Journal
NEUROPSYCHOPHARMACOLOGY
Volume 48, Issue 9, Pages 1377-1385Publisher
SPRINGERNATURE
DOI: 10.1038/s41386-022-01514-y
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The ability to update the value of actions is crucial for flexible decision making. This study investigated the effects of disrupting glutamate neurotransmission in early postnatal rats on decision making using the probabilistic reversal learning task. The results showed that the rats with disrupted glutamatergic transmission exhibited impaired decision making, and a deep neural network trained on their behavior could accurately predict the treatment group, suggesting the potential for using neural networks in schizophrenia diagnosis.
The ability to appropriately update the value of a given action is a critical component of flexible decision making. Several psychiatric disorders, including schizophrenia, are associated with impairments in flexible decision making that can be evaluated using the probabilistic reversal learning (PRL) task. The PRL task has been reverse-translated for use in rodents. Disrupting glutamate neurotransmission during early postnatal neurodevelopment in rodents has induced behavioral, cognitive, and neuropathophysiological abnormalities relevant to schizophrenia. Here, we tested the hypothesis that using the NMDA receptor antagonist phencyclidine (PCP) to disrupt postnatal glutamatergic transmission in rats would lead to impaired decision making in the PRL. Consistent with this hypothesis, compared to controls the postnatal PCP-treated rats completed fewer reversals and exhibited disruptions in reward and punishment sensitivity (i.e., win-stay and lose-shift responding, respectively). Moreover, computational analysis of behavior revealed that postnatal PCP-treatment resulted in a pronounced impairment in the learning rate throughout PRL testing. Finally, a deep neural network (DNN) trained on the rodent behavior could accurately predict the treatment group of subjects. These data demonstrate that disrupting early postnatal glutamatergic neurotransmission impairs flexible decision making and provides evidence that DNNs can be trained on behavioral datasets to accurately predict the treatment group of new subjects, highlighting the potential for DNNs to aid in the diagnosis of schizophrenia.
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