Aging-Related Dysfunction of Striatal Cholinergic Interneurons Produces Conflict in Action Selection

Abstract

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. VIDEO ABSTRACT.

DOI: 10.1016/j.neuron.2016.03.006

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@article{Matamales2016AgingRelatedDO, title={Aging-Related Dysfunction of Striatal Cholinergic Interneurons Produces Conflict in Action Selection}, author={Miriam Matamales and Zala Skrbis and Robert Hatch and Bernard W. Balleine and J{\"{u}rgen G{\"{o}tz and Jesus Bertran-Gonzalez}, journal={Neuron}, year={2016}, volume={90}, pages={362-373} }