title: Distinct synaptic and neurochemical changes to the granule cell-CA3 projection in Bassoon mutant mice.
abstract: Proper synaptic function depends on a finely-tuned balance between events such as protein synthesis and structural organization. In particular, the functional loss of just one synaptic-related protein can have a profound impact on overall neuronal network function. To this end, we used a mutant mouse model harboring a mutated form of the presynaptic scaffolding protein Bassoon (Bsn), which is phenotypically characterized by: (i) spontaneous generalized epileptic seizure activity, representing a chronically-imbalanced neuronal network; and (ii) a dramatic increase in hippocampal brain-derived neurotrophic factor (BDNF) protein concentration, a key player in synaptic plasticity. Detailed morphological and neurochemical analyses revealed that the increased BDNF levels are associated with: (i) modified neuropeptide distribution; (ii) perturbed expression of selected markers of synaptic activation or plasticity; (iii) subtle changes to microglial structure; and (iv) morphological alterations to the mossy fiber (MF) synapse. These findings emphasize the important contribution of Bassoon protein to normal hippocampal function, and further characterize the Bsn-mutant as a useful model for studying the effects of chronic changes to network activity.
authors.affiliation: Neurochemistry Laboratory, Department of Molecular Psychiatry, University Hospital Freiburg Freiburg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Dieni
authors.affiliation: Department of Neuroanatomy, Institute of Anatomy and Cell Biology, University of Freiburg Freiburg, Germany.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Nestel
authors.affiliation: Department of Neuroanatomy, Institute of Anatomy and Cell Biology, University of Freiburg Freiburg, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Sibbe
authors.affiliation: Institute for Structural Neurobiology, Center for Molecular Neurobiology Hamburg Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Frotscher
authors.affiliation: Neurochemistry Laboratory, Department of Molecular Psychiatry, University Hospital Freiburg Freiburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hellwig
keywords: dense-core vesicle; hippocampal ultrastructure; microglia; mossy fiber bouton; synaptic plasticity