PirB regulates a structural substrate for cortical plasticity

Significance Learning and memory are mediated by changes in synaptic structure and circuit connectivity; these changes are known as “synaptic plasticity.” In the normal brain, the amount of plasticity is fine tuned by regulating a balance between synaptic strengthening and weakening, both in a positive and a negative direction. Here we report that paired immunoglobulin-like receptor B (PirB), an innate immune receptor expressed by neurons, acts as a robust negative regulator of structural substrates for plasticity in visual cortex. Without PirB, there are excessive numbers of spines, accompanied by a shift in Hebbian plasticity favoring synaptic strengthening. These results suggest that PirB regulates spine density in cortex and imply that blocking PirB function could enhance cognition or recovery from injury. 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.