Involvement of dorsomedial prefrontal projections pathways to the basolateral amygdala and ventrolateral periaqueductal grey matter in conditioned fear expression
Le 27 septembre 2016
A central endeavour of modern neuroscience is to understand the neural basis of learningand how the selection of dedicated circuits modulates experience-dependent changes inbehaviour. Decades of research allowed a global understanding of the computations occurring inhard-wired networks during associative learning, in particular fear behaviour.
However, brainfunctions are not only derived from hard-wired circuits, but also depend on modulation of circuitfunction. It is therefore realistic to consider that brain areas contain multiple potential circuitswhich selection is based on environmental context and internal state. Whereas the role of entirebrain areas such as the amygdala (AMG), the dorsal medial prefrontal cortex (dmPFC) or theperiaqueductal grey matter (PAG) in fear behaviour is reasonably well understood at themolecular and synaptic levels, there is a big gap in our knowledge of how fear behaviour iscontrolled at the level of defined circuits within these brain areas. More particularly, whereas thedmPFC densely project to both the basolateral amygdala (BLA) and PAG, the contributions ofthese two projections pathway during fear behaviour are largely unknown. Beside theinvolvement of these neuronal pathways in the transmission of fear related-information, theneuronal mechanisms involved in the encoding of fear behaviour within these pathways are alsovirtually unknown. In this context, the present thesis work had two main objectives. First,evaluate the contribution of the dmPFC-BLA and dmPFC-vlPAG pathways in the regulation offear behaviour, and second, identify the neuronal mechanisms controlling fear expression in thesecircuits. To achieve these goals, we used a combination of single unit and local field potentialrecordings coupled to optogenetic approaches in behaving animals submitted to a discriminativefear conditioning paradigm.
Our results first, identified a novel neuronal mechanism of fear expression based on the development of 4 H oscillations within dmPFC-BLA circuits thatdetermine the dynamics of freezing behaviour and allows the long-range synchronization offiring activities to drive fear behaviour. Secondly, our results identified the precise circuitry at thelevel of the dmPFC and vlPAG that causally regulate fear behaviour. Together these data provideimportant insights into the neuronal circuits and mechanisms of fear behaviour. Ultimately thesefindings will eventually lead to a refinement of actual therapeutic strategies for pathological conditions such as anxiety disorders.
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- M. Georges Di Scala (DR-CNRS Bordeaux) Président
- Mme Thérèse Jay (DR-INSERM Paris) Rapporteur
- Mme. Nadine Ravel (CR-CNRS Lyon) Rapporteur
- M. Yann Humeau (CR-CNRS Bordeaux) Membre invité
- M. Sidney Wiener (DR-CNRS Paris) Examinateur
- M. François Georges (DR-CNRS Bordeaux) Examinateur
- M. Cyril Herry (DR-INSERM Bordeaux) Directeur de thèse
Cyril Herry est team leader de l’équipe : Neuronal circuits of associative learning . Neurocentre Magendie