Intra-neuronal Competition for Synaptic Partners Conserves the Amount of Dendritic Building Material

Abstract

SUMMARY Brain development requires correct targeting of multiple thousand synaptic terminals onto staggeringly complex dendritic arbors. The mechanisms by which input synapse numbers are matched to dendrite size, and by which synaptic inputs from different transmitter systems are correctly partitioned onto a postsynaptic arbor, are incompletely understood. By combining quantitative neuroanatomy with targeted genetic manipulation of synaptic input to an identified Drosophila neuron, we show that synaptic inputs of two different transmitter classes locally direct dendrite growth in a competitive manner. During development, the relative amounts of GABAergic and cholinergic synaptic drive shift dendrites between different input domains of one postsynaptic neuron without affecting total arbor size. Therefore, synaptic input locally directs dendrite growth, but intra-neuronal dendrite redistributions limit morphological variability, a phenomenon also described for cortical neurons. Mechanistically, this requires local dendritic Ca2+ influx through Dα7nAChRs or through LVA channels following GABAAR-mediated depolarizations.

Achieving functional neuronal dendrite structure through sequential stochastic growth and retraction

“…Having quantified the dynamics throughout development of both the growth and retraction of branches using high resolution time-lapse imaging, we were able to use these data to parameterise our model. Branch dynamics and morphometrics at this stage were well defined by a stochastic growth and retraction model, suggesting that c1vpda morphogenesis is possibly a non-deterministic process, in accordance with other previously found results for other cell types (Ryglewski et al, 2017;Özel et al, 2015).…”

“…It also possibly avoids the encoding of a deterministic morphogenetic program that may be more costly to implement genetically (Hiesinger and Hassan, 2018). In the future, it will be interesting to elucidate the mechanisms that control the temporal sequence of distinct stages of branch elaboration for the c1vpda sensory neurons Jinushi-Nakao et al, 2007;Nanda et al, 2019) and on a higher scale to understand to what extent similar self-organising processes and mechanisms are implicated in the formation of other cell types (Ryglewski et al, 2017;Özel et al, 2015), neuronal networks (Hassan and Hiesinger, 2015) and even in the emergence of non-neuronal branching organs (Hannezo et al, 2017).…”

Serial synapse formation through filopodial competition for synaptic seeding factors

“…This is reminiscent of other competitive processes that shape neuronal morphology, e.g. the restricting role of building material in the competitive development of dendritic branches in a motorneuron 49 . Our mutant analyses suggest that stable bulbs communicate negative feedback to other bulbs via the function of the RhoGEF Trio.…”

Tyramine action on motoneuron excitability and adaptable tyramine/octopamine ratios adjust Drosophila locomotion to nutritional state

“…Transient and sustained K + outward currents were separated as in Kadas et al (25). Ca 2+ imaging was conducted as in Ryglewski et al (43). ΔF/F was calculated by the formula [F(stim) − F(rest)]/F(rest).…”