Functional heterogeneity of striatopallidal subregions.

Abstract

Disruption of the striatopallidal system in humans can produce involuntary hyperkinetic movements, an impairment of action sequencing, and emotional changes such as major depression. Large lesions of the striatopallidal system in the rat produce a sensory-triggered hyperkinetic forelimb treading, an impairment of the serial order of grooming sequences and an enhancement of aversion to normally palatable tastes. The goals of this dissertation were to discover whether these changes are caused by damage to different striatopallidal subregions. A novel lesion mapping technique called the modified fractionator technique was invented to map the crucial site for each syndrome. The crucial site for hyperkinetic treading was within the ventromedial corner of the globus pallidus. Damage exceeding 60% neuron loss bilaterally within this 0.8 x 1.0 x 1.0mm subterritory produced this syndrome. Haloperidol, a dopamine receptor blocker, suppresses human hyperkinetic movements and was also found to reduce the hyperkinetic forelimb treading in the rat. The crucial site for disruption of the serial structure of grooming sequences was restricted to a dorsolateral portion of the neostriatum. Damage exceeding 72% neuron loss bilaterally within this 1.3 x 1.0 x 1.0mm subterritory produced this sequential impairment. The ability to initiate or execute grooming actions such as forelimb strokes or body licks was not impaired in rats that had sequencing deficits. Only the ability to sequence a set of grooming actions into a specific serial order was impaired. The crucial site for the enhancement of taste aversion was restricted to the ventromedial ventral pallidum/substantia innominata. Damage exceeding 70% neuron loss bilaterally within this 1.0 x 0.5 x 1.0mm subterritory produced this enhanced taste aversion. Bilateral lesions centered within the lateral hypothalamus itself did not produce a similar enhancement of taste aversion even though they produced aphagia. In conclusion, specific striatopallidal syndromes result from damage localized to different sites. This result has implications for the understanding of the functional heterogeneity of the striatopallidal system both for normal function and for motor, cognitive and emotional dysfunction in human striatopallidal disease.