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.