Gregory Reilly, MS - PhD Candidate, Neuroscience Graduate Program
Biological sex is a fundamental dimension of internal state that can have deep influences on behavior. Understanding the mechanisms behind these influences can provide insight into how shared neural circuits are tuned to produce sex-specific behavioral variation. Biological sex can influence both short-term behaviors and longer, more persistent forms of behavior known as behavioral states. In C. elegans, persistent motor behavior, called locomotor states, is well-studied in hermaphrodites. On a patch of food, hermaphrodites will switch between two states of foraging and feeding, called roaming and dwelling respectively. However, while some work has examined motor states in males, these remain poorly characterized. Previous work from our lab has demonstrated that male locomotion is sex-specific; the sexual state of muscle tissue and the nervous system is essential for sex differences in speed and body posture. Therefore, biological sex may also similarly influence locomotor states. We trained a supervised machine learning Random Forest model to detect three locomotor states: roaming, dwelling, and tail chase. In addition, we used a dimensionality reduction analysis, Linear Discrimination Analysis (LDA), to compare the overall characteristics of these states. Furthermore, to measure the transition probability between states, we used a Markov model. While both males and hermaphrodites share the locomotor states of roaming and dwelling, the characteristics of these differ by sex- the amount of time spent in each state, state durations, and transitions between states (temporal differences), as well as the linear speed, curvature, and other characteristics (feature differences), have sexual dimorphism. To understand how sex tunes these locomotor states, we manipulated the sex determination pathway to sex reverse the nervous system in both males and hermaphrodites. Interestingly, we found that pan-neuronally feminized males had similar locomotor state characteristics to hermaphrodites; both temporal and state feature sex differences were eliminated in the feminized males. Yet, masculinized hermaphrodites were indistinguishable from their wildtype counterparts indicating that either male-specific neurons or other tissue played a role in mediating these sex differences. To uncover the mechanisms that biological sex leverages to achieve this sex-specific variance in locomotor states, various neuromodulator knockout mutants known to affect locomotor states were tested. PDFR-1 emerged as a strong candidate as it removed differences in both temporal and features of locomotor states. Preliminary data suggests that PDFR-1 signaling may regulate the temporal sex differences through daf-7, a TGF-ß signal. daf-7 knockout mutants appear to maintain differences in state features but both spend similar amounts of time roaming and dwelling. Given that PDFR-1 signaling has been implicated as the mechanism that regulates sexual dimorphism in daf-7 expression in the ASJ neuron, these results remain promising. Together, our results provide a mechanistic framework for understanding how sex-specific neuronal tuning influences behavioral states.
Jun 14, 2024 @ 10:00 a.m.
Medical Center | SMD Lg. Aud. (2-6424)
Host: Advisor: Doug Portman, PhD