id_907. INTRACELLULAR SIGNALING PATHWAYS INVOLVED IN TRKB-DEPENDENT REGULATION OF PYRAMIDAL NEURONS IN THE MEDIAL PREFRONTAL CORTEX
Anna Wierucka1, Przemysław Kurowski1,2
1 Chair and Department of Pharmacotherapy and Pharmaceutical Care, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha St., Warsaw, Poland
2 Laboratory of Physiology and Pathophysiology, Centre for Preclinical Research and Technology, Medical University of Warsaw, 1b Banacha St., Warsaw, Poland
INTRODUCTION: A reduction in brain-derived neurotrophic factor (BDNF) levels negatively affects TrkB receptors, ultimately disrupting the activity of downstream signaling pathways. Decreased BDNF expression has been observed in several neuropsychiatric disorders, including depression. Key contributing mechanisms of depression include oxidative stress and neuroinflammation, which lead to dysfunction within the BDNF/TrkB signaling pathway. However, the intracellular signal transduction pathways regulated by TrkB receptors in pyramidal neurons of the medial prefrontal cortex (mPFC) are not fully understood.
AIM(S): The aim of this study was to identify intracellular signal transduction pathways involved in TrkB-dependent modulation of layer V pyramidal neurons in the mPFC, with particular focus on protein kinase A (PKA), phosphoinositide 3-kinase (PI3K), and protein kinase C (PKC).
METHOD(S): Whole-cell current-clamp recordings were performed in synaptically isolated pyramidal neurons in acute mPFC slices obtained from young male rats.
RESULTS: Pharmacological activation of TrkB receptors, using HIOC, induced significant changes in neuronal membrane potential. Co-application of HIOC with a selective TrkB antagonist abolished these effects, confirming the specificity of the agonist. Furthermore, the use of selective inhibitors revealed that PKA, PI3K, and PKC contribute to TrkB-dependent regulation of membrane excitability.
CONCLUSIONS: These findings indicate that TrkB receptors regulate the excitability of pyramidal neurons in the mPFC through modulation of PKA, PI3K, and PKC signaling pathways. The results highlight potential molecular targets for the development of novel antidepressant therapies.
FINANCIAL SUPPORT: This work was supported by the Ministry of Science and Higher Education, Poland (grant no. SKN/SP/630586/2025).