Mechanisms and functions of adaptation in the D. melanogaster olfactory system
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Abstract
Animals must navigate an ever-changing world in order to survive and reproduce. Plasticity endows sensory systems with the required flexibility to deal with changes on many different timescales and maintain robust outcomes. This is only possible if a balance between plasticity and robustness is achieved. To address this interplay, I studied two instances of plasticity in the olfactory system of Drosophila melanogaster: lifelong developmental plasticity and short-term stimulus-driven plasticity (adaptation). In both contexts, I focused on the antennal lobe. In this neuropil that constitutes the first sensory relay of the olfactory system, the combinatorial odor representation that relies on multiple olfactory receptor neuron (ORN) types emerges and is modulated by a network of local neurons that are mainly GABAergic.
The first manuscript reviews the current literature on adaptation at the periphery of the olfactory system, setting a starting point for my work. Here, we compare adaptation to a constant background in vision to olfaction. Photoreceptors and ORNs both have background-dependent responses, but they show different strategies for adaptation, endowing the former with contrast sensitivity at the single neuron level but not the latter. Surprisingly, ORN firing rate adaptation is undone in the antennal lobe and ORN presynaptic calcium responses are background invariant.
In the second manuscript, which is the main outcome of my work, I set out to investigate the molecular and circuit mechanisms that undo firing rate adaptation at the ORN output synapses and to understand the role of this transformation for odor coding. First, through optogenetic activation of a single ORN type, I found that multi-glomerular activation is not required for background-invariant responses in a single glomerulus. This experiment also confirmed previous observations that background invariance is asymmetric – it is only observed for ON stimuli (increases in concentration compared to the background). Then, I confirmed that ORN synaptic output is required by silencing specific ORN types and measuring presynaptic calcium transients in these ORNs. Since ORNs are cholinergic, this result was confirmed by pharmacologically blocking acetylcholine receptors. Finally, pharmacological blocking of GABA receptors identified a homeostatic feedback circuit that likely involves local neurons and achieves asymmetric background invariance in ORN axon terminal calcium responses. Interestingly, modelling of ORN responses shows that this feedback inhibition results in background-invariant presynaptic ORN responses only if single ORNs adapt differently from photoreceptors, by decreasing their response rather than shifting their sensitivity. When assessing the functional output of the antennal lobe, postsynaptic projection neuron (PN) responses, I found that they are also asymmetric background invariant. By testing a gain-of-function mutation that abolishes calcium-dependent synaptic plasticity in the active zone protein Unc13, I found that background invariance in PNs requires synaptic plasticity. Lastly, modelling of PN responses indicates that these novel functions of olfactory processing in the antennal lobe enable downstream circuits to drive background-robust odor-specific behaviors while tuning odor coding to ON stimuli, which are more behaviorally relevant.
In the third manuscript, I investigated how developmental plasticity affects odor coding in the antennal lobe. Changing the developmental temperature has been shown in our lab to substantially alter the wiring of the olfactory system, allowing us to probe developmental plasticity. I found that odor coding in PNs was not altered by the differences in connectivity induced by developmental temperature, suggesting a balance between excitatory and inhibitory pathways that ensures odor coding stability across environmental conditions.
Overall, I have found surprising robustness of odor representations in the antennal lobe, both in the face of different odor backgrounds and of differences in wiring caused by changes in developmental temperature. My work suggests that robustness in this neuropil is actively maintained and implicates local neurons in this process, warranting and providing a framework for further research into this network of functionally and anatomically diverse neurons.