Synapse density on cortical pyramidal neurons is modulated by experience. This process is highest during developmental critical periods, when mechanisms of synaptic plasticity are fully engaged. In mouse visual cortex, the critical period for ocular dominance (OD) plasticity coincides with developmental pruning of synapses. At this time, mice lacking Paired immunoglobulin-like receptor B (PirB) have excess numbers of dendritic spines on L5 neurons; these spines persist and are thought to underlie the juvenile-like OD plasticity observed in adulthood. Here we examine if PirB is required specifically in excitatory neurons to exert its effect on dendritic spine and synapse density during the critical period. In mice with a conditional allele of PirB (PirBfl/fl), PirB was deleted only from L2/3 cortical pyramidal neurons in vivo by timed in utero electroporation of Cre recombinase. Sparse mosaic expression of Cre produced neurons lacking PirB in a sea of wild-type neurons and glia. These neurons had significantly elevated dendritic spine density, as well as increased frequency of miniature excitatory postsynaptic currents (mEPSCs), suggesting that they receive a greater number of synaptic inputs relative to Cre– neighbors. The effect of cell-specific PirB deletion on dendritic spine density was not accompanied by changes in dendritic branching complexity or axonal bouton density. Together, results imply a neuron-specific, cell-autonomous action of PirB on synaptic density in L2/3 pyramidal cells of visual cortex. Moreover, they are consistent with the idea that PirB functions normally to co-repress spine density and synaptic plasticity, thereby maintaining headroom for cells to encode ongoing experience-dependent structural change throughout life.
Significance Statement: Dendritic spines, postsynaptic sites of excitatory synapses on pyramidal neurons, are regulated by experience and synaptic plasticity. Paired immunoglobulin receptor B (PirB) is known to restrict the extent of experience-dependent plasticity in visual cortex. Here we report that when PirB is removed in vivo from just a few isolated pyramidal neurons in layer 2/3 of mouse visual cortex, spine density as well as the frequency of miniature synaptic currents (a measure of the density of functional synapses) are elevated selectively in the cells lacking PirB. These results suggest that PirB expression in individual neurons is sufficient to limit excitatory synaptic density on pyramidal neurons. This cell intrinsic function of PirB could serve to ensure that pyramidal cells have sufficient structural reserve to encode new experiences.
Authors report no competing financial interests.
National Eye Institute R01 grant EY002858 and the G. Harold and Leila Y. Mathers Charitable Foundation to C.J.S., Regina Casper Stanford Graduate Fellowship and National Eye Institute F31 grant EY023518 to G.S.V., Stanford Bio-X Undergraduate Summer Research Fellowships to K.B. and R.W.S.