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Restoring the youthful state of striatal plasticity in aged mice re-enables cognitive control of action

Jesus Bertran-Gonzalez, Caroline Dinale, Miriam Matamales

Current Biology, 33, 1-11

May 2023


Multidisciplinary evidence suggests that the control of voluntary action arbitrates between two major forms of behavioral processing: cognitively guided (or goal directed) and autonomously guided (or habitual). Brain-state irregularities affecting the striatum—such as aging—commonly shift control toward the latter, although the responsible neural mechanisms remain unknown. Combining instrumental conditioning with cell-specific mapping and chemogenetics in striatal neurons, we explored strategies that invigorate goal-directed capacity in aged mice. We found that, under conditions favoring goal-directed control, aged animals resiliently expressed autonomously guided behavior, a response that was underpinned by a characteristic one-to-one functional engagement of the two main neuronal populations in the striatum—D1- and D2-dopamine receptor-expressing spiny projection neurons (SPNs). Chemogenetically induced desensitization of D2-SPN signaling in aged transgenic mice recapitulated the striatal plasticity state observed in young mice, an effect that shifted behavior toward vigorous, goal-directed action. Our findings contribute to the understanding of the neural bases of behavioral control and propose neural system interventions that enhance cognitive functioning in habit-prone brains.

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