Photoelectrochemical Fiber Cytometry With 60 nm Tip Size for Measuring Serotonin Dynamics at Edges of Cleft and Varicosities.

Tools and methods for investigating neurotransmitter dynamics at synaptic and nonsynaptic varicosities are essential for deciphering neural signaling events. Here, we first built a photoelectrochemical fiber cytometry with a tip size down to ∼60 nm for real-time collection of photoelectrochemical signals in brain slices. Meanwhile, a serotonin (5-HT)-selective photoelectrochemical probe kit was created using a dual-recognition strategy, integrating aptamer binding-induced selective recognition and photo-conversion electron transfer processes. The developed two-sensor probe kit enabled the monitoring of 5-HT dynamics, with linear detection ranges covering two distinct concentration windows from nM to mM. Leveraging the high selectivity, reversible response, and precise spatial positioning capability of this tool, volume transmission-associated 5-HT dynamics were measured at the edges of open synaptic clefts and non-synaptic varicosities in acute brain slices. The findings suggested that the P2X2 receptor modulated extracellular ATP (eATP)-induced 5-HT dynamics at edges of both open synaptic and non-synaptic varicosities. Moreover, the P2Y12 receptor exerted a stronger regulatory effect on 5-HT dynamics at the edge of open synaptic varicosities than at non-synaptic varicosities under eATP stimulation.