Mutations in Parkinsonism-linked endocytic proteins synaptojanin1 and auxilin have synergistic effects on dopaminergic axonal pathology.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by defective dopaminergic (DAergic) input to the striatum. Mutations in two genes encoding synaptically enriched clathrin-uncoating factors, synaptojanin 1 (SJ1) and auxilin, have been implicated in atypical Parkinsonism. SJ1 knock-in (SJ1-KIRQ) mice carrying a disease-linked mutation display neurological manifestations reminiscent of Parkinsonism. Here we report that auxilin knockout (Aux-KO) mice display dystrophic changes of a subset of nigrostriatal DAergic terminals similar to those of SJ1-KIRQ mice. Furthermore, Aux-KO/SJ1-KIRQ double mutant mice have shorter lifespan and more severe synaptic defects than single mutant mice. These include increase in dystrophic striatal nerve terminals positive for DAergic markers and for the PD risk protein SV2C, as well as adaptive changes in striatal interneurons. The synergistic effect of the two mutations demonstrates a special lability of DAergic neurons to defects in clathrin uncoating, with implications for PD pathogenesis in at least some forms of this condition.

The Effect of Temperature on Tactile Softness Perception.

We are adept at discriminating object properties such as softness and temperature using touch. Previous studies have investigated the nature of each object property, but the interactions between these properties are not fully understood. Tactile softness perception relies on multiple sensory cues such as the size of the contact area, indentation depth, and force exerted. In addition to these cues, the temperature of the stimulus may contribute to tactile softness perception by changing the sensitivity to changes in stimulus compliance. To test this hypothesis, we conducted two psychophysical experiments in which the subjects estimated the magnitude of perceived softness after touching deformable objects. We varied the compliance and temperature of the stimuli. The linear functions of compliance fit to the magnitude estimates under cold conditions (9-15°C) were steeper than the functions fit to the magnitude estimates under room temperature (21-25°C). These results indicate that temperature can sharpen our tactile softness perception of deformable surfaces by increasing the sensitivity to differences in compliance.