Abstract
In vitro studies have supported the occurrence of cerebellar long-term depression (LTD), an interaction between the parallel fibers and Purkinje cells (PCs) that requires the combined activation of the parallel and climbing fibers. To demonstrate the existence of LTD in alert animals, we investigated the plasticity of local field potentials (LFPs) evoked by electrical stimulation of the whisker pad. The recorded LFP showed two major negative waves corresponding to trigeminal (broken into the N2 and N3 components) and cortical responses. PC unitary extracellular recording showed that N2 and N3 occurred concurrently with PC evoked simple spikes, followed by an evoked complex spike. Polarity inversion of the N3 component at the PC level and N3 amplitude reduction after electrical stimulation of the parallel fiber volley applied on the surface of the cerebellum 2 ms earlier strongly suggest that N3 was related to the parallel fiber–PC synapse activity. LFP measurements elicited by single whisker pad stimulus were performed before and after trains of electrical stimuli given at a frequency of 8 Hz for 10 min. We demonstrated that during this later situation, the stimulation of the PC by parallel and climbing fibers was reinforced. After 8-Hz stimulation, we observed long-term modifications (lasting at least 30 min) characterized by a specific decrease of the N3 amplitude accompanied by an increase of the N2 and N3 latency peaks. These plastic modifications indicated the existence of cerebellar LTD in alert animals involving both timing and synaptic modulations. These results corroborate the idea that LTD may underlie basic physiological functions related to calcium-dependent synaptic plasticity in the cerebellum.
Highlights
The first experimental evidence of long-term depression (LTD) at the parallel fiber (PF)–Purkinje cell (PC) synapse was induced by conjunctive activation of parallel and climbing fiber (CF) inputs in decerebrated rabbit [1] and in slices [2]
This study demonstrated the existence of an LTD in the cerebellar cortex of alert mice
This LTD was characterized by a specific decrease in the N3 amplitude accompanied by an increase in the latency peaks of the N2 and N3 local field potentials (LFPs) components
Summary
The first experimental evidence of long-term depression (LTD) at the parallel fiber (PF)–Purkinje cell (PC) synapse was induced by conjunctive activation of parallel and climbing fiber (CF) inputs in decerebrated rabbit [1] and in slices [2]. This evidence was consistent with the Marr-Albus-Ito models of cerebellar learning [3,4,5]. Presynaptic [7] and postsynaptic [8] long-term potentiation (LTP) at the PF–PC synapse supported the concept of bidirectional plasticity controlled by intracellular Ca2+ signaling [9,10]. LTD was associated with both presynaptic [16] and postsynaptic [17] NMDA receptors
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