Reconstructing and Analyzing the Wiring Diagram of the Drosophila Larva Olfactory System

Abstract

The sense of smell enables animals to detect and react to long-distance cues according to internalized valences. Odors evoke responses from olfactory receptor neurons (ORNs), whose activities are integrated and processed in olfactory glomeruli in a brain region called the antennal lobe in insects and the olfactory bulb in vertebrates. These signals are then relayed by projection neurons (PNs) to higher brain centers. A wiring diagram with synaptic resolution of an initial olfactory neuropil would enable the formulation of circuit function hypotheses to explain physiological and behavioral observations. This thesis will discuss the mapping with electron microscopy of the complete wiring diagram of the left and right antennal lobes of Drosophila larva. The analysis of this reconstructed brain region revealed two parallel circuits processing ORN inputs. First, a canonical circuit that consists of uniglomerular PNs that relay normalized ORN inputs to a brain region required for learning and memory (mushroom body) as well as a brain center implicated in innate behaviors (lateral horn). Second, a novel circuit where multiglomerular PNs and hierarchically structured local neurons (LNs) extract complex features from odor space and relay them to diverse brain areas. We found two types of panglomerular inhibitory LNs: one primarily providing presynaptic inhibition (onto ORNs) and another also providing postsynaptic inhibition (onto PNs), indicating that these two functionally different types of inhibition are susceptible to independent modulation. The wiring diagram additionally revealed an LN circuit that putatively implements a bistable gain control mechanism, which either computes odor saliency through panglomerular inhibition, or allows a subset of glomeruli to respond to faint aversive odors in the presence of strong appetitive odor concentrations. This switch between operational modes is regulated by both neuromodulatory neurons and non-olfactory sensory neurons. Descending neurons from higher brain areas further indicate the context-dependent nature of early olfactory processing. The complete wiring diagram of the first olfactory neuropil of a genetically tractable organism will support detailed experimental and theoretical studies of circuit function towards bridging the gap between circuits and behavior.