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Nucleus accumbens neurons dynamically respond to appetitive and aversive associative learning
Authors:Catarina Deseyve  Ana Verónica Domingues  Tawan T A Carvalho  Gisela Armada  Raquel Correia  Natacha Vieitas-Gaspar  Marcelina Wezik  Luísa Pinto  Nuno Sousa  Bárbara Coimbra  Ana João Rodrigues  Carina Soares-Cunha
Institution:1. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal

Contribution: Conceptualization, Data curation, Formal analysis, ?Investigation, Methodology, Writing - original draft, Writing - review & editing;2. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal

Contribution: Conceptualization, Data curation, Formal analysis, ?Investigation, Writing - review & editing;3. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal

Contribution: Data curation, Formal analysis, ?Investigation, Writing - review & editing;4. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal

Contribution: Formal analysis, ?Investigation, Writing - review & editing;5. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal

Contribution: Data curation, ?Investigation, Writing - review & editing;6. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal

Contribution: ?Investigation, Writing - review & editing;7. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal

Clinical Academic Center-Braga (2CA), Braga, Portugal

Contribution: ?Investigation, Writing - review & editing;8. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal

Contribution: Funding acquisition, ?Investigation, Writing - original draft, Writing - review & editing;9. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

Abstract:To survive, individuals must learn to associate cues in the environment with emotionally relevant outcomes. This association is partially mediated by the nucleus accumbens (NAc), a key brain region of the reward circuit that is mainly composed by GABAergic medium spiny neurons (MSNs), that express either dopamine receptor D1 or D2. Recent studies showed that both populations can drive reward and aversion, however, the activity of these neurons during appetitive and aversive Pavlovian conditioning remains to be determined. Here, we investigated the relevance of D1- and D2-neurons in associative learning, by measuring calcium transients with fiber photometry during appetitive and aversive Pavlovian tasks in mice. Sucrose was used as a positive valence unconditioned stimulus (US) and foot shock was used as a negative valence US. We show that during appetitive Pavlovian conditioning, D1- and D2-neurons exhibit a general increase in activity in response to the conditioned stimuli (CS). Interestingly, D1- and D2-neurons present distinct changes in activity after sucrose consumption that dynamically evolve throughout learning. During the aversive Pavlovian conditioning, D1- and D2-neurons present an increase in the activity in response to the CS and to the US (shock). Our data support a model in which D1- and D2-neurons are concurrently activated during appetitive and aversive conditioning.
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Keywords:aversion  D1-neurons  D2-neurons  nucleus accumbens  Pavlovian conditioning  reward
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