Biology subjects

Vicq, E.

Publications and source records attributed to Vicq, E..

5 recordsLinked to original sources

bioRxiv2023

The interpeduncular nucleus blunts the rewarding effect of nicotine

Nicotine, by stimulating ventral tegmental area (VTA) dopaminergic neurons, has a rewarding effect that drives tobacco consumption. In turn, the interpeduncular nucleus (IPN) is thought to become activated at high nicotine doses to restrict drug intake. However, the dynamics of the IPN response to nicotine and its impact on the rewarding effect of the drug remain unknown. To address this issue, we have developed a genetically-modified mouse model, in which a "suicide" antagonist of nicotinic acetylcholine receptors (nAChRs) selectively attaches to a designer {beta}4 nAChR subunit. By locally infusing this antagonist in the IPN, we achieved pharmacologically-specific and sustained antagonism of nAChRs containing the {beta}4 subunit. By combining this chemogenetic method with in vivo electrophysiology, we show that even at low doses, nicotine activates and inhibits two different populations of IPN neurons, and that {beta}4-containing nAChRs are only involved in the activation response. Furthermore, blocking the response to nicotine selectively in the IPN increased both the sensitivity of the VTA to the drug and its rewarding effect in a conditioned place preference paradigm. These findings indicate that the IPN is engaged across a large range of nicotine doses and acts as a regulatory brake on the nicotine reward circuit.

neuroscience↗

bioRxiv2023

Basolateral amygdala circuits supporting negative emotional bias in a mouse model for depression

Negative emotional bias is an essential hallmark of depression reflected by negative shift in hedonic valence assignment to emotional stimuli. Pleasant cues become less attractive and unpleasant ones more aversive. Given the crucial role of amygdala in valence coding, we hypothesize that specific basolateral amygdala (BLA) circuits alterations might support negative emotional bias associated with depressive states. Using a translational assay, we evaluate odor valence assignment in an animal model for depression chronically administered by corticosterone (CORT). We show spontaneous negative bias in depressive-like mice that attribute more negative valences for both attractive and aversive odors, mimicking thus the bias observed in depressed bipolar patients. Combining CTB and rabies-based tracing with ex vivo measurements of neuronal activity and chemogenetics experiments, we find that the CORT treatment reduces BLA-to-nucleus accumbens (NAc) neuronal activity and increases BLA-to-central amygdala activity, circuits respectively known to be involved in positive and negative valence encoding. Alterations in presynaptic connectivity of BLA-projecting neurons accompany these activity shifts. Interestingly, inputs from the paraventricular thalamus nucleus (PVT) towards BLA-to-NAc neurons are reduced in CORT-treated mice. Finally, chemogenetically activating the BLA-to-NAc circuit attenuates the negative bias in CORT-treated mice as well as the depressive-like phenotype, similarly than Fluoxetine antidepressant treatment. Altogether, we demonstrate that depressive states are associated with negative emotional bias both in human and mice. This bias is supported by activity shifts of specific BLA circuits along with durable presynaptic connectivity changes, but it could be alleviated by antidepressant drug or activity manipulation of altered BLA circuit.

neuroscience↗

bioRxiv2022

Dopamine builds and reveals reward-associated latent behavioral attractors

Phasic variations in dopamine levels are interpreted as a teaching signal reinforcing rewarded behaviors. However, behavior also depends on the online, neuromodulatory effect of phasic dopamine signaling. Here, we unravel a new neurodynamical principle that reconciles these roles. In a biophysical recurrent network-based decision architecture, we showed that dopamine-mediated synaptic plasticity stabilized neural assemblies representing rewarded locations as latent, local attractors. Dopamine-modulated synaptic excitability activated these attractors online, and they became accessible as internal goals, even from remote animal positions. We experimentally validated these predictions in mice, using optogenetics, by demonstrating that online dopamine signaling specifically attracts animals toward rewarded locations, without off-target motor effects. We therefore propose that online dopamine signaling reveals potential goals by widening and deepening the basin of dopamine-built attractors representing rewards.

neuroscience↗

bioRxiv2022

Self-generation of goal-directed choices in a distributed dopaminergic andprefrontal circuit

Goal-directed choices that are not triggered by external cues arise from internal representations of the outcomes. The use of a stimulus to specify when to act, which option to take, or whether to explore, has led to consider the reward circuit as a feedforward set of modules carrying independent computations. Here, we develop an uncued task in which mice self-determine the initiation, direction, vigor and pace of their actions based on their knowledge of the outcomes. Using electrophysiological recordings, pharmacology and optogenetics, we identify a sequence of oscillations and firing in the ventral tegmental area (VTA), orbitofrontal (OFC) and prefrontal cortices (PFC) that co-encodes and co-determines self-initiation and choices. This sequence appeared with learning as an unguided realignment of spontaneous dynamics. The interactions between the structures depended on the reward context, in particular regarding the uncertainty associated with the different options. We suggest that self-generated choices arise from a distributed circuit based on an OFC-VTA core setting whether to wait or to initiate actions, while the PFC is specifically engaged by reward uncertainty to participate in both the selection and pace of actions. HighlightsO_LISelf-paced actions arise from contextual reorganization of mesocortical dynamics. C_LIO_LIVTA, PFC and OFC complementarily encode predictions and errors about outcomes. C_LIO_LIDistributed firing-then-oscillations dynamics set the goal, initiation and pace of actions. C_LIO_LIVTA and PFC antagonistically promote and inhibit motivation by reward uncertainty. C_LI

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↗