Complete representation of action space and value in all dorsal striatal pathways.

Moritz Weglage,Iakovos Lazaridis,Daniela Calvigioni,Ourania Tzortzi,Emil Wärnberg,Konstantinos Meletis

doi:10.1016/j.celrep.2021.109437

Moritz Weglage, Iakovos Lazaridis + Show 4 more

Open Access

https://doi.org/10.1016/j.celrep.2021.109437

Copy DOI

Journal: Cell Reports	Publication Date: Jul 1, 2021
Citations: 19	License type: cc-by

Affiliation: Karolinska Institutet

Abstract

The dorsal striatum plays a central role in the selection, execution, and evaluation of actions. An emerging model attributes action selection to the matrix and evaluation to the striosome compartment. Here, we use large-scale cell-type-specific calcium imaging to determine the activity of striatal projection neurons (SPNs) during motor and decision behaviors in the three major outputs of the dorsomedial striatum: Oprm1+ striosome versus D1+ direct and A2A+ indirect pathway SPNs. We find that Oprm1+ SPNs show complex tunings to simple movements and value-guided actions, which are conserved across many sessions in a single task but remap between contexts. During decision making, the SPN tuning profiles form a complete representation in which sequential SPN activity jointly encodes task progress and value. We propose that the three major output pathways in the dorsomedial striatum share a similarly complete representation of the entire action space, including task- and phase-specific signals of action value and choice.

Highlights

The context-dependent selection and evaluation of actions is essential for life in all animals
The activity of dorsomedial D1+, A2A+, and Oprm1+ striatal projection neurons (SPNs) during locomotion We imaged the activity of Oprm1+ SPNs (i.e., Oprm1-Cre for striosomes), D1+ SPNs (i.e., D1-Cre for direct pathway), and A2A+ SPNs (i.e., A2A-Cre for indirect pathway) using the genetically encoded calcium sensor GCaMP6s (Chen et al, 2013), through gradient index (GRIN) lenses implanted over the anterior part of the dorsomedial striatum (DMS) in the right hemisphere (Figures 1A, 1B, and S1)
To target Oprm1+ SPNs, we used Oprm1-Cre mice (Martin et al, 2019), and we confirmed that Oprm1+ SPNs in the DMS were localized to striosomes (88% in striosomes, 12% exopatch) and expressed the D1 receptor (95% ± 5%; Figure S2)

Summary

Introduction

The context-dependent selection and evaluation of actions is essential for life in all animals. A circuit model has emerged based on this dichotomous organization to explain movement disorders (Albin et al, 1989; Alexander and Crutcher, 1990; Nelson and Kreitzer, 2014). In this model, the direct and indirect pathways regulate motor behaviors through antagonistic signals, promoting and suppressing movement, respectively. In the context of decision making, it is hypothesized that actions are promoted by the direct pathway and suppressed by the indirect pathway (Cox and Witten, 2019)

Methods

Results

Discussion

Conclusion