The initial stage of reversal learning is impaired in mice hemizygous for the vesicular glutamate transporter (VGluT1)
Open accessAbstract
Behavioral flexibility is a complex cognitive function that is necessary for survival in changeable environments. Patients with schizophrenia or Parkinson's disease often suffer from cognitive rigidity, reducing their capacity to function in society. Patients and rodent models with focal lesions in the prefrontal cortex (PFC) show similar rigidity, owing to the loss of PFC regulation of subcortical reward circuits involved in behavioral flexibility. The vesicular glutamate transporter (VGluT1) is preferentially expressed at modulatory synapses, including PFC neurons that project to components of the reward circuit (such as the nucleus accumbens, NAc). VGluT1+/− mice display behavioral phenotypes matching many symptoms of schizophrenia, and VGluT1 expression is reduced in the PFC of patients with schizophrenia and Parkinson's disease. Thus, it appears likely that VGluT1‐expressing synapses from PFC play a key role in behavioral flexibility. To examine this hypothesis, we studied behavioral flexibility in VGluT1+/− mice by testing reversal learning in a visual discrimination task. Here, we show that VGluT1+/− mice acquired the initial visual discrimination at the same rate as controls. However, they failed to suppress responses to the previously rewarded stimulus following reversal of reward contingencies. Thus, our genetic disruption of modulatory glutamatergic signaling, including that arising from PFC, appears to have impaired the first stage of reversal learning (extinguishing responses to previously rewarded stimuli). Our data show that this deficit stems from a preservative phenotype. These findings suggest that glutamatergic regulation from the cortex is important for behavioral flexibility and the disruption of this pathway may be relevant in diseases such as schizophrenia.
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Mice hemizygous for vesicular glutamate transporter 1 show impaired reversal learning due to increased perseveration in a visual discrimination task.
“For example, mice hemizygous for the vesicular glutamate transporter 1, which controls the number and size of synaptic vesicles in excitatory synapses, show impaired reversal learning due to increased perseveration in a visual discrimination task (Granseth et al 2015).”
From Prefrontal cortex executive processes affected by stress in health and disease (2018) · cites this paper as Granseth et al 2015
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- Authors
- Granseth, B., Andersson, F. K., & Lindström, S. H.
- Affiliations
- Linköping University (SE)
- Corresponding author
- Lindström, S. H.
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2015-07
- Volume
- 14
- Issue
- 6
- Pages
- 477-485
- ISSN
- 1601-183X (ISSN-L)
- 1601-1848
- OpenAlex
- W1905939660
- Cited by
- 23
- References
- 36
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 2
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes Brain & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vetenskapsrådet (2862, 3050)
- Linköpings Universitet
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- reversal learning, VGLUT1, behavioral flexibility, prefrontal cortex, glutamatergic signaling, nucleus accumbens, reward systems, schizophrenia, cognitive rigidity, visual discrimination
- MeSH terms
- Behavior Rating Scale, Animals, Male, Parkinson Disease, Reversal Learning, Reward, Schizophrenia, Prefrontal Cortex, Mice, Knockout, Vesicular Glutamate Transport Protein 1, Mice, Hemizygote
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