Our memories are often as richly detailed as the world around us. A whiff of perfume can unfold the image of a day 20 years ago as if it were right before you. A few stray notes can conjure orchestras or songs sung in the shower. In order to hold such a vivid concept of the world around us, we have to be able to process the sensory inputs that constantly inundate us. Each of these sensations can be translated into chemical and electrical signals that follow unique pathways through the brain, instantly triggering connections between what we know and what we are currently experiencing. Over time, these pathways can be tuned to most efficiently process information that is particularly relevant to our experience.
These changes are governed by proteins known as activity-dependent transcription factors which themselves can control the activity of specific genes. Understanding the relationship between our immediate experience, the activity of these proteins, and the development of the cells they govern could revolutionize our understanding of how our brains process information. Yet, it was impossible to study the interaction between brain activity and transcription factor activation as it was happening in a living, functioning brain—until quite recently. Scientists in the Yasuda Lab at the Max Planck Florida Institute for Neuroscience (MPFI) developed specialized imaging techniques to visualize the function of transcription factors in mice as they experience something new, as their brains are adapting.
MPFI scientists have discovered that by bringing together two cutting-edge imaging techniques to visualize the variations of calcium and the activity of molecules in real-time, they could see a pattern with the interplay between sensory experience and overall activity as it occurred. The team designed biosensors that mark the activity of a particular transcription factor, called CREB, which is strongly linked to the regulation of learning and memory. Then, they expressed the biosensors in two groups of neurons that could be monitored as mice explored a new, high stimulus environment.
The scientists found CREB activity to follow a pattern that would be expected for neurons controlling sensory experiences. CREB activity increased to a sustained, high level as mice explored an unfamiliar environment but returned to normal after the mice had been removed from the area, indicating that the sensory input drove the increased CREB response. To expand this finding, they imaged neurons in the visual cortex of mice who had been raised in dark, low stimulus environments during as well as after a presentation of visual stimuli. These mice showed dramatically increased levels of CREB activation as compared to mice raised in a typical 12 hour light/dark cycle, which remained elevated for at least a day after the visual experience. Intriguingly, neural activity returned to baseline after the presentation had ended, suggesting that the experience of being raised in the dark had increased the sensitivity of the transcription factors to any future visual stimuli the dark-reared mice might encounter.
Building protein-specific bio-sensors is a new approach that can be broadly applied to many different proteins that control the activity of genes in the future and will allow an unprecedented opportunity better understand how experiences shape our brain. Above all, it gives us the chance to visualize the dynamic processes that underlie learning and memory as they happen in living brains, not too different from our own. Our brains are constantly refining themselves, helping us engage more keenly with the world around us, and to remember it in all its stunning detail.