The study shows the structural basis of memory formation in the mouse brain

The study shows the structural basis of memory formation in the mouse brain

In a study supported by the National Institutes of Health (NIH), researchers demonstrated the structural basis of memory formation in a broad network of neurons in the mouse brain. This work illuminates the fundamentally flexible nature of memory creation, describing learning-related changes at the cellular and subcellular levels with unprecedented resolution. Understanding this flexibility can explain why memory and learning processes sometimes go wrong.

The results, published inScienceshowed that neurons associated with a memory trace reorganized their connections to other neurons through an atypical connection called a multi-synaptic bouton. In a multi-synaptic bouton, the axon of the neuron that transmits the signal with information sales contacts several neurons that receive the signal. According to the researchers, multisynaptic boutons may enable the cellular flexibility of information coding observed in previous studies.

The researchers also found that neurons involved in memory formation were not preferentially connected to each other. This finding challenges the idea of ​​“neurons firing together,” as a traditional learning theory predicts.

In addition, the researchers observed that neurons associated with a memory trace reorganized certain intracellular structures that support energy and communication and plasticity in neuronal connections. These neurons also had increased interactions with supporting cells known as astrocytes.

Using a combination of advanced genetic tools, 3D electron microscopy and artificial intelligence, research scientists Marco Uytiepo, Anton Maximov, Ph.D.

This image shows an AI-assisted nanoscale 3D reconstruction of neuronal synapses in the mouse hippocampus.

To study structural features related to learning, the researchers exposed mice to a conditioning task and examined the hippocampus region of the brain about 1 week later. They chose this time because it occurs after memories are first encoded but before they are reorganized for long-term storage. Using advanced genetic techniques, researchers permanently labeled subsets of hippocampal neurons that activated during learning, allowing for reliable identification. They then used 3D electron microscopy algorithms and artificial intelligence to create nanoscale reconstructions of the excitatory neural networks involved in learning.

This study provides a comprehensive look at the structural hallmarks of memory formation in one brain region. It also raises new questions for further exploration. Future studies will be crucial to determine whether similar mechanisms operate across different time points and neural circuits. Additionally, further investigation of the molecular composition of multisynaptic boutons is required to determine their precise role in memory and other cognitive processes.

The research was supported by funding from the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and NIHBrain research by promoting innovative neurotechnologies® Initiative or The Brain Initiative®.

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