Presynaptic calcium signalling in cerebellar mossy fibres

Louiza B Thomsen

doi:10.3389/neuro.04.001.2010

Abstract

Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A tetrodotoxin (TTX)-sensitive fast Na+ spike faithfully followed repetitive depolarizing pulses with little change in spike duration or amplitude, while a strong outward rectification dominated responses to long-lasting depolarizations. High-threshold calcium spikes were uncovered following addition of potassium channel blockers. Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none TTX-sensitive calcium signal in simple and complex rosettes. All compartments of a complex rosette were activated during electrical activation of the mossy fibre, while individual simple and complex rosettes along an axon appeared to be isolated from one another in terms of calcium signalling. CGP55845 application showed that GABA B receptors mediated presynaptic inhibition of the calcium signal over the entire firing frequency range of mossy fibres. A paired-pulse depression of the calcium signal lasting more than 1 s affected burst firing in mossy fibres; this paired-pulse depression was reduced by GABA B antagonists. While our results indicated that a presynaptic rosette electrophysiologically functioned as a unit, topical GABA application showed that calcium signals in the branches of complex rosettes could be modulated locally, suggesting that cerebellar glomeruli may be dynamically sub-compartmentalized due to ongoing inhibition mediated by Golgi cells. This could provide a fine-grained control of mossy fibre-granule cell information transfer and synaptic plasticity within a mossy fibre rosette.

Highlights

Mossy fibres constitute one of the important input pathways to the cerebellum (Eccles et al, 1966)
We analysed the electrophysiological responses and the calcium signalling in cerebellar mossy fibres in the adult, intact cerebellum at physiological temperature for turtles, i.e. 15–35°C
Calcium imaging revealed Na+ spike-associated calcium signals from simple and complex rosettes. This calcium signal was reduced by GABA B-R activation over entire firing frequency range of mossy fibres in turtles

Summary

Introduction

Mossy fibres constitute one of the important input pathways to the cerebellum (Eccles et al, 1966). The mossy fibre rosette is the presynaptic element in the cerebellar glomerulus (Cajal, 1888), a unit of information transfer, which is formed by granule cell dendrites and GABAergic Golgi cell axonal terminals. In order to understand input processing to the cerebellum, the physiological properties of the glomerulus are of importance, and the anatomical organization suggests that each glomerulus is a semi-autonomous unit, isolated in chemical terms from the surrounding cellular elements by a glial sheath (Eccles et al, 1967; Palay and Chan-Palay, 1974; Jakab and Hamori, 1988). Taking advantage of the more intact network available in the turtle cerebellum preparation, we wished to further analyse the timecourse of presynaptic GABA B modulation

Methods

Results

Conclusion