A New Player in the Hippocampus: A Review on VGLUT3+ Neurons and Their Role in the Regulation of Hippocampal Activity and Behaviour

Int J Mol Sci. 2022 Jan 12;23(2):790. doi: 10.3390/ijms23020790.

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.

Keywords: cardiovascular regulation; emotions; hippocampus; learning and memory; sensory processes; stress; vesicular glutamate transporter.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Electrophysiological Phenomena
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Glutamic Acid / metabolism*
  • Hippocampus / physiology*
  • Humans
  • Mice
  • Mice, Knockout
  • Neurotransmitter Agents / metabolism
  • Pyramidal Cells / metabolism*
  • Signal Transduction
  • Synaptic Transmission
  • Vesicular Glutamate Transport Proteins / genetics*
  • Vesicular Glutamate Transport Proteins / metabolism*

Substances

  • Biomarkers
  • Neurotransmitter Agents
  • SLC17A8 protein, human
  • Vesicular Glutamate Transport Proteins
  • Glutamic Acid