PT - JOURNAL ARTICLE AU - Soyoung Chae AU - Jeong-woo Sohn AU - Sung-Phil Kim TI - Investigation of neural substrates of erroneous behavior in a delayed-response task AID - 10.1523/ENEURO.0490-21.2022 DP - 2022 Mar 31 TA - eneuro PG - ENEURO.0490-21.2022 4099 - http://www.eneuro.org/content/early/2022/03/31/ENEURO.0490-21.2022.short 4100 - http://www.eneuro.org/content/early/2022/03/31/ENEURO.0490-21.2022.full AB - Motor cortical neurons exhibit persistent selective activities (selectivity) during motor planning. Experimental perturbation of selectivity results in the failure of short-term memory retention and consequent behavioral biases, demonstrating selectivity as a neural characteristic of encoding previous sensory input or future action. However, even without experimental manipulation, animals occasionally fail to maintain short-term memory leading to erroneous choice. Here, we investigated neural substrates that lead to the incorrect formation of selectivity during short-term memory. We analyzed neuronal activities in anterior lateral motor cortex (ALM) of mice, a region known to be engaged in motor planning while mice performed the tactile delayed-response task. We found that highly selective neurons lost their selectivity while originally non-selective neurons showed selectivity during the error trials where mice licked toward incorrect direction. We assumed that those alternations would reflect changes in intrinsic properties of population activity. Thus, we estimated an intrinsic manifold shared by neuronal population (shared space), using factor analysis and measured the association of individual neurons with the shared space by communality, the variance of neuronal activity accounted for by the shared space. We found a positive correlation between selectivity and communality over ALM neurons, which disappeared in erroneous behavior. Notably, neurons showing selectivity alternations between correct and incorrect licking also underwent proportional changes in communality. Our results demonstrated that the extent to which an ALM neuron is associated with the intrinsic manifolds of population activity may elucidate its selectivity and that disruption of this association may alter selectivity, likely leading to erroneous behavior.Significance StatementAppropriate retaining of short-term memory can maximize a future reward. During retention, neurons in frontal cortex show persistent activity encoding a selection of future action, the collapse of which leads to erroneous behavior. This study addressed the underlying neural mechanism for changes of selectivity in erroneous behavior by investigating selectivity in rodent anterior lateral motor cortex (ALM) during the delayed-response task. We found that the stronger a neuron’s activity was coupled to an intrinsic shared space of ALM, the greater its selectivity was. Also, changes in selectivity during erroneous behavior were related to changes in coupling strength. Our work suggests that proper association with the shared space is key to orchestrating ALM neuronal activities for accurate planning for upcoming movement.