Comparative Electrophysiological Analysis of Trigeminal and Dorsal Root Ganglion Neurons in Mice

Cultured dissociated trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons are widely used to study peripheral sensory function, yet direct electrophysiological comparisons under identical experimental conditions remain limited. We compared intrinsic electrophysiological properties of mouse TG (mTG) and mouse DRG (mDRG) neurons using whole-cell patch-clamp electrophysiology from male mice. In addition to conventional comparisons of membrane properties, action potential waveform characteristics, and firing behavior, neurons were stratified by soma size and analyzed using principal component analysis (PCA) and Pearson correlation analyses to determine ganglia-specific electrophysiological signatures. mTG neurons exhibited enhanced stimulus-evoked excitability compared with mDRG neurons, characterized by shorter first-spike latency, increased repetitive firing, and greater action potential output despite similar resting membrane potential, rheobase, and input resistance. These differences were primarily driven by small-diameter neurons, which displayed increased rebound and repetitive firing, whereas differences in spontaneous activity were predominantly observed in large-diameter neurons. PCA revealed distinct clustering of TG and DRG neurons based on electrophysiological properties, while Pearson correlation analyses demonstrated tissue-specific relationships among electrophysiological parameters, particularly involving afterhyperpolarization, indicating that coordinated regulation of excitability differs between sensory ganglia. These findings demonstrate that TG and DRG neurons differ not only in individual electrophysiological properties but also in the coordinated organization of those properties. Together, these data provide a functional framework for understanding ganglion-specific regulation of peripheral sensory neuron excitability and establish a foundation for future mechanistic studies and the development of targeted therapies for peripheral pain disorders.Significance Statement Trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons are fundamental models for studying peripheral sensory physiology and pain mechanisms. Although previous studies have identified differences in their anatomy, central circuitry, and transcriptomic profiles, direct comparisons of their intrinsic electrophysiological properties under identical experimental conditions have been lacking. Here, we demonstrate that cultured dissociated TG and DRG neurons exhibit distinct excitability profiles, firing behaviors, and coordinated electrophysiological signatures. These findings establish a functional framework linking molecular diversity to neuronal function, provide an important reference for interpreting studies of peripheral sensory neurons, and may facilitate the identification of ganglion-specific therapeutic strategies for sensory diseases such as neuropathic pain.