Abstract

The protein tomosyn decreases synaptic transmission and release probability of vesicles, and is essential for modulating synaptic transmission in neurons. In this study, we provide a detailed description of the expression and localization patterns of tomosyn1 and tomosyn2 in the subareas of the mouse hippocampus. Using confocal and two-photon high-resolution microscopy we demonstrate that tomosyn colocalizes with several pre- and postsynaptic markers and is found mainly in glutamatergic synapses. Specifically, we show that tomosyn1 is differentially distributed in the mouse hippocampus and concentrated mainly in the hilus and mossy fibers. Surprisingly, we found that tomosyn2 is expressed in the subiculum, CA1 and CA2 pyramidal cell bodies, dendrites and spines, and colocalizes with PSD95, suggesting a postsynaptic role. These results suggest that in addition to the well-characterized presynaptic function of tomosyn in neurotransmitter release, tomosyn2 might have a postsynaptic function, and place tomosyn as a more general regulator of synaptic transmission and plasticity.

Highlights

  • The mouse hippocampus has been well characterized and is commonly divided into the following major areas: CA1, CA2, CA3, dentate gyrus, and hilus

  • A previous report examining the expression pattern of tomosyn1 and tomosyn2 mRNA in the mouse central nervous system showed non-homogenous distribution of tomosyn isoforms in the cell bodies in the hippocampus (Groffen et al, 2005)

  • Using confocal and two-photon high-resolution microscopy, we show that tomosyn is differentially distributed in the mouse hippocampus, with its main concentration in the hilus, mossy fibers, pyramidal cells of CA1, and, with a markedly high cytoplasmic concentration in the pyramidal cells of CA2

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Summary

Introduction

The mouse hippocampus has been well characterized and is commonly divided into the following major areas: CA1, CA2, CA3, dentate gyrus, and hilus. Synaptic transmission involves several steps, starting with neurotransmitter uptake to the synaptic vesicle, docking of the vesicle to the plasma membrane at active zones, priming of the vesicle [a process believed to represent formation of SNARE (soluble N-ethylamide-sensitive factor attachment protein receptor) protein complexes, which renders the vesicle fusion competent], and calcium-dependent fusion of the vesicle, leading to neurotransmitter release to the synaptic cleft (Richmond and Broadie, 2002; Sudhof, 2004; Becherer and Rettig, 2006; Rizo and Rosenmund, 2008; Verhage and Sorensen, 2008) This exocytotic process is followed by recycling of the vesicle through endocytotic pathways. As every subarea in the hippocampus has its own role and connectivity (e.g., place cells in CA1; Amaral and Witter, 1989), it is of interest to characterize the expression of a key modulator protein such as tomosyn in the subareas of this essential structure

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