overview: Researchers are investigating how a little-understood brain region called the zone of uncertainty communicates with the neocortex to rapidly control memory formation.
sauce: Max Planck Institute
The neocortex is the largest and most complex part of the brain and has long been recognized as the ultimate repository of memory. But how are the traces of past events and experiences placed there?
Scientists at the Max Planck Institute for Brain Research and the University of Freiburg Medical School have discovered that a poorly understood brain region, the immortal zone, has an unconventional way to communicate with the neocortex to rapidly control memory formation. I discovered that
Memory is one of the brain’s most fundamental and fascinating functions, allowing us to learn from our experiences and recall our past. Therefore, it is a central component of our personal and collective human identities.
Moreover, a mechanistic understanding of memory has implications ranging from the treatment of memory and anxiety disorders, to artificial intelligence, to efficient hardware and software design, and is therefore not only of great interest but also of great importance. I have.
In order to form memories, the brain uses a combination of sensory signals that come “bottom up” (or outside in) from the environment and internally generated “top down” signals that convey information about past experiences and the present. You have to build an association. Purpose. These top-down (or inside-out) signals are still shrouded in mystery and are therefore a major focus of current research.
Work over the past few years has begun to identify several such top-down projection systems, all of which showed some commonalities. They signaled by excitation, the standard way of transmitting information between cortical regions, and demonstrated a common mechanism for encoding memory. Stimuli with learned relevance evoke stronger responses in these systems, suggesting that this positive enhancement is one piece of the puzzle: memory tracing.
“In contrast to these systems, long-range inhibitory pathways are much sparse and few in number, but there is growing evidence that they can have surprisingly powerful effects on network function and behavior.” said Johannes Letzkus, professor at the university.Former research group at the Max Planck Institute for Brain Research, whose leader is the University of Freiburg, led a new study published in neuron.
“We set out to determine whether such inputs could exist in the neocortex, and if so, how they uniquely contribute to memory.”
Dr. Anna Schroeder, lead author of the study and a postdoctoral fellow in the Letzkus lab, chose to address this issue by focusing primarily on the inhibitory subthalamic nucleus, the zone of uncertainty. .
Although 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.
To study the plasticity of this system at all stages of learning, she implemented an innovative approach that allows tracking the responses of individual zone-of-uncertainty synapses in the neocortex before, during, and after the learning paradigm. I made it
“The results were amazing,” recalls Schroeder. “About half of the synapses showed a stronger positive response during learning, while the other half showed the opposite response. It was a nice redistribution.”
This suggests that uncertainty zone synapses encode previous experiences in a unique, bidirectional manner. 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,” says Schroeder.
“However, combining this with the redistribution of inhibition seen in learning indicates that this pathway likely yields even richer computational outcomes for neocortical processing.”
Scientists were particularly intrigued by populations of zona synapses exhibiting negative potentiation. I felt that I might offer it.
Further analysis, conducted in collaboration with Professor Henning Sprekeler and his team’s laboratory at the Technical University of Berlin, surprisingly shows that these negative responses are the main drivers of changes in stimulus representation that occur during learning itself. turned out to be a factor.
This work provides the first functional analysis of how long-range inhibition shapes neocortical computation. The signals identified in this study may be important not only for memory, but for many additional brain functions such as attention.
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, we hope that this work will inspire other researchers to continue to explore the role of long-range inhibition in regulating neocortical function, both from unidentified zones and from other as yet unidentified sources. I’m here.
About this memory research news
author: press office
sauce: Max Planck Institute
contact: Press Office – Max Planck Institute
image: image is public domain
Original research: open access.
Anna Schroeder et al. neuron
Inhibitory top-down prediction from immortality mediates neocortical memory
- Uncertainty zones send long-range inhibitory projections to the first layer of auditory cortex
- These axons convey integrated top-down information essential for learning
- Sensory stimulus encoding of intracortical boutons is highly experience-dependent
- Learned top-down associations are encoded in a bidirectional and balanced way
Top-down projections convey families of signals encoding previous experiences and current goals to the sensory neocortex, where they converge with external bottom-up information to enable perception and memory. Although top-down control has been attributed to excitatory pathways, the existence, connectivity and information content of inhibitory top-down prediction remain elusive.
Here, we combine synaptic two-photon calcium imaging, circuit mapping, cortex-dependent learning, and chemical genetics in mice to identify GABAergic sourcing from the subthalamic zone as a major source of top-down input to the neocortex. Identify the cardiac nerves. Intracortical transmission undergoes robust plasticity during learning that improves information transmission and mediates behavioral memory.
Unlike excitatory pathways, intracortical afferents encode learned top-down associations in a bidirectional fashion in which the rapid appearance of negative responses acts as the primary driver of changes in stimulus representation. form an inhibitory circuit.
Our results thus reveal a unique contribution of long-range (non)inhibitory afferents to the computational flexibility of neocortical circuits.