Studies of synapses reveal more about brain development

As a Wallenberg Scholar, Rickard Sandberg intends to study molecular rules in the proteins used by brain neurons to communicate. The goal is to learn how the brain develops and to what extent these interactions are cause of neurodegenerative and psychiatric diseases.

The brain works through a complex network of neurons in which information is transmitted through chemical contact points called synapses. The synapses are established with the help of different types of protein, which also determine their function. Synapse proteins are however often present in multiple variants through a process called alternative splicing.

Since genetic mutations in synaptic proteins are strongly associated with disease, insights into neurodegenerative and psychiatric diseases can be gained by studying how these synaptic proteins affect brain function. 

Wants to crack the code

Researchers now hypothesize that there might be a specific molecular code that governs which synapses are formed and how they work, but current data is unable to provide any details about the process. 

Rickard Sandberg and his research group are therefore developing new methods to address if there is a code and how it works. 

“We want to systematically study how the alternative splicing of synaptic proteins differs among different types of brain neuron and if these patterns can predict which synapses can be formed and their function,” says Professor Sandberg.

The first step is to examine alternative splicing across the different types of brain neuron in mice. The researchers then plan to study when during embryonic development these patterns are established, and to what extent they are maintainted in adult neurons. 

They also plan to use a method called Patch-seq to explore how different protein variants influence the electrical functioning of the neurons.

The researchers hope that by studying how variants of synaptic proteins affect brain function they will gain a better understanding of neurodegenerative and psychiatric diseases, such as Alzheimer’s and depression.

“We also want to pin down these molecular patterns in the human brain to better understand how genetic changes in neurodegenerative and psychiatric diseases affect the synapses in the brain and cause disease,” he says.