Sanz-Galvez, R. | Search bioRxiv

bioRxiv2025

The astroglial protein S100β regulates axon initial segment plasticity

One key regulator of neuronal excitability is the axon initial segment (AIS), a highly specialized axonal region, enriched in ion channels, where action potentials are initiated. The AIS can undergo significant morphological changes to fine-tune neuronal excitability in response to external perturbations. Long considered solely a homeostatic mechanism operating over long timescales (hours to days) to adjust excitability, we show here that this phenomenon can also occur rapidly, within minutes, following a brief period of high activity in layer 5 pyramidal neurons of the visual cortex. Because astrocytes have been known to regulate neuronal excitability, we explored the effects of gliotransmitters on this process and identified the calcium-binding protein S100{beta} from astrocytes to be required for the rapid reorganization of the AIS. O_FIG O_LINKSMALLFIG WIDTH=169 HEIGHT=200 SRC="FIGDIR/small/667937v3_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1765348org.highwire.dtl.DTLVardef@155bf98org.highwire.dtl.DTLVardef@95c300org.highwire.dtl.DTLVardef@356376_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

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bioRxiv2025

The gliotransmitter S100β regulates synaptic plasticity in the visual cortex

Synaptic plasticity is a fundamental mechanism of memory storage in the brain. Among the various rules governing changes in synaptic strength, Spike Timing-Dependent Plasticity (STDP) stands out for its strong physiological relevance in vivo. Ubiquitous across brain regions and neuronal types, STDP is a complex and multifactorial process influenced by factors such as neuromodulation, extracellular calcium levels, and activity patterns. However, one relatively understudied factor is the role of astrocytes, despite their well-established involvement in regulating synaptic transmission and neuronal excitability through gliotransmitter release. While some factors have garnered significant attention, others, like S100{beta}, have remained relatively underexplored despite their potential importance in regulating synaptic plasticity. S100{beta} is a calcium-binding protein, allowing it to influence extracellular Ca{superscript 2} concentration and potentially all Ca2+-dependent plasticity processes. Building on our previous research in the visual cortex, where we examined the regulation of neuronal excitability by S100{beta}, we chose to further investigate the role of astrocytes and S100{beta} in synaptic plasticity at layer 2/3-layer 5 synapses in the visual cortex. We demonstrated that S100{beta} is an important gliotransmitter to consider, capable of regulating long-term potentiation.

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