Biology subjects

Huguet, P.

Publications and source records attributed to Huguet, P..

4 recordsLinked to original sources

bioRxiv2024

Probing other's Presence: Probabilistic Inference Across Brain Scales Reveals Enhanced Excitatory Synaptic Efficacy

The presence of conspecifics is a fundamental and arguably invariant prerequisite of social cognition across numerous animal species. While the influence of social presence on behavior has been among the focal points of investigation in social psychology for over a century, its underlying neural mechanisms remain largely unexplored. Here, we attempt to bridge this gap by investigating how the presence of conspecifics changes synaptic efficacy from measurements across spatiotemporal brain scales, and how such changes could lead to modulations of task performance in monkeys and humans. In monkeys performing an association learning task, social presence increased excitatory synaptic efficacy in attention-oriented regions dorsolateral prefrontal cortex and anterior cingulate cortex. In humans performing a visuomotor task, the presence of conspecifics facilitated performance in one of the subject groups, and this facilitation was linked to enhanced excitatory synaptic efficacy within the dorsal and ventral attention networks. We propose that presence-induced improvements in task performance arise from attentional modulation mediated by changes in excitatory synaptic efficacy across three spatiotemporal brain scales, namely, micro-scale (single neurons), meso-scale (cortical columns) and macro-scale (whole-brain). Our findings from Bayesian learning converge to establish a novel, multi-scale framework for understanding the neural underpinnings of social presence effects. This probabilistic framework offers a fresh perspective on social presence research, and lays the groundwork for future investigations into the complex interplay between social presence, neural dynamics, and behavior.

neuroscience↗

bioRxiv2021

Microglial phagocytosis dysfunction during stroke is prevented by rapamycin

Microglial phagocytosis is rapidly emerging as a therapeutic target in neurodegenerative and neurological disorders. An efficient removal of cellular debris is necessary to prevent buildup damage of neighbor neurons and the development of an inflammatory response. As the brain professional phagocytes, microglia are equipped with an array of mechanisms that enable them to recognize and degrade several types of cargo, including neurons undergoing apoptotic cell death. While microglia are very competent phagocytes of apoptotic cells under physiological conditions, here we report their dysfunction in mouse and monkey (Macaca fascicularis and Callithrix jacchus) models of stroke by transient occlusion of the medial cerebral artery (tMCAo). The impairment of both engulfment and degradation was related to energy depletion triggered by oxygen and nutrients deprivation (OND), which led to reduced process motility, lysosomal depletion, and the induction of a protective autophagy response in microglia. Basal autophagy, which is in charge of removing and recycling intracellular elements, was critical to maintain microglial physiology, including survival and phagocytosis, as we determined both in vivo and in vitro using knock-out models of autophagy genes and the autophagy inhibitor MRT68921. Notably, the autophagy inducer rapamycin partially prevented the phagocytosis impairment induced by tMCAo in vivo but not by OND in vitro. These results suggest a more complex role of microglia in stroke than previously acknowledged, classically related to the inflammatory response. In contrast, here we demonstrate the impairment of apoptotic cell phagocytosis, a microglial function critical for brain recovery. We propose that phagocytosis is a therapeutic target yet to be explored and provide evidence that it can be modulated in vivo using rapamycin, setting the stage for future therapies for stroke patients.

neuroscience↗

bioRxiv2021

Peer presence and familiarity as key factors to reduce cocaine intake: an effect mediated by the Subthalamic Nucleus

Stimulant use, including cocaine, often occurs in a social context whose influence is important to understand to decrease intake and reduce associated harms. Given the regulatory role of the subthalamic nucleus (STN) on cocaine intake and emotions, we investigate its role on such influence of social context on cocaine intake. We explored the influence of peer presence and familiarity on the frequency of self-administered cocaine and its neurobiological basis. We first compared cocaine intake in various conditions (alone or with peers with different characteristics: observing or self-administering, familiar or not, cocaine-naive or not, dominant or subordinate) in rats (n=90). The risk of drug consumption was reduced when a peer was present, observing or self-administering as well, and further diminished when the peer was unfamiliar (vs familiar). The presence of a cocaine-naive peer further decreased cocaine consumption. The presence of a non-familiar and drug-naive peer represents thus key conditions to diminish cocaine intake. We tested the effects of STN lesions in these various conditions and also conducted social experiments to validate the role of STN in social cognition. The STN lesion by itself reduced cocaine intake to the level reached in presence of a stranger naive peer and affected social cognition, positioning the STN as one neurobiological substrate of social influence on drug intake. Finally, with a translational research approach, we compared the drug intake in these conditions in human drug users (n=77). This human study confirmed the beneficial effect of social presence, especially of strangers. Our results indirectly support the use of social interventions and harm reduction strategies, in particular supervised consumption rooms for stimulant users.

neuroscience↗

bioRxiv2018

Of Rats And Men: Peer Presence And Familiarity Are Key Factors Which Modulate Drug Intake

Social environment influences drug consumption, its persistence and evolution. Little is known regarding the influence of the presence of a peer during drug consumption and especially how the relationship between peers (familiarity and dominance) can influence drug consumption. We used here a translational and transdisciplinary approach to explore the influence of peer presence and peer familiarity in rats and humans that self-administer stimulants. In rats, cocaine intake was compared when rats were alone with intake when peers with different characteristics (familiar or not, cocaine naive or not, dominant or subordinate) were present. In humans, 77 cocaine and/or methylphenidate users were asked to detail their most recent drug use episodes and their relationship with peers present at consumption. The results show that in both humans and rats, the risk of cocaine/stimulant consumption was significantly reduced by 37% and 32%, respectively, when a peer was present. Moreover, the lowest risk of consumption was consistently observed when the peer was unfamiliar (vs familiar) with a further 38% and 17% risk reduction, respectively. In rats, a decreased risk of consumption was greater when the peer was cocaine naive (vs non-cocaine naive).\n\nThe presence of a non-familiar and possibly drug-naive peer is the most efficient condition to diminish stimulant intake. Our results indirectly support the use of harm reduction strategies, in particular supervised consumption rooms for stimulant users.

neuroscience↗