TRKB-DEPENDENT KINASE SIGNALING REGULATES EXCITABILITY OF MEDIAL PREFRONTAL CORTEX PYRAMIDAL NEURONS

In depression a reduction in brain-derived neurotrophic factor (BDNF) levels is observed, which negatively affects TrkB receptors, ultimately disrupting signalling pathways activity and causing altered cellular effector response. The intracellular signal transduction pathways regulated by the TrkB receptor in pyramidal neurons of the medial prefrontal cortex (mPFC) are not fully understood and the cellular effector of those pathways is unknown. The aim of this study was to identify intracellular signal transduction pathways involved in TrkB-dependent modulation of layer V mPFC pyramidal neurons. Whole-cell current-clamp recordings were performed in synaptically isolated pyramidal neurons in acute mPFC slices from young male rats. Pharmacological activation of TrkB receptors induces changes in neuronal membrane potential. Co-administration of selective inhibitors revealed that protein kinase A (PKA), phosphoinositide 3-kinase (PI3K) and protein kinase C (PKC) contribute to TrkB-dependent regulation of membrane excitability. Preliminary results suggest that sodium channels may act as downstream cellular effectors of these pathways. These findings indicate that TrkB receptor signaling modulates intrinsic excitability of mPFC pyramidal neurons via multiple kinase-dependent mechanisms, highlighting potential molecular targets for antidepressant strategies. This work was supported by the Ministry of Science and Higher Education, Poland (grant no. SKN/SP/630586/2025).