Neuronal and Glial Clocks Underlying Structural Remodeling of Pacemaker Neurons in Drosophila.

Anastasia Herrero,José M Duhart,Maria F Ceriani

doi:10.3389/fphys.2017.00918

Abstract

A number of years ago we reported that ventral Lateral Neurons (LNvs), which are essential in the control of rest-activity cycles in Drosophila, undergo circadian remodeling of their axonal projections. This structural plasticity gives rise to changes in the degree of connectivity, which could provide a means of transmitting time of day information. Thus far, work from different laboratories has shown that circadian remodeling of adult projections relies on activity-dependent and -independent mechanisms. In terms of clock- dependent mechanisms, several neuronal types undergoing circadian remodeling hinted to a differential effect of clock genes; while per mutants exhibited poorly developed axonal terminals giving rise to low complexity arbors, tim mutants displayed a characteristic hyper branching phenotype, suggesting these genes could be playing additional roles to those ascribed to core clock function. To shed light onto this possibility we altered clock gene levels through RNAi- mediated downregulation and expression of a dominant negative form exclusively in the adult LNvs. These experiments confirmed that the LNv clock is necessary to drive the remodeling process. We next explored the contribution of glia to the structural plasticity of the small LNvs through acute disruption of their internal clock. Interestingly, impaired glial clocks also abolished circadian structural remodeling, without affecting other clock-controlled outputs. Taken together our data shows that both neuronal and glial clocks are recruited to define the architecture of the LNv projections along the day, thus enabling a precise reconfiguration of the circadian network.

Highlights

Plasticity—the ability to make adaptive changes—is an integral property of the nervous system
We found that PIGMENT DISPERSING FACTOR (PDF) levels still change between the subjective day and night when the clock in glia is impaired; under these conditions PDF levels were not different from controls (Figure 4D), providing further evidence that these two clock outputs (PDF levels and structural remodeling) can be uncoupled (Depetris-Chauvin et al, 2011). Together these results indicate that circadian structural plasticity of the sLNvs depends on its own molecular clock, and that glial clocks actively contribute to this form of plasticity
A number of years ago we discovered that in wild type flies there are conspicuous structural changes in neurons that are key to the control of circadian locomotor activity, which undergo remodeling of their axonal arborizations on daily basis (Fernández et al, 2008)

Summary

Introduction

Plasticity—the ability to make adaptive changes—is an integral property of the nervous system. There are numerous examples of functional and structural plasticity in invertebrates and vertebrates (Holtmaat and Svoboda, 2009; Bozorgmehr et al, 2013), highlighting its relevance. Structural plasticity contributes to synaptic and circuit function, and it is affected during aging (Barnes, 2001) and disease (Bernardinelli et al, 2014); despite their relevance, the mechanisms underlying structural plasticity, especially large-scale terminal remodeling in the adult brain remains elusive. Examples of structural remodeling of neuronal terminals taking place along the day have accumulated (Pyza and Meinertzhagen, 1999; Mehnert et al, 2007; Becquet et al, 2008; Fernández et al, 2008; Appelbaum et al, 2010), and have been shown to depend on an intact circadian clock (Fernández et al, 2008).

Methods

Results

Conclusion