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Effects of Hyperexcitation of Layer V Neocortical Pyramidal Neurons During Early Postnatal Development on Adult Behavior

Description

Abstract:
Patterns of neuronal activity during early development are believed to guide the assembly of neural circuits. Thus, alterations of neuronal activity in this time window may cause structural and functional changes that persist into adulthood. Specific alterations may lead to unique patterns of aberrant circuit formation, a mechanism which has been implicated in neurodevelopmental disorders such as autism. Findings from human and animal studies suggest that multiple etiologically distinct forms of autism alter the physiology of specific deep-layer (layer V) prefrontal cortical neurons that project to subcortical targets. These neural populations play an important role in both normal and abnormal social behavior. To probe a potential functional link between development of cortical circuitry and adult behavior, we hyperexcited layer V cortical neurons during early postnatal development and assessed the effects on adult behavior. Mice conditionally expressing the excitatory luciferase-opsin fusion LMO3 (sbGluc fused to VChR1) were crossed with Rbp4-Cre mice, enabling LMO3 expression in layer V pyramidal neurons in offspring carrying both alleles. The luciferin coelenterazine (CTZ) was delivered to all pups in the litter intraperitoneally once per day during post-natal days 4-14. In presence of CTZ, light emission from sbGluc drives activation of VChR1 to depolarize the cell and evoke action potentials in Rbp4-LMO3 pups. Starting at postnatal day 60, we examined the behavior of all mice across several testing paradigms, including open field, water T maze, sociability, novel object, and rotarod. Where applicable and to standardize our quantification of behavioral data we implemented DeepLabCut, an open-source machine learning tool that leverages recent advances in computer vision to allow accurate, markerless tracking of animals across behavior testing videos.
Notes:
This research was supported by the the National Science Foundation (NSF) and its Division of Biological Infrastructure under Award No. 1707352

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Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
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In Copyright

Citation

Uprety, Anusha, McLean, Lily, Maharjan, Shashwat, et al., "Effects of Hyperexcitation of Layer V Neocortical Pyramidal Neurons During Early Postnatal Development on Adult Behavior" (2022). NeuroNex Data and Research Products. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/ykav-7668

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Collection:

  • NeuroNex Data and Research Products

    This collection contains publicly available research products, including data, codes, and publications, among others. The NeuroNex Technology Hub is supported by the National Science Foundation (NSF) and its Division of Biological Infrastructure under Award No. 1707352.
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