“Self” versus “Non-Self” Connectivity Dictates Properties of Synaptic Transmission and Plasticity

Huisheng Liu,Camin Dean,Edwin R Chapman,Anna Dunaevsky

doi:10.1371/journal.pone.0062414

Abstract

Autapses are connections between a neuron and itself. These connections are morphologically similar to “normal” synapses between two different neurons, and thus were long thought to have similar properties of synaptic transmission. However, this has not been directly tested. Here, using a micro-island culture assay in which we can define the number of interconnected cells, we directly compared synaptic transmission in excitatory autapses and in two-neuron micronetworks consisting of two excitatory neurons, in which a neuron is connected to one other neuron and to itself. We discovered that autaptic synapses are optimized for maximal transmission, and exhibited enhanced EPSC amplitude, charge, and RRP size compared to interneuronal synapses. However, autapses are deficient in several aspects of synaptic plasticity. Short-term potentiation only became apparent when a neuron was connected to another neuron. This acquisition of plasticity only required reciprocal innervation with one other neuron; micronetworks consisting of just two interconnected neurons exhibited enhanced short-term plasticity in terms of paired pulse ratio (PPR) and release probability (Pr), compared to autapses. Interestingly, when a neuron was connected to another neuron, not only interneuronal synapses, but also the autaptic synapses on itself exhibited a trend toward enhanced short-term plasticity in terms of PPR and Pr. Thus neurons can distinguish whether they are connected via “self” or “non-self” synapses and have the ability to adjust their plasticity parameters when connected to other neurons.

Highlights

Neuronal circuits are generally thought of as collections of neurons connected to eachother by interneuronal synapses
We found that autaptic synapses exhibited enhanced EPSC amplitude, charge, and readily releasable pool (RRP) size compared to interneuronal synapses
To test the idea that synaptic properties may differ in ‘‘self’’ versus ‘‘non-self’’ synapses we employed a micronetwork culture system using hippocampal neurons, where single cell autapses or two interconnected neurons were grown on micro-islands

Summary

Introduction

Neuronal circuits are generally thought of as collections of neurons connected to eachother by interneuronal synapses. In addition to these connections neurons can form autapses or ‘‘self synapses’’: connections between a neuron and itself. Autapses are relatively common in many brain regions [1,2], with some classes of neurons exhibiting extensive self-innervation [3]. Fast-spiking interneurons in the neocortex are selfinnervated by GABAergic autaptic connections that regulate spike timing to promote temporal precision of synaptic transmission [4,5]. Inhibitory autaptic synapses provide a self-stabilizing negative feedback influence on circuits, but excitatory autapses exist. Excitatory autapses in certain Aplysia neurons, for instance, cause persistent activity essential for the initiation and maintenance of feeding behavior [6]

Methods

Results

Conclusion