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Decades of research have identified a role for dopamine neurotransmission in prefrontal cortical function and flexible cognition. Abnormal dopamine neurotransmission underlies many cases of cognitive dysfunction. New techniques using optogenetics have allowed for ever more precise functional segregation of areas within the prefrontal cortex, which underlie separate cognitive functions. Learning theory predictions have provided a very useful framework for interpreting the neural activity of dopamine neurons, yet even dopamine neurons present a range of responses, from salience to prediction error signaling. The functions of areas like the Lateral Habenula have been recently described, and its role, presumed to be substantial, is largely unknown. Many other neural systems interact with the dopamine system, like cortical GABAergic interneurons, making it critical to understand those systems and their interactions with dopamine in order to fully appreciate dopamine's role in flexible behavior. Advances in human clinical research, like exome sequencing, are driving experimental hypotheses which will lead to fruitful new research directions, but how do (or should?) these clinical findings inform basic research? Following new information from these techniques, we may begin to develop a fresh understanding of human disease states which will inform novel treatment possibilities. However, we need an operational framework with which to interpret these new findings. Therefore, the purpose of this Research Topic is to integrate what we know of dopamine, the prefrontal cortex and flexible behavior into a clear framework, which will illuminate clear, testable directions for future research.

behavioral flexibility --- Dopamine --- medial prefrontal cortex (mPFC) --- Attentional set-shifting --- basal forebrain --- anterior cingulate cortex (ACC) --- endocannabinoid system --- lateral habenula (LHb) --- Locus coeruleus (LC) --- motivational salience

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Pendant la période prénatale et postnatale, l’organisme est très sensible aux facteurs environnementaux en raison de la mise en place et le développement des différents systèmes, tant psychologiques que biologiques. 
Les retardateurs de flamme (PBDEs), utilisés pour ralentir le processus de combustion, sont de polluants persistants qui interagissent avec l’axe thyroïdien. Cette propriété les identifie comme des perturbateurs endocriniens. Chez l’enfant, l’exposition aux PBDEs est associée à une diminution des scores de quotient intellectuel (QI), ainsi qu’à un risque augmenté de déficits d’attention et de troubles du spectre de l'autisme Les modèles animaux mettent en évidence des effets neurotoxiques de l’exposition aux PBDEs. Des altérations comportementales persistantes sont observées après une exposition périnatale, en particulier dans le domaine de l’activité locomotrice et de la cognition, ainsi qu’une diminution des concentrations plasmatiques des hormones thyroïdiennes.
Le but de cette étude est de déterminer les effets d’une exposition périnatale au BDE-47 – in utero et via la lactation –sur le fonctionnement biologique et le comportement. Dans ce but, nous avons exposé des souris C57bl/6 gestantes à une solution contrôle, ou contenant un PBDE, le BDE-47 (0.03 ou 1 mg/kg), du jour de gestation 6 jusqu’au 21e après la mise bas.
Chez les souriceaux, nous avons évalué l’accumulation du BDE-47 dans les cerveaux à travers une chromatographie en phase gazeuse couplée à la spectrométrie de masse (CG-MC). La fonction thyroïdienne a été examinée par dosage radio-immunologique (RIA) de la thyroxine sérique. La neurogenèse de l’hippocampe a été évaluée chez les animaux contrôles et exposés par immunohistochimie fluorescente. Nous avons aussi évalué la locomotion spontanée à travers le test Open Field, les capacités spatiales à travers le Barnes Maze test, et enfin les capacités attentionnelles par l’Attentional Set-Shifting Task.
Les résultats montrent une accumulation de BDE-47 dans le tissu cérébral des animaux exposés en période périnatale. Les taux de thyroxine ne sont pas significativement affectés par l’exposition au BDE-47. Nous avons observé une diminution modérée, non significative, des progéniteurs neuronaux chez les animaux exposés à la faible dose, mais pas à la dose élevée de BDE-47. Finalement, ni l’activité locomotrice ni les capacités spatiales ou attentionnelles ne semblent pas être affectées par l’exposition périnatale au BDE-47.

PBDEs --- cognition --- Barnes Maze --- Thyroide --- Himmunoistochimie --- Neurogenèse --- Hippocampe --- Flexibilité Cognitive --- Perturbateurs Endocriniens --- Attentional Set-Shifting Task --- Sciences sociales & comportementales, psychologie > Psychologie animale, éthologie & psychobiologie

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The present experiments investigated the role of the prelimbic-infralimbic areas in behavioral flexibility using a place-response learning paradigm. All rats received a bilateral cannula implant aimed at the prelimbic-infralimbic areas. To examine the role of the prelimbic-infralimbic areas in shifting strategies, rats were tested on a place and a response discrimination in a cross-maze. Some rats were tested on the place version first followed by the response version. The procedure for the other rats was reversed. Infusions of 2% tetracaine into the prelimbic-infralimbic areas did not impair acquisition of the place or response discriminations. Prelimbic-infralimbic inactivation did impair learning when rats were switched from one discrimination to the other (cross-modal shift). To investigate the role of the prelimbic-infralimbic areas in intramodal shifts (reversal learning), one group of rats was tested on a place reversal and another group tested on a response reversal. Prelimbic-infralimbic inactivation did not impair place or response intramodal shifts. Some rats that completed testing on a particular version in the cross-modal and intramodal experiments were tested on the same version in a new room for 3 d. The transfer tests revealed that rats use a spatial strategy on the place version and an egocentric response strategy on the response version. Overall, these results suggest that the prelimbic-infralimbic areas are important for behavioral flexibility involving crossmodal but not intramodal shifts

Acquisition. --- Animal-models. --- Anterior cingulate. --- Area. --- Attentional set shifting. --- Cannula. --- Caudate-nucleus. --- City. --- Cortex. --- Discrimination. --- Double dissociation. --- Electrolytic lesions. --- Experiment. --- Experiments. --- Flexibility. --- Group. --- Hippocampal. --- Infralimbic. --- Involvement. --- Learning. --- Prefrontal cortex. --- Prelimbic. --- Rat. --- Rats. --- Response. --- Reversal learning. --- Rodent. --- Spatial. --- Strategies. --- Strategy. --- Tasks. --- Test. --- Tests. --- Tetracaine. --- Working-memory.