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]

Our work is supported by the Australian Research Council and the National Health and Medical Research Council. Click for details

All experimental procedures are approved by the Animal Care and Ethics Commitee and the Gene Technology Research Commitee at UNSW.

Except where otherwise noted, by J.Bertran-Gonzalez & M. Matamales is subject to a Creative Commons Attribution 4.0 International license.