Synaptic development is an activity‐dependent process utilizing coordinated network activity to drive synaptogenesis and subsequent refinement of immature connections. Hippocampal CA3 pyramidal neurons (PYRs) exhibit intense burst firing (BF) early in development, concomitant with the period of mossy fibre (MF) development. However, whether developing MF–PYR synapses utilize PYR BF to promote MF synapse maturation remains unknown. Recently, we demonstrated that transient tonic depolarization of postsynaptic PYRs induces a persistent postsynaptic form of long‐term depression (depolarization‐induced long‐term depression, DiLTD) at immature MF–PYR synapses. DiLTD induction is NMDAR independent but does require postsynaptic Ca2+ influx through L‐type voltage gated Ca2+ channels (L‐VGCCs), and is expressed as a reduction in AMPAR function through the loss of GluR2‐lacking AMPARs present at immature MF–PYR synapses. Here we examined whether more physiologically relevant phasic L‐VGCC activation by PYR action potential (AP) BF activity patterns can trigger DiLTD. Using combined electrophysiological and Ca2+ imaging approaches we demonstrate that PYR BF effectively drives L‐VGCC activation and that brief periods of repetitive PYR BF, produced by direct current injection or intrinsic network activity induces NMDAR‐independent LTD by promoting Ca2+ influx through the activated L‐VGCCs. This BF induced LTD, just like DiLTD, is specific for developing MF–PYR synapses, is PICK1 dependent, and is expressed postsynaptically. Our results demonstrate that DiLTD can be induced by phasic L‐VGCC activation driven by PYR BF, suggesting the engagement of natural PYR network activity patterns for MF synapse maturation.

Background: Allergic rhinitis (AR) is an upper airways chronic inflammatory disease mediated by IgE, which affects 10%–20% of the population. The mainstay for allergic rhinitis nowadays include steroids and antihistamines, but their effects are less than ideal. Many patients therefore seek Chinese medicine for treatment and Yupingfeng Powder is one of the most common formulae prescribed. In this study, we aim to investigate the efficacy and safety of Yupingfeng Powder with variation for the treatment of allergic rhinitis.Study design: This is a double-blind, randomized, placebo-controlled trial. A 2-week screening period will be implemented, and then eligible subjects with allergic rhinitis will receive interventions of either “Yupingfeng Powder with variation” granules or placebo granules for 8 weeks, followed by post treatment visits at weeks 12 and 16. The change in the Total Nasal Symptom Score (TNSS) will be used as the primary outcome.Discussion: This trail will evaluate the efficacy and safety of Yupingfeng Powder in treating allergic rhinitis. The study may provide the solid evidence of Yupingfeng Powder with variation can produce better clinical efficacy than the placebo granules.Trial registration:ClinicalTrials.gov, identifier NCT04976023.