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Learning from social scents: from territory to identity

Periodic Reporting for period 4 - sociOlfa (Learning from social scents: from territory to identity)

Période du rapport: 2024-11-01 au 2025-10-31

Olfaction is a central sensory modality in most Mammals as it supports vital functions such as feeding, mating and social interactions. Social chemosignals (olfactory cues from urine or body secretions) are efficient communication cues carrying important information such as territory ownership, resources’ locations and identity. Remembering such information is a key advantage for individuals allowing them to adapt their behaviors based on prior experience. However, how social chemosignals are processed and stored in the brain for future recall is still unclear.
The goal of this project was to identify the brain-wide mechanisms underlying the contribution of social chemosignals to spatial and social memory in the mouse. The hippocampus is a key brain region for these two fundamental memory functions and it shares direct anatomical connections with the olfactory system that processes social odors.
During the course of this project, using a state-of-the-art method to monitor and analyze sniffing in freely moving mice combined with advanced technologies that enable recording large neuronal ensembles in freely moving mice, we have uncovered important neuronal mechanisms linking odors, breathing and hippocampal network activity during memory encoding and consolidation, focusing on the olfactory piriform cortex and the hippocampus, as well as their interactions.
Overall, this project provided important insights on the network mechanisms of memory function and contributed to our understanding of the neuronal bases of social behaviors.
During the course of this project, we have implemented a state-of-the-art method to monitor and analyze sniffing in freely moving mice with a high level of precision (thanks to miniaturized ultra-light pressure sensors), establishing the methodological framework for studies on social odor neuronal processing, and leading to new discoveries on the link between respiration and brain activity in the context of memory function (Casali et al., accepted in Nature Communications) and olfaction (Terral et al., Nature Communications 2024).
Combining this approach with advanced computational methods and cutting-edge technologies that enable recording large neuronal ensembles in freely moving mice, we have shed light on the mechanisms of memory consolidation during sleep: we found that these are strongly linked to bodily functions and in particular, the way the animal breath (Casali et al., accepted). This work yielded a machine-learning-based toolbox which can predict brain states (sleep states, wakefulness) solely based on the respiration signal. This toolbox will be shared with the community through an open-access platform.
We also uncovered that neurons in the olfactory piriform cortex replay past activity patterns after an olfactory learning task when the animal is asleep. Activity in this sensory cortex correlates with neuronal activity in the hippocampus and could therefore potentially instruct memory networks during memory consolidation (Moore, Terral et al., manuscript in preparation). Our results indeed show that the odors sampled during wakefulness, when mice explore two distinct territories, shape hippocampal activity both during wake and sleep (Moore, Ravassard et al., manuscript in preparation).
Finally, we have tracked the brain substrates of individuals’ identity in mice and studied the role of a pro-social neuropeptide, oxytocin, in the olfactory piriform cortex in the context of social behaviors.
Overall, this program has taken full advantage of advanced technologies to dissect the neural bases of functions with fundamental ecological relevance: the capacity to remember a path leading to vital resources (spatial/olfactory memory) and the capacity to remember or interact with others (social behaviors).
SociOlfa has contributed to the excellence and competitiveness of the European scientific community in different ways:
- It has provided key scientific insights on fundamental questions of broad interest for the neuroscience community and beyond: the mechanisms underlying memory consolidation and their link with olfaction and bodily functions (notably: respiration).
- It was at the forefront of innovation and technology by combining a unique set of advanced technologies that allow observing large neuronal ensembles, within and across brain regions, as the animal is engaged in ecologically relevant behaviors.
- It has tackled clinical, societal and economical challenges by unravelling important physiological mechanisms underpinning memory functions that can be impaired by brain diseases or aging. For instance, spatial and social recognition memory are affected in patients with Alzheimer disease. Impairments of social perception and cognition is also a core feature of autism spectrum disorders.
- It has also contributed to the dissemination of knowledge through publications (2 articles in Nature Communications, 3 articles in preparation), outreach events, as well as multiple international conferences.
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