Biology subjects

Onimus, O.

Publications and source records attributed to Onimus, O..

3 recordsLinked to original sources

bioRxiv2024

The gut-brain vagal axis scales hippocampal memory processes and plasticity

The vagus nerve serves as an interoceptive relay between the body and the brain. Despite its well-established role in feeding behaviors, energy metabolism, and cognitive functions, the intricate functional processes linking the vagus nerve to the hippocampus and its contribution to learning and memory dynamics remain still elusive. Here, we investigated whether and how the gut-brain vagal axis contributes to hippocampal learning and memory processes at behavioral, functional, cellular, and molecular levels. Our results indicate that the integrity of the vagal axis is essential for long-term recognition memories, while sparing other forms of memory. In addition, by combing multi-scale approaches, our findings show that the gut-brain vagal tone exerts a permissive role in scaling intracellular signaling events, gene expressions, hippocampal dendritic spines density as well as functional long-term plasticities (LTD and LTP). These results highlight the critical role of the gut-brain vagal axis in maintaining the spontaneous and homeostatic functions of hippocampal ensembles and in regulating their learning and memory functions. In conclusion, our study provides comprehensive insights into the multifaceted involvement of the gut-brain vagal axis in shaping time-dependent hippocampal learning and memory dynamics. Understanding the mechanisms underlying this interoceptive body-brain neuronal communication may pave the way for novel therapeutic approaches in conditions associated with cognitive decline, including neurodegenerative disorders. HighlightsO_LIThe gut-brain vagal axis contributes to long-term recognition memories C_LIO_LIThe gut-brain vagal axis is dispensable for short-term memories C_LIO_LIThe vagal axis regulates molecular and signaling dynamics in the hippocampus C_LIO_LIThe gut-brain vagal tone shapes the structural density of hippocampal dendritic spines C_LIO_LIThe gut-brain vagal tone ensures physiological forms of synaptic plasticity C_LI

neuroscience↗

bioRxiv2023

NAPE-PLD in the ventral tegmental area regulates reward events, feeding and energy homeostasis

The N-acyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) catalyzes the production of N-acylethanolamines (NAEs), a family of endogenous bioactive lipids, which are involved in various biological processes ranging from neuronal functions to energy homeostasis and feeding behaviors. Reward-dependent behaviors depend on the dopamine (DA) transmission between the ventral tegmental area (VTA) and the nucleus accumbens (NAc) which conveys reward-values and scales reinforced behaviors. However, whether and how NAPE-PLD may contribute to the regulation of feeding and reward-dependent behaviors has not been investigated yet. This biological question is of paramount importance since NAEs are altered in obesity and metabolic disorders. Here, we show that transcriptomic meta-analysis highlights a potential role for NAPE-PLD within the VTA[->]NAc circuit. Using brain-specific invalidation approaches, we report that the integrity of NAPE-PLD is required for the proper homeostasis of NAEs within the midbrain VTA and it affects food-reward behaviors. Moreover, region-specific knock-down of NAPE-PLD in the VTA resulted in enhanced food-reward seeking and reinforced behaviors which were associated with increased in vivo DA release dynamics in response to both food and non-food-related rewards together with heightened tropism towards food consumption. Furthermore, midbrain knock-down of NAPE-PLD, which led to increased energy expenditure and adapted nutrients partitioning, elicited a relative protection against high-fat diet-mediated body fat gain and obesity-associated metabolic features. In conclusion, these findings unravel a new key role of VTA NAPE-PLD in shaping DA-dependent events, feeding behaviors and energy homeostasis, thus providing new insights on the regulation of body metabolism. Highlights- NAPE-PLD and NAEs are enriched in the VTA and regulate food-reinforced behaviors and reward processes. - NAPE-PLD scales in vivo VTA[->]NAc dopamine dynamics. - NAPE-PLD in the VTA contributes to whole-body energy balance and metabolic efficiency. - Downregulation of VTA NAPE-PLD ameliorates obesity-associated metabolic features.

neuroscience↗

bioRxiv2022

Haloperidol-induced immediate early genes in striatopallidal neurons requires the converging activation of cAMP/PKA/DARPP-32 and mTOR pathways

Antipsychotics share the common pharmacological feature of antagonizing the dopamine 2 receptor (D2R) which is abundant in the striatum and involved in both the therapeutic and side effects of this drugs class. Pharmacological blockade of striatal D2R, by disinhibiting the D2R-containing medium-size spiny neurons (MSNs), leads to a plethora of molecular, cellular and behavioral adaptations which are central in the action of antipsychotics. Here, we focused on the cell type-specific (D2R-MSNs) regulation of some striatal immediate early genes (IEGs), such as cFos, Arc and Zif268. Taking advantage of transgenic mouse models, pharmacological approaches and immunofluorescence analyses, we found that haloperidol-induced IEGs in the striatum required the synergistic activation of A2a (adenosine) and NMDA (glutamate) receptors. At the intracellular signaling level, we found that the PKA/DARPP-32 and mTOR pathways synergistically cooperate to control the induction of IEGs by haloperidol. By confirming and further expanding previous observations, our results provide novel insights into the regulatory mechanisms underlying the molecular/cellular action of antipsychotics in the striatum.

neuroscience↗