Developmental maturation of frontal cortical circuits impacts decision-making

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In humans, frontal cortical circuit maturation parallels the development of higher cognitive functions and is estimated to occur over the course of 15-20 years. In mice, frontal association cortex (FAC) maturation occurs over the first 6-8 weeks with limited reports on changes after sexual maturation (∼7-8 weeks). Here we characterize frontal cortical circuits in mice across the first 6 months of life and uncovered cell-type and input-specific circuit refinement over this period, including a large increase in synaptic inhibition onto pyramidal cells relative to excitation. In parallel, we find age-related differences in the acquisition and execution of a FAC-dependent probabilistic 2-armed bandit task (2-ABT). Specifically, 4–6 month-old acquire the task more slowly and use different behavioral strategies to obtain rewards compared to younger mice. Lastly, we show that dampening the inhibitory activity in the FAC alters this behavior in a manner that counteracts the age-related differences. Together, these data present evidence for an extended period of structural synaptic maturation in FAC that directly impacts age-related changes in decision-making.

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