| First Author | Matamales M | Year | 2016 |
| Journal | Neuron | Volume | 90 |
| Issue | 2 | Pages | 362-73 |
| PubMed ID | 27100198 | Mgi Jnum | J:256386 |
| Mgi Id | MGI:6109544 | Doi | 10.1016/j.neuron.2016.03.006 |
| Citation | Matamales M, et al. (2016) Aging-Related Dysfunction of Striatal Cholinergic Interneurons Produces Conflict in Action Selection. Neuron 90(2):362-73 |
| abstractText | 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. |
