Sensory experience, and the lack thereof, can alter the function of excitatory synapses in the primary sensory cortices. Recent evidence suggests that changes in sensory experience can regulate the synaptic level of Ca2+-permeable AMPA receptors (CP-AMPARs). However, the molecular mechanisms underlying such a process have not been determined. We found that binocular visual deprivation, which is a well-established in vivo model to produce multiplicative synaptic scaling in visual cortex of juvenile rodents, is accompanied by an increase in the phosphorylation of AMPAR GluR1 (or GluA1) subunit at the serine 845 (S845) site and the appearance of CP-AMPARs at synapses. To address the role of GluR1-S845 in visual deprivation-induced homeostatic synaptic plasticity, we used mice lacking key phosphorylation sites on the GluR1 subunit. We found that mice specifically lacking the GluR1-S845 site (GluR1-S845A mutants), which is a substrate of cAMP-dependent kinase (PKA), show abnormal basal excitatory synaptic transmission and lack visual deprivation-induced homeostatic synaptic plasticity. We also found evidence that increasing GluR1-S845 phosphorylation alone is not sufficient to produce normal multiplicative synaptic scaling. Our study provides concrete evidence that a GluR1 dependent mechanism, especially S845 phosphorylation, is a necessary pre-requisite step for in vivo homeostatic synaptic plasticity.

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Renal medullary carcinoma (RMC) is a highly aggressive and rare malignancy found almost exclusively in young patients with sickle cell trait (SCT). Metastatic disease is commonly present at diagnosis. There is very limited experience treating disseminated disease and the prognosis is dismal. We report the case of a young 9-year-old boy with SCT, who presented with 4 months' progression of abdominal pain, nausea and vomiting associated with cough spells, dysphagia, and weight loss. Upon evaluation, he was underweight, pale, and in mild respiratory distress. Cervical lymphadenopathy was evident and abdomen was diffusely tender. A whole-body CT scan showed a left kidney lesion with associated cervical, mediastinal, and retroperitoneal lymphadenopathy. Biopsy of a cervical lymph node revealed metastatic RMC. Patient was started on combination chemotherapy with paclitaxel, carboplatin, and gemcitabine followed by left adrenalectomy. In spite of having advanced disease, our patient achieved an excellent response with a progression-free survival of 17 months. Although SCT is thought to be a "benign" condition, RMC is one devastating complication associated with it. Considering its rarity, the near uniform associated fatality should prompt the question of whether clinical practice should change regarding proper counseling of these patients and raise awareness in the medical community.

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