Activation of specific mushroom body output neurons inhibits proboscis extension and feeding behavior

Abstract

15The ability to modify behavior based on prior experience is essential to an animal's 16 survival. For example, animals may become attracted to a previously neutral odor or reject a 17 previously appetitive food source upon learning. In Drosophila, the mushroom bodies (MBs) are 18 critical for olfactory associative learning and conditioned taste aversion, but how the output of 19 the MBs affects specific behavioral responses is unresolved. In conditioned taste aversion, 20 Drosophila shows a specific behavioral change upon learning: proboscis extension to sugar is 21 reduced after a sugar stimulus is paired with an aversive stimulus. While studies have identified 22 MB output neurons (MBONs) that drive approach or avoidance behavior, whether the same 23 MBONs impact proboscis extension behavior is unknown. Here, we tested the role of MB 24 pathways in modulating proboscis extension and identified 10 MBON split-GAL4 lines that upon 25 activation significantly decreased proboscis extension to sugar. Activating several of these lines 26 also decreased sugar consumption, revealing that these MBONs have a general role in modifying 27 feeding behavior beyond proboscis extension. Although the MBONs that decreased proboscis 28 extension and ingestion are different from those that drive avoidance behavior in another context, 29 the diversity of their arborizations demonstrates that a distributed network influences proboscis 30 extension behavior. These studies provide insight into how the MB flexibly alters the response to 31 taste compounds and modifies feeding decisions.32 33 Introduction 34A key role of the brain is to prioritize relevant sensory information to guide behavior.35 Animals exhibit innate behaviors to a variety of sensory stimuli including tastes and odors, and 3 36 the ability to modify those behaviors based on contextual cues and prior experience is essential 37 to an animal's survival. 38In Drosophila, the mushroom body (MB) has long been implicated as a center for 39 learning and memory, and has been studied most extensively in the context of olfactory 40 associative learning (1-4). The dendrites of the principal cells of the MB, Kenyon cells (KCs), 41 receive sparse, random synaptic inputs from olfactory projection neurons (5). The parallel axonal 42 fibers of the KCs form the MB lobes, the output region of the MB. The axonal lobes comprised 43 of ~2000 KC axons are beautifully organized into 15 compartments, defined anatomically by the 44 dendrites of 21 types of MB output neurons (MBONs) (6). These compartments also contain the 45 axon terminals of 20 types of dopaminergic neurons (DANs), which similarly tile the MB lobes.46 The DANs convey signals of reward or punishment for sensory associations (7-14). In Pavlovian 47 terminology for a classical conditioning paradigm, the odor is designated the conditioned 48 stimulus (CS), and the DANs carry the unconditioned stimulus (US). 49In the current model of olfactory associative learning, behavior is determined through the 50 summation of activity in di...

Dietary sugar inhibits satiation by decreasing the central processing of sweet taste

“…In fruit flies, PAM DANs promote the formation of short-term associative memories based on taste and long-term associative memories based on nutrient density by modulating plasticity of the postsynaptic Mushroom Body Output Neurons (MBONs)(Cohn, Morantte, and Ruta 2015;Owald et al 2015) . MBONs are, in turn, connected to pre-motor areas like the Central Complex(Aso et al 2014) -the fly genetic and functional analog of the basal ganglia (Strausfeld and Hirth 2013) -providing an anatomical route to modulate aspects of feeding such as proboscis extension(Chia and Scott 2019) , the analogue of licking or chewing rate. Interestingly, some MBONs receive input from both the taste (β'2) and nutrient (γ5) compartments, raising the possibility that sensory and nutrient memories may be integrated in the same cells to regulate different aspects of the satiety cascade (satiation vs. satiety).…”

Evolving the olfactory system with machine learning

“…Individual Kenyon cells, the intrinsic neurons of the MB, receive unstructured input from ~4-10 PNs (Caron, Ruta, Abbott, & Axel, 2013;Li et al, 2020;Zheng et al, 2018) and densely innervate MBONs, the extrinsic output neurons of the mushroom body (Aso et al, 2014b;Caron et al, 2013;Chia & Scott, 2019;Hattori et al, 2017;Li et al, 2020;Tanaka et al, 2004;Zheng et al, 2018). Synaptic plasticity at the KC-MBON synapse results in olfactory conditioning and mediates learned behaviors (Cohn, Morantte, & Ruta, 2015;Felsenberg et al, 2018;Handler et al, 2019;Hige, Aso, Rubin, & Turner, 2015).…”