Stimulation within the cuneate nucleus suppresses synaptic activation of climbing fibers

Pontus Geborek,Fredrik Bengtsson,Henrik Jörntell

doi:10.3389/fncir.2012.00120

Abstract

Several lines of research have shown that the excitability of the inferior olive is suppressed during different phases of movement. A number of different structures like the cerebral cortex, the red nucleus, and the cerebellum have been suggested as candidate structures for mediating this gating. The inhibition of the responses of the inferior olivary neurons from the red nucleus has been studied extensively and anatomical studies have found specific areas within the cuneate nucleus to be target areas for projections from the magnocellular red nucleus. In addition, GABA-ergic cells projecting from the cuneate nucleus to the inferior olive have been found. We therefore tested if direct stimulation of the cuneate nucleus had inhibitory effects on a climbing fiber field response, evoked by electrical stimulation of the pyramidal tract, recorded on the surface of the cerebellum. When the pyramidal tract stimulation was preceded by weak electrical stimulation (5–20 μA) within the cuneate nucleus, the amplitude of the climbing fiber field potential was strongly suppressed (approx. 90% reduction). The time course of this suppression was similar to that found after red nucleus stimulation, with a peak suppression occurring at 70 ms after the cuneate stimulation. Application of CNQX (6-cyano-7-nitroquinoxaline-2,3-dione, disodium salt) on the cuneate nucleus blocked the suppression almost completely. We conclude that a relay through the cuneate nucleus is a possible pathway for movement-related suppression of climbing fiber excitability.

Highlights

Essential to all theories of cerebellar function is the causes and conditions of climbing fiber activation
Electrical stimulation within the inferior olive (IO) evoked a direct, non-synaptic climbing fiber field potential with a shorter response latency time than the climbing fiber response evoked from the pyramidal tract, consistent with a synaptic activation of inferior olivary neurons from the latter (Figure 3A) The site within the forelimb area of the C3 zone, at which the largest climbing fiber field potential was evoked from the pyramidal tract, was identified
We proceeded by testing if conditioning stimulation in the cuneate nucleus had effects on the climbing fiber field response evoked by the pyramidal tract stimulation

Summary

Introduction

Essential to all theories of cerebellar function is the causes and conditions of climbing fiber activation. During different phases of movements, like reach-to-grasp (Gellman et al, 1985; Horn et al, 2004) and locomotion (Lidierth and Apps, 1990; Apps, 1999) climbing fiber excitability in the rDAO, is strongly modulated Observations such as these have led to the idea of gating of synaptic transmission in the inferior olive (IO) during movement. It has been shown that stimulation of the magnocellular part of the red nucleus (RNm) inhibits responses evoked from the forelimb in rDAO neurons (Weiss et al, 1990; Horn et al, 1998; Gibson et al, 2002) This would represent a pathway by which the motor command itself can actively suppress climbing fiber discharge. Since the projection neurons of the RNm are not known to be inhibitory, RNm stimulation probably activates an additional pathway that has inhibitory effects in the IO

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