Abstract

Glutamate is the most abundant excitatory amino acid in the central nervous system. Neurons using glutamate as a neurotransmitter can be characterised by vesicular glutamate transporters (VGLUTs). Among the three subtypes, VGLUT3 is unique, co-localising with other “classical” neurotransmitters, such as the inhibitory GABA. Glutamate, manipulated by VGLUT3, can modulate the packaging as well as the release of other neurotransmitters and serve as a retrograde signal through its release from the somata and dendrites. Its contribution to sensory processes (including seeing, hearing, and mechanosensation) is well characterised. However, its involvement in learning and memory can only be assumed based on its prominent hippocampal presence. Although VGLUT3-expressing neurons are detectable in the hippocampus, most of the hippocampal VGLUT3 positivity can be found on nerve terminals, presumably coming from the median raphe. This hippocampal glutamatergic network plays a pivotal role in several important processes (e.g., learning and memory, emotions, epilepsy, cardiovascular regulation). Indirect information from anatomical studies and KO mice strains suggests the contribution of local VGLUT3-positive hippocampal neurons as well as afferentations in these events. However, further studies making use of more specific tools (e.g., Cre-mice, opto- and chemogenetics) are needed to confirm these assumptions.

Highlights

  • Introduction published maps and institutional affilIn the central nervous system (CNS), neurons are classified based on the neurotransmitters they express

  • VGLUT1 and 2 seem to be utmost important as their lack is fatal: VGLUT1 KO mice die around weaning, while VGLUT2 KO mice die at birth [96,97,98,99]

  • We found no ectopic expression. (C,D) Double immunofluorescent positive whole median raphe (MR). (B) Example of a proper Cre system functioning: VGLUT3+ neurons were able to neurons in the MR

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Summary

Gulyaeva

Even today, it is still regarded such that neurons have one main “classical” neurotransmitter type (e.g., excitatory glutamate (Glu) or inhibitory gamma aminobutyric acid (GABA)) and express numerous other secondary ones, mainly peptides. As these “classical” neurotransmitters are small molecules, they are often intermediates of the metabolism and detectable in all cells. In the second state, the transporter lets go of the Glu− and K+ inside and instead gains high affinity to Cl− and H+ , which are transported to the cytosol to restart the cycle These glutamatergic synaptic vesicles are diverse, forming one of the building blocks of neuronal heterogeneity [7].

Anatomical Distribution of VGLUT3 in the Central Nervous System
Electrophysiological Characteristics of VGLUT3
Implications of VGLUT3 in Physiology
Characteristics of the VGLUT3 KO Mice
The Hippocampus
Hippocampal
Role of the Hippocampal VGLUT3 Positivity
Findings
Conclusions
Full Text
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