Page 1
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
juan-carlosandaluz
Typewritten Text
juan-carlosandaluz
Typewritten Text
What happens if you don't eliminate synapses?
juan-carlosandaluz
Typewritten Text
juan-carlosandaluz
Typewritten Text
juan-carlosandaluz
Typewritten Text
juan-carlosandaluz
Typewritten Text
juan-carlosandaluz
Typewritten Text
juan-carlosandaluz
Typewritten Text
juan-carlosandaluz
Typewritten Text
juan-carlosandaluz
Typewritten Text
Page 2
Keller-Peck et al., 2001!
P7! P8! P9!
Elimination of motor neuron contact in vivo
motor axons (green) endplate (red)
juan-carlosandaluz
Typewritten Text
Page 3
Functional synapse elimination
juan-carlosandaluz
Typewritten Text
Page 4
Synapse elimination in visual cortex
LeVay et al., 1978; Crair et al., 2001!
P21
P14
P8
P92
P39
P22
Page 5
Hubel and Wiesel, 1962!
The geniculocortical pathway
Control
Page 6
Monocular deprivation
Wiesel and Hubel, 1963!
NR
Page 7
NR
Wiesel and Hubel, 1965!
Binocular deprivation
juan-carlosandaluz
Typewritten Text
Page 8
Hubel and Wiesel, 1965!
Strabismus
Page 9
Ocular Dominance
LeVay et al., 1980!
Critical periods Layer 4 Stripes
Age of Monocular Deprivation (mos)
Page 10
Stryker and Harris, 1986!
Spontaneous activity & synapse elimination Dark rear Action potential blockade
Page 11
Meister et al., 1991; Demas et al., 2003!
Spontaneous activity in the retina
Page 12
Tritsch et al., 2007!
Spontaneous activity in the cochlea
isolated cochlea
Page 13
Garaschuk et al., 2000!
Spontaneous activity in the cortex
juan-carlosandaluz
Typewritten Text
Page 14
Adelsberger et al., 2005!
Spontaneous activity in the cortex
Page 15
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!
Page 16
Stryker et al., 1978; Pasternak et al., 1985!
Influence of environment on coding properties
Page 17
Li et al., 2006, 2008!
Influence of environment on coding properties
Page 18
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
Page 19
Auditory system plasticity
Page 20
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
Page 21
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!
Page 22
Influence of environment on tonotopic map
Rear with!16+40 kHz tones!Control!
Yu et al., 2007
Page 23
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!
juan-carlosandaluz
Typewritten Text
Page 24
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!
Page 25
Synaptic mechanisms of plasticity
Page 26
Lo and Poo, 1992
Heterosynaptic depression in vitro
Synaptic depression & synapse elimination
Page 27
Li et al., 2001
presynaptic terminal
Synaptic depression & elimination
postsynaptic ACh receptors
Page 28
Yang et al., 2001
Synaptic depression & elimination
Page 29
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!
Page 30
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
Page 31
Synaptic depression depends on Ca+2
Cash et al., 1996!
Page 32
Activator of postsynaptic CaMKII decreases retinal axon arbor
Zhou and Cline, 1996!
Control axons!
Active CaMKII!
Page 33
NMDA receptors & excitatory synaptic plasticity
Page 34
Three-eyed frogs have stripes in tectum
Constantine-Paton and Law, 1978!
Page 35
Cline et al., 1987; Cline and Constantine-Paton, 1990!
Segregation of retinal axons & NMDA receptors
Page 36
Review: Hensch, 2005!
Critical period for MD in mice
Page 37
(a lot of) molecular mechanisms
Review: Tropea et al., 2009!
Page 38
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
Page 39
Only effective when cells are 33-35 days old
Inhibitory control of critical period
Page 40
Use-dependent plasticity of inhibitory synapses
Kotak et al., 205, 2008!
P10!
Sensorineural Hearing Loss"
cochlea!removal!
Page 41
Use-dependent plasticity of inhibitory synapses
Kotak et al., 205, 2008!
Page 42
Use-dependent plasticity of inhibitory synapses