The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Thalamic Control of Cognition and Social Behavior Via Regulation of Gamma-Aminobutyric Acidergic Signaling and Excitation/Inhibition Balance in the Medial Prefrontal Cortex
Open accessAbstract
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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“Dampening thalamic activity causes significant reductions of GABA signaling in the mPFC and concomitant abnormalities in cognition and social interaction, which is ameliorated by selectively activating mPFC PV+ interneurons 34.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [34]
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Medial Frontal Cortex Mediates Perceptual Attentional Set Shifting in the Rat
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Ferguson, B. R., & Gao, W.-J. (2018) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00037 · Cited by 594
Self-citationYan, Z., & Rein, B. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01092-3 · Cited by 300
Thalamic regulation of switching between cortical representations enables cognitive flexibility
Rikhye, R. V., Gilra, A., & Halassa, M. M. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0269-z · Cited by 324
Anterior cingulate cortex dysfunction underlies social deficits in Shank3 mutant mice
Guo, B., Chen, J., Chen, Q., Ren, K., Feng, D., Mao, H., Yao, H., Yang, J., Liu, H., Liu, Y., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0445-9 · Cited by 287
Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications
Jiang, C.-C., Lin, L., Long, S., Ke, X., Fukunaga, K., Lu, Y., & Han, F. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01081-0 · Cited by 295
Metadata
- Authors
- Ferguson, B. R., & Gao, W.-J.
- Affiliations
- Drexel University (US)
- Corresponding author
- Gao, Wen-Jun
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 83
- Issue
- 8
- Pages
- 657-669
- ISSN
- 0006-3223 (ISSN-L)
- 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
- 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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