Synapses compete for neuronal building blocks

Equilibrium between inhibitory and excitatory synaptic activity plays an important role in structural homeostasis

9 February 2017

During the development of neural circuits, neurons need to be properly connected to one another via thousands of synapses. For the most part, synapses interconnect with specialized structures of neurons known as dendrites. The role of dendrites is thus to receive information from other neurons. The principles and mechanisms that underlie the fine-tuning of the relative number of synapses and of the size of dendrites in relation to one another during the development of the nervous system are still largely unknown, as are those that determine how the different kinds of synapses are distributed on their target dendrites. Researchers at Johannes Gutenberg University Mainz (JGU) have now determined that different synapse types compete for the dendrites of their postsynaptic partner cells. If the activity of a particular type of synapse predominates during development, more dendritic material is allocated to its partner cell at the expense of another type. Synaptic activity thus determines how dendrites are positioned in a given neuron and the dominance of a particular competitor can impair the structure and functioning of the nerve cell. "We have been able to demonstrate in Drosophila neurons that synapses compete for dendritic building material," said Professor Carsten Duch of JGU's Institut of Developmental Biology and Neurobiology. The results of the study have recently been published in the scientific journal Neuron.

Synapses form a kind of bridge via which information is transmitted by electrochemical means from one neuron to the next. It is estimated that in the human brain some 100 billion nerve cells are interconnected through a total of about 100 trillion synapses. In the Drosophila melanogaster fruit fly model, Duch's team genetically manipulated the transfer of two different messenger substances, i.e., gamma-aminobutyric acid (GABA) and acetylcholine, which migrate through the synaptic cleft and bind to receptors on the postsynaptic dendrites.

This manipulation of the balance of the synaptic activity of both neurotransmitter systems influences dendritic growth and leads to redistribution of the synapses on the dendrites. "GABAergic and cholinergic synapses compete for building material to which they can connect," explained Dr. Stefanie Ryglewski, lead author of the study. An imbalance between the two competitors leads to incorrect distribution of the building material. On the mechanical level, this process requires local calcium signals induced by synaptic activity in the dendrites of the neurons. "An equilibrium in terms of inhibitory and excitatory synaptic activity is hugely important for the structural homeostasis of neurons," concluded Professor Carsten Duch.