Synapse elimination activates a coordinated homeostatic presynaptic response in an autaptic circuit

Cecilia D Velasco,Artur Llobet

doi:10.1038/s42003-020-0963-8

Abstract

The number of synapses present in a neuronal circuit is not fixed. Neurons must compensate for changes in connectivity caused by synaptic pruning, learning processes or pathological conditions through the constant adjustment of the baseline level of neurotransmission. Here, we show that cholinergic neurons grown in an autaptic circuit in the absence of glia sense the loss of half of their synaptic contacts triggered by exposure to peptide p4.2, a C-terminal fragment of SPARC. Synaptic elimination is driven by a reorganization of the periodic F-actin cytoskeleton present along neurites, and occurs without altering the density of postsynaptic receptors. Neurons recover baseline neurotransmission through a homeostatic presynaptic response that consists of the coordinated activation of rapid synapse formation and an overall potentiation of presynaptic calcium influx. These results demonstrate that neurons establishing autaptic connections continuously sense and adjust their synaptic output by tweaking the number of functional contacts and neurotransmitter release probability.

Highlights

The number of synapses present in a neuronal circuit is not fixed
In the current work, we characterize the neuronal response activated to counterbalance the cell-autonomous elimination of synaptic contacts triggered by p4.2, a peptide derived from the Cterminal region of SPARC13
Neurons grown in an autaptic circuit are capable of maintaining baseline neurotransmission without modifying their number of postsynaptic receptors

Summary

Introduction

The number of synapses present in a neuronal circuit is not fixed. Neurons must compensate for changes in connectivity caused by synaptic pruning, learning processes or pathological conditions through the constant adjustment of the baseline level of neurotransmission. Neurons recover baseline neurotransmission through a homeostatic presynaptic response that consists of the coordinated activation of rapid synapse formation and an overall potentiation of presynaptic calcium influx These results demonstrate that neurons establishing autaptic connections continuously sense and adjust their synaptic output by tweaking the number of functional contacts and neurotransmitter release probability. Synaptic connectivity varies as a function of the developmental stage, learning processes, or certain disease conditions, implying that homeostatic mechanisms have to somehow be able to account for changes in the functional number of contacts present in a given neuronal circuit[5]. During postnatal development there is a pruning of synapses formed exuberantly during embryogenesis, the correct processing of information must concur with a massive synapse loss It is unclear how neurons adjust a correct number of connections and what are the mechanisms used to balance formation and elimination[6]. The finding of a compensatory response based in the addition of new release sites coordinated with a potentiation of presynaptic calcium influx sheds light on how autaptic circuits maintain a constant synaptic output

Methods

Results

Conclusion