Biology subjects

Vignal, L.

Publications and source records attributed to Vignal, L..

5 recordsLinked to original sources

bioRxiv2026

Subthalamic Nucleus Optogenetic Inhibition Bidirectionally Regulates Social Motivation According to Familiarity and Social Hierarchy

BackgroundSocial behavior is a core component of mental health, and its disruption characterizes many neuropsychiatric disorders such as autism. Social operant paradigms enable the quantification of volitional aspects of social motivation and interactions. While sex differences have been shown to influence social motivation, factors such as familiarity and social hierarchy are also likely to play a critical role that remain insufficiently explored. In addition, the subthalamic nucleus (STN), traditionally studied in motor circuits, has emerged as an important regulator of reward and motivational processes and may contribute to social behavior processes. MethodsIn this study, we examined the influence of peer familiarity (cagemate vs. stranger) and social hierarchy (dominant vs. subordinate) 1) on operant volitional social interaction using a fixed ratio 1 (FR1) and 2) on social motivation using a progressive ratio (PR) schedule of reinforcement in non-isolated rats. To assess the causal contribution of the STN, we used optogenetic photo-inhibition during both tasks in male rats. ResultsMale rats displayed a reduction of social interest and motivation toward familiar peers, mainly driven by the social hierarchy, while female did not. STN photo-inhibition in males abolished the familiarity-driven reduction under FR1 but decreased motivation independently of familiarity or hierarchy in PR. ConclusionsThese findings highlight sex, familiarity, and hierarchy as key modulators of volitional social behavior and demonstrate a direct role of the STN in regulating social motivation. Together, they provide mechanistic insights into processes that may be disrupted in neuropsychiatric disorders characterized by social dysfunction.

neuroscience↗

bioRxiv2026

THE SUBTHALAMIC NUCLEUS IS INVOLVED IN SOCIAL MEMORY IN MALE RATS

Human social behavior depends on complex socio-cognitive abilities, many of which are disrupted in neuropsychiatric disorders. We previously found that subthalamic nucleus (STN) lesions abolish familiarity-based modulation of social reward in rats, implicating the STN in social recognition. Here, we used pharmacological lesions, electrical deep brain stimulation (DBS), and optogenetic manipulations to dissect the STNs role in social memory. STN lesions selectively impaired social discrimination memory without affecting social novelty discrimination or non-social memory. High-frequency optogenetic stimulation disrupted social discrimination memory only when applied during encoding, whereas STN optogenetic inhibition, and electrical DBS impaired social memory when applied during either encoding or retrieval. Notably, transient optogenetic inhibition abolished recognition of a cage-mate after short isolation, yet this ability was preserved after permanent lesions, suggesting compensatory adaptations. These results identify the STN as a key node for social memory and highlight the importance of considering its role in social cognition when implementing STN-targeted therapies.

neuroscience↗

bioRxiv2025

Cocaine extended access gates compulsive-like seeking in rats

When does compulsive-like drug seeking emerge? Despite decades of research, and critical advances in our understanding of brain processes leading to addiction, this question remains widely unanswered. So far, behavioral models assessing compulsive-like cocaine seeking following an extended access to cocaine failed to capture the development of its compulsive seeking. In fact, compulsive-like animals immediately displayed pathological seeking when facing its negative consequences of drug seeking, usually materialized by an unescapable mild electric shock on the paws. Here, we designed a new task, Punished Seeking during Extended access (PSE), by inserting punished seeking trials within the sessions of extended access to cocaine. We show that compulsive-like cocaine seeking progressively emerges after several PSE sessions, once cocaine intake has been escalated. We thus provide the addiction community a pertinent model to explore brain mechanisms sustaining the emergence of compulsive-like cocaine seeking.

neuroscience↗

bioRxiv2023

SUBTHALAMIC HIGH-FREQUENCY DEEP BRAIN STIMULATION REDUCES ADDICTION-LIKE ALCOHOL USE AND SUPPRESSES THE OVERCONSUMPTION INDUCED BY THE PEER S PRESENCE

RationalThe immediate social context significantly influences alcohol consumption in humans. Recent studies have revealed that peer presence could modulate drugs use in rats. The most efficient condition to reduce cocaine intake is the presence of a stranger peer, naive to drugs. Deep brain stimulation (DBS) of the Subthalamic Nucleus (STN), which was shown to have beneficial effects on addiction to cocaine or alcohol, also modulate the protective influence of peers presence on cocaine use. ObjectivesThis study aimed to: 1) explore how the presence of an alcohol-naive stranger peer affects recreational and escalated alcohol intake, and 2) assess the involvement of STN on alcohol use and in the modulation induced by the presence of an alcohol-naive stranger peer. MethodsRats with STN DBS and control animals self-administered 10% (v/v) ethanol in presence, or absence, of an alcohol-naive stranger peer, before and after escalation of ethanol intake (observed after intermittent alcohol (20% (v/v) ethanol) access). ResultsNeither STN DBS nor the presence of an alcohol-naive stranger peer modulated significantly recreational alcohol intake. After the escalation procedure, STN DBS gradually reduced ethanol consumption. The presence of an alcohol-naive stranger peer increased consumption only in low drinkers, which effect was suppressed by STN DBS. ConclusionsThese results highlight the influence of a peers presence on escalated alcohol intake, and confirm the role of STN in addiction-like alcohol intake and in the social influence on drug consumption.

neuroscience↗

bioRxiv2023

Peer's Presence Reverses Escalated Cocaine Intake In Rats

The immediate social context critically modulates drug consumption. The presence of an unfamiliar conspecific, naive to the drug, at the time of consumption reduces cocaine self-administration in male rats during short-access sessions, as well as drug intake in human cocaine users. The subthalamic nucleus (STN), a brain structure involved in cocaine addiction and limbic processes, has been proposed to mediate such social influence on this limited level of drug intake. Whether this influence extends to escalated drug consumption remains an open question. In this study, we compared the effect of the presence of an unfamiliar peer, naive to cocaine, on cocaine self-administration in rats having been exposed to either short (2h) or long-access sessions (6h). We showed that the presence of the peer drastically reduced both limited and escalated cocaine intake in males, while it had no effect on females during short-access sessions. Assessing the effect of STN photo-inhibition or high frequency (HF) stimulation in male rats, we demonstrated that it had no effect in the absence of the conspecific in short-access sessions, STN photo-manipulation suppressed the influence of the peers presence. Moreover, STN photo-inhibition and HF stimulation decreased drug consumption in long-access sessions, but no additive effect was observed when associated with the peers presence, confirming an overriding effect of STN manipulation. Taken together, these results highlight the potential influence of socially oriented manipulations on cocaine intake and further position the STN as a critical mediator of the effect of social presence on addictive-like behaviors.

neuroscience↗