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Rôle des afférences thalamiques au noyau accumbens dans les comportements motivés chez le rat.

Abstract : Humans and animals are motivated beings. In world where resources are limited, we constantly perform actions to reach the goals we set to ourselves. In the first place, we need to maintain homeostasis by searching food, water or shelter. The concept of motivation does not directly refer to these actions, but to the processes that augment the probability to perform them. Nonetheless, orienting these actions require to integrate environmental stimuli that inform us on the possibility to obtain rewards. The nucleus accumbens (NAc), the ventral part of the striatum, belongs to the basal ganglia system and is an essential element involved in the processes motivating the actions that allow to reach our goals, especially when they are guided by predictive stimuli. However, stimuli have two distinct types of properties. First, they incentivize our actions and second, they give us instructions about the specific actions to perform to reach the selected goal. In this PhD work, we first sought to understand the implication of the NAc in incentive and instructive stimuli processing. We manipulated and recorded NAc neurons in rats performing a GO/NOGO task involving these two types of stimuli. We observed that pharmacologically inactivating the NAc reduced the engagement in action in response to incentive stimuli but had no effect in the rats ‘ability to correctly respond to instructive stimuli. We observed stronger excitations to the incentive than the instructive stimuli. Moreover, these neurons displayed incentive stimuli-evoked excitations that depended on the motivational level of the animal. We called these neurons MOTIV+. Conversely, we observed a second population of neurons specifically activated by the incentive stimuli to which the animals did not engage in action in response to them. We called these neurons MOTIV-. We then showed that the population of MOTIV+ neurons was mostly made of medium spiny projection neurons while MOTIV- neurons were highly enriched in cholinergic interneurons. In a second study, we sought to determine how satiety information modulated motivation instantiated by incentive stimuli. The paraventricular nucleus of the thalamus (PVT) strongly projects to the NAc and receives orexin inputs from the lateral hypothalamus, a central player in the integration of metabolic information. We observed that in sated rats, PVT stimulation either with optogenetic or with local orexin injections was sufficient to restore excitations of MOTIV+ neurons and the engagement in actions in response to the incentive stimulus. The parafascicular nucleus of the thalamus (Pfn) projects to the NAc and synapses preferentially onto cholinergic interneurons. In a third study, we sought to determine whether Pf neuronal activity could explain MOTIV- neuronal activity in the NAc. We recorded Pf neurons in response to incentive stimuli in a reward-seeking task. We observed a bidirectional encoding of motivation with MOTIV+ and MOTIV- profiles. The temporal dynamic of Pf responses suggests that Pf MOTIV- neuronal responses could indeed be responsible for that found NAc MOTIV- neurons. Thus, this structure could play an important attentional role by inhibiting the stimuli that are not pertinent to the need the animal seeks to satisfy. Together, this work allowed to bring a new light on how the NAc integrates exteroceptive but also interoceptive information to modulate the level of motivation.
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Contributor : Mehdi Sicre Connect in order to contact the contributor
Submitted on : Thursday, July 15, 2021 - 1:31:16 PM
Last modification on : Friday, February 4, 2022 - 3:26:42 AM
Long-term archiving on: : Saturday, October 16, 2021 - 6:30:57 PM


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  • HAL Id : tel-03287053, version 1



Mehdi Sicre. Rôle des afférences thalamiques au noyau accumbens dans les comportements motivés chez le rat.. Neurobiologie. Aix Marseille Université, 2021. Français. ⟨NNT : ⟩. ⟨tel-03287053⟩



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