Study reveals how neighboring synapses coordinate their response to plasticity signals

Researchers from Bonn and Japan have elucidated how neighboring synapses coordinate their response to plasticity signals: Nerve cells in the brain receive thousands of synaptic signals via their “antenna”, the dendritic branch. Permanent changes in synaptic strength are correlated with changes in the size of the dendritic spines. However, it was not known until now how neurons implement these strength changes on several 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 School (OIST), and the RIKEN Center for Brain Sciences (CBS) assume that competition between spines for molecular resources and the spatial distance between simultaneously stimulated spines affect their resulting dynamics. The results of the study were published in the journal Nature Communications.

Neurons are the computing units of the brain. They receive thousands of synaptic signals through their dendrites, with each synapse undergoing activity-dependent plasticity. This synaptic plasticity is the mechanism underlying our memory and thinking and reflects long-lasting changes in synaptic strength.

When learning new memories, particularly active synapses strengthen their connections in a process known as long-term potentiation (LTP). However, how neurons allocate resources to translate changes in synaptic strength across space and time between neighboring synapses is unclear. Until now, it was assumed that each synapse decides independently of the others how it changes.

The study suggests a new perspective on how neighboring 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 others can respond.

“When several 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 potentiation of a few synapses can facilitate the plasticity of other synapses by the overflow of activated resources,” explains Professor Tatjana Tchumatchenko from the Institute for Experimental Research in Epileptology and Cognition at the UKB and member of the Transdisciplinary Research Area (TRA) “Modeling” at the University of Bonn. She led the study together with Professor Yukiko Goda from OIST in Japan.

Strong competition between neighboring thorns

The researchers from Bonn and Japan used the release of glutamate, an important excitatory neurotransmitter in the brain, in combination with computer-aided models to study the molecular processes of the plasticity of several spines. Spines, mushroom-shaped protrusions of nerve cells, are found in the brain and can strengthen synaptic connections.

“The release of glutamate allows for precise manipulation of selected synapses, which allowed us to observe exactly how many synapses are potentiating and to what extent,” says Dr. Thomas Chater, who led the research at the RIKEN Center for Brain Sciences in Japan.

“These data allowed us to design a model and fit its parameters to a set of three stimulated spinous processes, i.e. spines, and then predict how seven or fifteen spinous processes would behave,” explains Dr. Maximilian Eggl, who was until recently a postdoctoral fellow at the University of Bonn and conducted research at UKB. Chater and Eggl are both co-first authors of this study and worked closely together.

The study leaders, Professor Tchumatchenko and Professor Goda, were particularly surprised by the extent of competition between neighboring spinous processes, which was strongest in the first two to three minutes after the onset of plasticity 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, suggesting that multiple memories stored on the same dendrite can influence each other,” explains Professor Goda.

The lead researchers are confident 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.