Unilateral lesions of the pedunculopontine nucleus do not alleviate subthalamic nucleus-mediated anticipatory responding in a delayed sensorimotor task in the rat

Lesions of the subthalamic nucleus (STN) in the rat are known to cause anticipated movements in behavioral tasks requiring a preparatory period before the execution of externally cued conditioned movements. In the present study, we describe the effects of lesions of the pedunculopontine nucleus (PPN), a structure located on the outflow of the STN to lower brainstem and spinal motor nuclei, on the anticipatory responding caused by a unilateral lesion of the STN in a delayed sensorimotor task. Rats were instructed to keep a lever pressed down by the presentation of a composite visual and acoustic signal, and were required to hold the lever pressed until a trigger stimulus occurred after an unpredictable delay, The trigger stimulus required the animals to release the lever and to press a second lever for food reinforcement. The task was evaluated according to analysis of movement parameters and errors made by the animals during the preparative and executive phases of the conditioned movement. An ibotenate lesion was placed into the STN in either side of the brain. This lesion was followed 3 weeks later by an ibotenate lesion of the PPN ipsilaterally to the STN previously lesioned. The results indicate that the anticipatory responding induced by the STN lesion was not alleviated by the subsequent PPN lesion. However, the animals bearing the combined lesion were severely impaired in conditioned responding to salient stimuli involved in the paradigm and showed side-specific lengthening of reaction and movement times without global motor impairments. The results suggest that the anticipatory responses caused by STN lesions do not require the intervention of the PPN and that the disruption of the dopaminergic nigrostriatal pathway following the combined lesion may be responsible for impairments observed. (C) 2001 Elsevier Science B.V. All rights reserved.