Biology subjects

Tolu, S.

Publications and source records attributed to Tolu, S..

5 recordsLinked to original sources

bioRxiv2024

Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety.

Nicotine activates ventral tegmental area (VTA) dopaminergic (DA) neurons projecting to the nucleus accumbens (NAc) to drive its reinforcing effects. Simultaneously, it inhibits those projecting to the amygdala (Amg) to mediate anxiety through a process that remains unknown. Here we show that NAc- and Amg-projecting DA neurons respond with similar polarities to ethanol and nicotine, suggesting a shared network-based mechanism underlying the inhibitory effect of these otherwise pharmacologically-distinct drugs. Selective activation of NAc-projecting DA neurons, using genetic or optogenetic strategies, produced inhibition of Amg-projecting DA neurons, through a GABAergic feedback loop. Furthermore, optogenetically silencing this feedback loop prevented nicotine from inducing both inhibition of DA neurons and anxiety-like behavior. Therefore, nicotine-induced inhibition of the VTA-Amg DA pathway results from a VTA-NAc inhibitory feedback loop, mediating anxiety.

neuroscience↗

bioRxiv2023

Individual variations in reward-seeking adaptability emerge among isogenic mice living in a micro-society and predict their response to nicotine

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 personalities 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 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, mouse profiles in isolation also extended to correlate 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 inter-individual variability in behavior to gain insight into the mechanisms of decision making and addiction.

neuroscience↗

bioRxiv2021

Prolonged nicotine exposure reduces aversion to the drug in mice by altering nicotinic transmission in the interpeduncular nucleus.

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 a high heterogeneity in nicotine-drinking profiles in isogenic adult male mice, with about half of the mice persisting in consuming nicotine 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 {beta}4-containing nicotinic acetylcholine receptors of IPN neurons as the molecular and cellular correlates of nicotine aversion. Collectively, our results identify the IPN as a substrate of individual variabilities and adaptations in nicotine consumption.

neuroscience↗

bioRxiv2020

Distinct dopamine circuits transmit the reinforcing and anxiogenic effects of nicotine

Nicotine, the addictive component of tobacco, stimulates dopamine (DA) neurons of the ventral tegmental area (VTA) to establish and maintain reinforcement. Nicotine also induces negative emotional states such as anxiety, yet through an unknown circuitry. Here we show that nicotine at reinforcing doses drives opposite functional responses on two distinct populations of VTA DA neurons with anatomically segregated projections: it activates those that project to the nucleus accumbens (NAc) while it inhibits those that project to the amygdala nuclei (Amg). We further show that nicotine, by acting on {beta}2 subunit-containing nicotinic acetylcholine receptors of the VTA, mediates both reinforcement and anxiety. Finally, using optogenetic experiments we dissociate the roles of the VTA-NAc excitation and VTA-Amg inhibition in reinforcement and anxiety-like behavior, respectively. We thus propose that the positive and negative behavioral outcomes of nicotine consumption involve distinct subpopulations of VTA DA neurons with opposite responses to nicotine.

neuroscience↗

bioRxiv2017

Social interactions impact on the dopaminergic system and drive individuality

Individuality is a ubiquitous and well-conserved feature among animal species. The behavioral patterns of individual animals affect their respective role in the ecosystem and their prospects for survival. Even though some of the factors shaping individuality have been identified, the mechanisms underlying individuation are poorly understood and are generally considered to be genetics-based. Here we devised a large environment where mice live continuously, and observed that individuality, measured by both social and individual traits, emerged and settled within the group. Midbrain dopamine neurons underwent neurophysiological adaptations that mirrored this phenotypic divergence in individual behaviors. Strikingly, modifying the social environment resulted in a fast re-adaptation of both the animals personality and its dopaminergic signature. These results indicate that individuality can rapidly evolve upon social challenges, and does not just depend on the genetic or epigenetic initial status of the animal.

neuroscience↗