Biology subjects

Lepousez, G.

Publications and source records attributed to Lepousez, G..

4 recordsLinked to original sources

bioRxiv2026

Olfactory learning potentiates long-range cortical GABAergic inputs onto adult-born neurons.

Adult neurogenesis in the olfactory bulb (OB) contributes to structural and functional plasticity, influencing olfactory perception, learning, and memory. Adult-born granule cells (abGCs) exhibit unique morphological, electrophysiological, and synaptic properties compared to their neonatally born counterparts, suggesting a specialized role in olfactory processing. In the OB, such processing relies both on sensory inputs from the olfactory epithelium as well as top-down cortical feedback, which encompass both glutamatergic and GABAergic projections from the olfactory cortex back to the OB. While abGCs are known to integrate both bottom-up sensory inputs and top-down cortical projections, the specific connectivity and functional influence of cortical GABAergic inputs on abGCs remain largely unexplored. In this study, we investigated whether activity of cortical GABAergic projections is modulated by olfactory learning, how they impact olfactory behavior and whether these connections selectively influence mature abGCs. Using in vivo fiber photometry following odor-reward associative conditioning, we found odor- and reward-dependent activity of cortical GABAergic projections during learning session. Furthermore, their functional role was revealed using optogenetic activation which impaired both the acquisition and the reversal of an odor-reward association. Ex vivo patch-clamp recordings demonstrated that olfactory learning potentiates cortical GABAergic inputs specifically onto abGCs, and morphological analysis confirmed that learning increases the number of cortical GABAergic synapses. These findings highlight a novel mechanism by which top-down inhibitory control from the olfactory cortex selectively targets abGC activity during olfactory learning. Our results provide new insights into the functional specialization of abGCs and their role in adaptive olfactory behaviors.

neuroscience↗

bioRxiv2024

Dissecting the contribution of vagal subcircuits in sepsis-induced brain dysfunctions.

Sepsis, a life-threatening syndrome caused by a dysregulated host response to infection, induces a range of acute effects on the brain, including sickness behaviour and sepsis-associated encephalopathy. In addition, sepsis can lead to durable changes in neuronal circuits, resulting in long-term impairments such as post-traumatic stress disorder (PTSD). These brain dysfunctions are not directly caused by brain infection but result from peripheral inflammatory signals relayed to the brain via neural and humoral pathways. The vagal complex in the brainstem, composed of the nucleus of the solitary tract (NTS) and the area postrema, plays a crucial role in sensing and relaying these signals. Notably, the activation of the vagal complex triggers neurovegetative, neuroendocrine, and behavioural responses to infection. Chronic electrical vagus nerve stimulation has been used clinically to treat various brain disorders and is being investigated for its potential to alleviate inflammation and immune diseases through the anti-inflammatory reflex. However, a deeper understanding of the involvement of the vagus nerve and downstream brain circuits in sepsis-induced brain activation and dysfunction is needed to optimize therapeutic strategies. To investigate the role of the vagal complex in sepsis-induced brain dysfunction, various techniques were employed to manipulate vagus nerve activity and downstream circuits in a rodent model of sepsis by caecal ligation and puncture. Subdiaphragmatic vagotomy and pharmacogenetic manipulation of NTS and nodose (i.e. vagus sensory neurons) were implemented, revealing that vagotomy effectively reduced acute brain activation, inflammatory responses, and sickness behaviour triggered by sepsis. Additionally, transient activation of NTS neurons had a significant impact on inflammatory responses, sickness behaviour, and long-term PTSD-like consequences. This study underscores the complex interplay among the vagus nerve, brain circuits, and systemic inflammation during sepsis, emphasizing the critical importance of understanding these interactions in the development of targeted therapeutic interventions.

neuroscience↗

bioRxiv2020

Long-range GABAergic projections contribute to cortical feedback control of sensory processing.

Cortical sensory areas send excitatory projections back to earlier stage of sensory processing. Here, we uncover for the first time the existence of a corticofugal inhibitory feedback between two sensory areas, paralleling the well-documented excitatory feedback. In the olfactory system, we reveal that a subpopulation of GABAergic neurons in the anterior olfactory nucleus and anterior piriform cortex target the olfactory bulb. These long-range inhibitory inputs synapse with both local and output olfactory bulb neurons, mitral and tufted cells. Optogenetic stimulation coupled to in vivo imaging and network modeling showed that activation these inhibitory inputs drives a net subtractive inhibition of both spontaneous and odor-evoked activity in local as well as mitral and tufted cells. Further, cortical GABAergic feedback stimulation enhanced separation of population odor responses in tufted cells, but not mitral cells. Targeted pharmacogenetic silencing of cortical GABAergic axon terminals in the OB impaired discrimination of similar odor mixtures. We propose here that cortical GABAergic feedback represents a new circuit motif in sensory systems, involved in refining sensory processing and perception.

neuroscience↗

bioRxiv2019

The impact of gut microbiota on depressive-like behaviors and adult hippocampal neurogenesis requires the endocannabinoid system

Depression is the leading cause of disability worldwide. Recent observations have revealed an association between mood disorders and alterations of the intestinal microbiota, but causality remains yet to be established. Here, using unpredictable chronic mild stress (UCMS) as a mouse model of depression, we show that the UCMS mice display phenotypic alterations -- characterized by an altered gut microbiota composition, a reduced adult hippocampal neurogenesis and a depressive-like behaviors -- which could be transferred from UCMS donors to naive recipient mice by fecal microbiota transplantation. The cellular and behavioral alterations observed in recipient mice were accompanied by a decrease in the endocannabinoid (eCB) signaling due to lower peripheral levels of fatty acid precursors of eCB ligands. The adverse effects of UCMS-transferred microbiota on adult neurogenesis and behavior in naive recipient mice were alleviated by selectively enhancing the central eCB tone or by adding arachidonic acid, a fatty acid precursor of eCB ligands, to the diet. In the gut of both UCMS donors and recipients, the microbiota composition was characterized by a relative decrease in Lactobacilli abundance, and complementation of the UCMS recipient microbiota with a strain of the Lactobacilli genus was sufficient to restore normal eCB brain levels, hippocampal neurogenesis and to alleviate depressive-like behaviors. Our findings provide a mechanistic scenario for how chronic stress, diet and gut microbiota dysbiosis generate a pathological feed-forward loop that contributes to despair behavior via the central eCB system.

neuroscience↗