The Functional Localization of VTA in Ketamine-Induced Dysfunction of Auditory Decision-Making
DOI: 10.23977/phpm.2025.050217 | Downloads: 5 | Views: 131
Author(s)
Fanrui Liu 1
Affiliation(s)
1 Yali Middle School, Hunan, 428 Laodong Western Road, Yuhua District, Changsha, Hunan, 410007, China
Corresponding Author
Fanrui LiuABSTRACT
This study investigates the functional localization of the ventral tegmental area (VTA) in ketamine-induced disruptions of auditory decision-making in mice, with the broader goal of elucidating the neural mechanisms underlying perceptual disturbances, such as hallucinations. Although ketamine is increasingly used in clinical settings, particularly for treatment-resistant depression, the specific brain circuits mediating its adverse cognitive and perceptual effects remain inadequately characterized. To address this knowledge gap, we employed a multi-modal experimental approach integrating behavioral testing, stereotaxic microinjections, immunofluorescence staining, and in vivo neuroimaging techniques to assess the VTA’s role in sensory-cognitive processing following ketamine administration. Mice were trained in a two-alternative forced choice auditory task designed to evaluate their ability to discriminate between different tone frequencies. Compared to controls, ketamine-treated mice exhibited significantly flattened psychometric function, indicative of impaired auditory discrimination and degraded stimulus-response mapping, resembling hallucinatory-like behavior. Immunofluorescence analysis revealed robust upregulation of c-Fos expression within the VTA, suggesting increased neuronal activity. In parallel, in vivo measurements of 8 auditory-evoked trunk signal intensity showed attenuated responses in the ketamine group, further implicating disrupted sensory signal transmission. These converging data indicate that ketamine induces both functional and molecular alterations in the VTA, a dopaminergic hub implicated in reward, motivation, and sensory modulation.
KEYWORDS
Auditory Decision-Making, VTA, Ketamine, AcousmaCITE THIS PAPER
Fanrui Liu, The Functional Localization of VTA in Ketamine-Induced Dysfunction of Auditory Decision-Making. MEDS Public Health and Preventive Medicine (2025) Vol. 5: 116-123. DOI: http://dx.doi.org/10.23977/phpm.2025.050217.
REFERENCES
[1] Verharen JPH, de Jong JW, Roelofs TJM, Huffels CFM, van Zessen R, Luijendijk MCM, Hamelink R, Willuhn I, den Ouden HEM, van der Plasse G, Adan RAH, Vanderschuren LJMJ. A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states. Nat Commun. 2018 Feb 21;9(1):731. doi: 10.1038/s41467-018-03087-1 . PMID: 29467419; PMCID: PMC5821846.
[2] Adams SA, Nasrallah HA. Multiple retinal anomalies in schizophrenia. Schizophr Res. 2018 May; 195: 3-12. doi: 10.1016/j.schres.2017.07.018. Epub 2017 Jul 27. PMID: 28755877.
[3] Kim JW, Suzuki K, Kavalali ET, Monteggia LM. Ketamine: Mechanisms and Relevance to Treatment of Depression. Annu Rev Med. 2024 Jan 29;75: 129-143. doi: 10.1146/annurev-med-051322-120608. Epub 2023 Sep 20. PMID: 37729028.
[4] Carboni E, Carta AR, Carboni E, Novelli A. Repurposing Ketamine in Depression and Related Disorders: Can This Enigmatic Drug Achieve Success? Front Neurosci. 2021 Apr 30;15:657714. doi: 10.3389/fnins.2021.657714. PMID: 33994933; PMCID: PMC8120160.
[5] Egerton A, Grace AA, Stone J, Bossong MG, Sand M, McGuire P. Glutamate in schizophrenia: Neurodevelopmental perspectives and drug development. Schizophr Res. 2020 Sep;223:59-70. doi: 10.1016/j.schres. 2020. 09.013. Epub 2020 Oct 16. PMID: 3307107
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