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 (2023) Restoring the youthful state of striatal plasticity in aged mice re-enables cognitive control of action. Current Biology. [Journal Article][Preprint]
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
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All experimental procedures are approved by the Animal Care and Ethics Commitee and the Gene Technology Research Commitee at UNSW.
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