Mathieu Wolff, Fabien Alcaraz et al. in eLife

Thalamocortical and corticothalamic pathways differentially contribute to goal-directed behaviors in the rat. https://elifesciences.org/articles/32517 Fabien Alcaraz, Virginie Fresno, Alain R Marchand, Eric J Kremer, Etienne Coutureau, Mathieu Wolff Is a corresponding author. CNRS, INCIA, UMR 5287, France Université de Bordeaux, INCIA, UMR 5287, France Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, France © 2018 eLife Sciences Publications / Research Article Feb 6, 2018

Adaptive decision-making and the directionality of information flows within thalamocortical circuits.

Reaching specific goals within volatile environments requires complex cognitive abilities thought to be supported by highly evolved brain regions such as the prefrontal cortex. Within the neural circuits involved, the mediodorsal thalamus appears of special interest due to the extensive reciprocal projections connecting these two areas. (left, M. Wolff, right, F. Alcaraz)

In this study, we examined the respective contribution of thalamocortical and corticothalamic pathways connecting the medial prefrontal cortex and the mediodorsal thalamus. To do so, we developed a dual-viral chemogenetic strategy to reversibly inhibit projection-defined thalamic and cortical neurons (see figures below). This enabled us to test selectively the functional contribution of each of these pathways with respect to the two main goal attributes: current goal value and current action-outcome contingency.

Interestingly, these manipulations produced dissociable behavioral alterations. While inhibiting the thalamocortical pathway impaired both the ability to guide choice based on current goal value and, to a much larger extent, current action-outcome contingency, inhibiting the corticothalamic pathway only impeded choice based on current goal value. Thus the ability to perform adaptive actions is differentially supported by thalamocortical and corticothalamic pathways.

These results confirm the crucial role of thalamocortical circuits in adaptive cognition. Moreover, they indicate that the direction of information flow within these circuits is one of their fundamental features, which has possible functional relevance for virtually any neural circuit with reciprocal connections. This may also be important to better apprehend mental dysfunctions conceptualized as connectivity disorders such as Schizophrenia.

Figure caption. Left, dual-viral strategy to target either PFC-projecting MD cells (top) or MD-projecting PFC cells (bottom). Resulting DREADD expression (revealed by mCherry) at the level of the MD (top) or the PFC (bottom). After initial instrumental training during which rats learned that performing two distinct actions enabled to gain two specific food rewards, specific choice tests were conducted to assess either current action-outcome contingency or current goal value. Inhibiting the MD-to-PFC was particularly detrimental for the former ability (top, CNO) while inhibiting the PFC-to-MD route only impaired the latter (bottom, CNO).

Mathieu Wolff CR, CNRS, Institut de Neurosciences Cognitives et Intégratives d’Aquitaine