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Individual animals differ in their traits and preferences, which shape their social interactions, survival, and susceptibility to disease, including addiction. Nicotine use is highly heterogenous and has been linked to the expression of personality traits. Although these relationships are well documented, we have limited understanding of the neurophysiological mechanisms that give rise to distinct behavioral profiles and their connection to nicotine susceptibility. To address this question, we conducted a study using a semi-natural and social environment called "Souris-City" to observe the long-term behavior of individual male mice. Souris-City provided both a communal living area and a separate test area where mice engaged in a reward-seeking task isolated from their peers. Mice developed individualistic reward-seeking strategies when choosing between water and sucrose in the test compartment, which, in turn, predicted how they adapted to the introduction of nicotine as a reinforcer. Moreover, the profiles mice developed while isolated in the test area correlated with their behavior within the social environment, linking decision-making strategies to the expression of behavioral traits. Neurophysiological markers of adaptability within the dopamine system were apparent upon nicotine challenge and were associated with specific profiles. Our findings suggest that environmental adaptations influence behavioral traits and sensitivity to nicotine by acting on dopaminergic reactivity in the face of nicotine exposure, potentially contributing to addiction susceptibility. These results further emphasize the importance of understanding interindividual variability in behavior to gain insight into the mechanisms of decision-making and addiction. What are the neurophysiological mechanisms of the relationship between individual traits and nicotine use? This study uses a semi-natural and social environment for mice and revealed neurophysiological markers within the dopamine system that were apparent upon nicotine challenge and were associated with specific behaviors. [ABSTRACT FROM AUTHOR]

Negative emotional contagion—witnessing others in distress—affects an individual’s emotional responsivity. However, whether it shapes coping strategies when facing future threats remains unknown. We found that mice that briefly observe a conspecific being harmed become resilient, withstanding behavioral despair after an adverse experience. Photometric recordings during negative emotional contagion revealed increased serotonin (5-HT) release in the lateral habenula. Whereas 5-HT and emotional contagion reduced habenular burst firing, limiting 5-HT synthesis prevented burst plasticity. Enhancing raphe-to-habenula 5-HT was sufficient to recapitulate resilience. In contrast, reducing 5-HT release in the habenula made witnessing a conspecific in distress ineffective to promote the resilient phenotype after adversity. These findings reveal that 5-HT supports vicarious emotions and leads to resilience by tuning definite patterns of habenular neuronal activity. [ABSTRACT FROM AUTHOR]

Nicotine intake is likely to result from a balance between the rewarding and aversive properties of the drug, yet the individual differences in neural activity that control aversion to nicotine and their adaptation during the addiction process remain largely unknown. Using a two-bottle choice experiment, we observed considerable heterogeneity in nicotine-drinking profiles in isogenic adult male mice, with about half of the mice persisting in nicotine consumption even at high concentrations, whereas the other half stopped consuming. We found that nicotine intake was negatively correlated with nicotine-evoked currents in the interpeduncular nucleus (IPN), and that prolonged exposure to nicotine, by weakening this response, decreased aversion to the drug, and hence boosted consumption. Lastly, using knock-out mice and local gene re-expression, we identified ß4-containing nicotinic acetylcholine receptors of IPN neurons as molecular and cellular correlates of nicotine aversion. Collectively, our results identify the IPN as a substrate for individual variabilities and adaptations in nicotine consumption. [ABSTRACT FROM AUTHOR]

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Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels widely expressed in the central nervous system and the periphery. They play an important modulatory role in learning, memory and attention, and have been implicated in various diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, schizophrenia and addiction. These receptors are activated by the endogenous neurotransmitter acetylcholine, or by nicotine, the alkaloid found in tobacco leaves. Both molecules open the ion channel and cause the movement of cations across the membrane, which directly affects neuronal excitability and synaptic plasticity. nAChRs are very heterogeneous in their subunit composition (α2-10 et β2-4), in their brain distribution (cortex, midbrain, striatum…) and in their sub-cellular localization (pre- vs post-synaptic, axonal, dendritic…). This heterogeneity highly contributes to the very diverse roles these receptors have in health and disease. The ability to activate or block a specific nAChR subtype, at a defined time and space within the brain, would greatly help obtaining a clearer picture of these various functions. To this aim, we are developing novel optogenetic pharmacology strategies for optically controlling endogenous nAChR isoforms within the mouse brain. The idea is to tether a chemical photoswitch on the surface of a cysteine-modified nAChR, and use light for rapidly and reversibly turning that receptor mutant on and off. Here we will discuss the history of optogenetic pharmacology, and the recent advances for the optical control of brain nicotinic receptors in vivo., (© Société de Biologie, 2017.)