Homer1a/Vesl-1S is an activity-dependently induced member of the scaffold protein family Homer/Vesl, which is known to link group I metabotropic glutamate receptors (mGluRs) to endoplasmic calcium release channels and to regulate them. Here we studied roles of Homer 1a in inducing long-term depression (LTD) in rat visual cortex slices. Homer 1a protein was injected by diffusion from whole-cell patch pipettes. In layer VI pyramidal cells, LTD was reduced in magnitude with Homer 1a. LTD in layer VI was suppressed by applying antagonists of mGluR5, a subtype of group I mGluRs expressed with higher density than mGluR1 in neocortex pyramidal cells, or inositol-1,4,5-triphosphate receptors (IP3Rs), but not that against N-methyl-D-aspartate receptors (NMDARs). In layer II/III or layer V, Homer 1a injection was unable to affect LTD, which is mostly dependent on NMDARs but not on group I mGluRs. To examine the effects of endogenous Homer 1a, electroconvulsive shock (ECS) was applied. Homer 1a thereby induced, as well as Homer 1a injected, reduced LTD magnitude in layer VI pyramidal cells, and failed to do so in layer II/III or layer V pyramidal cells. These results indicate that both exogenous and endogenous Homer 1a suppressed LTD in a cortical layer-specific manner and its layer-specificity may be explained by the high affinity of Homer 1a to group I mGluRs.