Experience-driven circuit changes underlie learning and memory. Monocular deprivation (MD) engages synaptic mechanisms of ocular dominance (OD) plasticity and generates robust increases in dendritic spine density on L5 pyramidal neurons. Here we show that the paired immunoglobulin-like receptor B (PirB) negatively regulates spine density, as well as the threshold for adult OD plasticity. In PirB −/− mice, spine density and stability are significantly greater than WT, associated with higher-frequency miniature synaptic currents, larger long-term potentiation, and deficient long-term depression. Although MD generates the expected increase in spine density in WT, in PirB −/− this increase is occluded. In adult PirB −/− , OD plasticity is larger and more rapid than in WT, consistent with the maintenance of elevated spine density. Thus, PirB normally regulates spine and excitatory synapse density and consequently the threshold for new learning throughout life.visual cortex | adult plasticity |

The purpose of this study was to investigate the role of intracellular calcium buffering in retinal ganglion cells. We performed a quantitative analysis of calcium homeostasis in ganglion cells of early postnatal and adult mice by simultaneous patch-clamp recordings in sliced tissue and microfluorometric calcium measurements with Fura-2. Endogenous calcium homeostasis was quantified by using the 'added buffer' approach which uses amplitudes and decay time constants of calcium transients to give a standard for intracellular calcium buffering. The recovery phase of depolarization-induced calcium transients was well approximated by a mono-exponential function with a decay time constant that showed a linear dependence on dye concentration. Endogenous calcium binding ratios were found to be 575 (n = 18 cells) in early postnatal and 121 (n = 18 cells) in adult retinal ganglion cells. With respect to ganglion cell degeneration at early postnatal stages, our measurements suggest that neuroprotection of a majority of developing ganglion cells partially results from a specialized calcium homeostasis based on high buffering capacities. Furthermore, the dramatic decrease of the intracellular calcium buffering capacity during ganglion cell development may enhance their vulnerability to neurodegeneration.