Distinct Target-Specific Mechanisms Homeostatically Stabilize Transmission at Pre- and Post-synaptic Compartments.

Pragya Goel,Samantha Nishimura,Xiling Li,Dion Dickman,Karthik Chetlapalli,Catherine Chen

doi:10.3389/fncel.2020.00196

Abstract

Neurons must establish and stabilize connections made with diverse targets, each with distinct demands and functional characteristics. At Drosophila neuromuscular junctions (NMJs), synaptic strength remains stable in a manipulation that simultaneously induces hypo-innervation on one target and hyper-innervation on the other. However, the expression mechanisms that achieve this exquisite target-specific homeostatic control remain enigmatic. Here, we identify the distinct target-specific homeostatic expression mechanisms. On the hypo-innervated target, an increase in postsynaptic glutamate receptor (GluR) abundance is sufficient to compensate for reduced innervation, without any apparent presynaptic adaptations. In contrast, a target-specific reduction in presynaptic neurotransmitter release probability is reflected by a decrease in active zone components restricted to terminals of hyper-innervated targets. Finally, loss of postsynaptic GluRs on one target induces a compartmentalized, homeostatic enhancement of presynaptic neurotransmitter release called presynaptic homeostatic potentiation (PHP) that can be precisely balanced with the adaptations required for both hypo- and hyper-innervation to maintain stable synaptic strength. Thus, distinct anterograde and retrograde signaling systems operate at pre- and post-synaptic compartments to enable target-specific, homeostatic control of neurotransmission.

Highlights

Synapses are spectacularly diverse in their morphology, architecture, and functional characteristics
At Drosophila larval neuromuscular junctions (NMJs), motor neurons distribute their synaptic terminals roughly evenly between two distinct targets—as demonstrated by the NMJs made onto muscles 6 and 7 (Figure 1A; left)
Immunostaining of M6 >Fasciculin II (FasII) NMJs confirmed biased innervation with ∼150% of boutons above controls on muscle 6, and a parallel reduction of ∼50% in boutons on muscle 7 (Figures 1A–E), consistent with the previous study (Davis and Goodman, 1998). Despite these opposing changes in bouton numbers, electrophysiological recordings of M6 >FasII found that synaptic strength, measured by the excitatory postsynaptic potential (EPSP) amplitude, was similar on both targets and unchanged from their respective controls (Figures 1C–E)

Summary

Introduction

Synapses are spectacularly diverse in their morphology, architecture, and functional characteristics. The structure and function of synapses can vary substantially across terminals of an individual neuron (Guerrero et al, 2005; Grillo et al, 2018; Fekete et al, 2019) and drive input-specific presynaptic plasticity (Letellier et al, 2019). Both Hebbian and homeostatic plasticity mechanisms can work locally and globally at specific synapses to tune synapse function, enabling stable yet flexible ranges of synaptic strength (Turrigiano, 2012; Vitureira and Goda, 2013; Diering and Huganir, 2018). Studies have begun to elucidate the factors that enable both local and global modes of synaptic plasticity at synaptic compartments, it is less appreciated how and why specific synapses undergo plasticity within the context and needs of information transfer in a neural circuit

Methods

Results

Conclusion