Persistent Stress-Induced Neuroplastic Changes in the Locus Coeruleus/Norepinephrine System

Figure 1

Model of signal transduction pathways induced by stress in LC neurons. (a) Pathways which mediate short-term effects of stressor exposure. CRF interacts with CRFR1, which through Gs-coupled receptor mechanisms increases intracellular cAMP levels, reducing potassium conductance resulting in cell depolarization. Through unknown mechanisms, CRF decreases glutamatergic synaptic transmission through AMPARs. (b) Pathways which mediate long-term effects of stressor. Initial CRF activation of Gs-coupled CRFR1 increases PKA activity, which phosphorylates CREB to initiate expression of stress-induced genes. These could potentially include genes regulating AMPAR and voltage-gated ion channel expression. Inactivation of RhoA by PKA phosphorylation disinhibits Rac1 to increase neurite outgrowth via actin remodeling and microtubule stabilization.