Summary: New computational work proposes that glial cells—particularly astrocytes—play an active, central role in cognitive processing.
Source: University Health Network
Researchers at the Krembil Brain Institute of the University Health Network in Toronto, in collaboration with colleagues at Duke University, have produced the first computer model that predicts how cortical glial cells contribute to cognition.
Their study is published in Proceedings of the National Academy of Sciences (PNAS).
“Neurons and their role in brain function are well studied, but neurons exist alongside abundant glial cells, and many synapses are closely associated with glia,” explains Dr. Maurizio De Pittà of the Krembil Brain Institute, first author of the paper. “We still lack a clear picture of how neurons and glia cooperate, and how glial dysfunction might lead to cognitive problems.”
Glial cells are widespread throughout the brain and support neural circuits in many ways. Historically considered passive support elements—providing structural support, delivering nutrients, and clearing waste—glia are now known to communicate chemically with neurons in ways that resemble neuronal signaling.
This paper introduces a formal theory and computational framework for how one major glial type, the astrocyte, can shape cognitive processing. “Astrocytes can modulate circuit activity and influence behavior,” says Dr. De Pittà.
The team focused on working memory—the brain’s ability to hold and manipulate information over short periods, necessary for tasks like following a story, performing mental arithmetic, or temporarily holding a phone number.
“Astrocytes release specific chemical signals, and our model shows how that signaling can produce different measurable manifestations of working memory,” Dr. De Pittà notes. Incorporating astrocyte–synapse signaling into network models helps explain how the brain can support multiple forms of working memory within the same circuitry.
Understanding neuron–glia interactions also sheds light on what might go wrong when working memory fails. Working memory impairments are common early signs in numerous neurological disorders, and the new theory suggests that disrupted glial signaling could contribute to such deficits.
“To fully understand working memory dysfunction, we must consider how glial cells and neurons interact,” he adds.
Key points highlighted in the article:
• Traditionally, synapses were viewed as transmitting information on a single “frequency” or mode. Including astrocytes reveals that synaptic communication can operate across multiple frequency bands or modes.
• It is often assumed that distinct forms of working memory depend on different neural circuits. The model demonstrates that the same integrated neuron–glia circuits can encode multiple working memory formats.
• The spatial arrangement and coupling of astrocytes with nearby neurons may set limits on working memory capacity—affecting how many items we can hold in mind simultaneously.
At present, recording glial activity directly in the human brain remains technically challenging. The authors aim to build a high-fidelity “digital twin” of neuron–glia circuits, spanning from genes to cellular networks, which would enable better characterization of neuron–glia biomarkers and potential therapeutic targets.
A validated model that integrates neuron–glia signaling could reveal markers of dysfunctional interactions and guide improved diagnosis and treatment strategies for brain diseases including Alzheimer’s disease, Parkinson’s disease and epilepsy.
“Our theory moves beyond a binary view of neurons being simply active or inactive,” says Dr. De Pittà. “By bringing glia and their signaling into the picture, we obtain a richer, multicolor view of cellular communication and the brain’s complexity.”
As computational techniques and experimental methods advance, De Pittà and his team plan to use these models to design interventions that modulate neuron–glia circuit dynamics with therapeutic intent. “Our long-term aim is to identify new treatment targets rooted in neuron–glia interactions,” he explains.
Funding: This research was supported by an FP7 Marie Skłodowska-Curie International Outgoing Fellowship. Ongoing research in Dr. De Pittà’s laboratory receives operating support from the Krembil Research Institute, the European Research Commission, the Krembil Foundation and the UHN Foundation.
About this cognitive processing research news
Author: Ana Fernandes
Source: University Health Network
Contact: Ana Fernandes – University Health Network
Image: The image is in the public domain
Original Research: Closed access.
“Multiple forms of working memory emerge from synapse–astrocyte interactions in a neuron–glia network model” by Maurizio De Pittà et al. PNAS
Abstract
Multiple forms of working memory emerge from synapse–astrocyte interactions in a neuron–glia network model
Persistent neuronal activity, time-varying patterns across populations, and activity-silent mechanisms supported by internal states have all been proposed as mechanisms for working memory (WM). Whether these mechanisms are mutually exclusive or can coexist within the same circuit has remained unclear, as have their underlying biophysical bases.
Although working memory has typically been attributed to neuronal processes, cortical networks also contain astrocytes capable of modulating neural function. We present and analyze a network model that explicitly includes both neurons and glia, demonstrating that astrocyte–synapse interactions can produce multiple stable modes of synaptic transmission. These interactions, depending on model parameters, give rise to distinct patterns of network activity that may serve as substrates for the various forms of working memory observed experimentally.