By Elena Blanco-Suárez
The session that I was most looking forward to at this year’s Society for Neuroscience (SfN) conference took place on Sunday November 13. The minisymposium titled ‘Astrocytes as active participants in neural circuits: from cells to systems’ gathered Cagla Eroglu, Anna Molofsky, Alfonso Araque, Kira Poskanzer, James Schummers and Benjamin Deneen; all familiar names to the astrocyte connoisseur.
Kira Poskanzer, chair of the minisymposium, opened the session stating how astrocytes are still today relegated to a corner of the neuroscience field. Traditionally, astrocytes are known for homeostatic maintenance, repair, protection and metabolic support of neurons, among other functions. But the focus has more recently shifted to their involvement in synapse development and maintenance. Sharing their most recent and exciting research, the speakers highlighted the diversity of astrocytes and their important role in neural circuits.
Cagla Eroglu, from Duke University, discussed previous discoveries on astrocyte-secreted factors, reminding us that these factors have the ability to structure silent synapses (Thrombospondin and Hevin a.k.a. SPARCL1) and also recruit AMPARs to these structures (Glypican4 and 6). Astrocytes secrete many different factors responsible for the correct formation and function of synapses, and novel studies are still trying to elucidate the exact mechanisms by which these factors exert their function on synapses. Eroglu’s lab is particularly interested in the mechanism of action of the astrocytic factor Thrombospondin, and its interaction with the gabapentin receptor α2δ-1 that promotes synaptogenesis. Eroglu guided us through their latest studies, which looked into the downstream pathway of the Thrombospondin-α2δ-1 interaction. This included exciting new data indicating the involvement of Rac1, a small Rho GTPase involved in spine and synapse formation and modification.
Anna Molofsky, from UCSF, started her presentation by describing astrocytes as the “guideposts” that keep brain circuits in place. This was in reference to astrocytes’ capability to store positional information while the brain grows. Molofsky identified Sema3a as a key regulator to determine astrocyte-induced neuronal circuit organization in the ventral horn of the spinal cord. Loss of this gene has been proven to alter excitatory and inhibitory synapses in motor neurons, as well as promoting mis-positioning of synapses, and finally loss of motor neurons. Molofsky is also looking into astrocytes as microglia remodelers, through which they regulate synaptic pruning.
Alfonso Araque, from the University of Minnesota, talked about the endocannabinoid regulation of the neuron-astrocyte interaction. Endocannabinoids released from medial spiny neurons (MSN) promote Ca2+ elevation and glutamate release from surrounding astrocytes. Araque’s lab has studied this mechanism in the dorsal striatum, identifying astrocytes that specifically respond to the stimulation of either D1 or D2 MSNs. Astrocytes that responded to one particular type of MSN only elicited synaptic potentiation in neurons of the same type. This observation indicates that synaptic regulation by astrocytes is restricted to particular subsets of astrocytes and specific circuits. Their latest research also suggests that animal behavior may be controlled by astrocytes and the circuit-specific synaptic regulation they perform.
Kira Poskanzer, also from UCSF, studies spontaneous activity in the brain. She is tackling the question of whether astrocytes can regulate cortical circuits during different neuronal states. Stimulation of a single astrocyte initiated the stimulation of a whole astrocytic network, promoting depolarization of neurons within that particular circuit. Poskanzer observed that Ca2+ signals in astrocytes correlated with slow oscillation across the brain and this correlation occurs across behavioral states, indicating that astrocytes may be regulating these cortical circuits. During slow-wave sleep, depolarized and hyperpolarized neuronal states are key in oscillatory activity. Since astrocytes are involved in the regulation of the depolarization of neurons, she speculates about the role of astrocytes in the regulation of sleep, or even in attention or memory consolidation, where depolarized neuronal states are also crucial.
James Schummers, from the Max Planck Florida Institute, showed us his research on the visual cortex organization in ferrets. I must confess, it was nice to see some research done in a different animal model, other than the common mouse model. He explained the special organization that neurons display in the visual cortex of ferrets. Neurons are arranged in columns, which place astrocytes in a privileged position to regulate specific connections. Schummer’s work has demonstrated that different classes of astrocytes are specific to the circuit, and that the organization of astrocytes is not conserved across species or even across brain regions. He suggests that current models of astrocytes need to be revised in order to account for their diversity across circuits and species.
Benjamin Deneen, from Baylor College of Medicine in Houston, told us how his lab uses the term ‘astropoiesis’ to refer to the subdivision of astrocytes that determines their function. They have initially identified five astrocytic subdivisions: olfactory bulb, cortex, cerebellum, hypothalamus and brain stem. They found conserved molecular signatures across the different brain regions, but they also identified consistently different antigens that allowed them to confidently subdivide the astrocytes into those five sub-populations. Astrocytic differentiation into these sub-populations is found to trigger synapse formation. The Deneen lab has found that astrocytic differentiation in glioma coincided with an increase in seizure frequency. This is potentially caused by the triggered increase in synapse number due to the sub-division of astrocytes, or by a loss of inhibition. This finding opens a new avenue of research into the importance of astrocyte heterogeneity in epilepsy and excitatory/inhibitory synaptic balance.
In summary, the minisymposium revealed new research into the diverse nature of astrocytes, and their functions that differ according to the circuit they regulate or the brain region or sub-population they are part of. This is a thrilling prospect for upcoming research in brain circuits, where astroglia should definitely not be relegated to a corner anymore.
Image credit Elena Blanco-Suárez
Any views expressed are those of the author, and do not necessarily reflect those of PLOS.
Elena Blanco-Suárez is a postdoc in the molecular neurobiology lab of Nicola Allen, at the Salk Institute in San Diego. She studies novel astrocyte-secreted factors involved in synaptogenesis during development.