LAMP5 Fine-Tunes GABAergic Synaptic Transmission in Defined Circuits of the Mouse Brain

PLoS One. 2016 Jun 7;11(6):e0157052. doi: 10.1371/journal.pone.0157052. eCollection 2016.

Abstract

LAMP5 is member of the LAMP family of membrane proteins. In contrast to the canonical members of this protein family, LAMP1 and LAMP2, which show widespread expression in many tissues, LAMP 5 is brain specific in mice. In C. elegans, the LAMP5 ortholog UNC-46 has been suggested to act a trafficking chaperone, essential for the correct targeting of the nematode vesicular GABA-transporter UNC-47. We show here that in the mouse brain LAMP5 is expressed in subpopulations of GABAergic forebrain neurons in the striato-nigral system and the olfactory bulb. The protein was present at synaptic terminals, overlapping with the mammalian vesicular GABA-transporter VGAT. In LAMP5-deficient mice localization of the transporter was unaffected arguing against a conserved role in VGAT trafficking. Electrophysiological analyses in mutants showed alterations in short term synaptic plasticity suggesting that LAMP5 is involved in controlling the dynamics of evoked GABAergic transmission. At the behavioral level, LAMP5 mutant mice showed decreased anxiety and deficits in olfactory discrimination. Altogether, this work implicates LAMP5 function in GABAergic neurotransmission in defined neuronal subpopulations.

MeSH terms

  • Animals
  • Corpus Striatum / metabolism
  • GABAergic Neurons / metabolism*
  • Lysosome-Associated Membrane Glycoproteins / genetics*
  • Lysosome-Associated Membrane Glycoproteins / metabolism*
  • Male
  • Mice
  • Olfactory Bulb / metabolism
  • Presynaptic Terminals / metabolism*
  • Substantia Nigra / metabolism
  • Synaptic Transmission
  • Vesicular Inhibitory Amino Acid Transport Proteins / metabolism*

Substances

  • LAMP5 protein, mouse
  • Lysosome-Associated Membrane Glycoproteins
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Viaat protein, mouse

Grant support

HC and PP received funding from Agence National pour la Recherche (ANR BadLampLayers), and EG from ARC Subvention libre « BAD-LAMP function in multiple myeloma » and A*MIDEX project ANR-11-IDEX-0001-02 funded by the "Investissements d'Avenir" French government program.