title: Hilar mossy cell degeneration causes transient dentate granule cell hyperexcitability and impaired pattern separation.
abstract: Although excitatory mossy cells of the hippocampal hilar region are known to project both to dentate granule cells and to interneurons, it is as yet unclear whether mossy cell activity's net effect on granule cells is excitatory or inhibitory. To explore their influence on dentate excitability and hippocampal function, we generated a conditional transgenic mouse line, using the Cre/loxP system, in which diphtheria toxin receptor was selectively expressed in mossy cells. One week after injecting toxin into this line, mossy cells throughout the longitudinal axis were degenerated extensively, theta wave power of dentate local field potentials increased during exploration, and deficits occurred in contextual discrimination. By contrast, we detected no epileptiform activity, spontaneous behavioral seizures, or mossy-fiber sprouting 5-6 weeks after mossy cell degeneration. These results indicate that the net effect of mossy cell excitation is to inhibit granule cell activity and enable dentate pattern separation.
authors.affiliation: Unit on Genetics of Cognition and Behavior, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Jinde
authors.forename: Veronika
authors.initials: V
authors.lastname: Zsiros
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Jiang
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Nakao
authors.forename: James
authors.initials: J
authors.lastname: Pickel
authors.forename: Kenji
authors.initials: K
authors.lastname: Kohno
authors.forename: Juan E
authors.initials: JE
authors.lastname: Belforte
authors.forename: Kazu
authors.initials: K
authors.lastname: Nakazawa
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology*; D004167:Diphtheria Toxin; D004827:Epilepsy / Q000503:physiopathology*; D005106:Exploratory Behavior; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D009410:Nerve Degeneration / Q000139:chemically induced; D009474:Neurons / Q000166:cytology / Q000502:physiology; D046709:Pattern Recognition, Physiological / Q000502:physiology*; D013826:Theta Rhythm / Q000502:physiology
chemical_list: D004167:Diphtheria Toxin