A fundamental issue with population aging is the age-related gross and fine motor declines. It is recognized by now that the basal ganglia circuits are one of the most vulnerable to age-related effects. However, how these changes are regulated during aging remains unclear.
Recently, the Minichiello lab has established a unique mouse model that provides a rare example of age-dependent locomotor defect. They have demonstrated that loss of BDNF/TrkB signalling in striatopallidal neurons leads to age-dependent spontaneous hyperlocomotion, associated with reduced striatopallidal activation (Besusso D. et al, (2013), Nat Commun).
My project seeks to identify genes and pathways regulated by aging in a TrkB-dependent manner in striatopallidal neurons. We are doing this by combining state-of-the-art technologies including spatially restricted genetic manipulation, global gene expression analysis of specific neuronal populations (RNA-seq), smFISH, intracellular signalling and protein chemistry. The use of combinatorial state-of-the-art approaches will allow us first of all to understand basic molecular mechanisms regulating age-dependent locomotor activity and at the same time will open novel avenues to explore therapeutic interventions against loss of quality of life during aging.