The Presynaptic Scaffold Protein Bassoon in Forebrain Excitatory Neurons Mediates Hippocampal Circuit Maturation: Potential Involvement of TrkB Signalling

A presynaptic active zone organizer protein Bassoon orchestrates numerous important functions at the presynaptic active zone. We previously showed that the absence of Bassoon exclusively in forebrain glutamatergic presynapses (Bsn(Emx1)cKO) in mice leads to developmental disturbances in dentate gyrus (DG) affecting synaptic excitability, morphology, neurogenesis and related behaviour during adulthood. Here, we demonstrate that hyperexcitability of the medial perforant path-to-DG (MPP-DG) pathway in Bsn(Emx1)cKO mice emerges during adolescence and is sustained during adulthood. We further provide evidence for a potential involvement of tropomyosin-related kinase B (TrkB), the high-affinity receptor for brain-derived neurotrophic factor (BDNF), mediated signalling. We detect elevated TrkB protein levels in the dorsal DG of adult mice (similar to 3-5 months-old) but not in adolescent (similar to 4-5 weeks-old) mice. Electrophysiological analysis reveals increased field-excitatory-postsynaptic-potentials (fEPSPs) in the DG of the adult, but not in adolescent Bsn(Emx1)cKO mice. In line with an increased TrkB expression during adulthood in Bsn(Emx1)cKO, blockade of TrkB normalizes the increased synaptic excitability in the DG during adulthood, while no such effect was observed in adolescence. Accordingly, neurogenesis, which has previously been found to be increased in adult Bsn(Emx1)cKO mice, was unaffected at adolescent age. Our results suggest that Bassoon plays a crucial role in the TrkB-dependent postnatal maturation of the hippocampus.

Automated summary

Bassoon, an active zone organizer protein, plays a crucial role in coordinating various functions at the presynaptic active zone. The absence of Bassoon in forebrain glutamatergic synapses leads to developmental disturbances in the dentate gyrus and may affect signaling pathways related to TrkB and neurogenesis.