Circadian Neural Circuits

The fly brain contains 100,000 neurons including ~150 that are dedicated circadian pacemakers. The image below details some of these (their cell bodies are stained yellow).

The 150 clock neurons are synchronous, but they control different phasic outputs.

All clocks tell the same molecular time, yet we have shown that in vivo they produce multi-phasic neuronal outputs via a stereotyped sequence of daily activity periods. That sequence is diagrammed below.

The colors relate different pacemaker groups (left) to their typical phases of elevated neuronal activation (center and right).

Our working hypothesis is that all the pacemakers in this system are morning clocks by default, but only a subset (the ‘true’ morning oscillators) can assume that role. Others must be assigned to different phases of the day and night and this involves delaying their clock-dictated activity period away from the morning. Neuropeptide signaling provides much of the critical delaying function to help create this normal stereotyped and sequential periods of activation. For example, neuropeptide PDF is released by Morning pacemakers and delays activity in the Evening pacemakers (blue) and Early Night pacemakers (purple) by 8 -14 hours each day. Broadly, we are interested in defining the signaling pathway downstream of the PDF receptor – a G protein coupled receptor. We are also interested in how these neuronal activity period (putative circadian output phases) control different downstream neural circuits.

Neuropeptide Cell Biology

Our laboratory also has long-standing interests in the cell and molecular biology of peptidergic neurons and peptidergic signaling. This broad set of topics includes:

  • Neuropeptide gene regulation
  • Peptidergic cell differentiation including
    • The role of a transcription factor (DIMMED) that confers phenotypic hallmarks of the neuroendocrine cell type
    • Expression of secretory granule components
  • Mechanisms of neuropeptide release
  • Mechanisms of neuropeptide receptor desensitization