Ca2+ requirements for cerebellar long-term synaptic depression: role for a postsynaptic leaky integrator

Area of Science:

• Neuroscience
• Cellular Neuroscience
• Synaptic Plasticity

Background:

• Cerebellar long-term synaptic depression (LTD) is a crucial form of synaptic plasticity.
• The precise role of postsynaptic calcium concentration ([Ca2+]i) in triggering LTD requires detailed characterization.

Purpose of the Study:

• To elucidate the dependence of cerebellar LTD on postsynaptic Ca2+ concentration.
• To investigate the cooperative nature and temporal integration of Ca2+ signals in LTD induction.

Main Methods:

• Utilized photolysis of a caged Ca2+ compound to precisely control postsynaptic [Ca2+]i.
• Developed and employed a computational model incorporating protein kinase C and MAP kinase positive-feedback loops.
• Performed experimental manipulations to disrupt the proposed feedback cycle.

Main Results:

• Elevated [Ca2+]i alone was sufficient to induce LTD, independent of other synaptic activity signals.
• A sigmoidal relationship demonstrated a highly cooperative triggering of LTD by Ca2+.
• The duration of [Ca2+]i transients influenced LTD's apparent Ca2+ affinity, consistent with a leaky integrator model (0.6 s time constant).

Conclusions:

• Cerebellar LTD is initiated by a mechanism that integrates postsynaptic Ca2+ signals over time.
• A positive-feedback cycle involving protein kinase C and MAP kinase likely underlies this Ca2+ signal integration.
• Experimental disruption of this feedback cycle altered the Ca2+ dependence of LTD as predicted by the model.