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.
Matamales M*, Skrbis Z*, Hatch RJ, Balleine BW, Götz J, Bertran-Gonzalez J (2016) Aging-related dysfunction of striatal cholinergic interneurons produces conflict in action selection. Neuron 90 (2), 362-373. [Journal Article]
Research Highlight (2016) How old age limits adaptability. Nature 532, 417. [Journal Article]
Paxinos-Watson Award from the Australasian Neuroscience Society to J. Bertran-Gonzalez and Miriam Matamales, to the most significant paper published by a Society member in 2016.
Other articles related to this work:
Bradfield LA, Matamales M, Bertran-Gonzalez J (2018) The thalamostriatal pathway and the hierarchical control of action. Neuron 100 (3), 521-523. [Journal Article]
Bradfield LA, Bertran-Gonzalez J, Chieng BC, Balleine BW (2013) The thalamostriatal pathway and cholinergic control of goal-directed action: interlacing new with existing learning in the striatum. Neuron 79 (1), 153-166. [Journal Article]
GRANT FUNDING
Our work is supported by the Australian Research Council, the National Health and Medical Research Council and the Tourette Association of America . 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.
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