The neocortex is the largest and most complex part of the brain and has long been considered the ultimate repository of long-term memory. But how are the imprints of past events and experiences put there? Researchers at the University of Freiburg Medical School, led by Dr. Johannes Letzkus, and at the Max Planck Institute for Brain ‘Regions of uncertainty’ or ‘zones of uncertainty’, areas of uncertainty, stimulate the neocortex in unconventional ways to rapidly control memory formation. Their study provides the first functional analysis of how long-range inhibition shapes neocortical information processing. The signals identified in this study may be important not only for memory, but also for many additional brain functions such as attention.The result was published in a magazine neuron.
“Top-down signals” at the heart of research
Memory is one of the most basic functions of the brain, allowing people to learn from their experiences and recall their past. Moreover, a mechanistic understanding of memory has implications ranging from the treatment of memory and anxiety disorders, to the development of artificial intelligence, to efficient hardware and software design. To form memories, the brain must associate sensory ‘bottom-up’ signals from the environment with internally generated ‘top-down’ signals that convey information about past experiences and current goals. These top-down signals are the central focus of current research.
In recent years, researchers have begun to identify several such top-down projection systems. They all share many common characteristics. General regime for memory encoding. Stimuli with learned relevance elicit stronger responses in these systems. This suggests that this positive enhancement is one piece of the memory imprint puzzle.
Impact on network functionality
In contrast to these systems, long-range inhibitory pathways are much sparse and few in number, but growing evidence indicates that they can have surprisingly powerful effects on network function and behavior. Former research group leader at the Freiburg and Max Planck Institute for Brain Research. “We set out to determine whether such inputs could exist in the neocortex.
Doctor Anna SchroederThe lead author of this study and a postdoctoral fellow in the Letzkus lab., decided to focus on the Zona Uncertainty, the predominantly inhibitory subthalamic nucleus, to address this question. While the function of this brain region, as its name suggests, remains a mystery, her preliminary findings suggest that inhibitory neurons selectively innervate regions of the neocortex known to be important for learning. Her preliminary findings showed that sending projections. In an effort to study the plasticity of this system at all stages of learning, she implemented an innovative approach that can track the responses of individual zone-of-uncertainty synapses in the neocortex before, during, and after the learning paradigm. I made it
Redistribution of activities during learning
“The results were amazing,” recalls Schroeder. “About half of the synapses showed stronger positive responses during learning, while the other half did the exact opposite. In fact, what we observed was a complete redistribution of inhibition within the system due to learning.” This suggests that synapses in the uncertainty zone encode previous experiences in a unique, bidirectional way. This was especially clear when scientists compared the magnitude of plasticity with the strength of acquired memory. They found a positive correlation. This indicates that uncertainty zone projections encode learned relevance of sensory stimuli.
In another experiment, Schroeder found that silencing these projections during the learning phase impairs memory traces later. This indicates that the bidirectional plasticity that occurs in these projections is necessary for learning. She also found that these inhibitory projections preferentially form functional connections with other inhibitory neurons in the neocortex, indeed forming long-range disinhibition circuits. “This connectivity means that activation of the zone of uncertainty results in a net excitation of neocortical circuits,” she says Schroeder. “However, combining this with the redistribution of inhibition seen in learning indicates that this pathway likely yields richer computational outcomes for neocortical processing.”
Change in stimulus expression
Scientists were particularly intrigued by populations of zona synapses exhibiting negative potentiation. Further analysis, carried out in collaboration with Prof. Henning Sprekeler and his team’s laboratory at the Technical University of Berlin, surprisingly found that these negative responses were associated with learning itself. revealed to be a major factor in the changes in stimulus representation that occur during
Moreover, the uncertainty zone is one of the few regions that canonically be targeted for deep brain stimulation in human Parkinson’s disease patients, opening up interesting possibilities for future translational studies. “Ultimately, this work will inspire others to continue exploring the role of long-range inhibition in regulating neocortical function, both from immortality and from additional as-yet-unidentified sources.” I hope so,” says Letzkus.
