AUTHOR=Dieni Sandra , Nestel Sigrun , Sibbe Mirjam , Frotscher Michael , Hellwig Sabine TITLE=Distinct synaptic and neurochemical changes to the granule cell-CA3 projection in Bassoon mutant mice JOURNAL=Frontiers in Synaptic Neuroscience VOLUME=7 YEAR=2015 URL=https://www.frontiersin.org/journals/synaptic-neuroscience/articles/10.3389/fnsyn.2015.00018 DOI=10.3389/fnsyn.2015.00018 ISSN=1663-3563 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.