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The initial stage of reversal learning is impaired in mice hemizygous for the vesicular glutamate transporter (VGluT1)
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.ORCID-id: 0000-0001-7526-923X
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.ORCID-id: 0000-0001-7952-8120
2015 (engelsk)Inngår i: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 14, nr 6, s. 477-485Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Wiley: 12 months , 2015. Vol. 14, nr 6, s. 477-485
Emneord [en]
Behavioral flexibility; dorsomedial thalamus; modulatory synapse; nucleus accumbens; prefrontal cortex; reversal learning; schizophrenia; striatum; VGLUT; visual discrimination
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Identifikatorer
URN: urn:nbn:se:liu:diva-120746DOI: 10.1111/gbb.12230ISI: 000358429300004PubMedID: 26113146OAI: oai:DiVA.org:liu-120746DiVA, id: diva2:848194
Merknad

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

Tilgjengelig fra: 2015-08-24 Laget: 2015-08-24 Sist oppdatert: 2018-01-25

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