Home > Research > Publications & Outputs > Ketamine Restores Thalamic-Prefrontal Cortex Fu...

Electronic data

  • Hughes et al., 2019

    Rights statement: This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. You are not required to obtain permission to reuse this article.

    Final published version, 1.07 MB, PDF document

    Available under license: CC BY: Creative Commons Attribution 4.0 International License

Links

Text available via DOI:

View graph of relations

Ketamine Restores Thalamic-Prefrontal Cortex Functional Connectivity in a Mouse Model of Neurodevelopmental Disorder-Associated 2p16.3 Deletion

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Published

Standard

Ketamine Restores Thalamic-Prefrontal Cortex Functional Connectivity in a Mouse Model of Neurodevelopmental Disorder-Associated 2p16.3 Deletion. / Hughes, Rebecca; Whittingham-Dowd, Jayde; Simmons, Rachel; Clapcote, Stephen; Broughton, Susan; Dawson, Neil.

In: Cerebral Cortex, Vol. 0, No. 4, 01.04.2020, p. 2358–2371.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

APA

Vancouver

Author

Bibtex

@article{4f2793d339e1473c8587777e952ca03b,
title = "Ketamine Restores Thalamic-Prefrontal Cortex Functional Connectivity in a Mouse Model of Neurodevelopmental Disorder-Associated 2p16.3 Deletion",
abstract = "2p16.3 deletions, involving heterozygous NEUREXIN1 (NRXN1) deletion, dramatically increase the risk of developing neurodevelopmental disorders, including autism and schizophrenia. We have little understanding of how NRXN1 heterozygosity increases the risk of developing these disorders, particularly in terms of the impact on brain and neurotransmitter system function and brain network connectivity. Thus, here we characterize cerebral metabolism and functional brain network connectivity in Nrxn1α heterozygous mice (Nrxn1α+/− mice), and assess the impact of ketamine and dextro-amphetamine on cerebral metabolism in these animals. We show that heterozygous Nrxn1α deletion alters cerebral metabolism in neural systems implicated in autism and schizophrenia including the thalamus, mesolimbic system, and select cortical regions. Nrxn1α heterozygosity also reduces the efficiency of functional brain networks, through lost thalamic “rich club” and prefrontal cortex (PFC) hub connectivity and through reduced thalamic-PFC and thalamic “rich club” regional interconnectivity. Subanesthetic ketamine administration normalizes the thalamic hypermetabolism and partially normalizes thalamic disconnectivity present in Nrxn1α+/− mice, while cerebral metabolic responses to dextro-amphetamine are unaltered. The data provide new insight into the systems-level impact of heterozygous Nrxn1α deletion and how this increases the risk of developing neurodevelopmental disorders. The data also suggest that the thalamic dysfunction induced by heterozygous Nrxn1α deletion may be NMDA receptor-dependent.",
keywords = "autism, functional brain imaging, graph theory, NMDA receptor, schizophrenia",
author = "Rebecca Hughes and Jayde Whittingham-Dowd and Rachel Simmons and Stephen Clapcote and Susan Broughton and Neil Dawson",
year = "2020",
month = apr,
day = "1",
doi = "10.1093/cercor/bhz244",
language = "English",
volume = "0",
pages = "2358–2371",
journal = "Cerebral Cortex",
issn = "1047-3211",
publisher = "Oxford University Press",
number = "4",

}

RIS

TY - JOUR

T1 - Ketamine Restores Thalamic-Prefrontal Cortex Functional Connectivity in a Mouse Model of Neurodevelopmental Disorder-Associated 2p16.3 Deletion

AU - Hughes, Rebecca

AU - Whittingham-Dowd, Jayde

AU - Simmons, Rachel

AU - Clapcote, Stephen

AU - Broughton, Susan

AU - Dawson, Neil

PY - 2020/4/1

Y1 - 2020/4/1

N2 - 2p16.3 deletions, involving heterozygous NEUREXIN1 (NRXN1) deletion, dramatically increase the risk of developing neurodevelopmental disorders, including autism and schizophrenia. We have little understanding of how NRXN1 heterozygosity increases the risk of developing these disorders, particularly in terms of the impact on brain and neurotransmitter system function and brain network connectivity. Thus, here we characterize cerebral metabolism and functional brain network connectivity in Nrxn1α heterozygous mice (Nrxn1α+/− mice), and assess the impact of ketamine and dextro-amphetamine on cerebral metabolism in these animals. We show that heterozygous Nrxn1α deletion alters cerebral metabolism in neural systems implicated in autism and schizophrenia including the thalamus, mesolimbic system, and select cortical regions. Nrxn1α heterozygosity also reduces the efficiency of functional brain networks, through lost thalamic “rich club” and prefrontal cortex (PFC) hub connectivity and through reduced thalamic-PFC and thalamic “rich club” regional interconnectivity. Subanesthetic ketamine administration normalizes the thalamic hypermetabolism and partially normalizes thalamic disconnectivity present in Nrxn1α+/− mice, while cerebral metabolic responses to dextro-amphetamine are unaltered. The data provide new insight into the systems-level impact of heterozygous Nrxn1α deletion and how this increases the risk of developing neurodevelopmental disorders. The data also suggest that the thalamic dysfunction induced by heterozygous Nrxn1α deletion may be NMDA receptor-dependent.

AB - 2p16.3 deletions, involving heterozygous NEUREXIN1 (NRXN1) deletion, dramatically increase the risk of developing neurodevelopmental disorders, including autism and schizophrenia. We have little understanding of how NRXN1 heterozygosity increases the risk of developing these disorders, particularly in terms of the impact on brain and neurotransmitter system function and brain network connectivity. Thus, here we characterize cerebral metabolism and functional brain network connectivity in Nrxn1α heterozygous mice (Nrxn1α+/− mice), and assess the impact of ketamine and dextro-amphetamine on cerebral metabolism in these animals. We show that heterozygous Nrxn1α deletion alters cerebral metabolism in neural systems implicated in autism and schizophrenia including the thalamus, mesolimbic system, and select cortical regions. Nrxn1α heterozygosity also reduces the efficiency of functional brain networks, through lost thalamic “rich club” and prefrontal cortex (PFC) hub connectivity and through reduced thalamic-PFC and thalamic “rich club” regional interconnectivity. Subanesthetic ketamine administration normalizes the thalamic hypermetabolism and partially normalizes thalamic disconnectivity present in Nrxn1α+/− mice, while cerebral metabolic responses to dextro-amphetamine are unaltered. The data provide new insight into the systems-level impact of heterozygous Nrxn1α deletion and how this increases the risk of developing neurodevelopmental disorders. The data also suggest that the thalamic dysfunction induced by heterozygous Nrxn1α deletion may be NMDA receptor-dependent.

KW - autism

KW - functional brain imaging

KW - graph theory

KW - NMDA receptor

KW - schizophrenia

U2 - 10.1093/cercor/bhz244

DO - 10.1093/cercor/bhz244

M3 - Journal article

VL - 0

SP - 2358

EP - 2371

JO - Cerebral Cortex

JF - Cerebral Cortex

SN - 1047-3211

IS - 4

ER -