Figure 1
From: Neuronal and microglial mechanisms of neuropathic pain
Signaling pathways for NMDA receptor-dependent LTP in the ACC. Neural activity releases glutamate in the ACC synapses. Subsequent to activation of glutamate NMDA receptors, Ca2+ binds to CaM and leads to activation of calcium-stimulated ACs, including AC1 and AC8 and Ca2+/CaM dependent protein kinases (PKC, CaMKII and CaMKIV). Activation of CaMKIV, a kinase predominantly expressed in the nuclei, will trigger CaMKIV-dependent CREB. In addition, activation of AC1 and AC8 lead to activation of PKA, and subsequently CREB. CREB and other immediate early genes (e.g., Egr1) in turn activate targets that are thought to lead to more permanent structural changes. Inset box: the simplified neuronal network for sensory synaptic transmission, plasticity and regulation in the central nervous system. DRG: dorsal root ganglion.