Circuit Mechanisms of Context-dependent Memory-based Action Selection

Abstract

Brain structures such as the Striatum (vertebrates) and the Mushroom Body (MB) (invertebrates) are thought to carry out classical conditioning (Eichler et al., 2017; Heisenberg, 2003; Suri & Schultz, 1999). This process allows animals to associate conditioned stimuli (CSs) with rewards or punishments (Pavlov, 1927). The output of these structures is thought to represent the stimulus’ learned value which can influence the selected behavioural response (Aso, Sitaraman, et al., 2014; Costa et al., 2019; Eschbach et al., 2021). Specific behavioural outcomes are determined by specific motor command or command-like neurons (Jing, 2009; Kupfermann & Weiss, 1978). They represent a bottleneck for all the information contributing to action selection including both learned and innate drives (Sokolov & Nezlina, 2008). As such, the influence of a CS on behaviour will depend on its learned value and the innate context. The circuits that allow learned value signals and innate contextual information to converge onto motor command neurons are not well understood. The Drosophila larva is an excellent model system for such investigations due to its rich behavioural repertoire (Eschbach & Zlatic, 2020; Ohyama et al., 2013) with identified command neurons (Clark et al., 2018; Ohyama et al., 2015; Takagi et al., 2017), extensive genetic toolkit (Jenett et al., 2012; Kvon et al., 2014; Lai & Lee, 2006; Owald et al., 2015) and fully reconstructed brain connectome (Winding et al., 2024) which includes the MB (Eichler et al., 2017). In this thesis, I demonstrate that aversive olfactory conditioning can modulate larval escape behaviour in a context-dependent manner. I identify a functional, excitatory descending input to the command neuron for rolling escape and demonstrate that this neuron receives input from both the MB and innate nociceptive pathways. Finally, I propose a mechanism through which this circuit could carry out context-dependent memory- based action selection.