# The role of non-canonical neural codes in behavior

> **NIH NIH R35** · CASE WESTERN RESERVE UNIVERSITY · 2022 · $386,030

## Abstract

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...

## Key facts

- **NIH application ID:** 10458115
- **Project number:** 5R35GM142490-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Masashi Tabuchi
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $386,030
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458115

## Citation

> US National Institutes of Health, RePORTER application 10458115, The role of non-canonical neural codes in behavior (5R35GM142490-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10458115. Licensed CC0.

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