Nanosensor Detection of Synaptic Glutamate Release and Its Enhancement in Long‐term Potentiation

Long-term potentiation (LTP) performing as long-lasting increase in synaptic strength after tetanic stimulation, is one kind of vital synaptic plasticity in hippocampal neurons and involved in learning and memory mechanisms. Postsynaptic effect through protein expression and receptor migration in LTP has been widely studied, while presynaptic contribution remains indeterminate for lack of strategy for real-time monitoring glutamate (Glu) release and exocytotic dynamics change inside the synapse. Herein, a novel Glu nanosensor is fabricated which is equipped with a conical tip and can be inserted into synaptic cleft of cultured hippocampal neurons. This Glu nanosensor possessing excellent electrochemical performance and spatio-temporal resolution, is applied to monitor vesicular Glu release inside single synaptic cleft and its dynamic variations during LTP process. The results indicate that Glu release from presynaptic terminal is enhanced in LTP, and the enhancement may arise from increasing exocytotic events, releasing more Glu from individual vesicles and changing exocytotic dynamics. This work provides a promising method to explore the regulatory mechanism of Glu release inside synaptic cleft and new directions to reveal synaptic plasticity.