title: Improved reversal learning and working memory and enhanced reactivity to novelty in mice with enhanced GABAergic innervation in the dentate gyrus.
abstract: The balance between excitation and inhibition controls fundamental aspects of the hippocampal function. Here, we report an increase in the ratio of inhibitory to excitatory neurons in the dentate gyrus, accompanied by γ-aminobutyric acid(A) (GABA(A)) receptor-dependent impairment of synaptic plasticity and enhancement of activity-dependent changes in excitability in anesthetized adult mice deficient for the extracellular matrix glycoprotein tenascin-R (TNR). TNR-deficient mice showed faster reversal learning, improved working memory, and enhanced reactivity to novelty than wild-type littermates. Remarkably, in wild-type and TNR-deficient mice, faster reversal learning rates correlated at the individual animal level with ratios of parvalbumin-positive interneurons to granule cells and densities of parvalbumin-positive terminals on somata of granule cells. Our data demonstrate that modification of the extracellular matrix by ablation of TNR leads to a new structural and functional design of the dentate gyrus, with enhanced GABAergic innervation, that is, enhanced ratio of inhibitory to excitatory cells, and altered plasticity, promoting working memory and reversal learning. In wild-type mice, the enhanced ratio of inhibitory to excitatory cells in the dentate gyrus also positively correlated with reversal learning, indicating that level of inhibition regulates specific aspects of learning independent of the TNR gene.
authors.affiliation: Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. fabio.morellini@enp.org
authors.forename: Fabio
authors.initials: F
authors.lastname: Morellini
authors.forename: Elena
authors.initials: E
authors.lastname: Sivukhina
authors.forename: Luminita
authors.initials: L
authors.lastname: Stoenica
authors.forename: Elena
authors.initials: E
authors.lastname: Oulianova
authors.forename: Olena
authors.initials: O
authors.lastname: Bukalo
authors.forename: Igor
authors.initials: I
authors.lastname: Jakovcevski
authors.forename: Alexander
authors.initials: A
authors.lastname: Dityatev
authors.forename: Andrey
authors.initials: A
authors.lastname: Irintchev
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D003071:Cognition / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000502:physiology; D019063:Tenascin / Q000172:deficiency* / Q000235:genetics*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
chemical_list: D019063:Tenascin; C074638:tenascin R; D005680:gamma-Aminobutyric Acid