Academic Journal
Mediodorsal Thalamus Hypofunction Impairs Flexible Goal-Directed Behavior
| العنوان: | Mediodorsal Thalamus Hypofunction Impairs Flexible Goal-Directed Behavior |
|---|---|
| المؤلفون: | Parnaudeau, Sebastien, Taylor, Kathleen, Bolkan, Scott S., Ward, Ryan D., Balsam, Peter D., Kellendonk, Christoph |
| المساهمون: | Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), National Alliance for Research on Schizophrenia and Depression young investigator awards from the Brain and Behavior Research Foundation, National Institutes of Health MH068073, National Institute of Mental Health 1K99MH095835-01, National Institute of Neurological Disorders and Stroke |
| المصدر: | ISSN: 0006-3223 ; Biological Psychiatry ; https://hal.archives-ouvertes.fr/hal-01544141 ; Biological Psychiatry, Elsevier, 2015, 77 (5), pp.445-453. ⟨10.1016/j.biopsych.2014.03.020⟩. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Mediodorsal thalamus, Goal-directed behavior, DREADD system, Behavioral flexibility, Pavlovian-to-instrumental transfer, Schizophrenia, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], psy |
| الوصف: | International audience ; BACKGROUND: Cognitive inflexibility is a core symptom of several mental disorders including schizophrenia. Brain imaging studies in schizophrenia patients performing cognitive tasks have reported decreased activation of the mediodorsal thalamus (MD). Using a pharmacogenetic approach to model MD hypofunction, we recently showed that decreasing MD activity impairs reversal learning in mice. While this demonstrates causality between MD hypofunction and cognitive inflexibility, questions remain about the elementary cognitive processes that account for the deficit. METHODS: Using the Designer Receptors Exclusively Activated by Designer Drugs system, we reversibly decreased MD activity during behavioral tasks assessing elementary cognitive processes inherent to flexible goal-directed behaviors, including extinction, contingency degradation, outcome devaluation, and Pavlovian-to-instrumental transfer (n = 134 mice). RESULTS: While MD hypofunction impaired reversal learning, it did not affect the ability to learn about nonrewarded cues or the ability to modulate action selection based on the outcome value. In contrast, decreasing MD activity delayed the ability to adapt to changes in the contingency between actions and their outcomes. In addition, while Pavlovian learning was not affected by MD hypofunction, decreasing MD activity during Pavlovian learning impaired the ability of conditioned stimuli to modulate instrumental behavior. CONCLUSIONS: Mediodorsal thalamus hypofunction causes cognitive inflexibility reflected by an impaired ability to adapt actions when their consequences change. Furthermore, it alters the encoding of environmental stimuli so that they cannot be properly utilized to guide behavior. Modulating MD activity could be a potential therapeutic strategy for promoting adaptive behavior in human subjects with cognitive inflexibility. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://hal.archives-ouvertes.fr/hal-01544141 |
| الاتاحة: | https://hal.archives-ouvertes.fr/hal-01544141 |
| Rights: | undefined |
| رقم الانضمام: | edsbas.2E6F981D |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |