Probability Learning In Genetically Modified Mouse Lines

Tkachenko A.A.(1), Ranneva S.V.(1,2), Loskutova L.V.(1), Lipina T.V.(1,2) 1-Novosibirsk State University, 1, Street Pirogova, Novosibirsk, 630090, Russia, 2-Federal State Budgetary Scientific Institution, Scientific Research Institute of Physiology and Basic Medicine, r. 904, 4, str. Timakova, Novosibirsk, 630117, Russia е-mail: lipina@physiol.ru

Abstract

Understanding of the neurobiological mechanisms of schizophrenia is a complex task for researchers, since the etiology and neurobiological mechanisms of this disorder are not fully understood, and a number of symptoms, including delusions and hallucinations, hard to model on experimental animals. Nevertheless, it was suggested to consider bizarre ideas as a problem associated with the formation of strange beliefs [1]. This in turn can be detected by assessing the probability of events that is disrupted in patients with schizophrenia [2]. Relatively recently, the phenomenon of probabilistic learning has been successfully introduced into the field of experimental models of schizophrenia in rodents [3, 4]. Thus, it was considered relevant to evaluate this endophenotype on the genetic mouse model of schizophrenia - the DISC1-L100P mutant mouse line, as well as in knockout mice with the сalsyntenin2 gene (Clstn2-KO), the genetic model of autism, to detect the specificity of impaired probabilistic learning associated with schizophrenia- or autism-related behavior. It turns out, DISC1-L100P mutant males did not differ from wild type mice in the task with 100% reward. However, when reward was presented in 80% trials (test 80/20), the DISC1-L100P mice learned faster when acquiring a short-term skill, were reliably faster trained when the location of the feeder was changed, and made fewer regressive errors, which generally indicates on overestimation of the probability of events in DISC1-L100P male mice. At the same time, Clsnt2-KO mice acquired faster short-term learning of spatial location of reward given in 100%, but Clstn2-KO males expressed deficit of retention of the acquired learning, indicating on deficit of their long-term spatial memory. Therefore, comparative analysis of probabilistic learning in mouse genetic lines – DISC1-L100P and Clstn2-KO, revealed abnormal estimation of probability evaluation of events in DISC1-L100P strain, but found deficient basic cognitive process in Clstn2-KO mice. Hence, probabilistic learning might be a new cognitive endophenotype of schizophrenia, which depends on the genotype, requiring further research.

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