Study reveals how neighboring synapses compete for plasticity resources

Nerve cells in the brain receive thousands of synaptic signals through their ‘antenna’, the so-called dendritic branch. Permanent changes in synaptic strength correlate with changes in the size of dendritic spines. However, it was previously unclear how the neurons implement these force changes in different synapses that are close to each other and active at the same time. Researchers from the University Hospital Bonn (UKB), the University of Bonn, the Okinawa Institute of Science and Technology Graduate University (OIST) and the RIKEN Center for Brain Science (CBS) assume that competition between spines for molecular resources and the spatial distance between simultaneously stimulated spines influences the resulting dynamics. The results of the study have now been published in the journal “Nature Communications”.

Neurons are the computing units of the brain. They receive thousands of synaptic signals through their dendrites, with individual synapses undergoing activity-dependent plasticity. This synaptic plasticity is the mechanism underlying our memory and thinking and reflects long-term changes in synaptic strength. When learning new memories, active synapses in particular strengthen their connections in a process known as ‘long-term potentiation’ (LTP). However, how neurons allocate resources to translate synaptic strength changes across space and time between adjacent synapses is unclear. Until now, it was assumed that each synapse decides how to change independently of the others

A recent study suggests a new perspective on how adjacent synapses coordinate their response to plasticity signals. Researchers from Bonn and Japan have found that sharing proteins and calcium makes synaptic plasticity a collective action in which the behavior of one synapse influences how the others can respond.

“When multiple synapses want to potentiate at the same time and are close to each other, they compete with each other so that each synapse potentiates less than if it were alone. On the other hand, the simultaneous strengthening of some synapses can facilitate the plasticity of other synapses through the overflow of activated resources,” says Prof. Tatjana Tchumatchenko, from the Institute for Experimental Epileptology and Cognition Research at the UKB and member of the Transdisciplinary Research Area (TRA) “Modeling” at the University of Bonn. She led the study together with Prof. Yukiko Goda from the OIST in Japan.

Strong competition between neighboring spines

The researchers from Bonn and Japan used the release of glutamate, a key excitatory neurotransmitter in the brain, in combination with computer-aided modeling to investigate the molecular processes of the plasticity of different spines. Spines, mushroom-shaped projections of nerve cells, are found in the brain and can strengthen synaptic connections. “The release of glutamate allows precise manipulation of selected synapses, allowing us to observe exactly how many synapses strengthen and to what extent.”” explains Dr. Thomas Chater, who conducted the research at the RIKEN Center for Brain Science in Japan.”With this data we were able to design a model and fit its parameters to a set of three stimulated spinous processes, i.e. the spines, and then predict how seven or fifteen spinous processes would behave.” explains Dr. Maximilian Eggl, who until recently was a postdoc at the University of Bonn and did research at the UKB. Chater and Eggl are both co-first authors of this study and worked closely together.

Study leaders Prof. Tchumatchenko and Prof. Goda were particularly surprised by the degree of competition between adjacent spinous processes, which was strongest in the first two to three minutes after plasticity was activated and influenced the direction and extent of plasticity.

“Our results show that the spatial arrangement of simultaneously stimulated synapses significantly influences the dynamics of spine growth or shrinkage, indicating that multiple memories stored on the same dendrite can influence each other.” explains Prof. Goda. The lead researchers believe that understanding how neurons manage synaptic resources will contribute to a better understanding of cognitive processes in the healthy brain and thus to the development of new strategies to combat Alzheimer’s disease, autism spectrum disorders and other cognitive disorders.