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Calcium stores regulate the polarity and input specificity of synaptic modification.
M Nishiyama1, K Hong, K Mikoshiba
1Department of Biology, University of California at San Diego, La Jolla 92093-0357, USA.
Nature
|December 16, 2000
Summary
Activity-induced synaptic plasticity, like long-term potentiation (LTP) or depression (LTD), depends on postsynaptic calcium. Calcium influx and release from internal stores regulate synaptic modification polarity and specificity.
Area of Science:
- Neuroscience
- Synaptic Plasticity
- Molecular Biology
Background:
- Synaptic modification, including long-term potentiation (LTP) and long-term depression (LTD), is crucial for nervous system development and plasticity.
- Activity-dependent changes in synaptic efficacy are fundamental to learning and memory.
- A key question is whether these modifications are confined to activated synapses.
Purpose of the Study:
- To investigate the role of postsynaptic calcium influx and internal calcium stores in regulating synaptic plasticity.
- To determine the input specificity of long-term potentiation (LTP) and long-term depression (LTD) induction.
- To elucidate the mechanisms underlying the polarity and specificity of activity-induced synaptic modifications.
Main Methods:
- Electrophysiological recordings in the CA1 region of the hippocampus.
- Pharmacological blockade of NMDA (N-methyl-D-aspartate) receptors to modulate postsynaptic calcium influx.
- Inhibition of ryanodine receptors and inositol triphosphate (InsP3) receptors to study intracellular calcium release.
- Genetic deletion of type 1 InsP3 receptors.
Main Results:
- Partial blockade of NMDA receptors converted LTP to LTD and induced LTD at heterosynaptic inputs.
- Induction of homosynaptic LTD required functional ryanodine receptors, while heterosynaptic LTD required InsP3 receptors.
- Blocking ryanodine receptors abolished homosynaptic LTD but not heterosynaptic LTD.
- Genetic deletion of type 1 InsP3 receptors converted LTD to LTP and eliminated heterosynaptic LTD.
Conclusions:
- Postsynaptic calcium, influenced by influx and release from ryanodine and InsP3 receptors, dictates both the direction (LTP/LTD) and specificity of synaptic modifications.
- Differential activation of intracellular calcium stores plays a critical role in determining homosynaptic versus heterosynaptic plasticity.
- These findings reveal a sophisticated mechanism controlling synaptic plasticity based on calcium dynamics.
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