Authors: Pasqualino De Luca, Miranda Mele, Francesca Napoli, Philemon Mshelia, Rui O. Costa, and Carlos B. Duarte
Brain, 05 May 2026
Researchers used Maestro MEA recordings to show that BDNF-driven regulation of GluN2A-containing NMDA receptors promotes network hyperexcitability in hippocampal neurons, identifying a signaling pathway linked to epileptiform activity.
Brain-derived neurotrophic factor (BDNF) is a key regulator of synaptic plasticity and neuronal excitability, but its role in driving network hyperactivity associated with epilepsy remains incompletely understood. In this study, researchers investigated how BDNF signaling influences GluN2A-containing NMDA receptors and contributes to hyperexcitable activity in hippocampal neuronal networks.
Using the Maestro MEA platform, the team monitored network activity under baseline and epileptiform conditions. Induction of hyperexcitability increased both burst frequency and network burst frequency, while scavenging BDNF signaling with TrkB-Fc significantly reduced these responses. The researchers further showed that selective inhibition of GluN2A-containing NMDA receptors similarly suppressed bursting activity, indicating that BDNF-dependent regulation of GluN2A receptors contributes to network hyperexcitability.
Together, the findings identify a TrkB-PKC-Pyk2-hnRNPK signaling pathway that links BDNF signaling to GluN2A receptor expression and synchronized network activity. This work provides new insight into molecular mechanisms that may contribute to epilepsy and other disorders characterized by excessive neuronal excitation.
