How Does the Brain Build Sensory Memories?

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The brain encodes information collected by our senses. However, to perceive our environment and interact with it constructively, these sensory signals must be interpreted in the context of our previous experiences and current goals. In the latest issue of Science, Max Planck Brain Research Institute Research Group Leader Dr. A team of scientists led by Johannes Letzkus identified the source of top-down information linked to this experience.

The largest area of ​​the human brain is the neocortex.
This region expands, differentiates greatly during mammal evolution. And the many capacities that separate people from their closest relatives are thought to mediate most. Moreover, dysfunction in this region also plays a central role in psychiatric disorders. All higher cognitive functions of the neocortex are activated by bringing together two distinct streams of information: a ‘bottom-up’ stream that carries signals from the surrounding environment, and a ‘top-down’ stream that transmits internally generated information that encodes our past experiences and current goals.

“Decades of research have revealed how sensory input from the environment is processed. However, what we know about internally generated information is still in its infancy. This is one of the biggest gaps in our understanding of higher brain functions such as sensory perception. ” says Letzkus. This situation motivated the team to look for sources of top-down signals.

“Previous studies by us and many other scientists have suggested that the top layer of the neocortex is an important site that receives inputs carrying information from top to bottom. Taking this as a starting point allowed us to identify a region of the thalamus (a brain area buried deep within the forebrain) as a key candidate source of such internal information.

The first author of the study and postdoctoral researcher in the Letzkus lab, Dr. M. Belén Pardi; motivated by these observations, developed an innovative approach that can measure the responses of single thalamic synapses in the mouse neocortex before and after a learning paradigm. “The results were clear,” says Pardi.

Letzkus: “While irrelevant neutral stimuli were encoded by small and transient responses in this pathway, they strongly increased learning activities. And over time it made the signals both faster and more continuous. ” This indicates that the thalamic synapses in the neocortex encode the animal’s previous experience. “When we compared the strength of memory gained with the change in thalamic activity, we were truly convinced that this was the case. This revealed a strong positive relationship, showing that inputs from the thalamus prominently encode the learned behavioral interest of the stimuli. says.

But is this mechanism selective for these top-down memory-related signals?

Sensory stimuli may be related to what we have learned to associate with them, but also solely because of their physical properties. For example, loud sounds attract attention more easily in both humans and animals. However, this is a low-level function that has little to do with previous experience. “Surprisingly, we found very different, indeed opposite, coding mechanisms for this bottom-up form of relevance,” Pardi said. says.

Scientists predicted that given their central importance, the way these signals are received in the neocortex must be tightly regulated. Pardi and his colleagues, Dr. In collaboration with the Henning Sprekeler lab and its team at Technische Universität Berlin, addressed this issue in subsequent experiments combined with computational modeling. The results identified a previously unknown mechanism that could fine-tune information along this path.

And he described a particular type of neuron in the uppermost layer of the neocortex as a dynamic guardian of these top-down signals. These results reveal thalamic inputs to the sensory neocortex as an important source of information about past experiences associated with sensory stimuli. Such top-down signals are disrupted in a range of brain disorders such as autism and schizophrenia, and we hope that the current findings will also allow a deeper understanding of the maladaptive changes underlying these severe conditions. ” says Letzkus.

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