Researchers Identify Mechanism for Neurotransmitter‐Receptor Matchmaking

Sustained transmitter exposure proven to be enough to induce receptors to appear

February 26, 2020

By Mario Aguilera

Application of glutamate to muscle cells in the embryo (blue dot) stimulates the appearance of glutamate receptors in the muscle cells of the tadpole (red box). This suggests a mechanism for transmitter-receptor matching during embryonic development or in peripheral nerve regeneration following injury.

Over the past decade, scientists have delved deeply into how the intricate wiring systems of the brain and nervous system change in response to experience. They describe a phenomenon in which neurotransmitters, which carry signals from nerve cell to nerve cell, intriguingly switch from one type to another.

This ability of neurons to change the transmitters they release, referred to as a form of "neuroplasticity," has been well documented in recent years. It identifies another way in which the brain changes in response to natural stimulation. Yet nuances of the mechanisms involved have remained unclear. One area of ambiguity includes the neurotransmitter receptor portion of the process. When a neurotransmitter changes in one neuron, the receptors on the other neuron must change along with it or the result is a mismatched and dysfunctional connection.

Now researchers at the University of California San Diego have found a mechanism explaining how this receptor matchmaking unfolds. The details are described in Proceedings of the National Academy of Sciences.

The simple explanation is sustained exposure. In experiments with isolated muscle cells, as well as with in vivo studies with tadpoles, exposing muscle cells to a low concentration of the neurotransmitter glutamate was sufficient to stimulate the appearance of glutamate receptors.

"Lo and behold it was almost like magic, the glutamate receptors appeared in the postsynaptic cell," said Nick Spitzer, the Atkinson Family Chair in the Biological Sciences Section of Neurobiology and a director of the Kavli Institute for Brain and Mind. "The conclusion we have from these experiments is that the application of the transmitter itself is enough to cause upregulation of the appropriate receptors."

Spitzer said the new receptor-matching findings open the door to new approaches to facilitating reinnervation of damaged muscles after injury. Contact of muscle cells by neurons that express an inappropriate neurotransmitter, glutamate, can lead to the appearance of matching glutamate receptors.

In addition to Spitzer, coauthors of the paper include first-author Dena Hammond-Weinberger, Yunxin Wang (master’s student at the time of the research) and Alex Glavis-Bloom.

The research was supported by National Institute of Health Grants NS 015918 and NS 057690.