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
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
DOI: 10.1007/s00429-018-1692-3
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