Circadian Pacemaker Neurons Change Synaptic Contacts across the Day

Abstract

Summary Daily cycles of rest and activity are a common example of circadian control of physiology. In Drosophila rhythmic locomotor cycles rely on the activity of 150-200 neurons grouped in seven clusters [1, 2]. Work from many laboratories points to the small Lateral Neurons ventral (sLNvs) as essential for circadian control of locomotor rhythmicity [3-7]. sLNv neurons undergo circadian remodeling of their axonal projections opening the possibility for a circadian control of connectivity of these relevant circadian pacemakers [8]. Here we show that circadian plasticity of the sLNv axonal projections has further implications than mere structural changes. First, we found that the degree of daily structural plasticity exceeds that originally described [8] underscoring that changes in the degree of fasciculation as well as extension or pruning of axonal terminals could be involved. Interestingly, the quantity of active zones changes along the day, lending support to the attractive hypothesis that new synapses are formed while others are dismantled between late night and the following morning. More remarkably, taking full advantage of the GFP Reconstitution Across Synaptic Partners (GRASP) technique [9] we showed that, in addition to new synapses being added or removed, sLNv neurons contact different synaptic partners at different times along the day. These results lead us to propose that the circadian network, and in particular the sLNv neurons, orchestrates some of the physiological and behavioral differences between day and night by changing the path through which information travels.

Circadian Rhythms in Rho1 Activity Regulate Neuronal Plasticity and Network Hierarchy

“…We found that VRI oscillations were similar to control flies in s-LNvs and DN1s (Figure S5E and data not shown), but had slightly altered rhythms in LNds (Figure S5E), whose connectivity with s-LNvs is rhythmic (Gorostiza et al, 2014). Thus s-LNv plasticity is required for optimal signaling with downstream neurons.…”

“…(Gorostiza et al, 2014) recently showed that rhythms in s-LNv projection morphology are accompanied by rhythms in the number of pre-synaptic active zones. We used a fluorescently-tagged Bruchpilot-short (BRP short-strawberry ) transgene to detect active zones and confirmed that s-LNv projections have more BRP puncta at ZT2* than ZT14* (Figure 7A and S6).…”

“…(Gorostiza et al, 2014) added two levels of s-LNv plasticity beyond morphology: s-LNvs change connections with other neurons over 24hr and show rhythms in the numbers of pre-synaptic sites. We found rhythms in post-synaptic markers at s-LNv termini in antiphase to pre-synaptic markers.…”

“…Mean staining intensity was quantified using Fiji (http://pacific.mpi-cbg.de/wiki/index.php/Main_Page), with background staining levels subtracted. BRP puncta were quantified as in (Gorostiza et al, 2014). …”

Synchrony and desynchrony in circadian clocks: impacts on learning and memory

“…Dendrite length also is circadianly regulated in the optic lobe with larger dendritic trees observed early in the (subjective) day (Weber et al 2009;Damulewicz and Pyza 2011). Notably for the regulation of output processes, the small ventral lateral circadian pacemaker neurons of Drosophila form differential synaptic contacts dependent upon the time of day (Fernández et al 2008;Gorostiza et al 2014). Rhythmic axonal remodeling occurs through matrix metalloproteinase regulation of the circadian neurotransmitter PDF , presumably due to the circadian regulation of matrix metalloproteinases (Kadener et al 2007;Nagoshi et al 2010).…”