Researchers at Leipzig University’s Carl Ludwig Institute for Physiology, in collaboration with Johns Hopkins University, have achieved a major advance in neuroscience. For the first time, they have successfully applied the zap-and-freeze technique to acute brain slices from both mice and humans, enabling scientists to visualise neural signal transmission within milliseconds.
Visualising Learning in Real Time
This development opens new possibilities for studying how nerve cells adapt their communication while they are active. In particular, it allows researchers to observe how neurotransmitter release and synaptic plasticity—the ability of synapses to change during learning—evolve in real time.
How the Zap-and-Freeze Technique Works
Using the zap-and-freeze method, scientists electrically stimulate nerve cells and then rapidly freeze the tissue just a few milliseconds later. This rapid freezing preserves cellular movements, which researchers can subsequently examine using electron microscopy. In a study published in Neuron, the international research team demonstrated that this technique works effectively in intact brain tissue from both mice and humans.
Insights from Mouse Brain Tissue
Initially, the researchers focused on mouse brain samples. After stimulating nerve cells with the zap-and-freeze method, they observed how synaptic vesicles—tiny membrane-bound sacs—recycle after releasing neurotransmitters. In healthy brains, this vesicle recycling process is essential for transmitting information between neurons and plays a critical role in learning and memory formation.
Human Brain Tissue Shows the Same Mechanism
The team then applied the same approach to human brain tissue and observed identical processes. In both mouse and human samples, the researchers identified the protein Dynamin1xA at the sites where synaptic vesicles are recycled. This finding confirms that the underlying mechanisms of neurotransmitter release and membrane renewal function in essentially the same way across species.
Direct Observation of Learning Processes
Commenting on the findings, Dr. Kristina Lippmann of Leipzig University’s Carl Ludwig Institute for Physiology and corresponding author of the study, said the team was able, for the first time, to directly observe how the human brain rapidly renews its cell membranes after neurotransmitter release. She added that the technique allows scientists to observe brain cells as they learn, reinforcing the importance of model organisms in fundamental neuroscience research.
Methodological Strengths Enable New Discoveries
The institute’s expertise in two-photon microscopy and electrophysiology played a central role in the study. Moreover, the Leipzig team successfully adapted the zap-and-freeze technique for use with brain slices. During the process, they discovered that the method is particularly well suited for selectively stimulating nerve fibres aligned with the electrical field, such as the parallel fibres of the cerebellum.
Inducing Short-Term Synaptic Plasticity
Importantly, the researchers also demonstrated that this approach can induce presynaptic short-term plasticity, a fundamental mechanism that underpins learning in the brain. This finding further highlights the potential of the zap-and-freeze technique for exploring dynamic neural processes.
Future Focus on the Cerebellar Cortex
Looking ahead, the team plans to use the zap-and-freeze method to study presynaptic short-term plasticity in the cerebellar cortex in greater detail. This brain region plays a key role in motor control and offers valuable insights into how learning occurs throughout development, ageing, and disease.
Built on Earlier Collaborative Work
The current study builds on earlier work published in Nature Neuroscience, where researchers first tested the zap-and-freeze technique on cultured nerve cells. The collaboration between Leipzig University and Johns Hopkins University began during Dr. Lippmann’s research stay in the United States, where she met Professor Shigeki Watanabe, one of the developers of the zap-and-freeze method.