Project Summary/Abstract
Neurons “encode” sensory stimuli into patterns of electrical activity. This activity is then transformed or
“decoded” by downstream neurons to guide behavior. However, in different contexts, the same sensory input
can drive different behavioral outputs. For instance, the smell of food can be attractive leading up to a meal,
but aversive or neutral right after a meal. While we have an emerging understanding of how peripheral sensory
neurons change their encoding, we have almost no understanding of how downstream central neurons decode
this information, or how decoding changes with behavioral contexts, such as hunger. The gap in our
knowledge about neural decoding exists because it is difficult to identify all the neurons in a population that
participate in a code. Additionally, identifying and recording from neurons postsynaptic to that population is
usually restrictive.
Here, I will overcome these barriers to understanding neural decoding by using the tractable olfactory
system of the fruit fly, Drosophila melanogaster. In the fly, 2nd-order projection neurons (PNs, analogous to
mitral/tufted cells in vertebrates) form a well-characterized code for odor. 3rd-order neurons called lateral horn
neurons (LHNs) receive stereotyped olfactory input from PNs innervating multiple glomeruli. The specific
goals of this proposal are to establish how LHNs decode spike patterns from PNs and how
neuromodulatory signaling alters this process. I will use 2-photon optogenetics to directly control spike
patterns in PNs of multiple glomeruli simultaneously with cellular and <10 msec resolution. I will simultaneously
record from identified, postsynaptic LHNs in vivo, to determine what properties of the PN odor code are truly
relevant for driving LHN activity. Then, I will incorporate pharmacology and genetic manipulations to identify
how dopamine signaling changes how LHNs decode PN activity. Finally, I will use established molecular
genetics methods to probe the cellular specificity of hunger-induced changes in dopamine receptor expression
to determine how internal state changes the dopaminergic “landscape” in the lateral horn.
Altogether, this project will provide fundamental knowledge of how the brain reads and dynamically
shapes its own olfactory code at the systems, cellular, and molecular level. This proposal supports my
continued interdisciplinary training in in vivo electrophysiology and molecular biology, and provides new
training in optogenetics and 2-photon microscopy. Moreover, it addresses NIDCD’s stated priorities to
understand the fundamental biology of chemosensory function and the central control of smell.