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Neuronal Mechanism of State Control in Drosophila melanogaster


Inagaki, Hidehiko K. (2014) Neuronal Mechanism of State Control in Drosophila melanogaster. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/MPZX-TN59.


The changes in internal states, such as fear, hunger and sleep affect behavioral responses in animals. In most of the cases, these state-dependent influences are “pleiotropic”: one state affects multiple sensory modalities and behaviors; “scalable”: the strengths and choices of such modulations differ depending on the imminence of demands; and “persistent”: once the state is switched on the effects last even after the internal demands are off. These prominent features of state-control enable animals to adjust their behavioral responses depending on their internal demands. Here, we studied the neuronal mechanisms of state-controls by investigating energy-deprived state (hunger state) and social-deprived state of fruit flies, Drosophila melanogaster, as prototypic models. To approach these questions, we developed two novel methods: a genetically based method to map sites of neuromodulation in the brain and optogenetic tools in Drosophila.

These methods, and genetic perturbations, reveal that the effect of hunger to alter behavioral sensitivity to gustatory cues is mediate by two distinct neuromodulatory pathways. The neuropeptide F (NPF) – dopamine (DA) pathway increases sugar sensitivity under mild starvation, while the adipokinetic hormone (AKH)- short neuropeptide F (sNPF) pathway decreases bitter sensitivity under severe starvation. These two pathways are recruited under different levels of energy demands without any cross interaction. Effects of both of the pathways are mediated by modulation of the gustatory sensory neurons, which reinforce the concept that sensory neurons constitute an important locus for state-dependent control of behaviors. Our data suggests that multiple independent neuromodulatory pathways are underlying pleiotropic and scalable effects of the hunger state.

In addition, using optogenetic tool, we show that the neural control of male courtship song can be separated into probabilistic/biasing, and deterministic/command-like components. The former, but not the latter, neurons are subject to functional modulation by social experience, supporting the idea that they constitute a locus of state-dependent influence. Interestingly, moreover, brief activation of the former, but not the latter, neurons trigger persistent behavioral response for more than 10 min. Altogether, these findings and new tools described in this dissertation offer new entry points for future researchers to understand the neuronal mechanism of state control.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Neuroscience, behavior, Drosophila, neuromodulator, state control, optogenetics
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Neurobiology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Anderson, David J.
Thesis Committee:
  • Elowitz, Michael B. (chair)
  • Zinn, Kai George
  • Prober, David A.
  • Anderson, David J.
Defense Date:22 October 2013
Funding AgencyGrant Number
Nakajima FoundationUNSPECIFIED
NIH1RO1 DA031389
Record Number:CaltechTHESIS:02112014-133121063
Persistent URL:
Related URLs:
URLURL TypeDescription for ch. 1 for ch. 3
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8068
Deposited By: Hidehiko Inagaki
Deposited On:31 Oct 2014 16:28
Last Modified:08 Nov 2023 00:22

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