase long-term potentiation
NMDA receptors mediate synaptic plasticity (the 3-eyed frog expt)
Blocking NMDA receptors defocuses input to barrel cortex
CO staining sites in microlesions from stimulated electrode
Loss of plasticity in the adult visual system
Critical period in visual system: when synapses can adapt to
change
The older you are, the less adaptable your visual cortex is
Mechanisms of critical period
closure
• Developmental changes in NMDA function
• Developmental changes in inhibition
• Developmental changes in extracellular matrix
components (perineural nets)
• Developmental changes in trophic factor release or
uptake
• Developmental changes in spine motility
NMDA receptor structure
NR2A
NR1
A
NR2 B
2A:2B: • Shortens duration of NMDAR currents
• Alters protein complexes within PSD
NR2B
B
NR2 A
Mechanisms of critical period
closure
• Developmental changes in NMDA function
• Developmental changes in inhibition
• Developmental changes in extracelluar matrix
components (perineural nets)
• Developmental changes in trophic factor release or
uptake
• Developmental changes in spine motility
Mechanisms of critical period
closure
• Developmental changes in NMDA function
• Developmental changes in inhibition
• Developmental changes in extracelluar matrix
components (perineural nets)
• Developmental changes in trophic factor release or
uptake
• Developmental changes in spine motility
Perineuronal nets: proteoglycans inhibitory to synaptic plasticity
Perineuronal nets in visual cortex
http://www.in.pi.cnr.it/Pizzorusso/Pizzorusso.htm
Crtl1
PNN
PNNs are regulated during development and by early visual
experience
Crtl1-/- : expanded critical period (plasticity) & attenuated PNNs
Repeated broadband stimulus in young rodents inhibits
synaptic refinement
Clicks cause many auditory nerves to fire simultaneously
IC neurons less selective in response to various sound levels
 at which neurons respond
Broadened frequency curves remain throughout development
Limited visual experience leads to limited neuronal responses