Venue: CARF
Zoom: https://u-bordeaux-fr.zoom.us/j/411548697
Meeting ID: 411 548 6972
Title
Differential contribution of distinct prefrontal neuronal populations to danger representations
Abstract
Animals can be confronted to a high diversity of dangerous situations in natural environments. Their ability to be in a vigilant state about their surroundings, prepared to recognize and respond to danger, as well as to recognize sensory stimuli associated to specific threats, allows the expression of optimal behavioral responses to successfully cope with them. Dysfunctions in the response to threats are implicated in various psychiatric conditions such as anxiety disorders, phobias, or post-traumatic stress disorder. Thus, understanding the neural mechanisms underlying defensive behaviors is essential to unravel the neuronal bases of these severe conditions. Defensive behaviors are shaped by multiple interconnected brain regions. Among them, the prefrontal cortex (PFC), a site involved in the multimodal integration of stimuli and top-down control of complex behaviors, has largely been evidenced as a key regulator of defensive responses. Most of what is known about the implication of the PFC in defensive behaviors has been based on fear conditioning paradigms in which one single sensory stimulus drives the concomitant expression of a single defensive behavior (e.g. freezing or avoidance). Such simple paradigms make it difficult to pinpoint the exact processes PFC neurons are involved in (identification or discrimination of threatening stimuli, implementation of an aversive state or execution of a defensive response) and how specific their activity is. Moreover, the literature is focused on the function of the largest cell group of the dorsomedial PFC (dmPFC) – excitatory pyramidal neurons (Pyr) – or mixed neuronal populations. Nonetheless, Pyr activity is extensively orchestrated by a heterogeneous network of GABAergic interneurons (INs), among which Somatostatin-expressing (SST+) and Parvalbumin-expressing (PV+) neurons are the most abundant types. A limited body of evidence shows the critical role of dmPFC INs in the formation of an aversive memory and defensive freezing expression. Thus, a more comprehensive view of how dmPFC neurons, especially INs, process threatening information is still missing and would require more complex settings. In this work, we sought to determine the role of the main dmPFC neuronal populations (Pyr, SST+ and PV+ neurons) in the encoding of defensive states and specific threatening features to ultimately control the expression of defensive behaviors. To this end, we combined cell-type specific in vivo calcium imaging and optogenetic manipulations of the dmPFC with a novel behavioral paradigm in which mice face different threatening situations and must select the most pertinent defensive behavior to each of them in order to avoid an aversive outcome. We demonstrated that each of the studied neuronal populations encode threat-related information differently. The populations of excitatory neurons and SST+ INs have well-differentiated representations of threatening and non-threatening conditions. In addition, the SST+ population discriminates specific threatening information, a process that was necessary for the selection of appropriate defensive behaviors. In contrast, the population activity of PV+ INs encoded in a more unspecific manner the presence of task stimuli regardless of their emotional value and was essential for mice to overall respond to threats. Together, these data suggest the presence of a gradient of representations of threatening events – from more general to more specific – in different dmPFC neuronal populations, allowing a collective encoding of danger.
Keywords: Prefrontal cortex, interneurons, defensive behaviors, danger, calcium imaging
Jury
M. François GEORGES – Directeur de recherche, IMN, Bordeaux – president
Mme Nadine GOGOLLA – Directrice de recherche, Max Planck Institute of Psychiatry, Munich – rapportrice
M. Philip TOVOTE – Professor, Institute of Clinical Neurobiology, Würzburg – rapporteur
M. Antoine BESNARD – CRCN, Institut de Génomique Fonctionnelle, Montpellier – examinateur
Mme Lisa ROUX – Chargée de recherche, IINS, Bordeaux – examinatrice
Publications
Menegolla AP, Lopez-Fernandez G, Herry C, Martin-Fernandez M. Differential contribution of distinct neuronal populations to danger representations. bioRxiv 2024.01.24.577067. doi: 10.1101/2024.01.24.577067
Martin-Fernandez M, Menegolla AP, Lopez-Fernandez G, Winke N, Jercog D, Kim HR, Girard D, Dejean C, Herry C. Prefrontal circuits encode both general danger and specific threat representations. Nat Neurosci. 2023 Dec;26(12):2147-2157. doi: 10.1038/s41593-023-01472-8