plasticity 2012
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Plasticity How are synapse number & strength adjusted?
anatomical evidence
electrophysiological evidence
Elimination of synapses during development
Visual deprivation
The role of spontaneous activity
Sensory experience: activity influences synaptic connections
Activity-dependent synaptic depression
Calcium and NMDA receptors
Mechanisms of synaptic plasticity
Keller-Peck et al., 2001!
P7! P8! P9!
Elimination of motor neuron contact in vivo
motor axons (green) endplate (red)
Functional synapse elimination
Synapse elimination in visual cortex
LeVay et al., 1978; Crair et al., 2001!
P21
P14
P8
P92
P39
P22
Hubel and Wiesel, 1962!
The geniculocortical pathway
Control
Monocular deprivation
Wiesel and Hubel, 1963!
NR
NR
Wiesel and Hubel, 1965!
Binocular deprivation
Hubel and Wiesel, 1965!
Strabismus
Ocular Dominance
LeVay et al., 1980!
Critical periods Layer 4 Stripes
Age of Monocular Deprivation (mos)
Stryker and Harris, 1986!
Spontaneous activity & synapse elimination Dark rear Action potential blockade
Meister et al., 1991; Demas et al., 2003!
Spontaneous activity in the retina
Tritsch et al., 2007!
Spontaneous activity in the cochlea
isolated cochlea
Garaschuk et al., 2000!
Spontaneous activity in the cortex
Adelsberger et al., 2005!
Spontaneous activity in the cortex
Sretavan and Shatz, 1986: Stellwagen et al., 2002!
Increase spontaneous activity in one eye
contra projection ipsi projection More active projection expands
Spontaneous activity & synapse elimination
Forskolin!
larger
contra ipsi
Control!
cAMP!
Stryker et al., 1978; Pasternak et al., 1985!
Influence of environment on coding properties
Li et al., 2006, 2008!
Influence of environment on coding properties
Rapid induction of direction selectivity
Li et al., 2008!
Imaging the intrinsic signal of visual cortex in response to moving bars
Visually inexperienced ferrets
stimulus direction
exposure time (hours)
responds to rightward moving bar
Auditory system plasticity
24 hours stimulation !
T1-weighted brain images!Sound Stimulation!
16 kHz (4 Hz AM)! 40 kHz (4 Hz AM)!
0.4 mmol/kg!
MnCl2 injection!
Brain imaging with Mn-enhanced MRI
Yu et al., 2007
7-Tesla horizontal magnet! 100 µm resolution!
pre-IP injection 24 h post-injection
Rearing: 16 + 40 KHz (75 dB SPL; AM; 20-23 hr/day)
dB SPL
kHz
Two-tone rearing protocol
16 32 64 0 0
80
40
P19
16 kHz
or
40 kHz
Stim Mn
Quiet
P18
pre-injection 24h post-injection
P9 P20
Image
7-Tesla horizontal magnet! 100 µm resolution!
Influence of environment on tonotopic map
Rear with!16+40 kHz tones!Control!
Yu et al., 2007
Rear with 7.1 kHz tone
?
Han et al., 2007
7.1 kHz Control
28
14
7.0
3.5
1.8
Cha
ract
eris
tic fr
eqen
cy (k
Hz)
Rear with 7.1 kHz tone!
Influence of environment on tonotopic map!
Influence of environment on auditory behavior
Han et al., 2007!
Rear with 7.1 kHz tone!
100!
0!
Discrimination Performance at ∆0.1 octave!
(%)!
5.0! 5.9! 7.1! 8.4! 10! 11.9!14.1!16.8!20!Frequency (kHz)!
Control!
7.1k-reared!
*!
*!
*!80!
60!
40!
20!
Synaptic mechanisms of plasticity
Lo and Poo, 1992
Heterosynaptic depression in vitro
Synaptic depression & synapse elimination
Li et al., 2001
presynaptic terminal
Synaptic depression & elimination
postsynaptic ACh receptors
Yang et al., 2001
Synaptic depression & elimination
LTD correlated with elimination in hippocampus
Label pre and postsynaptic cells
pre
post
Stimulate presynaptic to induce LTD
pre
post yellow is area of colocalization
Bastrikova et al., 2008!
Bastrikova et al., 2008!
LTD (% of initial baseline)
Col
ocal
izat
ion
(% o
f bas
elin
e)
More LTD is correlated with less colocalization
LTD correlated with elimination in hippocampus
Synaptic depression depends on Ca+2
Cash et al., 1996!
Activator of postsynaptic CaMKII decreases retinal axon arbor
Zhou and Cline, 1996!
Control axons!
Active CaMKII!
NMDA receptors & excitatory synaptic plasticity
Three-eyed frogs have stripes in tectum
Constantine-Paton and Law, 1978!
Cline et al., 1987; Cline and Constantine-Paton, 1990!
Segregation of retinal axons & NMDA receptors
Review: Hensch, 2005!
Critical period for MD in mice
(a lot of) molecular mechanisms
Review: Tropea et al., 2009!
Review: Hensch, 2005!
Inhibitory control of critical period
Enhance GABA Function critical period ends early
Pla
stic
ity (r
espo
nse
to m
onoc
ular
dep
rivat
ion)
Age (days postnatal) 30 13
Reduce GABA Function critical period ends late
Only effective when cells are 33-35 days old
Inhibitory control of critical period
Use-dependent plasticity of inhibitory synapses
Kotak et al., 205, 2008!
P10!
Sensorineural Hearing Loss"
cochlea!removal!
Use-dependent plasticity of inhibitory synapses
Kotak et al., 205, 2008!
Use-dependent plasticity of inhibitory synapses
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