Dentate gyrus is selectively vulnerable to microglial activation at the early stage of experimental multiple sclerosis. Dentate gyrus disruption causes memory impairment at the early stage of experimental multiple sclerosis. Intra-dentate gyrus or systemic injections of minocycline prevent memory impairment in experimental multiple sclerosis. High-resolution diffusion tensor imaging can capture in vivo the selective alteration of the dentate gyrus.