Finding molecular traces of learning in rats and mice

The brain of mice and rats functions similarly to the human brain. It constantly responds to environmental inputs, processes information, and forms and stores memories. Our scientists investigates molecular traces of learning in nerve cells, also known as neurons. After all, learning and memories must leave a molecular footprint within the cells.

For many of our studies, we use isolated nerve cells from mice and rats, which we culture in petri dishes. Neurons in culture can be directly examined under the microscope and easily manipulated through genetic engineering or by adding drugs to the culture medium.

Neurons are brain cells with long extensions that communicate with each other by sending and receiving signals at special contact points called synapses. A neuron has thousands of synapses along its extensions and processes the inputs of many other neurons simultaneously.

Some learning processes can be observed at the cellular level: individual synapses can become stronger or weaker during the transfer of information. However, it was previously unclear how a neuron can selectively and precisely change a single synapse among the thousands it possesses.

Using neuron cultures and rodent tissue, our research has revolutionized the understanding of how neurons function and how learning takes place at the cellular level. We discovered that proteins critical for communication between nerve cells, memory formation, and overall brain development are not all produced in the cell body, as previously believed. Some are locally synthesized near synapses, allowing them to precisely alter the composition of individual synapses. A significant portion of our work focuses on making this local protein production visible.

With neuron cultures, we have developed several methods that are now used by other researchers worldwide. These methods enable the distinction between newly formed and older proteins, allow for the cessation of protein production in specific cells, and enable the extraction of proteins formed in particular cells or synapses from a network of cells. Many of these methods rely on genetic engineering, through which we have altered the genetic makeup of mice using genetically modified stem cells.

Since real learning processes only occur in a living animal, we investigated whether the molecular traces we found in cultured neurons could also be observed in living animals.

Genetically modified mice as tissue donors have recently helped us to decipher the diversity of synapses in the brain. For example, we identified a factor in a specific synapse type that explains the vulnerability of neurons that degenerate in Parkinson's disease. Now that we know much about the processes in the brains of healthy mice, we can study what goes wrong in various brain diseases.