Kozachkov, L., Slotine, J., & Krotov, D. (2025).
Proceedings of the National Academy of Sciences,
122(21).
Abstract
Astrocytes, the most abundant type of glial cell, play a fundamental role in memory. Despite most hippocampal synapses being contacted by an astrocyte, there are no current theories that explain how neurons, synapses, and astrocytes might collectively contribute to memory function. We demonstrate that fundamental aspects of astrocyte morphology and physiology naturally lead to a dynamic, high-capacity associative memory system. The neuron–astrocyte networks generated by our framework are closely related to popular machine learning architectures known as Dense Associative Memories. Adjusting the connectivity pattern, the model developed here leads to a family of associative memory networks that includes a Dense Associative Memory and a Transformer as two limiting cases. In the known biological implementations of Dense Associative Memories, the ratio of stored memories to the number of neurons remains constant, despite the growth of the network size. Our work demonstrates that neuron–astrocyte networks follow a superior memory scaling law, outperforming known biological implementations of Dense Associative Memory. Our model suggests an exciting and previously unnoticed possibility that memories could be stored, at least in part, within the network of astrocyte processes rather than solely in the synaptic weights between neurons.
Significance
Recent experiments have challenged the belief that glial cells, which compose at least half of brain cells, are just passive support structures. Despite this, a clear understanding of how neurons and glia work together for brain function is missing. To close this gap, we present a theory of neuron–astrocytes networks for memory processing, using the Dense Associative Memory framework. Our findings suggest that astrocytes can serve as natural units for implementing this network in biological “hardware.” Astrocytes enhance the memory capacity of the network. This boost originates from storing memories in the network of astrocytic processes, not just in synapses, as commonly believed. These process-to-process communications likely occur in the brain and could help explain its impressive memory processing capabilities.
Here are some thoughts:
This research represents a paradigm shift in our understanding of memory formation and storage. The paper examines how "astrocytes, the most abundant type of glial cell, play a fundamental role in memory" and notes that "most hippocampal synapses being contacted by an astrocyte."
For psychologists, this is revolutionary because it challenges the traditional neuron-centric view of memory. Previously, memory research focused almost exclusively on neuronal connections and synaptic plasticity. This study demonstrates that astrocytes - previously thought to be merely supportive cells - are active participants in memory processes. This has profound implications for:
Cognitive Psychology: It suggests memory formation involves a more complex cellular network than previously understood, potentially explaining individual differences in memory capacity and the mechanisms behind memory consolidation.
Learning Theory: The findings may require updating models of how associative learning occurs at the cellular level, moving beyond simple neuronal networks to include glial participation.
Memory Disorders: Understanding astrocyte involvement opens new avenues for researching conditions like Alzheimer's disease, where both neuronal and glial dysfunction occur.
Significance for Psychopharmacology
This research has transformative implications for drug development and treatment approaches:
Novel Drug Targets: If astrocytes are crucial for memory, pharmaceutical interventions could target astrocytic functions rather than focusing solely on neuronal receptors. This could lead to entirely new classes of cognitive enhancers or treatments for memory disorders.
Mechanism of Action: Many psychoactive drugs may work partially through astrocytic pathways that weren't previously recognized. This could explain why some medications have effects that aren't fully accounted for by their known neuronal targets.
Treatment Resistance: Some patients who don't respond to traditional neurotropic medications might benefit from drugs that target the astrocyte-neuron memory system.
Precision Medicine: Understanding the dual neuron-astrocyte system could help explain why individuals respond differently to the same medications, leading to more personalized treatment approaches.
This research fundamentally expands our understanding of the biological basis of memory beyond neurons to include the brain's most abundant cell type, potentially revolutionizing both theoretical frameworks in psychology and therapeutic approaches in psychopharmacology.
