Synaptic plasticity: Introduction
• Different induction protocols
• Basic properties
• Key elements of the biophysics
• Site of change: pre or post-synaptic
• More on Mechanism
Rate based induction (show on board)
But: Heterosynaptic LTD – from Abraham (note – in vivo)
Note about the different meanings of hetero
Christie et. Al 1995
Pairing induced plasticity
Feldman, 2000
Show voltage clamp
Spike timing dependent plasticity
Markram et. al. 1997
Anatomy figure from Markram 97
Spike timing dependent plasticity
Markram et. al. 1997
Bi and Poo J. Neurosci. 1998
Some properties (observations) of synaptic plasticity
• Synapse specificity (but)
• Associatively: LTP when pre and post occur together.
• Cooperativety: Two different input pathways can boost each other.
Some key elements of the biophysics of induction
1. NMDA receptors are necessary (in many systems) for the induction of LTP and LTD
Bi and Poo, 1998
Control
With APV
Same holds for LTD – but some forms of plasticity are NMDAR independent
1. Voltage dependence
2. Calcium permeability
Partial blockade of NMDA-R
Cummings et. al , 1996
Plasticity is dependent on Calcium influx through NMDA Receptors
2. Calcium influx is necessary for plasticity
and its level determines the sign and magnitude of plasticity
(Cho et. al. 2001)
And might be sufficient
Yang, Tang Zucker, 1999
• Moderate, but prolonged calcium elevation = LTD
• High calcium elevation = LTP
( brief is sufficient, but what will long do? )
High/Correlated activity
LTP
LTP
Low/uncorrelated activity
LTD
Magic Magic
High NMDA-R activation
Moderate NMDA-R activation
Phosphatases and Kinases are necessary for synaptic plasticity:
• Kinases: CaMKII, PKA, PKC…
• Phosphatases: PP1, PP2B (Calcinurin)
Giese et. al 1998
• What changes during synaptic plasticity?
• What is the mechanism responsible for the induction of synaptic plasticity? (magic?)
• Can every form of plasticity be accounted for by STDP?
• What are the rules governing synaptic plasticity?
• How is synaptic plasticity maintained?
• Presynaptic release probability
• The number of postsynaptic receptors.
• Properties of postsynaptic receptors
What can change during synaptic plasticity?
Possible evidence for a presynaptic mechanism
1. Change in failure rate (minimal stimulation)
2. Change in paired pulse ratio
(explain on board – for both ppf and ppd)
3. The MK 801 test
Probability of failure: K vesicles, Pr – prob of release
Reminder: short term synaptic dynamics:
depression facilitation
Nu Nr
1/τu
Are there other possible reasons for change in PPR?
Postsynaptic spine
What would happen when we have PPF?
Evidence for postsynaptic change:
1. No change in failures 2. No change in PPR 3. No change in NMDA-R component 4. Different change for AMPA and NMDA-R currents 5. No change in MK-801
The story of silent synapses
Concepts • Minimal stimulation • Effect of depolarization on NMDA-R
Model of synaptic plasticity
Summary – up to here.