Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is an important regulator of phosphatidylinositol-(3,4,5,)-trisphosphate signalling, which controls cell growth and differentiation. However, PTEN is also highly expressed in the adult brain, in which it can be found in dendritic spines in hippocampus and other brain regions. Here, we have investigated specific functions of PTEN in the regulation of synaptic function in excitatory hippocampal synapses. We found that NMDA receptor activation triggers a PDZ-dependent association between PTEN and the synaptic scaffolding molecule PSD-95. This association is accompanied by PTEN localization at the postsynaptic density and anchoring within the spine. On the other hand, enhancement of PTEN lipid phosphatase activity is able to drive depression of AMPA receptor-mediated synaptic responses. This activity is specifically required for NMDA receptor-dependent long-term depression (LTD), but not for LTP or metabotropic glutamate receptordependent LTD. Therefore, these results reveal PTEN as a regulated signalling molecule at the synapse, which is recruited to the postsynaptic membrane upon NMDA receptor activation, and is required for the modulation of synaptic activity during plasticity.

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The unrelenting changes associated with aging progressively affects all structures of the spinal units. The degenerative process starts early during the first decade of life at the disc level. Discal degeneration is associated with biochemical changes followed by macroscopic alterations including tears and fissures, which may lead to discal herniation, the main cause of radiculopathy in the young adult. Moreover, nociceptive nerve fibers have been demonstrated in degenerated discs. They may be a source of nociception and of pure low-back pain. Facet joint changes are usually secondary to discal degeneration. They include subluxation, cartilage alteration and osteophytosis. Facet hypertrophy and laxity, associated with discal degeneration, and enlargement of the ligamentum flavum progressively create narrowing of the spinal canal as well as degenerative instabilities such as spondylolisthesis and scoliosis, which are the main causes of neurogenic claudication and radiculopathy in old persons. Vertebral bodies are the static elements of the spinal unit. With advancing age, osteoporosis weakens the bony structures and facilitates bone remodeling and rotatory deformities. Finally, aging of bone, discs, facets, ligaments, and muscles may ultimately lead to rotatory scoliosis, destabilization, and rupture of equilibrium.