Organisation of central amygdala circuits regulating appetitive and aversive behaviours

Ponserre, Marion (2018): Organisation of central amygdala circuits regulating appetitive and aversive behaviours. Dissertation, LMU München: Fakultät für Biologie

Abstract

An organism’s survival is contingent on its ability to evaluate whether environmental cues predict a threat or an opportunity. The amygdala has long been studied for its pivotal role in providing an emotional tag to environmental stimuli so that individuals can engage in the appropriate behavioural response. The amygdala is composed of a collection of nuclei including the basolateral (BLA) and central amygdala nuclei (CeA), which have been proposed to participate in the formation of memories that link sensory information to aversive or rewarding representations, and to provide the output pathway through which these memories are translated into behavioural actions, respectively. Although previous work has provided a wealth of information on the amygdala circuits that govern aversive behaviours, such as avoidance of threats or potentially poisonous substances, information on CeA circuits that process appetitive signals is incomplete. In this context, this study aimed to decipher the organisation of CeA circuits that control feeding and rewarding behaviours. By using a combination of behavioural and optogenetic approaches, it was revealed that increase in the activity of CeA neurons expressing the serotonin receptor 2a (Htr2a) can counteract the anorexigenic effect induced by the activation of protein kinase C delta- (PKCδ) expressing neurons. The mechanisms underlying this behaviour were untangled by showing that CeAHtr2a neurons promote food consumption and positive reinforcement via inhibition of the parabrachial nucleus (PBN) (experiments conducted by Amelia M. Douglas). Yet, the question of how the appetitive information is relayed onto PBN-projecting CeAHtr2a neurons remained. Using recombinant rabies virus technology, I found a reciprocal inhibitory interaction between PBN-projecting CeAHtr2a and CeAPKCδ neurons - a motif circuit by which they might exert opposing influences on food intake. I further examined putative sources of excitatory inputs and demonstrated that CeAHtr2a neurons are composed of several subpopulations by virtue of their specific presynaptic partners. Those CeAHtr2a neurons projecting to the PBN constitute one distinct unit that receives monosynaptic inputs from a specific combination of brain nuclei with known roles in reward processing and food intake. Interestingly, these regions were found to preferentially innervate CeAHtr2a cells compared to CeAPKCδ neurons. In an attempt to further characterize all the CeAHtr2a subunits, I obtained preliminary results indicating that sensory information from the cortex and thalamus might not directly target CeA projection neurons, suggesting that the encoding of the value of a stimulus and the instruction of the underlying behaviour to downstream effectors might be mediated by two distinct populations of CeA neurons. In summary, this work substantially extends our knowledge of the organisation of CeA circuits that govern appetitive and aversive behaviours, and provides insights into how they can select output pathways targeting distinct downstream structures depending on the pattern of their monosynaptic inputs.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
• Fakultäten: Fakultät für Biologie
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 9. Oktober 2018
• 1. Bericht­erstatter:in: Klein, Rüdiger