Investigating the neural circuitry of the Mushroom body calyx in <em>Drosophila melanogaster</em>

Abstract

In Drosophila melanogaster, the mushroom body (MB) is essential for the formation and retrieval of olfactory associative memories. Within its input region, the MB calyx, olfactory information is delivered from second order projection neurons (PN) to MB intrinsic neurons. These cells form characteristic synaptic complexes called Microglomeruli (MGi). Previous studies suggest that MGi include modulatory neurons, which connect the calyx with other brain regions. However, these studies were unable to identify the cell types and to which extent they contribute to the MG complex. Furthermore, studies in other insect models suggest that the organization of the MB calyx underlies plastic changes induced by experience and changes in the sensory environment. <br /> This thesis consists of three projects with the aim to help understand the function and the structure of the MB calyx in Drosophila. First, a complete reconstruction of a Microglomerulus (MG) synaptic complex identified all neurons and their local pre- and postsynaptic connections. This local connectome suggests that MGi are complex local microcircuits that include modulatory GABAergic neurons. Second, the possibility of learning induced plastic changes in the organization of the MB calyx was investigated. By visualizing the pre- and postsynaptic partners within MGi, we could reveal a structural reorganization of the calyx accompanied by the formation of new MGi following olfactory conditioning. In a second approach, the odors were substituted by manipulating neuronal activity with light-sensitive cation channels. This approach however, could not induce memory. The third project gives a first description of a neuron found in the MG reconstruction, called mushroom body neuron 1 (MB-C1). The neuron was identified as GABAergic and to connect the MB calyx with the center for innate behavior, the Lateral horn (LH). Silencing the neuron during odor application and conditioning experiments however did not allow an unambiguous conclusion about the function of MB-C1. <br /> Overall, the data represented here suggest that the MG is a complex local microcircuit that undergoes structural changes upon the formation of associative memory. These findings provide the basis for further studies to investigate the olfactory processing in the calyx and the cellular mechanisms involved in plasticity.