Restoring goal-direction encoding in aged striatal circuits

Multidisciplinary evidence suggests that instrumental performance is governed by two major forms of behavioural control: goal-directed and autonomous processes. Brain-state abnormalities affecting the striatum, such as ageing, often shift control towards autonomous – habit-like – behaviour, although the neural mechanisms responsible for this shift remain unknown. Here, combining instrumental conditioning with cell-specific functional mapping and manipulation in striatal neurons, we explored strategies that invigorate goal-directed action capacity in aged mice. In animals performing instrumental actions, D2- and D1-neurons of the aged striatum were engaged in a characteristically counterbalanced manner, something that related to the propensity to express autonomous behaviour. Long-lasting, cell-specific desensitisation of D2-neurons in aged transgenic mice recapitulated the uneven D2- to D1-neuron functional correspondence observed in young mice, an effect that enabled successful goal-directed action. Our findings contribute to the understanding of the neural bases of behavioural control and propose neural system interventions that enhance cognitive functioning in habit-prone brains.

Bertran-Gonzalez J, Dinale C & Matamales M (2022) Restoring functional D2- to D1-neuron correspondence enables goal-directed action control in long-lived striatal circuits. bioRxiv. [Preprint]

GRANT FUNDING
Our work is supported by the Australian Research Council and the National Health and Medical Research Council. 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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