Hilar Mossy Cell Degeneration Causes Transient Dentate Granule Cell Hyperexcitability and Impaired Pattern Separation

By S. Jinde, V. Zsiros, Zhihong Jiang, Kazuhito Nakao, J. Pickel, K. Kohno, J. Belforte, K. Nakazawa. 2012

190 citations recorded by the source corpus.

Summary Although excitatory mossy cells of the hippocampal hilar region are known to project both to dentate granule cells and to interneurons, it is as yet unclear whether mossy cell activity’s net effect on granule cells is excitatory or inhibitory. To explore their influence on dentate excitability and hippocampal function, we generated a conditional transgenic mouse line, using the Cre/loxP system, in which diphtheria toxin receptor was selectively expressed in mossy cells. One week after injecting toxin into this line, mossy cells throughout the longitudinal axis were degenerated extensively, theta wave power of dentate local field potentials increased during exploration, and deficits occurred in contextual discrimination. By contrast, we detected no epileptiform activity, spontaneous behavioral seizures, or mossy-fiber sprouting 5–6 weeks after mossy cell degeneration. These results indicate that the net effect of mossy cell excitation is to inhibit granule cell activity and enable dentate pattern separation.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Developmental Neuroscience

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Citations in the corpus

Re-evaluating circuit mechanisms underlying pattern separation (2019, neutral): “Mossy cell deletion studies have also found mixed effects on granule cell activity (Ratzliff et al., 2004; Jinde et al., 2012).”
Dendrites of dentate gyrus granule cells contribute to pattern separation by controlling sparsity (2016, methodology): “, 2015) and experimental studies (Nitz and McNaughton, 2004; Jinde et al., 2012) have proposed that inhibition controls GC activity which, in turn, mediates pattern separation (Myers and Scharfman, 2009, 2011; Ikrar et al.”
Pattern separation in the hippocampus through the eyes of computational modeling (2017, background): “Moreover, afferents from MCs to interneurons and consequently, their inhibitory net effect (Jinde et al., 2012), were not included in this first model.”
Physiological properties and behavioral correlates of hippocampal granule cells and mossy cells (2017, unknown): “How do mossy cells and granule cells interact to perform pattern separation across various contexts? The selective degeneration of mossy cells results in increased firing of granule cells and impaired contextual discrimination (Jinde et al., 2012).”
In vivo imaging of dentate gyrus mossy cells in behaving mice (2017, background): “Indeed, an active role for MCs in pattern separation and a disinhibitory influence of MCs on GCs are supported by previous experiments in which MC loss caused transient GC hyperexcitability and impaired contextual fear learning (Jinde et al., 2012).”
Spatial representations of granule cells and mossy cells of the dentate gyrus (2017, background): “, 2012; Henze and Buzsáki, 2007), and loss of mossy cells leads to deficits in context discrimination (Jinde et al., 2012).”