The purpose of this study is to determine mechanisms by which internal states generate variability in behavior. According to the NIMH, behavior changes account for almost 40% of the risk associated with preventable premature deaths in the United States. Despite the importance, it is extremely difficult to identify neurons in the brain that control behaviors and generate variations associated with different states. This has hindered the field?s progress in understanding mechanisms of how neuron activities are altered and influence behavior patterns. In order to advance the field, an experimentally tractable platform is required that can identify specific sets of behavior regulating neurons and allow us to study how their activities change in different states. Understanding how the neurons function normally will allow us to study the neural underpinnings of altered behavior. My preliminary data indicates internal states like the ovarian cycle sensitizes such well defined sets of olfactory sensory neurons. This has a Boolean effect on behavior: only when these neurons are sensitized, can the female initiate social behavior whereas when the neurons are silent, she displays no response. It has been thought the function of the olfactory system is to detect environmental cues and relay all the information indiscriminately to the brain. However, my data shows the olfactory neurons are bifunctional and detect internal ligands such as hormones that surge at various points in the reproductive cycle. The neurons integrate the external and internal chemical signals and relay to the brain such information that is relevant to the specific state the individual is in. To study this unexpected new function of the olfactory neurons my aims will 1) identify the hormone receptors on the olfactory neurons that detect ovarian hormones and 2) determine the mechanisms by which neuron sensitization occurs. The olfactory system provides a simple experimental platform with easily accessible neurons that can be studied using straightforward molecular and genetic tools. Completion of these aims will open new horizons to examine the breadth of functions performed by the olfactory system. The results of this study will provide a molecular blueprint to investigate how internal states affect the more complex brain. I anticipate the findings will bring new knowledge on how the sensory system works in tandem with the brain to generate differences in behavior.
The proposed research is relevant to public health because it will provide a new simple experimental platform to investigate how changes in internal endocrine states alter neural activity. Completion of the aims will provide guidance for future research to effectively study the action of hormones throughout the brain.
