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 anti cipated movements in behavioral tasks requiring a preparatory period before the execution of externally cued conditioned movements. In the present stu dy, we describe the effects of lesions of the pedunculopontine nucleus (PPN ), a structure located on the outflow of the STN to lower brainstem and spi nal motor nuclei, on the anticipatory responding caused by a unilateral les ion 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 acousti c signal, and were required to hold the lever pressed until a trigger stimu lus occurred after an unpredictable delay, The trigger stimulus required th e animals to release the lever and to press a second lever for food reinfor cement. 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 i n either side of the brain. This lesion was followed 3 weeks later by an ib otenate lesion of the PPN ipsilaterally to the STN previously lesioned. The results indicate that the anticipatory responding induced by the STN lesio n was not alleviated by the subsequent PPN lesion. However, the animals bea ring the combined lesion were severely impaired in conditioned responding t o salient stimuli involved in the paradigm and showed side-specific lengthe ning of reaction and movement times without global motor impairments. The r esults suggest that the anticipatory responses caused by STN lesions do not require the intervention of the PPN and that the disruption of the dopamin ergic nigrostriatal pathway following the combined lesion may be responsibl e for impairments observed. (C) 2001 Elsevier Science B.V. All rights reser ved.