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Decision-making is necessary to adapt to the variable environment in everyday life. During this process, our goal is to select the most beneficial course of action in order to obtain the best outcome, to develop efficient choice strategies. That is, estimating the probability to obtain any of the available outcomes as well as their value. Moreover, poor decision-making ability is a common symptom to several psychiatric disorders, such as pathological gambling, depression, schizophrenia and bipolar disorder.The cognitive and emotional mechanisms controlling decision-making processes depend, among others, on the striatum, Basal Ganglia’s main input nucleus. The striatum is divided into the dorsal striatum, responsible for motor and cognitive control that initiate actions (Dorsomedial Striatum, DMS) and generate habits (Dorsolateral Striatum, DLS), and Nucleus Accumbens (NAc) which manages reward and the influence of motivation on motor behavior. A2A-expressing and D1-expressing medium spiny neurons (iMSNs and dMSNs, respectively), accounting for 95% of striatal neurons act in coordination to generate adaptive behavioral responses. It has been shown that imbalanced activity between these two populations leads to abnormal behaviors: overactivation of striatonigral neurons promotes an increased locomotion as well as a higher sensitivity for reward, whereas overactivation of striatopallidal neurons produces the exact opposite effects. However, the specific contributions to decision-making of these two populations in each striatal territory remains unclear. Here, we made use of a chemogenetic (DREADD) tool to manipulate striatal projection neurons’ activity within each specific striatal area and tested their role in a decision-making operant protocol. To do so, we used two different mouse models that allowed us to target specifically iMSNs (A2A-Cre mice) or dMSNs (D1-Cre mice) and induce neuronal-specific expression of the hM3Dq DREADD receptor. CNO-mediated activation of, Doctorat en Sciences biomédicales et pharmaceutiques (Médecine), info:eu-repo/semantics/nonPublished

The basal ganglia (BG) control action selection, motor programs, habits, and goal-directed learning. The striatum, the principal input structure of BG, is predominantly composed of medium-sized spiny neurons (MSNs). Arising from these spatially intermixed MSNs, two inhibitory outputs form two main efferent pathways, the direct and indirect pathways. Striatonigral MSNs give rise to the activating, direct pathway MSNs and striatopallidal MSNs to the inhibitory, indirect pathway (iMSNs). BG output nuclei integrate information from both pathways to fine-tune motor procedures and to acquire complex habits and skills. Therefore, balanced activity between both pathways is crucial for harmonious functions of the BG. Despite the increase in knowledge concerning the role of glutamate NMDA receptors (NMDA-Rs) in the striatum, understanding of the specific functions of NMDA-R iMSNs is still lacking. For this purpose, we generated a conditional knock-out mouse to address the functions of the NMDA-R in the indirect pathway. At the cellular level, deletion of GluN1 in iMSNs leads to a reduction in the number and strength of the excitatory corticostriatopallidal synapses. The subsequent scaling down in input integration leads to dysfunctional changes in BG output, which is seen as reduced habituation, delay in goal-directed learning, lack of associative behavior, and impairment in action selection or skill learning. The NMDA-R deletion in iMSNs causes a decrease in the synaptic strength of striatopallidal neurons, which in turn might lead to a imbalanced integration between direct and indirect MSN pathways, making mice less sensitive to environmental change. Therefore, their ability to learn and adapt to the environment-based experience was significantly affected., SCOPUS: ar.j, info:eu-repo/semantics/published

Certain molecular mechanisms of Cd tolerance and accumulation have been identified in the model species Arabidopsis halleri, while intraspecific variability of these traits and the mechanisms of shoot detoxification were little addressed. The Cd tolerance and accumulation of metallicolous and non-metallicolous A. halleri populations from different genetic units were tested in controlled conditions. In addition, changes in shoot cell wall composition were investigated using Fourier transform infrared spectroscopy. Indeed, recent works on A. halleri suggest Cd sequestration both inside cells and in the cell wall/apoplast. All A. halleri populations tested were hypertolerant to Cd, and the metallicolous populations were on average the most tolerant. Accumulation was highly variable between and within populations, and populations that were non-accumulators of Cd were identified. The effect of Cd on the cell wall composition was quite similar in the sensitive species A. lyrata and in A. halleri individuals; the pectin/polysaccharide content of cell walls seems to increase after Cd treatment. Nevertheless, the changes induced by Cd were more pronounced in the less tolerant individuals, leading to a correlation between the level of tolerance and the extent of modifications. This work demonstrated that Cd tolerance and accumulation are highly variable traits in A. halleri, suggesting adaptation at the local scale and involvement of various molecular mechanisms. While in non-metallicolous populations drastic modifications of the cell wall occur due to higher Cd toxicity and/or Cd immobilization in this compartment, the increased tolerance of metallicolous populations probably involves other mechanisms such as vacuolar sequestration., info:eu-repo/semantics/published

info:eu-repo/semantics/published

info:eu-repo/semantics/published