Generating sexually differentiated motor rhythms

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Many neuronal circuits in male and female brains are functionally distinct, but the mechanisms underlying these differences are poorly understood. The overarching goal of this work is to discover how hormone-dependent differences in gene expression during development lead to sexually differentiated activity of neurons and neuronal circuits. Central pattern generators (CPGs) are networks that can autonomously generate rhythmic motor patterns and are powerful study systems for discovering general principles of nervous system function. Our research investigates the hindbrain CPG that generates vocal motor patterns of the frog, Xenopus laevis. Because CPGs can generate motor output without sensory input, they can be readily studied in ex vivo preparations. The X. laevis vocal CPG can be activated in isolated brains, generating sex-specific motor patterns similar to those recorded in living animals. CPG masculinization occurs naturally in males during a juvenile surge in androgen levels, and can also be experimentally induced in testosterone-treated adult females. The proposal has two specific aims: 1) identify genes in the CPG with distinct expression patterns that vary between sex, developmental stage, and/or testosterone exposure, and 2) identify the emergence of cellular, network, and morphological properties of CPG neurons that correlate with the appearance sex-specific motor patterns. To achieve these aims we will perform RNA sequencing and whole-cell recordings of CPG premotor neurons in two experimental contexts: naturally developing juveniles, and testosterone-treated adult females. The rationale for this strategy is that CPG characteristics that correlate with masculinization in both contexts will be those that are most likely to have a causal relation to CPG function. By identifying both genes and circuit properties associated with masculinization, novel links between hormones, cell signaling pathways, and neuron function may be revealed.