Periodic Reporting for period 2 - sociOlfa (Learning from social scents: from territory to identity)
Periodo di rendicontazione: 2021-11-01 al 2023-04-30
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.
This project aims at identifying 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. Using advanced computational methods and cutting-edge technologies that enable recording and manipulating large neuronal ensembles in freely moving mice, we will:
- shed light on the mechanisms of spatial memory consolidation: we hypothesize that a dialog between the olfactory cortex and the hippocampus during sleep underlies the memory of an environment marked by social scents.
- track the brain substrates of individuals’ identity in mice and their dependence on olfactory inputs: we hypothesize that during social learning, the response of neuronal circuits (1) reflects the unique olfactory signature of the encountered individual, and that (2) it changes as this individual becomes familiar.
- test whether a coordination between olfactory and memory networks is essential to the formation of social recognition memory.
Overall, this project will provide important insights on the network mechanisms of memory function and will contribute to our understanding of social behaviors.
This project aims at identifying 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. Using advanced computational methods and cutting-edge technologies that enable recording and manipulating large neuronal ensembles in freely moving mice, we will:
- shed light on the mechanisms of spatial memory consolidation: we hypothesize that a dialog between the olfactory cortex and the hippocampus during sleep underlies the memory of an environment marked by social scents.
- track the brain substrates of individuals’ identity in mice and their dependence on olfactory inputs: we hypothesize that during social learning, the response of neuronal circuits (1) reflects the unique olfactory signature of the encountered individual, and that (2) it changes as this individual becomes familiar.
- test whether a coordination between olfactory and memory networks is essential to the formation of social recognition memory.
Overall, this project will provide important insights on the network mechanisms of memory function and will contribute to our understanding of social behaviors.
1- We have successfully implemented an approach which allows measuring respiration in freely moving mice thanks to miniaturized ultra-light pressure sensors. They can be easily carried by mice and measure the variations in the air pressure within the nasal cavity. Using computational methods on the signals obtained, we were able to isolate the periods of active olfactory sampling (“sniffing”) which can be linked to social interactions between mice and investigation of social scent marks.
2- In collaboration with the Pasteur Institute, we have set up a tracking system for automatic profiling of mouse behaviors in social groups. We conducted preliminary experiments with the system and contributed to the development of additional features. This system uses depth cameras and machine learning to track individual mice in a group and automatically detect defined behavioral motives, some of them in real-time. The ability to detect specific types of social interactions in real-time will allow us to perform optogenetic manipulations triggered by the animals’ behaviors in a closed-loop manner.
3- In parallel, we developed another behavioral setup where mice located in 2 separate chambers can interact through a small “window” and obtain a reward depending on their ability to recognize the encountered mouse. This fully automatized system presents the advantage of (1) increasing the number of interaction events, (2) precisely detect the interactions epochs and (3) quantify memory performance and study error trials.
4- We have tested and optimized the surgical procedures necessary to perform challenging in vivo neuronal recordings in the specific regions at the core of this project: the hippocampus and the olfactory cortex. To do so, we have performed histological verifications with immunostainings.
5- We have recorded neurons in a brain region that is key for social memory, which is located in a very small part of the hippocampus. Using optogenetics, we have managed to control their activity in freely moving mice using finely-tuned light stimuli.
6- We have analyzed neuronal recordings conducted in the hippocampus and the olfactory cortex and started characterizing the dialog between these two regions, in particular during sleep where it can play a central role in memory consolidation.
7- We took advantage of the method we set up to precisely monitor nasal airflow in freely moving mice and our neuronal recordings to conduct two studies which will submitted for publication within the next months. The first manuscript describes the intimate link with nasal airflow and the vigilance state of the animal (sleep types, wakefulness) and provides a tool based on machine-learning which uses the respiration signal to predict brain states. The second manuscript makes use of the precision obtained with nasal pressure sensors to revisit the link between respiration and brain activity.
2- In collaboration with the Pasteur Institute, we have set up a tracking system for automatic profiling of mouse behaviors in social groups. We conducted preliminary experiments with the system and contributed to the development of additional features. This system uses depth cameras and machine learning to track individual mice in a group and automatically detect defined behavioral motives, some of them in real-time. The ability to detect specific types of social interactions in real-time will allow us to perform optogenetic manipulations triggered by the animals’ behaviors in a closed-loop manner.
3- In parallel, we developed another behavioral setup where mice located in 2 separate chambers can interact through a small “window” and obtain a reward depending on their ability to recognize the encountered mouse. This fully automatized system presents the advantage of (1) increasing the number of interaction events, (2) precisely detect the interactions epochs and (3) quantify memory performance and study error trials.
4- We have tested and optimized the surgical procedures necessary to perform challenging in vivo neuronal recordings in the specific regions at the core of this project: the hippocampus and the olfactory cortex. To do so, we have performed histological verifications with immunostainings.
5- We have recorded neurons in a brain region that is key for social memory, which is located in a very small part of the hippocampus. Using optogenetics, we have managed to control their activity in freely moving mice using finely-tuned light stimuli.
6- We have analyzed neuronal recordings conducted in the hippocampus and the olfactory cortex and started characterizing the dialog between these two regions, in particular during sleep where it can play a central role in memory consolidation.
7- We took advantage of the method we set up to precisely monitor nasal airflow in freely moving mice and our neuronal recordings to conduct two studies which will submitted for publication within the next months. The first manuscript describes the intimate link with nasal airflow and the vigilance state of the animal (sleep types, wakefulness) and provides a tool based on machine-learning which uses the respiration signal to predict brain states. The second manuscript makes use of the precision obtained with nasal pressure sensors to revisit the link between respiration and brain activity.
SociOlfa will contribute to the excellence and competitiveness of the European scientific community in different ways:
- It will provide key scientific insights on fundamental questions of broad interest for the neuroscience community and beyond: the brain-wide mechanisms underlying memory function and the neuronal bases of individuality.
- It will be at the forefront of innovation and technology by combining a unique set of advanced technologies that allow observing and manipulating large neuronal ensembles, within and across brain regions, as the animal is engaged in ecologically relevant behaviors.
- It will tackle 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 will also contribute to the dissemination of knowledge in Europe through publications with open access, as well as international conferences.
- It will provide key scientific insights on fundamental questions of broad interest for the neuroscience community and beyond: the brain-wide mechanisms underlying memory function and the neuronal bases of individuality.
- It will be at the forefront of innovation and technology by combining a unique set of advanced technologies that allow observing and manipulating large neuronal ensembles, within and across brain regions, as the animal is engaged in ecologically relevant behaviors.
- It will tackle 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 will also contribute to the dissemination of knowledge in Europe through publications with open access, as well as international conferences.