Inhibition of mediodorsal thalamus disrupts thalamofrontal connectivity and cognition
Open accessAbstract
Cognitive deficits are central to schizophrenia, but the underlying mechanisms still remain unclear. Imaging studies performed in patients point to decreased activity in the mediodorsal thalamus (MD) and reduced functional connectivity between the MD and prefrontal cortex (PFC) as candidate mechanisms. However, a causal link is still missing. We used a pharmacogenetic approach in mice to diminish MD neuron activity and examined the behavioral and physiological consequences. We found that a subtle decrease in MD activity is sufficient to trigger selective impairments in prefrontal-dependent cognitive tasks. In vivo recordings in behaving animals revealed that MD-PFC beta-range synchrony is enhanced during acquisition and performance of a working memory task. Decreasing MD activity interfered with this task-dependent modulation of MD-PFC synchrony, which correlated with impaired working memory. These findings suggest that altered MD activity is sufficient to disrupt prefrontal-dependent cognitive behaviors and could contribute to the cognitive symptoms observed in schizophrenia.
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Chemogenetic technology has not yet been used to directly investigate OCD, but has been used to probe circuits underlying schizophrenia and major depressive disorder.
“Though this technology has not yet been used to directly investigate OCD, it has already been used to probe circuits underlying complex neuropsychiatric disorders such as schizophrenia 97 and major depressive disorder 98.”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [97]
Individuals with schizophrenia have deficits in cognitive, but not motor, learning.
“Individuals with this disorder may experience impairments in executive function and have been found to have deficits in cognitive, but not motor, learning (Foerde et al., 2008; Parnaudeau et al., 2013).”
From Cortico-striatal-thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment (2016) · cites this paper as Parnaudeau et al., 2013
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- Authors
- Parnaudeau, S., O’Neill, P.-K., Bolkan, S. S., Ward, R. D., Abbas, A. I., Roth, B. L., Balsam, P. D., Gordon, J. A., & Kellendonk, C.
- Affiliations
- New York State Psychiatric Institute (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Gordon, Joshua A.
- Kellendonk, Christoph
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 77
- Issue
- 6
- Pages
- 1151-1162
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3629822
- OpenAlex
- W2039170261
- Cited by
- 387
- References
- 61
- Citations by year
- 2026: 17 · 2025: 25 · 2024: 22 · 2023: 25 · 2022: 29 · 2021: 48 · 2020: 37 · 2019: 17 · 2018: 37 · 2017: 33 · 2016: 27 · 2015: 36 · 2014: 18 · 2013: 16
- FWCI
- 22.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 384 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- HAL (submittedVersion)
- UNC Libraries
- Funders
- Hope for Depression Research Foundation
- International Mental Health Research Organization
- Leon Levy Foundation
- National Alliance for Research on Schizophrenia and Depression
- Fondation Fyssen
- National Institutes of Health (5r01mh096274-06)
- National Institute of Mental Health (U19MH082441, R01-MH096274, R01MH061887, R21MH093887, R01MH081968, R25MH086466)
- National Institute of General Medical Sciences (T32GM007250)
- National Institute of Neurological Disorders and Stroke
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007430)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- mediodorsal thalamus, prefrontal cortex, working memory, schizophrenia, cognitive impairment, beta oscillations, neuronal synchronization, mouse model
- MeSH terms
- Animals, Cognition, Male, Memory, Short-Term, Mice, Inbred C57BL, Neural Inhibition, Neural Pathways, Psychomotor Performance, Prefrontal Cortex, Mediodorsal Thalamic Nucleus, Mice
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