Innovative Imaging Technique Reveals Brain-Wide Neuronal Connection Changes

Researchers have introduced a groundbreaking imaging technique that enables the mapping of neuronal connections across the entire brain. This innovative approach, developed by teams at Janelia Research Campus, provides insights into how synaptic connections change during learning processes, advancing our understanding of brain functionality.

Neurons communicate through signals transmitted across synapses, with the strength of these connections changing based on experiences--a phenomenon known as synaptic plasticity, which is fundamental to learning and memory. Despite its significance, the specific locations of these changes within the brain during learning have remained largely elusive.

The newly developed imaging method, termed DELTA, allows scientists to create a comprehensive map of alterations in individual synaptic proteins over time. This is crucial because synaptic proteins are known to undergo degradation or synthesis as synaptic connections evolve, thus tracking these changes provides vital information on how synapses adapt during learning.

The research team, led by experts in the Spruston and Lavis labs, along with contributions from Karel Svoboda, a former senior group leader at Janelia, published their findings in the journal Nature Neuroscience.

According to the researchers, understanding the specific locations where synaptic changes occur is essential for identifying the molecules responsible for these modifications. Boaz Mohar, a research scientist involved in the study, noted the challenge of pinpointing these changes, stating that previous methods lacked the capability to focus on the most relevant brain areas.

DELTA works by labeling a synaptic protein of interest with a fluorescent dye, allowing researchers to visualize changes in synaptic connections during learning tasks. The study involved trained mice that learned to associate visual cues with a water reward. Following the initial labeling of synaptic proteins, the mice were divided into two groups: one continued to receive water randomly at the cues, while the other group was conditioned to associate only one cue with the reward.

After several days, the researchers labeled the same synaptic protein with a different dye in both groups. This process revealed alterations in the synaptic protein GluA2 in specific brain regions in response to the modified learning task. Additionally, the team examined how synaptic protein turnover differed in mice placed in enriched environments compared to those in standard conditions, finding widespread changes in GluA2 across the brain in enriched settings.

By unveiling these brain-wide changes in synaptic proteins, DELTA serves as a vital tool for researchers aiming to explore the cellular and molecular mechanisms underlying learning and memory. The team intends to enhance DELTA's capabilities to identify the exact timing of protein changes during the learning process.

Nelson Spruston, one of the project leaders, highlighted the collaborative nature of the research, with contributions from various experts in chemistry, imaging, behavior, and genetics, as well as external validation from researchers at Northwestern University. The project exemplifies the collaborative spirit of the Janelia research community and aims to facilitate global collaborations through the Visiting Scientist Program, allowing other researchers to utilize DELTA in their studies of synaptic changes.

With this novel imaging technique, the field of neuroscience stands to gain significant insights into the mechanisms of learning and memory, paving the way for future research into neuronal connectivity.