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Electrical Silencing of PDF Neurons Advances the Phase of non-PDF Clock Neurons in Drosophila

Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT

Guan Cao

Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT

Michael N. Nitabach

Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT, michael.nitabach{at}yale.edu

Drosophila clock neurons exhibit self-sustaining cellular oscillations that rely in part on rhythmic transcriptional feedback loops. We have previously determined that electrical silencing of the pigment dispersing factor (PDF)-expressing lateral-ventral (LN_V) pacemaker subset of fly clock neurons via expression of an inward-rectifier K⁺ channel (Kir2.1) severely disrupts free-running rhythms of locomotor activity—most flies are arrhythmic and those that are not exhibit weak short-period rhythms—and abolishes LN_V molecular oscillation in constant darkness. PDF is known to be an important LN_V output signal. Here we examine the effects of electrical silencing of the LN_V pacemakers on molecular rhythms in other, nonsilenced, subsets of clock neurons. In contrast to previously described cell-autonomous abolition of free-running molecular rhythms, we find that electrical silencing of the LN_V pacemakers via Kir2.1 expression does not impair molecular rhythms in LN_D, DN1, and DN2 subsets of clock neurons. However, free-running molecular rhythms in these non-LN_V clock neurons occur with advanced phase. Electrical silencing of LN_Vs phenocopies PDF null mutation (pdf ⁰¹ ) at both behavioral and molecular levels except for the complete abolition of free-running cellular oscillation in the LN_Vs themselves. LN_V electrically silenced or pdf 01 flies exhibit weak free-running behavioral rhythms with short period, and the molecular oscillation in non-LN_V neurons phase advances in constant darkness. That LN _V electrical silencing leads to the same behavioral and non-LN _V molecular phenotypes as pdf 01 suggests that persistence of LN_V molecular oscillation in pdf 01 flies has no functional effect, either on behavioral rhythms or on non-LN_V molecular rhythms. We thus conclude that functionally relevant signals from LN_Vs to non-LN_V clock neurons and other downstream targets rely both on PDF signaling and LN_V electrical activity, and that LN _Vs do not ordinarily send functionally relevant signals via PDF-independent mechanisms.

Key Words: pacemaker neuron • cellular oscillation • clock protein • phase advance • K+ channels • dose-dependent

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				G. Cao and M. N. Nitabach Circadian Control of Membrane Excitability in Drosophila melanogaster Lateral Ventral Clock Neurons J. Neurosci., June 18, 2008; 28(25): 6493 - 6501. [Abstract] [Full Text] [PDF]