In mammalian cells, G-quadruplexes are nucleic acid secondary structures that are pervasive throughout the genomic DNA. These structures can regulate gene expression through several different mechanisms, but many details of these mechanisms are poorly understood. In the olfactory bulb, Tyrosine Hydroxylase (Th) and Glutamic Acid Decarboxylase 1 (Gad1) encode rate-limiting enzymes for the production of dopamine and GABA neurotransmitters, and we have shown that G-quadruplexes contribute to the regulation of these genes. Expression levels for Th and Gad1 within olfactory bulb are also dependent the amount of synaptic activity generated by odorant stimulation. We have recently shown that the formation of G-quadruplex structures in the genomic DNA regulatory regions for Th and Gad1 is also dependent the amount of odorant-induced synaptic activity. These findings suggest that synaptic activity regulates Th and Gad1 expression by altering G-quadruplex stability. We currently engaged in studies to establish the molecular mechanistic details that connect synaptic activity with the regulation of Th and Gad1 expression through G-quadruplexes. These studies will provide novel insight into a molecular mechanism by which changes in sensory input and synaptic activity can modify gene expression in neurons.