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Principal Investigator: Masashi Tabuchi
Organization: CASE WESTERN RESERVE UNIVERSITY
Fiscal Year: 2022
Award: $386,030
Funding agency: National Institute of General Medical Sciences
Project Summary/Abstract
The idea that information processing depends on neuronal firing rate (rate coding) has long been a central
dogma in neurobiology. However, other non-canonical coding schemes (temporal and “analog” codes) have
been proposed to carry meaningful information and be more computationally powerful than rate coding.
Importantly, the field has lacked powerful genetic model systems to disentangle non-canonical coding processes,
and I addressed this gap by defining two neural circuits in Drosophila that can be used to study temporal and
analog codes. I found that temporal coding underlies the circadian regulation of sleep in the Drosophila
DN1p clock neurons, whereas analog and potentially “hybrid” (analog + spiking) codes are used to
achieve axon-specific hunger processing in Drosophila DA-WED feeding neurons.
As a model system to understand how spiking temporal codes impact molecular signaling and behavior, we
will focus on Drosophila DN1p clock neurons having specific spiking patterns to control sleep quality through a
novel form of synaptic plasticity, SPDP (Spike Pattern Dependent Plasticity). To examine the molecular process
of SPDP formation, we will first characterize essential elements of the temporal structures within irregular spiking
patterns in DN1ps, as well as identify their biophysical origins. Next, we will investigate molecular mechanisms
that act downstream of presynaptic spiking patterns to transform electrical signals into biochemical responses.
We will also leverage the power of Drosophila genetics to delineate the entire molecular pathway required for
SPDP in DN1ps synapses.
As a model system to understand how nonspiking neuronal codes impact signaling and behavior, we will
focus on Drosophila DA-WED feeding neurons having local plasticity to control protein hunger behavior. Neural
coding paradigms have generally focused on “digital” all-or-none spike-based models. In mammals, pure
“analog” coding occurs in the retina, but recent work has shown that analog signaling modulates spike-based
signaling (“hybrid” coding) in the hippocampus and cortex. However, the function of these codes in neural
plasticity and behavior remains unclear. We recently discovered that the “protein coding” axonal branch, but not
the “sugar coding” axonal branch, exhibits sub-threshold membrane potential fluctuations of DA-WED feeding
neurons, following mild protein deprivation. Following severe protein deprivation, such analog signaling interacts
with spiking events to generate “hybrid” processing to achieve stronger and longer-lasting protein feeding
behavior. Thus, we will study the molecular processes mediating “analog” and “hybrid” signaling and how
“hybrid” codes may underlie localized branch-specific plasticity. In conclusion, these studies using Drosophila
DN1p clock neurons and DA-WED feeding neurons should elucidate fundamental principles for non-canonical
neural codes, determine the role of these neural codes in long-lasting behaviors and plasticity, and identify their
underlying molecular mechanisms.
Terms: <Address><Ammon Horn><Animal Behavior><Axon><Behavior><Biochemical><Biologic Models><Biological Models><Biophysics><CNS plasticity><Cell Communication and Signaling><Cell Signaling><Code><Coding System><Cornu Ammonis><Drosophila><Drosophila genus><Elements><Event><Exhibits><Feeding behaviors><Genetic><Genetic Models><Hippocampus><Hippocampus (Brain)><Hunger><Hybrids><Ingestive Behavior><Intracellular Communication and Signaling><Mammalia><Mammals><Mediating><Membrane Potentials><Model System><Modeling><Molecular><Nerve Cells><Nerve Unit><Neural Cell><Neurobiology><Neurocyte><Neuronal Plasticity><Neurons><Pathway interactions><Pattern><Physiology><Process><Proteins><Resting Potentials><Retina><Role><Scheme><Signal Transduction><Signal Transduction Systems><Signaling><Structure><Synapses><Synaptic><Synaptic plasticity><Transmembrane Potentials><Work><analog><base><biological signal transduction><biophysical foundation><biophysical principles><biophysical sciences><central nervous system plasticity><circadian regulation><deprivation><digital><feeding><feeding-related behaviors><fruit fly><hippocampal><information processing><neural><neural circuit><neural circuitry><neural plasticity><neurobiological><neurocircuitry><neuronal><neurophysiological><neurophysiology><neuroplastic><neuroplasticity><novel><nutrient intake activity><pathway><presynaptic><quality of sleep><relating to nervous system><response><sleep control><sleep quality><sleep regulation><social role><sugar><synapse><synaptic circuit><synaptic circuitry>