Conditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and cognitive behaviors

Inhibitory interneurons mediate the gating of synaptic transmission and modulate the activities of neural circuits. Disruption of the function of inhibitory networks in the forebrain is linked to impairment of social and cognitive behaviors, but the involvement of inhibitory interneurons in the cere...

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Main Authors: Tantra, M., Guo, L., Kim, J., Norliyana Zainolabidin, Eulenburg, V., Augustine, George J., Chen, Albert I-Ming
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2020
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Online Access:https://hdl.handle.net/10356/138934
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1389342023-02-28T17:10:14Z Conditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and cognitive behaviors Tantra, M. Guo, L. Kim, J. Norliyana Zainolabidin Eulenburg, V. Augustine, George J. Chen, Albert I-Ming School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) Science::Biological sciences Autism Spectrum Disorder Cadherin 13 Inhibitory interneurons mediate the gating of synaptic transmission and modulate the activities of neural circuits. Disruption of the function of inhibitory networks in the forebrain is linked to impairment of social and cognitive behaviors, but the involvement of inhibitory interneurons in the cerebellum has not been assessed. We found that Cadherin 13 (Cdh13), a gene implicated in autism spectrum disorder and attention-deficit hyperactivity disorder, is specifically expressed in Golgi cells within the cerebellar cortex. To assess the function of Cdh13 and utilize the manipulation of Cdh13 expression in Golgi cells as an entry point to examine cerebellar-mediated function, we generated mice carrying Cdh13-floxed alleles and conditionally deleted Cdh13 with GlyT2::Cre mice. Loss of Cdh13 results in a decrease in the expression/localization of GAD67 and reduces spontaneous inhibitory postsynaptic current (IPSC) in cerebellar Golgi cells without disrupting spontaneous excitatory postsynaptic current (EPSC). At the behavioral level, loss of Cdh13 in the cerebellum, piriform cortex and endopiriform claustrum have no impact on gross motor coordination or general locomotor behaviors, but leads to deficits in cognitive and social abilities. Mice lacking Cdh13 exhibit reduced cognitive flexibility and loss of preference for contact region concomitant with increased reciprocal social interactions. Together, our findings show that Cdh13 is critical for inhibitory function of Golgi cells, and that GlyT2::Cre-mediated deletion of Cdh13 in non-executive centers of the brain, such as the cerebellum, may contribute to cognitive and social behavioral deficits linked to neurological disorders. MOE (Min. of Education, S’pore) NMRC (Natl Medical Research Council, S’pore) Published version 2020-05-14T04:07:35Z 2020-05-14T04:07:35Z 2018 Journal Article Tantra, M., Guo, L., Kim, J., Norliyana Zainolabidin., Eulenburg, V., Augustine, G. J., & Chen, A. I.-M. (2018). Conditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and cognitive behaviors. Genes, brain, and behavior, 17(6), e12466-. doi:10.1111/gbb.12466 1601-1848 https://hdl.handle.net/10356/138934 10.1111/gbb.12466 29446202 2-s2.0-85043699590 6 17 en Genes, brain, and behavior © 2018 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
Autism Spectrum Disorder
Cadherin 13
spellingShingle Science::Biological sciences
Autism Spectrum Disorder
Cadherin 13
Tantra, M.
Guo, L.
Kim, J.
Norliyana Zainolabidin
Eulenburg, V.
Augustine, George J.
Chen, Albert I-Ming
Conditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and cognitive behaviors
description Inhibitory interneurons mediate the gating of synaptic transmission and modulate the activities of neural circuits. Disruption of the function of inhibitory networks in the forebrain is linked to impairment of social and cognitive behaviors, but the involvement of inhibitory interneurons in the cerebellum has not been assessed. We found that Cadherin 13 (Cdh13), a gene implicated in autism spectrum disorder and attention-deficit hyperactivity disorder, is specifically expressed in Golgi cells within the cerebellar cortex. To assess the function of Cdh13 and utilize the manipulation of Cdh13 expression in Golgi cells as an entry point to examine cerebellar-mediated function, we generated mice carrying Cdh13-floxed alleles and conditionally deleted Cdh13 with GlyT2::Cre mice. Loss of Cdh13 results in a decrease in the expression/localization of GAD67 and reduces spontaneous inhibitory postsynaptic current (IPSC) in cerebellar Golgi cells without disrupting spontaneous excitatory postsynaptic current (EPSC). At the behavioral level, loss of Cdh13 in the cerebellum, piriform cortex and endopiriform claustrum have no impact on gross motor coordination or general locomotor behaviors, but leads to deficits in cognitive and social abilities. Mice lacking Cdh13 exhibit reduced cognitive flexibility and loss of preference for contact region concomitant with increased reciprocal social interactions. Together, our findings show that Cdh13 is critical for inhibitory function of Golgi cells, and that GlyT2::Cre-mediated deletion of Cdh13 in non-executive centers of the brain, such as the cerebellum, may contribute to cognitive and social behavioral deficits linked to neurological disorders.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Tantra, M.
Guo, L.
Kim, J.
Norliyana Zainolabidin
Eulenburg, V.
Augustine, George J.
Chen, Albert I-Ming
format Article
author Tantra, M.
Guo, L.
Kim, J.
Norliyana Zainolabidin
Eulenburg, V.
Augustine, George J.
Chen, Albert I-Ming
author_sort Tantra, M.
title Conditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and cognitive behaviors
title_short Conditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and cognitive behaviors
title_full Conditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and cognitive behaviors
title_fullStr Conditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and cognitive behaviors
title_full_unstemmed Conditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and cognitive behaviors
title_sort conditional deletion of cadherin 13 perturbs golgi cells and disrupts social and cognitive behaviors
publishDate 2020
url https://hdl.handle.net/10356/138934
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