Animal nervous systems have evolved species specific adaptive behaviors which allows them to cope with adverse environmental conditions. For example, in temperate climates, the onset of winter marks a steep decline in environmental temperatures, leading to food scarcity and adverse thermal effects. Animals must respond to these thermal fluctuations in their environment in order to maintain body homeostasis which is critical for their survival. Many animal species have the ability to undergo some type of programmed dormancy to avoid such conditions. For example, most insects and some mammals respond to a sharp decrease in day length and/or temperature with an arrest in development and reproduction that protects them or their progeny from lethality. During this dormant state, often triggered by cold temperatures, metabolic rate is significantly decreased and developmental processes are slowed down. Despite decades of research on the biology of dormancy, our understanding of how the nervous system integrates changes in temperature and light conditions to decrease metabolic rate and reproductive potential is limited. Especially we still do not know the molecular and neural mechanisms that regulate the changes in excitatory and inhibitory transmission of temperature sensitive neurons during thermal fluctuations in the environment. Here, we propose to use a genetically tractable model organism, the fly (Drosophila melanogaster), to investigate temperature sensitive neural circuits that change activity in response to cold temperatures and trigger reproductive dormancy. Flies are an excellent model to investigate how nervous system responds to adverse environmental conditions, because flies have 1000-fold fewer neurons in the brain than vertebrates, and yet they still show temperature specific behaviors. Furthermore, the fly nervous system is more accessible for genetic modifications, anatomical studies and monitoring the activity of large populations of neurons in behaving animals. Our preliminary results suggest that a neuropeptide, Allatostatin C (AstC) and its receptor (AstC-R2) in the brain might be a key player in triggering reproductive dormancy during cold temperatures and short-day lengths. In this project, we will first identify the neural circuits that AstC and AstC-R2 act on to regulate reproductive dormancy in flies. Next, we will capture the activity of AstC and AstC-R2 neurons in vivo and observe how they change activity in response to changes in temperature and day light levels. Last, we will test whether the function of AstC-R2 is conserved in the yellow fever mosquito, Aedes aegypti. Our results will not only contribute to the basic understanding of neural mechanisms regulating reproductive dormancy in insects but also will identify novel targets for the development of drugs that can control insect populations especially disease carrying mosquitoes in the wild.

Public Health Relevance

This project will provide new insights into an important longstanding question in biology; how are environmental changes perceived and processed in the nervous system to regulate metabolic states and reproduction. We aim to use a genetic model organism the fly, Drosophila melanogaster, and the yellow fever mosquito, Aedes aegypti to investigate how environmental temperature and circadian rhythm is integrated by the nervous system to regulate reproductive dormancy at the level of genes, cells and circuits. Our results in the long-term might yield to methods relevant for insect population control, particularly against anthropophilic mosquitoes that are vectors for human diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI149772-01
Application #
9876354
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2020-01-09
Project End
2021-12-31
Budget Start
2020-01-09
Budget End
2020-12-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Cornell University
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850