TI - Activity -dependent ERK activation in vivo . AB - An interesting finding of this paper is that both , ERK1/2 and the GluA1 subunit are important in activity -dependent changes in the ACC in vivo . Peripheral injuries are known to lead to a sustained PHOSphorylation and activation of ERK1/2 in sensory neurons of the dorsal root ganglia as well as in spinal dorsal neurons [62-64] . Here we report a rapid and sustained PHOSphorylation of ERK1/2 in neurons of the ACC induced by persistent activation of nociceptors following CFA injection . These observations , coupled to our previous finding that ERK activation is necessary for LTP in the ACC [14] strongly suggests that ERK activation is an important step in triggering long-lasting potentiation of cortical neurons , which is critically linked with induction and maintenance of chronic pain . Interestingly , GluA1-/- mice demonstrated a diminished activation of cortical ERK in responses to persistent nociception in vivo and a loss of cortical potentiation ex-vivo . This is consistent with our previous findings that GluA1-/- mice demonstrate diminished behavioral hyperalgesia in models of inflammatory pain [62] . Thus , the composition of cortical as well as spinal AMPA receptors may be a key determinant for pathological pain states which are triggered by persistent activation of nociceptors in inflamed or injured tissue . In summary , we demonstrate the strong ex-vivo as well as in-vivo evidence that the ERK-GluA1 pathway is essential for synaptic plasticity in pain-related cortical regions . This study might further improve our understanding of cellular and molecular mechanisms of cortical plasticity and help to identify new targets for the treatment of patients with chronic pain .