Why older individuals struggle to adapt to change?
For goal-directed action to remain adaptive, new strategies are required to accommodate environmental changes, a process for which parafascicular thalamic modulation of cholinergic interneurons in the striatum (PF-to-CIN) appears critical. In the elderly, however, previously acquired experience frequently interferes with new learning, yet the source of this effect has remained unexplored. Here, combining sophisticated behavioral designs, cell-specific manipulation, and extensive neuronal imaging, we investigated the involvement of the PF-to-CIN pathway in this process. We found functional alterations of this circuit in aged mice that were consistent with their incapacity to update initial goal-directed learning, resulting in faulty activation of projection neurons in the striatum. Toxicogenetic ablation of CINs in young mice reproduced these behavioral and neuronal defects, suggesting that age-related deficits in PF-to-CIN function reduce the ability of older individuals to resolve conflict between actions, likely contributing to impairments in adaptive goal-directed action and executive control in aging.
GRANT FUNDING Our work is supported by the Australian Research Council (Project Grant to J. B-G and M. M; Future Fellowship to J. B-G) and the National Health and Medical Research Council (Project Grant to J. B-G and M. M). Click for details
RESEARCH ETHICS & SAFETY All experimental procedures are approved by the Animal Care and Ethics Commitee and the Gene Technology Research Commitee at UNSW.