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

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.

Parental warmth interacts with several genes to affect executive function components: a genome-wide environment interaction study

“…We found that LAMP5, SLC4A7, and LRRK1 interacted with PW to affect updating. LAMP5 is extensively expressed in mouse brain, can alter short term synaptic plasticity, and is involved in GABAergic transmission [32]. This is consistent with the facts that dynamic synaptic plasticity is vital for working memory (i.e., updating) [33] and that GABAergic interneurons in the prefrontal cortex are involved in EF [2].…”

Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3Cre mouse

“…Sst , Kif26b , Mab21l2 , and Lamp5 mRNAs are also highly enriched and expressed in C‐neurons (Figure h). Sst encodes the hormone Somatostatin (Patel, ); Kif26b encodes a kinesin that regulates cell polarity (Guillabert‐Gourgues et al, ; Marikawa, Fujita, & Alarcon, ); Mab21l2 encodes a nuclear protein that interacts with the BMP4 signaling pathway and has been implicated in neural tube formation and eye morphogenesis (Baldessari, Badaloni, Longhi, Zappavigna, & Consalez, ; Huang, ); Lamp5 encodes a lysosome‐associated membrane protein implicated in GABAergic neurotransmission (Tiveron et al, ). In situ hybridization for these mRNAs in brachial spinal cord transverse sections from E11.5 Robo3 Cre/+ ; ROSA26 LSL‐tdTomato/+ embryos confirmed expression in various subgroups of C‐neurons and revealed additional sites of expression (Figure a–h).…”

Neuronal integration in the adult olfactory bulb is a non-selective addition process

“…Stainings were done on 50 µm floating vibratome sections as described before (Tiveron et al, 2016). Primary antibodies: GFP (rabbit IgG, Life technologies,1 1:1000 or chicken Ig, AVES, 1:1000), Calretinin (mouse IgG1, Synaptic Systems; 1:2000), Tyrosine Hydroxylase (chicken Ig, AVES; 1:1000), IBA1 (life technologies, 1:500), GFAP (life technologies, 1:500), cleaved-caspase3 (Cell Signalling Technology: #9662, 1:500).…”