What is a silent synapse

The brain networks itself

Research Report 2017 - Max Planck Institute for Experimental Medicine

Brose, Nils; Sigler, Albrecht; Imig, Cordelia; Altas, Bekir; Kawabe, Hiroshi; Cooper, Benjamin; Kwon, Hyung-Bae; Rhee, Jeong-Seop
According to the common doctrine, nerve cells in the brain must actively communicate with one another in order to establish functioning networks. New results now show that nerve cells in a brain region that is important for learning and memory processes can connect to normally structured networks at their synaptic contact points without any active signal transmission.

introduction

The human brain processes information in a gigantic network of 100 billion nerve cells (neurons), which are connected to one another by over 100 billion contact points, so-called synapses. At these synapses, electrical impulses from a transmitting nerve cell lead to the release of messenger substances in the presynapse, which are received by downstream nerve cells at the postsynapse and converted back into electrical signals. The communication of all nerve cells, which are responsible for controlling all body functions in the form of networks, is based on this principle of chemical signal transmission.

Glutamate causes "thorns" to grow in the brain

The most important messenger substance in the brain, glutamate, is transmitted to so-called postsynaptic thorn synapses, among other things. With the "thorns" (spines) it is, like a rose, small protuberances of the cell membrane of neuronal processes (Fig. 1). The Spanish anatomist Santiago Ramón y Cajal (1852-1934) first described the microscopic processes and suggested that they could play a special role in the storage of information in the brain. As we now know, he was right: that spines carry receptors that register when a synapse becomes active by binding the glutamate released by the presynapse and triggering a response in the downstream cell. In this way, thorn synapses function as tiny neural switching units. On the one hand they are responsible for normal signal transmission, on the other hand they can change dynamically in order to carry out complex brain functions, e.g. B. to support learning processes. For example, if a synapse is particularly active and accordingly releases a lot of glutamate, the thorns of the downstream nerve cell grow, or additional thorn synapses are even created - this is known as synaptic plasticity. On the basis of these and many similar observations, the dogma has been valid in brain research for decades that the formation of thorn synapses both during brain development and in the mature brain depends on an active release of glutamate by the sending nerve cell.

A genetic trick refutes a dogma in neuroscience

This dogma has now been refuted by researchers at the Max Planck Institute for Experimental Medicine together with scientists at the Max Planck Florida Institute for Neuroscience [1]. To analyze the effect of active synaptic glutamate release on the formation of thorn synapses, the scientists used a genetically modified mouse model (Munc13-DKO), in which the release of synaptic messenger substances is specifically and completely switched off very early in development, while all other cell functions that are important for the development and survival of the cell are preserved [2]. For the experiments, sections from the hippocampus, a brain region important for memory, from normal and Munc13-DKO- Cultivated animals. After three different time intervals in culture, individual nerve cells in these sections were first analyzed electrophysiologically in order to determine the expected blockage of synaptic signal transmission Munc13-DKO- Detect sections, stained with a fluorescent dye and completely reconstructed with the aid of a microscope. Surprisingly, it was found that nerve cells of the Munc13-DKO-Mouse mutants can develop normally without any glutamate release and - as with healthy synapses - they continue to develop thorn synapses. In fact, the thorns differed in the "disused" Munc13DKO-Brain preparations neither in shape, size nor their distribution from those of the control preparations. These synapses were also partially functional despite the lack of messenger substance release, because the thorns of the downstream cell continued to react to artificially released glutamate (glutamate uncaging).

Silent nerve cells also come together to form functional networks

As the results show, nerve cells in the hippocampus have a cellular program that controls their synaptic interconnection and in which synaptic glutamate signals play no role. Instead, so-called adhesion molecules very likely perform an important function: They are formed by the pre- and post-synapse, interact with each other outside the cells to bring the two compartments together, and thus induce the formation of thorn synapses. In addition, certain growth factors and signal molecules are important for the correct interconnection of nerve cells during development. Only the resulting network then forms the basis for changes in the synapses interconnection triggered by brain activity - synaptic activity is apparently not necessary during the initial network development.

Bibliography

Sigler, A .; Oh, W.C .; Imig, C .; Altas, B .; Kawabe, H .; Cooper, B.H .; Kwon, H.-B., Rhee, J.-S., Brose, N.
Formation and maintenance of functional spines in the absence of presynaptic glutamate release
Neuron 94, 304-311 (2017)
Varoqueaux, F; Sigler, A; Rhee, J.-S .; Brose, N .; Enk, C .; Reim, K .; Rosenmund, C.
Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming
Proceedings of the National Academy of Sciences of the United States of America 99 (13), 9037-9042 (2002)