Our response to the world is not simply the sum of what our sensory organs detect, but also how our brain chooses to represent these detections, and act upon them. However, knowledge of how sensory inputs are interpreted by our brains to yield behavioral outputs is lacking. Unlike simple reflexes, the majority of our behaviors are governed by an internal representation of the external world. This internal state is not static; but shows dynamic activity during both awake and sleep periods. In short, we are always thinking. Even in sensory deprived contexts, nearly all regions of our brain remain active. Therefore, the central challenge with predicting behavioral output from sensory input is that our perception of the world is dynamic and highly variable, rendering many behaviors unpredictable. Understanding the functional underpinnings of how internal dynamics arise in complex brains is limited. However, dynamic internal states also influence perception and behavior in simple animals such as Caenorhabditis elegans. It is currently the only organism where we have a detailed map of every neuron and synapse. We can simultaneously manipulate and monitor the activity of every neuron in the brain. This exquisite ability to manipulate specific neurons in a fully mapped brain makes C. elegans the ideal organism to understand the complexity of resting state dynamics in a reduced system. My long-term goal is to understand how neural circuits generate resting state dynamics on different timescales, and how these states influence perception and behavior. Understanding this process will provide a foundation for understanding the learning process, and the principles that govern how behavioral novelty arises and adapts to the environment.

Public Health Relevance

Our brain creates a dynamic internal representation of the outside world that influences our behavior. In mental disorders such as schizophrenia, this internal representation improperly filters sensory information so that behaviors are governed by an internal representation that is cutoff from the external world. Understanding how a dynamic and highly variable internal representation is generated in a complex brain is challenging, but attainable in the worm Caenorhabditis elegans that has a simple, fully mapped brain. Like humans and other animals, the worm?s perception of the world is influenced by their brain?s internal state. The aim of this proposal is to understand how this internal state is generated and influences perception and behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
5R35GM124883-04
Application #
9987663
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Sesma, Michael A
Project Start
2017-09-01
Project End
2022-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205