The representation and modulation of sensory information in the learning and memory center of the Drosophila brain

The brain uses the combined physiology of many cells to transform incoming sensory signals into internal
representations. This process is critical for the animal’s survival because it underlies the animal’s ability to identify
environmental cues and associate them with the condition of their situation. While sensory representation at the
somatic level is well-studied, exploration of this phenomenon at the synaptic level is lacking. This is a significant
gap in our understanding because individual presynaptic boutons of a single axon can be modulated
independently, and this variability likely affects learning and memory. Therefore, the objective of this proposal is
to expand the mechanistic understanding of the generation of a sensory signal at the presynaptic level and
evaluate its role in learning-related synaptic plasticity. Preliminary data suggests that this representational activity
may be variably tuned at the presynaptic level along a single axon. Based on this, the hypothesis of this proposal
is that representational presynaptic activity is subject to local modulation that shapes an individual synapse’s
susceptibility to plasticity. A fitting model for studying this phenomenon is that of olfactory processing in
Drosophila. Olfactory information is relayed to Kenyon cells (KCs) within the mushroom body (MB), the learning
and memory center of the insect brain. With a focus on individual KC axonal boutons, this proposal will explore
synaptic representation and subsequent learning-induced plasticity by pursuing the following aims: (1) Analyze
representational activity at the synaptic and somatic levels. (2) Determine the origin of local presynaptic
modulation. (3) Evaluate the link between presynaptic representational activity and susceptibility to synaptic
plasticity. This will be achieved using in vivo functional imaging and electrophysiology to study the odor response
at the presynaptic and somatic levels, respectively, and using cell type-specific manipulations of potential
sources of axoaxonic modulation, recently identified by the MB connectome. Completion of this project will further
reveal how the nervous system represents sensory information and modulates that information during learning.
This will contribute to the BRAIN Initiative’s long-term goal of understanding how sensory information gives rise
to higher-order processes, like learning and sensorimotor integration. This is accomplished by using “synthetic
strategies” that cross levels of biological hierarchy (from synapse to cell to circuit) to pursue the Initiative’s near-
term goal of observing the brain in action using genetic tools that enable visualization and intervention. The
proposal also bolsters the training of the next generation of neuroscientists by expanding the applicant’s technical
expertise and promoting the applicant’s intellectual development by supporting training in a rigorous and
collaborative environment that is led by a team of qualified advisors with diverse expertise. The sponsor’s
laboratory is situated at the interface of the University of North Carolina’s School of Medicine and College of Arts
and Sciences, and it is well-connected to the many Drosophila and neuroscience groups in North Carolina’s
Research Triangle, equipping the applicant with abundant resources for preparing for an independent career.