• Skip to primary navigation
  • Skip to main content
  • Skip to primary sidebar

NIDA IRP

National Institute on Drug Abuse - Intramural Research Program

  National Institute on Drug Abuse | NIH IRP | Treatment Info | Emergency Contacts
  • Home
  • News
    • Featured Paper of the Month
    • Reviews to Read
    • Hot off the Press
    • IRP News
    • Awards
    • Technology Development Initiative Paper of the Month
    • Seminar Series
    • Addiction Grand Rounds
  • About
    • About NIDA IRP
    • Contact Us
    • Directions and Map
    • Careers at NIDA IRP
    • Emergency Contacts
    • Employee Assistance Resources
  • Organization
    • Faculty
    • Office of the Scientific Director
    • Office of the Clinical Director
    • Office of Education and Career Development
    • Administrative Management Branch
    • Molecular Targets and Medications Discovery Branch
    • Cellular and Neurocomputational Systems Branch
    • Molecular Neuropsychiatry Research Branch
    • Neuroimaging Research Branch
    • Behavioral Neuroscience Research Branch
    • Integrative Neuroscience Research Branch
    • Translational Addiction Medicine Branch
    • Core Facilities
    • Community Outreach Group
  • Training Programs
    • Office of Education and Career Development
    • OECD Awards
    • Summer Internship Program
    • Postbaccalaureate Program
    • Graduate Partnership Program
    • Postdoctoral Program
    • NIDA Speakers Bureau
    • Clinical Electives Program
    • Clinical Mentoring Program
  • Study Volunteers

Reversing anterior insular cortex neuronal hypoexcitability attenuates compulsive behavior in adolescent rats

Hot Off the Press – May 27, 2022

 Kshitij Jadhav, MD, Ph.D.Published in Proceedings of the National Academy of Sciences (PNAS) by Dr. Kshitij Jadhav (2019 Predoctoral trainee at NIDA-IRP), Dr. Benjamin Boutrel (Ph.D. supervisor, University of Lausanne, Switzerland) and Dr. Carl Lupica (Project Supervisor, Electrophysiology Research Section, NIDA-IRP).

Summary

Adolescents are labelled as high risk-taking impulsive individuals despite knowledge of the risks associated with this behavior.  This challenges prevailing theories of decreased top-down control of behavior thought to result from the still ‘under-developed’ prefrontal cortex in adolescence. In this new study, we found that adolescent rats demonstrated highly inflexible behaviors when making decisions in conflictual situations (for example, seeking food during mild electric shock) compared to adult rats. We found that this inflexible or compulsive behavior was associated with lower excitability of pyramidal neurons in the anterior insular cortex in adolescent rats, as well as a weaker excitatory synaptic input to these neurons. Surprisingly, there was no difference in the excitability of the pyramidal neurons in the prefrontal cortex of adolescent rats. We then found that activating the anterior insular cortex pyramidal neurons in adolescent rats with chemogenetics decreased the inflexible behavior.  This indicates a central role for the immature or undeveloped insular cortex in the expression of inflexible compulsive behavior in adolescent rats that may also be present in adolescent humans.

Publication Information

Jadhav, Kshitij S; Bernheim, Aurélien P; Aeschlimann, Léa; Kirschmann, Guylène; Decosterd, Isabelle; Hoffman, Alexander F; Lupica, Carl R; Boutrel, Benjamin

Reversing anterior insular cortex neuronal hypoexcitability attenuates compulsive behavior in adolescent rats Journal Article

In: Proc Natl Acad Sci U S A, vol. 119, no. 21, pp. e2121247119, 2022, ISSN: 1091-6490.

Abstract | Links

@article{pmid35584117,
title = {Reversing anterior insular cortex neuronal hypoexcitability attenuates compulsive behavior in adolescent rats},
author = {Kshitij S Jadhav and Aurélien P Bernheim and Léa Aeschlimann and Guylène Kirschmann and Isabelle Decosterd and Alexander F Hoffman and Carl R Lupica and Benjamin Boutrel},
url = {https://pubmed.ncbi.nlm.nih.gov/35584117/},
doi = {10.1073/pnas.2121247119},
issn = {1091-6490},
year = {2022},
date = {2022-05-01},
urldate = {2022-05-01},
journal = {Proc Natl Acad Sci U S A},
volume = {119},
number = {21},
pages = {e2121247119},
abstract = {SignificanceClinical evidence suggests that adolescents engage in dangerous activities despite understanding the risks involved, questioning the theory of decreased top-down control of the immature prefrontal cortex promoting adolescent disinhibited behaviors. In the present study, we report that adolescent rats show a much higher degree of inflexible behavior when making decisions under conflict compared to adults. Unexpectedly, we identified a lower excitability of layer 5 pyramidal neurons in the anterior insular cortex (AIC) of adolescent rats and smaller synaptic glutamatergic inputs to these cells but no difference in layer 5 prefrontal cortex pyramidal neurons. Chemogenetic activation of AIC neurons reduced persistent reward-seeking despite punishment, suggesting that the delayed maturation of the insula may promote inflexible reward-related behaviors in adolescent rats.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

SignificanceClinical evidence suggests that adolescents engage in dangerous activities despite understanding the risks involved, questioning the theory of decreased top-down control of the immature prefrontal cortex promoting adolescent disinhibited behaviors. In the present study, we report that adolescent rats show a much higher degree of inflexible behavior when making decisions under conflict compared to adults. Unexpectedly, we identified a lower excitability of layer 5 pyramidal neurons in the anterior insular cortex (AIC) of adolescent rats and smaller synaptic glutamatergic inputs to these cells but no difference in layer 5 prefrontal cortex pyramidal neurons. Chemogenetic activation of AIC neurons reduced persistent reward-seeking despite punishment, suggesting that the delayed maturation of the insula may promote inflexible reward-related behaviors in adolescent rats.

Close

  • https://pubmed.ncbi.nlm.nih.gov/35584117/
  • doi:10.1073/pnas.2121247119

Close

Primary Sidebar

News

  • All News and Featured Publications
  • Featured Paper of the Month
  • Hot off the Press
  • Reviews to Read
  • IRP News
  • Awards
  • Technology Development Initiative Paper of the Month
  • Seminar Series
Home / News Main / Hot off the Press / Reversing anterior insular cortex neuronal hypoexcitability attenuates compulsive behavior in adolescent rats
  • National Institute on Drug Abuse
  • NIH Intramural Research Program
  • National Institutes of Health
  • Health and Human Services
  • USA.GOV
  • Emergency Contacts
  • Employee Assistance
  • Treatment Information
  • Contact Us
  • Careers at NIDA IRP
  • Accessibility
  • Privacy
  • HHS Vulnerability Disclosure
  • Freedom of Information Act
  • Document Viewing Tools
  • Offsite Links
  • National Institute on Drug Abuse
  • NIH Intramural Research Program
  • National Institutes of Health
  • Health and Human Services
  • USA.GOV
  • Emergency Contacts
  • Employee Assistance
  • Treatment Information
  • Contact Us
  • Careers at NIDA IRP
  • Accessibility
  • Privacy
  • HHS Vulnerability Disclosure
  • Freedom of Information Act
  • Document Viewing Tools
  • Offsite Links

  • Home
  • News
    ▼
    • Featured Paper of the Month
    • Reviews to Read
    • Hot off the Press
    • IRP News
    • Awards
    • Technology Development Initiative Paper of the Month
    • Seminar Series
    • Addiction Grand Rounds
  • About
    ▼
    • About NIDA IRP
    • Contact Us
    • Directions and Map
    • Careers at NIDA IRP
    • Emergency Contacts
    • Employee Assistance Resources
  • Organization
    ▼
    • Faculty
    • Office of the Scientific Director
    • Office of the Clinical Director
    • Office of Education and Career Development
    • Administrative Management Branch
    • Molecular Targets and Medications Discovery Branch
    • Cellular and Neurocomputational Systems Branch
    • Molecular Neuropsychiatry Research Branch
    • Neuroimaging Research Branch
    • Behavioral Neuroscience Research Branch
    • Integrative Neuroscience Research Branch
    • Translational Addiction Medicine Branch
    • Core Facilities
    • Community Outreach Group
  • Training Programs
    ▼
    • Office of Education and Career Development
    • OECD Awards
    • Summer Internship Program
    • Postbaccalaureate Program
    • Graduate Partnership Program
    • Postdoctoral Program
    • NIDA Speakers Bureau
    • Clinical Electives Program
    • Clinical Mentoring Program
  • Study Volunteers