Selective postnatal excitation of neocortical pyramidal neurons results in distinctive behavioral and circuit deficits in adulthood

Summary: In genetic and pharmacological models of neurodevelopmental disorders, and human data, neural activity is altered within the developing neocortical network. This commonality begs the question of whether early enhancement in excitation might be a common driver, across etiologies, of characte...

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Main Authors:	William E. Medendorp, Andreas Bjorefeldt, Emmanuel L. Crespo, Mansi Prakash, Akash Pal, Madison L. Waddell, Christopher I. Moore, Ute Hochgeschwender
Format:	Article
Language:	English
Published:	Elsevier 2021-03-01
Series:	iScience
Subjects:	Behavioral Neuroscience Developmental Neuroscience Cellular Neuroscience
Online Access:	http://www.sciencedirect.com/science/article/pii/S2589004221001255

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spelling	doaj-2fac34280f43468297b5619b71767bfc2021-03-22T12:51:49ZengElsevieriScience2589-00422021-03-01243102157Selective postnatal excitation of neocortical pyramidal neurons results in distinctive behavioral and circuit deficits in adulthoodWilliam E. Medendorp0Andreas Bjorefeldt1Emmanuel L. Crespo2Mansi Prakash3Akash Pal4Madison L. Waddell5Christopher I. Moore6Ute Hochgeschwender7Program in Neuroscience, Central Michigan University, Mount Pleasant, MI 48859, USA; College of Medicine, Central Michigan University, Mount Pleasant, MI 48859, USAProgram in Neuroscience, Central Michigan University, Mount Pleasant, MI 48859, USA; Department of Neuroscience, Brown University, Providence, RI 02906, USAProgram in Neuroscience, Central Michigan University, Mount Pleasant, MI 48859, USA; College of Medicine, Central Michigan University, Mount Pleasant, MI 48859, USACollege of Medicine, Central Michigan University, Mount Pleasant, MI 48859, USAProgram in Neuroscience, Central Michigan University, Mount Pleasant, MI 48859, USA; College of Medicine, Central Michigan University, Mount Pleasant, MI 48859, USAProgram in Neuroscience, Central Michigan University, Mount Pleasant, MI 48859, USADepartment of Neuroscience, Brown University, Providence, RI 02906, USA; Carney Institute for Brain Science, Brown University, Providence, RI 02906, USA; Corresponding authorProgram in Neuroscience, Central Michigan University, Mount Pleasant, MI 48859, USA; College of Medicine, Central Michigan University, Mount Pleasant, MI 48859, USA; Corresponding authorSummary: In genetic and pharmacological models of neurodevelopmental disorders, and human data, neural activity is altered within the developing neocortical network. This commonality begs the question of whether early enhancement in excitation might be a common driver, across etiologies, of characteristic behaviors. We tested this concept by chemogenetically driving cortical pyramidal neurons during postnatal days 4–14. Hyperexcitation of Emx1-, but not dopamine transporter-, parvalbumin-, or Dlx5/6-expressing neurons, led to decreased social interaction and increased grooming activity in adult animals. In vivo optogenetic interrogation in adults revealed decreased baseline but increased stimulus-evoked firing rates of pyramidal neurons and impaired recruitment of inhibitory neurons. Slice recordings in adults from prefrontal cortex layer 5 pyramidal neurons revealed decreased intrinsic excitability and increased synaptic E/I ratio. Together these results support the prediction that enhanced pyramidal firing during development, in otherwise normal cortex, can selectively drive altered adult circuit function and maladaptive changes in behavior.http://www.sciencedirect.com/science/article/pii/S2589004221001255Behavioral NeuroscienceDevelopmental NeuroscienceCellular Neuroscience
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	William E. Medendorp Andreas Bjorefeldt Emmanuel L. Crespo Mansi Prakash Akash Pal Madison L. Waddell Christopher I. Moore Ute Hochgeschwender
spellingShingle	William E. Medendorp Andreas Bjorefeldt Emmanuel L. Crespo Mansi Prakash Akash Pal Madison L. Waddell Christopher I. Moore Ute Hochgeschwender Selective postnatal excitation of neocortical pyramidal neurons results in distinctive behavioral and circuit deficits in adulthood iScience Behavioral Neuroscience Developmental Neuroscience Cellular Neuroscience
author_facet	William E. Medendorp Andreas Bjorefeldt Emmanuel L. Crespo Mansi Prakash Akash Pal Madison L. Waddell Christopher I. Moore Ute Hochgeschwender
author_sort	William E. Medendorp
title	Selective postnatal excitation of neocortical pyramidal neurons results in distinctive behavioral and circuit deficits in adulthood
title_short	Selective postnatal excitation of neocortical pyramidal neurons results in distinctive behavioral and circuit deficits in adulthood
title_full	Selective postnatal excitation of neocortical pyramidal neurons results in distinctive behavioral and circuit deficits in adulthood
title_fullStr	Selective postnatal excitation of neocortical pyramidal neurons results in distinctive behavioral and circuit deficits in adulthood
title_full_unstemmed	Selective postnatal excitation of neocortical pyramidal neurons results in distinctive behavioral and circuit deficits in adulthood
title_sort	selective postnatal excitation of neocortical pyramidal neurons results in distinctive behavioral and circuit deficits in adulthood
publisher	Elsevier
series	iScience
issn	2589-0042
publishDate	2021-03-01
description	Summary: In genetic and pharmacological models of neurodevelopmental disorders, and human data, neural activity is altered within the developing neocortical network. This commonality begs the question of whether early enhancement in excitation might be a common driver, across etiologies, of characteristic behaviors. We tested this concept by chemogenetically driving cortical pyramidal neurons during postnatal days 4–14. Hyperexcitation of Emx1-, but not dopamine transporter-, parvalbumin-, or Dlx5/6-expressing neurons, led to decreased social interaction and increased grooming activity in adult animals. In vivo optogenetic interrogation in adults revealed decreased baseline but increased stimulus-evoked firing rates of pyramidal neurons and impaired recruitment of inhibitory neurons. Slice recordings in adults from prefrontal cortex layer 5 pyramidal neurons revealed decreased intrinsic excitability and increased synaptic E/I ratio. Together these results support the prediction that enhanced pyramidal firing during development, in otherwise normal cortex, can selectively drive altered adult circuit function and maladaptive changes in behavior.
topic	Behavioral Neuroscience Developmental Neuroscience Cellular Neuroscience
url	http://www.sciencedirect.com/science/article/pii/S2589004221001255
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Selective postnatal excitation of neocortical pyramidal neurons results in distinctive behavioral and circuit deficits in adulthood

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