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 currently supported by the Australian Research Council, the National Health and Medical Research Council, the Tourette Association of America and UNSW. 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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