Astrocytes: the star-shaped glial cells that shape synapses and support neurons

Astrocytes are star-shaped glial cells in the brain and spinal cord that support and regulate neurons. They clear neurotransmitters and ions from synapses, supply metabolic support, help maintain the blood-brain barrier, and actively help form, strengthen and remove synapses. In brain organoids, astrocytes appear after neurons and shape how networks mature.

Key takeaways

• Astrocytes are glia, not neurons: they do not fire action potentials, but they sense and respond to neural activity, often through internal calcium signals.
• They regulate the chemical environment of synapses by taking up glutamate and buffering potassium, which affects how excitable neurons are.
• Astrocytes secrete proteins that promote synapse formation and can engulf synapses during remodeling, as reviewed by Allen and Eroglu (Neuron, 2017).
• In human cortical spheroids, astrocytes mature slowly, shifting from fetal-like to more mature states over many months (Sloan et al., Neuron, 2017).
• For biocomputing, astrocyte content is an experimental variable that can influence activity, plasticity and reproducibility.

What are astrocytes? #

Astrocytes are one of the main types of glial cell, the non-neuronal cells of the nervous system. Their name comes from their star-like shape: a cell body with many branching processes that reach out to touch synapses, other astrocytes and blood vessels. Allen and Eroglu describe them as the most abundant glial cells in the mammalian brain.

For much of the history of neuroscience, glia were treated as passive scaffolding (“glia” comes from the Greek for glue). That view has changed. Astrocytes are now understood as active participants in brain development and signaling, even though they communicate differently from neurons. Where a neuron signals with fast electrical action potentials, an astrocyte typically responds to neighboring activity with slower changes in internal calcium, which researchers often track with calcium imaging.

Astrocytes compared with other brain cells #

The last row matters for organoids: microglia come from outside the neural lineage, so standard brain organoid protocols usually lack them unless they are added. Astrocytes, by contrast, can arise within the organoid itself.

What do astrocytes do at synapses? #

The tripartite synapse #

In 1999, Araque and colleagues argued in Trends in Neurosciences that glia are “the unacknowledged partner” at synapses. Their tripartite synapse model treats a synapse as three components: the sending neuron, the receiving neuron and the fine astrocyte processes that surround them. Astrocytes sense the transmitters released during synaptic activity and can release signaling molecules in return, a two-way exchange.

Housekeeping that sets excitability #

Several astrocyte functions keep neural signaling stable:

• Glutamate uptake. Transporters on astrocytes clear the excitatory transmitter glutamate from synapses, ending signals and protecting neurons from overexcitation.
• Potassium buffering. Active neurons release potassium ions; astrocytes absorb and redistribute them so neurons are not pushed toward excess firing.
• Metabolic support. Astrocytes help supply energy substrates to neurons.
• Vascular contact. Astrocyte endfeet wrap blood vessels and contribute to the blood-brain barrier.

Because these functions set how readily neurons fire, changes in astrocytes can change population activity such as network bursts.

Building and pruning synapses #

Astrocytes do more than maintain synapses; they help make them. Christopherson et al. reported in Cell (2005) that thrombospondins, proteins secreted by astrocytes, promote the formation of synapses in the central nervous system. Allen and Eroglu’s 2017 review summarizes a broader set of astrocyte-secreted factors that influence synapse formation and maturation, along with evidence that astrocytes can engulf and eliminate synapses. In short, astrocytes help decide which connections exist at all.

How do astrocytes affect synaptic plasticity and learning? #

Synaptic plasticity, the strengthening and weakening of connections, is the cellular basis of learning. Astrocytes can influence it in several ways: by controlling how much transmitter lingers at a synapse, by releasing signaling molecules that modulate receptors, and by adding or removing synapses over longer timescales. These effects reach forms of plasticity such as long-term potentiation and slower homeostatic plasticity, though the exact mechanisms and their importance in different brain regions are still actively studied, and some findings remain debated.

The practical lesson is simple: a network’s capacity to learn is not determined by neurons alone. If astrocytes are missing, immature or unusually abundant, rules such as Hebbian learning may play out differently.

Do brain organoids contain astrocytes? #

Yes, in most protocols, but timing and maturity vary. During brain development, neural progenitors first generate neurons and later switch to producing glia. Organoids grown from induced pluripotent stem cells follow a similar order, so astrocytes usually become prominent only after weeks to months in culture.

Two studies from Sergiu Paşca’s group at Stanford illustrate this:

1. Paşca et al. (Nature Methods, 2015) described human cortical spheroids, a 3D culture method that produced both functional cortical neurons and astrocytes from pluripotent stem cells.
2. Sloan et al. (Neuron, 2017) purified astrocyte-lineage cells from such spheroids at stages up to 20 months in vitro and compared them with primary human brain cells using RNA sequencing. The spheroid-derived astrocytes closely resembled primary human fetal astrocytes and, over time, shifted toward a more mature state, with accompanying changes in their ability to engulf material and in their effects on neuronal calcium signaling.

The key implication is that organoid astrocytes may remain developmentally young for a long time. For a guide to how cultures are made, see how brain organoids are grown.

Astrocytes and organoid limitations #

Astrocytes interact closely with blood vessels in the brain, but standard organoids have none. Efforts toward organoid vascularization may therefore change astrocyte behavior as well as nutrient supply. Multi-region assembloids may also differ in glial composition from single-region organoids.

Why do astrocytes matter for organoid intelligence? #

Organoid intelligence research tries to use living neural tissue for computation through stimulation and recording on a microelectrode array, a program outlined by Smirnova et al. in Frontiers in Science (2023). Because astrocytes shape synapses and excitability, they are part of the substrate being programmed, whether or not an experiment measures them.

For anyone designing or comparing experiments, astrocytes raise practical questions:

• Cell composition. What fraction of the culture is astrocytes, and how mature are they?
• Culture age. Results from a young organoid with few astrocytes may not transfer to an older one.
• Plasticity. If a closed-loop stimulation protocol produces learning-like changes, astrocytes may be part of the mechanism.
• Reproducibility. Batch-to-batch variation in glial content is a plausible source of variation in activity.

None of these questions can be answered from electrode recordings alone, which mainly capture neuronal spikes and local field potentials. They require complementary measurements such as imaging, staining or sequencing. The connection between synaptic change and task learning is covered in how neurons learn in a dish.

What are the open questions? #

• How closely do organoid astrocytes match adult human astrocytes, given the long maturation reported by Sloan et al.?
• How much do astrocytes contribute to learning-like changes in cultured networks, compared with purely neuronal mechanisms?
• Does adding vasculature or microglia change astrocyte roles in organoids?
• What astrocyte metrics should be reported as standard metadata alongside electrophysiology data?

Treating cell composition as part of an experiment’s record is one reason we think metadata and provenance belong in the core of the Organoid Programming platform: when results differ, knowing which cells were in the dish helps explain why. Astrocytes are a reminder that the “living” in living neurons includes a supporting cast that shapes every signal.

Frequently asked questions

What do astrocytes do in the brain?

Astrocytes support and regulate neurons. They take up neurotransmitters such as glutamate after synaptic transmission, buffer potassium ions, supply metabolic support, contact blood vessels and help maintain the blood-brain barrier. They also secrete signals that help neurons form synapses and can engulf and remove synapses during development and remodeling. Allen and Eroglu reviewed these roles in Neuron (2017).

Are astrocytes neurons?

No. Astrocytes are glial cells, a separate class of brain cells. Unlike neurons, they do not fire action potentials. They do respond to neural activity, often with changes in internal calcium concentration, and they can release signaling molecules that influence nearby synapses. This is why many researchers describe synapses as three-part, or tripartite, structures that include astrocytes.

What is the tripartite synapse?

The tripartite synapse is a model in which a synapse has three partners: the presynaptic neuron, the postsynaptic neuron and the fine processes of an astrocyte wrapped around them. Araque and colleagues popularized the term in Trends in Neurosciences (1999). The model emphasizes that astrocytes sense synaptic activity and can modulate it, rather than serving only as passive support.

Do brain organoids contain astrocytes?

Yes, many protocols produce astrocytes, though they usually appear after the first waves of neurons, mirroring development. Sloan et al. (Neuron, 2017) purified astrocyte-lineage cells from human cortical spheroids grown for up to 20 months and found they began fetal-like and became progressively more mature over time. Astrocyte content and maturity vary between protocols and batches.

Why do astrocytes matter for biocomputing?

Learning in living neural networks depends on synapses changing strength, and astrocytes help build, stabilize and remove synapses. They also control the chemical environment that sets how excitable neurons are. A culture with more or fewer astrocytes, or with immature ones, may show different activity and plasticity. Reporting astrocyte content helps make biocomputing experiments interpretable and reproducible.

Sources

1. Allen, N. J. & Eroglu, C. (2017). Cell Biology of Astrocyte-Synapse Interactions. Neuron.
2. Araque, A., Parpura, V., Sanzgiri, R. P. & Haydon, P. G. (1999). Tripartite synapses: glia, the unacknowledged partner. Trends in Neurosciences.
3. Christopherson, K. S. et al. (2005). Thrombospondins Are Astrocyte-Secreted Proteins that Promote CNS Synaptogenesis. Cell.
4. Sloan, S. A. et al. (2017). Human Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells. Neuron.
5. Paşca, A. M. et al. (2015). Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nature Methods.
6. Smirnova et al. (2023). Organoid intelligence (OI): the new frontier in biocomputing and intelligence-in-a-dish. Frontiers in Science.