Abstract
Plasticity at the cerebellar parallel fiber to Purkinje cell synapse may underlie information processing and motor learning. In vivo, parallel fibers appear to fire in short high frequency bursts likely to activate sparsely distributed synapses over the Purkinje cell dendritic tree. Here, we report that short parallel fiber tetanic stimulation evokes a ∼7–15% depression which develops over 2 min and lasts for at least 20 min. In contrast to the concomitantly evoked short-term endocannabinoid-mediated depression, this persistent posttetanic depression (PTD) does not exhibit a dependency on the spatial pattern of synapse activation and is not caused by any detectable change in presynaptic calcium signaling. This persistent PTD is however associated with increased paired-pulse facilitation and coefficient of variation of synaptic responses, suggesting that its expression is presynaptic. The chelation of postsynaptic calcium prevents its induction, suggesting that post- to presynaptic (retrograde) signaling is required. We rule out endocannabinoid signaling since the inhibition of type 1 cannabinoid receptors, monoacylglycerol lipase or vanilloid receptor 1, or incubation with anandamide had no detectable effect. The persistent PTD is maximal in pre-adolescent mice, abolished by adrenergic and dopaminergic receptors block, but unaffected by adrenergic and dopaminergic agonists. Our data unveils a novel form of plasticity at parallel fiber synapses: a persistent PTD induced by physiologically relevant input patterns, age-dependent, and strongly modulated by the monoaminergic system. We further provide evidence supporting that the plasticity mechanism involves retrograde signaling and presynaptic diacylglycerol.
Highlights
The cerebellum is essential for fine tuning of motor coordination and motor learning [1,2]
The N1 peak was barely affected by NBQX (3.861.4%, n = 9; Fig. 1B–C), an efficient blocker of parallel fibers (PFs) to Purkinje cell (PC) fast synaptic transmission [21], and was assimilated to the fiber volley (FV), providing a readout of the action potential propagation along the stimulated PFs
The N2 peak was assimilated to the field excitatory postsynaptic potential, providing a measure of PF to PC synaptic transmission
Summary
The cerebellum is essential for fine tuning of motor coordination and motor learning [1,2]. Its induction mechanism has remained controversial [5,6,7,8], it is generally accepted that it requires a large postsynaptic calcium rise and that its expression is mediated by postsynaptic AMPA receptor phosphorylation and internalization [6,9,10] This postsynaptic LTD has later been shown to be reversible: a postsynaptic long-term potentiation (LTP) can be evoked by protocols producing smaller postsynaptic calcium rises [11,12]. A single burst of high frequency PF firing evoked by tetanic stimulation is known to induce endocannabinoid-mediated shortterm depression [7,16,17], but only for spatially dense input patterns [17,18], the occurrence of which is unclear in vivo. That this novel form of plasticity is permitted by tonic levels of monoamines
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