UCLA

During development, the brain becomes electrically active even before it is ready to receive sensory stimuli. Such intrinsic developmental activity has been studied for 3 decades in vertebrate model systems and is known to be critical for the proper wiring of neural circuits. However, the complexity of the vertebrate brain and the technical limitations of studying its development have challenged progress towards identifying the precise mechanisms that initiate activity, whether and how it occurs throughout the brain, and its relevance to adult behavior and health. The recent discovery of patterned, stimulus-independent, neural activity (PSINA “see-nah”) in Drosophila has made it feasible to begin addressing these open questions. PSINA begins at the onset of synapse formation and engages the entire brain in highly coordinated and structured cycles of activity throughout the last half of metamorphosis. The global activity patterns are further textured with cell-type specific dynamics that are more correlated between future neuron-pairs compared to neurons that do not synapse together. A small neuronal population (<2% of the brain) expressing the cation channel Trpγ serves as an activity template for the rest of the brain. Attenuated PSINA, either in trpγ mutants or from pan-neuronal silencing approaches, leads to altered synaptic structure at the cell-type level in the visual system. Here, I describe how neuropeptide signaling functions to regulate the wildtype activity patterns of PSINA. Specifically, I detail how the Trpγ+ neuron activity template is patterned by four neurons that produce the neuropeptide SIFamide (SIFa). Signaling through the SIFa Receptor (SIFaR), SIFa modulates the activity of both SIFa and Trpγ+ neurons to establish the brain-wide activity cycles of PSINA. In turn, Trpγ+ neurons regulate SIFa neuron activity through a recurrent interaction. This work highlights a novel role for neuropeptide signaling in the modulation of developmental activity. Lastly, I conclude with a chapter on how disrupted PSINA may lead to changes to adult behavior.