Ablation of the presynaptic organizer Bassoon in excitatory neurons retards dentate gyrus maturation and enhances learning performance
| Autor: | Eckart D. Gundelfinger, Wolfgang Tischmeyer, Sabrina Müller, Frank Angenstein, Eike Budinger, Anna Fejtova, Dirk Montag, Gürsel Çalışkan, Anil Annamneedi, Oliver Stork |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Knockout mice Bassoon Immature DG Contextual fear memory Neurogenesis Spatial memory physiology [Spatial Memory] physiology [Hippocampus] Hippocampus Synaptic Transmission Mice 0302 clinical medicine physiology [Dentate Gyrus] diagnostic imaging [Cerebral Cortex] physiology [Neuronal Plasticity] Cerebral Cortex Neurons diagnostic imaging [Hippocampus] Mice Knockout Neuronal Plasticity General Neuroscience Fear physiology [Neurogenesis] Magnetic Resonance Imaging medicine.anatomical_structure metabolism [Neurons] metabolism [Presynaptic Terminals] Excitatory postsynaptic potential Original Article physiology [Nerve Tissue Proteins] Anatomy Presynaptic active zone Behavioral Research pathology [Dentate Gyrus] Histology Presynaptic Terminals Nerve Tissue Proteins Biology Neurotransmission Inhibitory postsynaptic potential Bsn protein mouse Statistics Nonparametric 03 medical and health sciences Glutamatergic medicine Animals ddc:610 Dentate gyrus metabolism [Synapses] Perforant path 030104 developmental biology methods [Behavioral Research] physiology [Synaptic Transmission] Dentate Gyrus Synapses Neuroscience 030217 neurology & neurosurgery physiology [Fear] |
| Zdroj: | Brain structure & function 223(7), 3423-3445 (2018). doi:10.1007/s00429-018-1692-3 Brain Structure & Function Brain structure & function, 223(7):3423-3445 |
| Popis: | Bassoon is a large scaffolding protein of the presynaptic active zone involved in the development of presynaptic terminals and in the regulation of neurotransmitter release at both excitatory and inhibitory brain synapses. Mice with constitutive ablation of the Bassoon (Bsn) gene display impaired presynaptic function, show sensory deficits and develop severe seizures. To specifically study the role of Bassoon at excitatory forebrain synapses and its relevance for control of behavior, we generated conditional knockout (Bsn cKO) mice by gene ablation through an Emx1 promoter-driven Cre recombinase. In these animals, we confirm selective loss of Bassoon from glutamatergic neurons of the forebrain. Behavioral assessment revealed that, in comparison to wild-type littermates, Bsn cKO mice display selectively enhanced contextual fear memory and increased novelty preference in a spatial discrimination/pattern separation task. These changes are accompanied by an augmentation of baseline synaptic transmission at medial perforant path to dentate gyrus (DG) synapses, as indicated by increased ratios of field excitatory postsynaptic potential slope to fiber volley amplitude. At the structural level, an increased complexity of apical dendrites of DG granule cells can be detected in Bsn cKO mice. In addition, alterations in the expression of cellular maturation markers and a lack of age-dependent decrease in excitability between juvenile and adult Bsn cKO mice are observed. Our data suggest that expression of Bassoon in excitatory forebrain neurons is required for the normal maturation of the DG and important for spatial and contextual memory. Electronic supplementary material The online version of this article (10.1007/s00429-018-1692-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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