Brain circuitry is complex and requires regulatory stability to maintain healthy neural plasticity and excitability. Minor fluctuations in signaling pathways lead to significant aberrations in these circuits, giving rise to clinical manifestations of neuropsychiatric disease such as schizophrenia, depression, and Alzheimer’s disease. The precise pathways involved in neuropsychiatric disorders must be resolved to understand how disease arises, and to subsequently design modulators capable of stabilizing neuronal circuitry. Voltage-gated sodium (Nav) channels form the basis of electrical excitability in these circuits, in particular those located at the axonal initial segment (AIS), the site of action potential initiation. These ion channels form highly regulated macromolecular complexes, and their biophysical properties are modulated by fibroblast growth factor 14 (FGF14) and glycogen synthase kinase 3-beta (GSK3-beta), an enzyme implicated in nearly all neuropsychiatric disorders. I am interested in exploring how changes in inflammatory and regenerative cell signaling events seen in disease contribute to the dysregulation of sodium channel complexes. I use both biophysical and cell-based techniques to study the protein:protein interactions between FGF14, Nav1.6, and GSK3-beta, and aim to understand how these interactions change based on activation of either the TNF receptor (TNFR1) or the receptor for BDNF, TrkB.