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Updated: Sep 9, 2025

Evaluation of Synapse Density in Hippocampal Rodent Brain Slices
Published on: October 6, 2017
Inhibiting JNK and PI3K-Akt signaling pathways altered spontaneous network bursts and developmental trajectories of
Xiaoli Jia1,2, Qiuyan Zhu1,2, Hailin Lu3
1State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, People's Republic of China.
Abstract:
Objective.Spontaneous network bursts (NBs) are critical for neuronal circuit development, influencing synaptogenesis and functional organization. While JNK and PI3K-Akt signaling pathways are known to regulate synaptic plasticity, their specific roles in governing NBs dynamics and functional network organization remain poorly understood. This study investigates the roles of JNK and PI3K-Akt signaling in regulating spontaneous NBs dynamics and network organization in cultured neuronal networks.Approach.Using longitudinal microelectrode array (MEA) recordings from cultured cortical neurons (DIV14-49), we pharmacologically inhibited JNK (SP600125, JNK-IN-8) and PI3K-Akt (LY294002, GDC-0941) pathways. We quantitatively analyzed NBs profiles (maximum firing rate/MFR, burst length/BL, rising phase/RP) and functional network properties (modularity, betweenness centrality) during development.Main results.JNK inhibition increased MFR but reduced RP and FP, and decreased betweenness centrality and network modularity, particularly in DIV21. PI3K-Akt inhibition caused delayed effects: decreased MFR at DIV49 with increased RP, while enhancing network modularity. Developmental analysis revealed a transition from core-node-driven NBs (strong MFR-betweenness and BL-betweenness correlation at DIV14) to modularly organized NBs (strong BL-modularity and MFR-modularity correlation at DIV49), with pathway inhibitors differentially altering these relationships.Significance.Our findings demonstrate that JNK and PI3K-Akt pathways play distinct temporal roles in regulating NBs dynamics and network organization. JNK signaling is crucial for maintaining early core-node functionality, whereas PI3K-Akt signaling promotes the development of mature modular architecture. Our findings enhance the understanding of how molecular signaling influences neuronal network dynamics, contributing to a broader framework for studying neurodevelopmental principles.
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