Biology subjects

Melon, C.

Publications and source records attributed to Melon, C..

4 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↗

bioRxiv2025

Chamber Implant for Chronic Optical Recordings from the Cerebral Cortex of Marmosets

We describe a novel imaging chamber for chronic optical recordings from the marmoset cerebral cortex, together with the surgery needed for its implantation and that of an associated headpost. MRI data allow optimizing positioning on the skull. The chamber is implanted into a precisely matched craniotomy, improving mechanical stability. For maximal biocompatibility, chamber and headpost are made out of titanium. It consists of an outer cylinder into which screws adjustably an inner one, called "well", with a glass window on its bottom. This allows easy opening and closing whenever access to the cortex is needed, while preserving a sterile seal when closed. Moreover, simply rotating the well allows fine adjustment of the windows distance with respect to the underlying cortex. Together with using a curved - rather than flat - glass window, this allows achieving gentle but continuous contact with the underlying cortex, which helps to delay tissue regrowth, notably of a neomembrane that must otherwise be surgically removed. The chambers sealing system combines a silicone elastomer and O-ring, minimizing infection risk and CSF leakage. Data from longitudinal two-photon imaging using genetically encoded fluorescent calcium sensors reveal high optical quality over months, with excellent resolution of neurons and their activity. We also demonstrate the feasibility of two-photon imaging of genetically encoded voltage sensors in the marmoset cortex in-vivo. Finally, although the chamber provides a durable, adaptable solution for long-term imaging studies in marmosets already in its current version, we discuss a few straightforward modifications that could likely improve its performance even further.

neuroscience↗

bioRxiv2025

Cocaine withdrawal enhances subthalamic reward sensitivity

High-frequency stimulation of the subthalamic nucleus (STN) has shown therapeutic potential in preclinical models of addiction. However, its rewarding properties remain unclear. Here, we show that cocaine withdrawal enhances STN intracranial self-stimulation, revealing a reward-based mechanism that may contribute to the beneficial effects of STN deep brain stimulation in addiction and related neuropsychiatric disorders.

neuroscience↗

bioRxiv2021

Inhibition of cholinergic interneurons potentiates corticostriatal transmission in D1 receptor-expressing medium-sized spiny neurons and restores motor learning in parkinsonian condition

Striatal cholinergic interneurons (CINs) respond to salient or reward prediction-related stimuli after conditioning with brief pauses in their activity, implicating them in learning and action selection. This pause is lost in animal models of Parkinsons disease. How this signal regulates the functioning of the striatum remains an open question. To address this issue, we examined the impact of CIN firing inhibition on glutamatergic transmission between the cortex and the medium-sized spiny projection neurons expressing dopamine D1 receptors (D1 MSNs). Brief interruption of CIN activity had no effect in control condition whereas it increased glutamatergic responses in D1 MSNs after nigrostriatal dopamine denervation. This potentiation was dependent upon M4 muscarinic receptor and protein kinase A. Decreasing CIN firing by opto/chemogenetic strategies in vivo rescued long-term potentiation in some MSNs and alleviated motor learning deficits in parkinsonian mice. Taken together, our findings demonstrate that the control exerted by CINs on corticostriatal transmission and striatal-dependent motor-skill learning depends on the integrity of dopaminergic inputs.

neuroscience↗