Evidence for homeostatic and Hebbian plasticity components in cortical layer 2/3 neurons

Previous studies have shown that cortical layer 2/3 neurones show Hebbian forms of synaptic plasticity. The layer 4 to layer 2/3 pathway shows both LTP and LTD. LTP is absent in this pathway in mutants lacking autophosphorylation of CaMKII, as is experience dependent potentiation induced by single whisker experience. LTD occurs in this pathway in the deprived whisker's barrel-column, but can be occluded by whisker deprivation. In this study, we wished to determine whether homeostatic plasticity could also be detected in layer 2/3 neurones. We deprived C57BL/6J mice of all whiskers unilaterally for 1, 3, 7 or 14 days and measured principal whisker responses to a standard whisker deflection. Responses were depressed after a single day of whisker deprivation but returned toward baseline after 3 days in a homeostatic fashion despite continued whisker input deprivation. Principal whisker responses slightly overshot baseline values after 7 and 14 days deprivation. The homeostatic response was prevented in mice lacking synaptic scaling (C57BL/6OlaHsd, Ranson et al 2012, PNAS 109, 1311) and by administration of XPro1595 (Xencor, CA), a selective inhibitor of soluble TNF. TNF-alpha has itself been implicated in synaptic scaling (Stellwagen and Malenka 2006, Nature 440, 1054). We conclude that layer 2/3 neurones exhibit both Hebbian and homeostatic components of synaptic plasticity in the barrel cortex.