Presynaptically expressed long-term depression at cerebellar parallel fiber synapses

Area of Science:

• Neuroscience
• Cellular Biology
• Synaptic Plasticity

Background:

• Synaptic plasticity at parallel fiber (PF) and Purkinje neuron (PN) synapses models cerebellar learning.
• While postsynaptic plasticity is bidirectional, presynaptic plasticity was limited to potentiation.

Purpose of the Study:

• To investigate presynaptically expressed long-term depression (preLTD) at PF-PN synapses.
• To characterize the induction and mechanisms of PF preLTD.

Main Methods:

• Pharmacological prevention of presynaptically expressed PF long-term potentiation (preLTP).
• Induction of PF preLTD using 4 Hz PF stimulation.
• Assessment of cannabinoid CB1 receptor and NMDA receptor involvement.

Main Results:

• Presynaptically expressed PF long-term depression (preLTD) was observed when preLTP was blocked.
• PF preLTD induction is most efficient with 4 Hz stimulation and requires cannabinoid CB1 receptor activation.
• Endocannabinoid release during preLTD induction is NMDA receptor-dependent but mGlu1 receptor-independent.

Conclusions:

• Bidirectional plasticity mechanisms exist for both presynaptic and postsynaptic components of cerebellar learning.
• This study identifies presynaptic long-term depression as a novel mechanism in cerebellar plasticity.