Periodic Reporting for period 2 - MarmOT (The role of oxytocin in vocal communication and brain-to-brain synchrony of socially interacting marmosets)
Período documentado: 2024-01-01 hasta 2024-12-31
Primates interact with each other primarily through visual and acoustic communication. However, while primate social vision has been extensively studied, little is known about the neuronal basis of acoustic communication in primates. More specifically, we ignore how oxytocin, a neurohormone that regulates social behavior in mammals and a promising therapeutic target for psychiatric disorders, modulates acoustic communication. Based on preliminary evidence, I hypothesize that oxytocin (1) acts in the auditory cortex to increase signal to noise ratio in response to social auditory stimuli, (2) is required for normal communication behavior and (3) is critical to brain-to-brain coordination between two interacting individuals. This Global Fellowship proposal has been designed to unveil how oxytocin influences primates’ acoustic communication at the neuronal and behavioral levels. To do so, I combined state of the art techniques, such as chemogenetic manipulation of oxytocin neurons and wireless electrophysiology, in marmoset monkeys. This highly vocal primate was key to this project and a rapidly growing animal model in neuroscience. I learnt to work with them during my Outgoing phase in San Diego (USA) and transfered this knowledge back to Europe during the incoming phase, by participating in the inception of a marmoset laboratory in Lyon (France). This project greatly enhanced my career opportunities in academia as it gave me a unique theoretical and technical background. It placed me in a good spot to explore innovative research pathways, with a great potential scientific impact. All the outcomes from MarmOT are or will be published strictly following the Open Science objective of H2020. This project can benefit society by enhancing our understanding of primate communication and the role of oxytocin, which is a therapeutic target for many psychiatric disorders including autism.
The conclusion of the action is that using chemogenetics methods to activate or inhibit oxytocin neurons in non human primate is feasible, and that the Area 24 of the cortex encodes both emission and perception of vocalizations as well as contextual information such as whether a call is an answer or an isolated call. On a side project, we also found that oxytocin fibers are similarly distributed in the brain of primates and rodents, allowing us to hope for a high degree of translationability between animal models.
The conclusion of the action is that using chemogenetics methods to activate or inhibit oxytocin neurons in non human primate is feasible, and that the Area 24 of the cortex encodes both emission and perception of vocalizations as well as contextual information such as whether a call is an answer or an isolated call. On a side project, we also found that oxytocin fibers are similarly distributed in the brain of primates and rodents, allowing us to hope for a high degree of translationability between animal models.
During the outgoing phase, I have learnt how to use marmoset monkeys for neuroscience research, performed several experiments, managed a student, established a solid network within the north American marmoset research community and started to disseminate the results.
The main results are the successful development of a viral chemogenetic method to manipulate oxytocin neurons in the marmoset brain. This powerful tool can now be applied to manipulate marmosets' social behavior, notably vocalizations, but also opens new possibilities of research.
I also performed an anatomical mapping of oxytocin fibers, which has led to the publication of a preprint article, revealing where is oxytocin released in the primate brain.
Finally, I have performed electrophysiological recording of the anterior cingulate cortex in freely moving, freely behaving marmosets, and found that this brain region is important for the production of vocalizations but also for their perception, and also regulates whether the subject's decision to answer or not a call from the partner.
These results have been disseminated in various scientific meetings were I have given poster and oral presentations. No action towards the general audience have taken place yet as I am still in the data analysis phase and the results are still preliminary.
The main results are the successful development of a viral chemogenetic method to manipulate oxytocin neurons in the marmoset brain. This powerful tool can now be applied to manipulate marmosets' social behavior, notably vocalizations, but also opens new possibilities of research.
I also performed an anatomical mapping of oxytocin fibers, which has led to the publication of a preprint article, revealing where is oxytocin released in the primate brain.
Finally, I have performed electrophysiological recording of the anterior cingulate cortex in freely moving, freely behaving marmosets, and found that this brain region is important for the production of vocalizations but also for their perception, and also regulates whether the subject's decision to answer or not a call from the partner.
These results have been disseminated in various scientific meetings were I have given poster and oral presentations. No action towards the general audience have taken place yet as I am still in the data analysis phase and the results are still preliminary.
This is the first time that neural activity in a freely behaving and vocally interacting marmoset is recorded and it shows the role of ACC in the process. Most notably, ACC was thought to be solely involved in motor output, controlled by the vlPFC (equivalent of Broca area) but finding neurons encoding vocalisation type and more critically answers from the partner indicates that this region is at the heart of the network controlling vocal interaction. A result coherent to studies in macaques that have shown that ACC tracks variables related to other individuals.
I am now focused on combining this paradigm together with the manipulation of oxytocin neurons. I expect to be able to upregulate or inhibit the number of vocalizations that the subject emits. This would be a tremendous achievement for the field.
The main impact of MarmOT is the further understanding of the neuronal basis of primate acoustic communication, and at a wider level the possibility to manipulate the endogenous oxytocin system could have significant consequences for clinical research, as it could be a lot more efficient than administering oxytocin intranasally, as it is done currently. This would impact patients suffering from a wide range of disorders, as oxytocin is a therapeutic target for autism, schizophrenia, depression, obesity and more.
I am now focused on combining this paradigm together with the manipulation of oxytocin neurons. I expect to be able to upregulate or inhibit the number of vocalizations that the subject emits. This would be a tremendous achievement for the field.
The main impact of MarmOT is the further understanding of the neuronal basis of primate acoustic communication, and at a wider level the possibility to manipulate the endogenous oxytocin system could have significant consequences for clinical research, as it could be a lot more efficient than administering oxytocin intranasally, as it is done currently. This would impact patients suffering from a wide range of disorders, as oxytocin is a therapeutic target for autism, schizophrenia, depression, obesity and more.