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Eduardo Gascon

INT, France

Molecular manipulation of target microRNAs in the medial prefrontal cortex

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 Non-human primates (NHPs) have been extensively used in research, especially in neuroscience, as they represent the closest homologue of the human brain. For over a century, neuroscientists have combined complex behavioral paradigms and anatomical/physiological recordings in NHPs to obtain important insights into neuroanatomy and function of the brain. In addition, they have also provided a valuable platform for understanding human brain disorders. Among hundreds of primates, marmosets have emerged as a reference model because of their small size, rapid maturation and social abilities. 

 
Recent technological advances in viral manipulation has endowed researchers with novel tools to explore brain function in the marmoset. Thus, calcium indicators or optogenetics enable monitoring or manipulating, respectively, neuronal activity with unprecedented resolution in behaving marmosets. In parallel, the Cas9 nuclease technology has been a long awaited tool for manipulation of genomes at will. In the last decade, it has been successfully applied to multiple biological systems has become the most popular genome editing technology in history.

 

Here, we present our work regarding how ventro-medial prefrontal cortex (vmPFC) controls the responses to ambiguous threatens in the marmoset. Taking advantage of naturally occurring genetic polymorphisms, we show that molecular profiling of the marmoset cortex uncovered unexpected regional differences within the vmPFC. More importantly, our data suggest that specific molecular factors might participate not only in the behavioral responses but also in the responsiveness to antidepressants. We also provide evidences that it is now possible to specifically manipulate gene networks in vivo and that these tools can be used in the near future to establish casual links between molecular networks, precise neuronal circuits and the elaboration of adapted responses to different  types of threatens.

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