Lesions to the ventral, but not the dorsal, medial prefrontal cortex enhance latent inhibition
Open accessAbstract
The acquisition of a conditioned response to a stimulus when it is paired with a reinforcer is retarded if the stimulus has previously been repeatedly pre‐exposed in the absence of the reinforcer. This effect, called latent inhibition, has previously been found to be insensitive to lesions of the medial prefrontal cortex (mPFC) in rats. Using an on‐baseline conditioned emotional response procedure, which is especially sensitive to small variations in the absolute magnitude of latent inhibition, we found increased latent inhibition following excitotoxic lesions of the mPFC (Experiment 1) or the ventral mPFC alone (Experiment 2) as compared with sham‐operated control rats. Lesions restricted to the dorsal mPFC, however, were without effect (Experiment 2). These results are consistent with those of experiments employing another type of interference procedure, extinction. Together, these findings suggest that when different contingencies between a stimulus and a reinforcer are established in separate learning phases, lesions to the ventral mPFC result in increased interference between first‐learned and second‐learned contingencies. As a consequence, retrieval of the second‐learned contingency is impaired, and performance is dominated by the first‐learned contingency. These findings are discussed in light of the use of latent inhibition to model cognitive deficits in schizophrenia.
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Extensive research in rodents and non-human primates emphasises major roles of fronto-striatal circuits in the ability to respond flexibly.
“Extensive research in rodents and non-human primates emphasises the major roles of fronto-striatal circuits in the ability to respond flexibly [34–42].”
Cites
The role of ventromedial prefrontal cortex in the recovery of extinguished fear
Quirk, G. J., Russo, G. K., Barron, J. L., & Lebron, K. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-16-06225.2000 · Cited by 957 · cited 1× · see citing works
“Several studies have also reported enhanced spontaneous recovery, reinstatement and context renewal of conditioned responding following extinction in animals with IL lesions (Quirk et al., 2000; Rhodes & Killcross, 2004, 2007).”
BackgroundExtinction of emotional learning: contribution of medial prefrontal cortex
Morgan, M. A., Romanski, L. M., & LeDoux, J. E. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90241-c · Cited by 897 · cited 1× · see citing works
“Morgan et al. (1993) found that lesioned animals required more sessions of extinction training to reach criterion performance than did control animals.”
BackgroundRay, J. P., & Price, J. L. (1992) · Journal of Comparative Neurology · doi:10.1002/cne.903230204 · Cited by 326 · see citing works
Neural circuits subserving behavioral flexibility and their relevance to schizophrenia
Floresco, S. B., Zhang, Y., & Enomoto, T. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.12.001 · Cited by 298 · see citing works
Extinction memory is impaired in schizophrenia
Holt, D. J., Lebron-Milad, K., Milad, M. R., Rauch, S. L., Pitman, R. K., Orr, S. P., Cassidy, B. S., Walsh, J. P., & Goff, D. C. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.09.017 · Cited by 170 · cited 1× · see citing works
“…those seen in patients with schizophrenia: an enhanced latent inhibition effect has been observed in patients with chronic schizophrenia (Rascle et al., 2001; Gal et al., 2009), and Holt et al. (2009) have recently shown that schizophrenic patient fail to recall extinction of fear conditioning.”
BackgroundWeiner, I., Gal, G., Rawlins, J. N. P., & Feldon, J. (1996) · Behavioural Brain Research · doi:10.1016/s0166-4328(96)00051-4 · Cited by 146 · see citing works
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Enomoto, T., Tse, M. T., & Floresco, S. B. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.09.038 · Cited by 179 · see citing works
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Haddon, J. E., Titherage, D., Heckenast, J. R., Carter, J., Owen, M. J., Hall, J., Wilkinson, L. S., & Jones, M. W. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02969-x · Cited by 6 · see citing works
“In addition to the reduced accumbens connectivity seen in Cy fi p1 + / − rats, increased input from the prefrontal cortex and hippocampus — both regions that are linked with cognitive fl exibility [37, 76] and neurodevelopmental disease [77, 78] — was also observed.”
BackgroundSelf-citation
- Authors
- George, D. N., Duffaud, A. M., Pothuizen, H. H. J., Haddon, J. E., & Killcross, S.
- Affiliations
- Cardiff University (GB)
- Institut National de la Recherche Agronomique (FR)
- ETH Zurich (CH)
- UNSW Sydney (AU)
- Corresponding author
- George, David N.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2010-04
- Volume
- 31
- Issue
- 8
- Pages
- 1474-1482
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2049540001
- Cited by
- 27
- References
- 6
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 4 · 2013: 1 · 2012: 2
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Repository@Hull (Worktribe) (University of Hull) (submittedVersion, cc-by)
- Funders
- Eli Lilly and Company
- Royal Society
- Cardiff University
- Biotechnology and Biological Sciences Research Council (BB/E011969/1)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- latent inhibition, medial prefrontal cortex, ventromedial prefrontal cortex, dorsomedial prefrontal cortex, excitotoxic lesions, conditioned emotional response, extinction
- MeSH terms
- Animals, Conditioning, Classical, Emotions, Inhibition, Psychological, Male, Neuropsychological Tests, Photomicrography, Reinforcement, Psychology, Reinforcement Schedule, Prefrontal Cortex, Rats
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