liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
The initial stage of reversal learning is impaired in mice hemizygous for the vesicular glutamate transporter (VGluT1)
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
2015 (English)In: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 14, no 6, 477-485 p.Article in journal (Refereed) Published
Abstract [en]

Behavioral flexibility is a complex cognitive function that is necessary for survival in changeable environments. Patients with schizophrenia or Parkinsons 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 Parkinsons 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.

Place, publisher, year, edition, pages
Wiley: 12 months , 2015. Vol. 14, no 6, 477-485 p.
Keyword [en]
Behavioral flexibility; dorsomedial thalamus; modulatory synapse; nucleus accumbens; prefrontal cortex; reversal learning; schizophrenia; striatum; VGLUT; visual discrimination
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-120746DOI: 10.1111/gbb.12230ISI: 000358429300004PubMedID: 26113146OAI: oai:DiVA.org:liu-120746DiVA: diva2:848194
Note

Funding Agencies|Linkoping University; Swedish Research Council [2862, 3050]

Available from: 2015-08-24 Created: 2015-08-24 Last updated: 2016-04-11

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Granseth, BjörnLindström, Sarah H
By organisation
Division of Cell BiologyFaculty of Medicine and Health Sciences
In the same journal
Genes, Brain and Behavior
Neurosciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 79 hits
ReferencesLink to record
Permanent link

Direct link