Cited by 186Neuroscience and Neuropharmacology ResearchNeural dynamics and brain functionMemory and Neural Mechanisms

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Thalamic Control of Cognition and Social Behavior Via Regulation of Gamma-Aminobutyric Acidergic Signaling and Excitation/Inhibition Balance in the Medial Prefrontal Cortex

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Ferguson, Brielle R., Gao, Wen-Jun·2018·Biological Psychiatry

DOI 10.1016/j.biopsych.2017.11.033PMC PMC5862785

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Abstract

Background The mediodorsal thalamus plays a critical role in cognition through its extensive innervation of the medial prefrontal cortex (mPFC), but how the two structures cooperate at the single-cell level to generate associated cognitive functions and other mPFC-dependent behaviors remains elusive. Maintaining the proper balance between excitation and inhibition (E/I balance) is of principal importance for organizing cortical activity. Furthermore, the PFC E/I balance has been implicated in successful execution of multiple PFC-dependent behaviors in both animal research and the context of human psychiatric disorders.Methods Here, we used a pharmacogenetic strategy to decrease mediodorsal thalamic activity in adult male rats and evaluated the consequences for E/I balance in PFC pyramidal neurons as well as cognition, social interaction, and anxiety.Results We found that dampening mediodorsal thalamic activity caused significant reductions in gamma-aminobutyric acidergic signaling and increased E/I balance in the mPFC and was concomitant with abnormalities in these behaviors. Furthermore, by selectively activating parvalbumin interneurons in the mPFC with a novel pharmacogenetic approach, we restored gamma-aminobutyric acidergic signaling and E/I balance as well as ameliorated all behavioral impairments.Conclusions These findings underscore the importance of thalamocortical activation of mPFC gamma-aminobutyric acidergic interneurons in a broad range of mPFC-dependent behaviors. Furthermore, they highlight this circuitry as a platform for therapeutic investigation in psychiatric diseases that involve impairments in PFC-dependent behaviors.

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Authors: Ferguson, B. R., & Gao, W.-J.
Affiliations: Drexel University (US)
Corresponding author: Gao, Wen-Jun
ORCID: Ferguson, Brielle R.
Gao, Wen-Jun
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2018-04
Volume: 83
Issue: 8
Pages: 657-669
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2017.11.033
PMC: PMC5862785
OpenAlex: W2774489697
Cited by: 186
References: 59
Citations by year: 2026: 24 · 2025: 26 · 2024: 27 · 2023: 26 · 2022: 18 · 2021: 24 · 2020: 19 · 2019: 17 · 2018: 5
FWCI: 5.48
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health/National Institute of Mental Health (F31MH111361, R01MH085666, R21MH111609)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: mediodorsal thalamus, medial prefrontal cortex, excitation-inhibition balance, GABAergic neurotransmission, parvalbumin interneurons, thalamocortical circuits, cognition, social behavior, anxiety, pyramidal neurons, mental illness
MeSH terms: Animals, Behavior, Animal, Cognition, gamma-Aminobutyric Acid, Interneurons, Male, Pharmacogenetics, Social Behavior, Signal Transduction, Rats, Sprague-Dawley, Prefrontal Cortex, Patch-Clamp Techniques, GABA Agents, Excitatory Postsynaptic Potentials, Mediodorsal Thalamic Nucleus, Rats, Inhibitory Postsynaptic Potentials, GABAergic Neurons

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Thalamic Control of Cognition and Social Behavior Via Regulation of Gamma-Aminobutyric Acidergic Signaling and Excitation/Inhibition Balance in the Medial Prefrontal Cortex

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