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Aspiration removal of orbitofrontal cortex disrupts cholinergic fibers of passage to anterior cingulate cortex in rhesus macaques

Lookup NU author(s): Dr Mark EldridgeORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.The study of anthropoid nonhuman primates has provided valuable insights into frontal cortex function in humans, as these primates share similar frontal anatomical subdivisions (Murray et al. 2011). Causal manipulation studies have been instrumental in advancing our understanding of this area. One puzzling finding is that macaques with bilateral aspiration removals of orbitofrontal cortex (OFC) are impaired on tests of cognitive flexibility and emotion regulation, whereas those with bilateral excitotoxic lesions of OFC are not (Rudebeck et al. 2013). This discrepancy is attributed to the inadvertent disruption of fibers of passage by aspiration lesions but not by excitotoxic lesions. Which fibers of passage are responsible for the impairments observed? One candidate is cholinergic fibers originating in the nucleus basalis magnocellularis (NBM) and passing nearby or through OFC on their way to other frontal cortex regions (Kitt et al. 1987). To investigate this possibility, we performed unilateral aspiration lesions of OFC in three macaques, and then compared cholinergic innervation of the anterior cingulate cortex (ACC) between hemispheres. Histological assessment revealed diminished cholinergic innervation in the ACC of hemispheres with OFC lesions relative to intact hemispheres. This finding indicates that aspiration lesions of the OFC disrupt cholinergic fibers of passage, and suggests the possibility that loss of cholinergic inputs to ACC contributes to the impairments in cognitive flexibility and emotion regulation observed after aspiration but not excitotoxic lesions of OFC.


Publication metadata

Author(s): Eldridge MAG, Mohanty A, Hines BE, Kaskan PM, Murray EA

Publication type: Article

Publication status: Published

Journal: Brain Structure and Function

Year: 2024

Volume: 229

Issue: 4

Pages: 1011-1019

Print publication date: 01/05/2024

Online publication date: 19/03/2024

Acceptance date: 19/02/2024

Date deposited: 19/02/2025

ISSN (print): 1863-2653

ISSN (electronic): 1863-2661

Publisher: Springer Science and Business Media Deutschland GmbH

URL: https://doi.org/10.1007/s00429-024-02776-6

DOI: 10.1007/s00429-024-02776-6

Data Access Statement: The full dataset is available in the Figshare repository, DOI: https://doi.org/10.6084/m9.figshare.244991

PubMed id: 38502331


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Funding

Funder referenceFunder name
Department of Health and Human Services (annual report number ZIAMH002887
Intramural Research Program
National Institute of Mental Health
National Institutes of Health

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