2018 — 2021 |
Tabuchi, Masashi |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. R00Activity Code Description: To support the second phase of a Career/Research Transition award program that provides 1 -3 years of independent research support (R00) contingent on securing an independent research position. Award recipients will be expected to compete successfully for independent R01 support from the NIH during the R00 research transition award period. |
Mechanisms Mediating the Relationship Between Temporal Coding and Sleep @ Johns Hopkins University
Emerging data suggest that, in addition to sleep amount, sleep quality is important for human health and performance. However, the molecular and neural pathways underlying sleep quality remain unclear. Drosophila is now well-established as a model organism for studying sleep, and my preliminary behavioral and electrophysiological data in Drosophila define a new molecular pathway linking the circadian clock to temporal-specific neural coding to regulate sleep quality. These findings suggest that sleep quality is determined by clock-driven temporal coding in an arousal circuit. Thus, in the proposed work, I will study the relationship between sleep and temporal coding in specific neural circuits. Specifically, I will (1) characterize the molecular mechanisms mediating sleep quality, (2) examine circuit mechanisms underlying temporal coding of sleep quality, and (3) investigate how ionic flux regulates temporal coding of sleep quality. My long-term career goal is to become an independent scientist in academia, and my long-term research goal is to understand how neural coding emerges from specific spike sequences to generate behavioral states such as sleep. To achieve these goals, I will undertake extensive training in molecular biology and biochemistry, in vivo functional imaging, and computational modeling. This new training will complement by previous background in patch-clamp electrophysiology, signal processing skills, Drosophila genetics, and behavioral analyses. The Johns Hopkins University and my mentors and consultants will provide a stellar environment for my scientific growth and guidance in career development. The proposed fellowship will allow me to build my own area of research in neuroscience, and be a competitive investigator with broad expertise from biology to engineering and from molecular and cellular neuroscience to computational neuroscience.
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2021 |
Tabuchi, Masashi |
R35Activity Code Description: To provide long term support to an experienced investigator with an outstanding record of research productivity. This support is intended to encourage investigators to embark on long-term projects of unusual potential. |
The Role of Non-Canonical Neural Codes in Behavior @ Case Western Reserve University
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.
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