The role of central amygdala neuron subpopulations in appetitive behaviours

Fermani, Federica (2022): The role of central amygdala neuron subpopulations in appetitive behaviours. Dissertation, LMU München: Fakultät für Biologie

Abstract

Nutrient ingestion is regulated by homeostatic needs, that increase the motivation to eat when energy stores are low, and by hedonic pathways that increase the desire to consume rewarding food even when there is abundant energy. Animals looking for food must constantly rely on environmental signals in order to discriminate between dangers and rewards. The amygdala comprises a collection of nuclei including the basolateral complex (BLA) and the central amygdala (CeA). The CeA, with its lateral (CeL) and medial (CeM) divisions orchestrates a wide range of behaviours, including defensive and appetitive responses. The CeA, indeed, is a node within different structures known to process taste and interoceptive information and integrates emotionally salient environmental stimuli to generate appropriate behaviours1. All the studies presented in this thesis investigate the role of CeA in appetitive behaviours. In the first study, I combined behavioural, optogenetic and in vivo recordings of neuronal activity, to explore the roles of different CeA subpopulations in associative learning of contextual food cues. Using a behavioural task of appetitive conditioning, in which the mice explore an arena across different cues looking for food, I found that two CeA subpopulations, Somatostatin (Sst) and Protein kinase C delta (PKCd), acquire a specific response to contextpositive environmental cues. Interestingly, while the proportion of food responsive cells was higher in Sst neurons, only optogenetic inhibition of PKCd impaired both the learning and the retrieval of contextual food memory, suggesting their involvement in linking the sensory characteristics of the environment with the salience of the food reward. However, Sst cells could be responsible for correlating the physical properties of the food, such as texture and taste, with the context. In the second study, I examined the role of 5-Hydroxytryptamine receptor 2A (Htr2a) and Sst neurons in CeL versus CeM in consummatory and rewarding behaviours. Although CeA has been recently studied in appetitive paradigms, the relative contribution of the two major CeA subdivisions is still relatively unclear. The role of CeAHtr2a neurons in feeding, previously described in our lab2, raised the question of whether their function is specific to feeding, or they are involved in other consummatory behaviours such as drinking. Moreover, the activity of Sst neurons (that partially overlap with Htr2a), has been shown as positively reinforcing and their inhibition in the CeL reduced water intake3. For these reasons, I investigated theinvolvement of Htr2a and Sst neurons in CeA, CeM and CeL in drinking, feeding, and rewarding behaviours. To do so, we generated a novel transgenic mouse line that expresses a Tamoxifen-inducible version of the Flp recombinase under regulatory elements of the Wfs1 gene (Wfs1-FlpoER) where the FlpoER is expressed specifically in the majority of CeLHtr2a/Sst neurons. Crossing Htr2a-Cre/Sst-Cre and Wfs1-FlpoER mice generates double transgenic intersectional mice in which CeLHtr2a/Sst cells are positive for both Cre and Flp, while CeMHtr2a/Sst cells are positive for Cre only. Stimulation of CeMHtr2a and CeMSst neurons promoted drinking and positive reinforcement behaviour. Stimulation of CeMHtr2a, but not CeMSst, neurons increased food intake. Photoactivation of the corresponding CeL subpopulations failed to elicit appetitive responses. Ongoing analysis of intra-CeA and long-range projections will provide further insights into the specific roles of CeL and CeM subpopulations in appetitive responses. In summary, this work extends our knowledge about the role of CeA in different appetite behaviours, analysing the function of the different CeA neuronal subpopulations and of the two main CeA subdivisions, CeL and CeM.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Central amygdala, Appetitive behaviours, Appetitive conditioning, Optogenetics, Calcium imaging
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
• Fakultäten: Fakultät für Biologie
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 26. Juli 2022
• 1. Bericht­erstatter:in: Klein, Rüdiger