Synaptic plasticity of the interpositorubral pathway functionally related to forelimb flexion movements
Authors: Pananceau M. , Rispal-Padel L. , Meftah E. M. 
Published: December 2017

1. Some connections from the afferents to the magnocellular red nucleus (RNm), like the corticorubral synapses, have plastic properties that are thought to contribute to long-term changes such as functional readaptation, motor learning, and the establishment of conditioned responses. Because previous studies have focused on corticorubral synaptic reorganization after these events, we attempted to investigate cerebellorubral connections in intact adult cats during associative conditioning by pairing electrical stimulation of interpositus nucleus [the conditional stimulus (CS)] with electrical simulation of the forelimb [the unconditional stimulus (UCS)]. A large increase in the amplitude of the forelimb flexion (conditioned response) induced by the CS was observed after several days of paired CS-UCS presentations. 2. For this purpose, both behavioral and electrophysiological methods were used to correlate synaptic plasticity with changes in the motor responses. The somatotopically organized sensorimotor network functionally related to the control of the elbow joint movements was studied in awake adult cats. This circuit was defined on the basis of sites at which elbow flexions could be evoked both as a CS and a UCS. The CS was applied in the cerebellar interpositus nucleus (IN) site and the UCS was given to the skin on the dorsum of the distal part of the forepaw. Daily classical conditioning consisted of repetitive pairings of CS and UCS with an interstimulus interval (ISI) of 100 ms. 3. The transmission efficacy resulting from the conditioning was tested in various targets of the cerebellar efferent pathway, including the RNm. Electrophysiological responses evoked in these relay structures by the CS and the forelimb angular deviations were simultaneously recorded throughout each daily conditioning session. The surface areas of the rubral responses to CS and the percentage response rate, the angular deviation (amplitude), and the latency of the motor responses were systematically measured throughout the conditioning procedure. Test sessions were also performed before and after each period of conditioning. Quantification and statistical analysis were carried out to determine whether changes observed in interpositorubral synaptic transmission and in the motor responses evoked by the CS were correlated. 4. Daily repetition of paired CS and UCS according to a predefined and fixed temporal schedule led to an increase in the response rate and amplitude of the forelimb flexions. A procedure with repeated presentation of CS preceded by UCS was used to produce extinction of the enhanced motor responses. The associative nature of these changes was confirmed by the fact that the CS given alone for 11 days in a control condition failed to produce any modification of the motor response. 5. The changes in the flexion movements were accompanied by a nearly parallel increase of the amplitude of the “postsynaptic field potentials” evoked in the RNm by the CS (IN stimulation). Changes in the transmission efficacy of the interpositorubral synapses stayed stable even after several days of interruption and remained constant up the extinction period. Changes affecting both the motor and the central responses were significantly correlated, suggesting that modifications in the interpositorubral transmission efficacy might be one of the plastic correlates of forelimb flexion conditioning. 6. Examination of the neuronal excitability within either the IN or the RNm or in the spinal cord failed to show any evidence of facilitation suggesting that the increases in the postsynaptic rubral field potential were attributable to a plasticity of the interpositorubral connections. The long-lasting duration of the increase of cerebellorubral synaptic transmission suggests that structural changes were induced by conditioning in the intact animal. (ABSTRACT TRUNCATED)