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GABAergic synaptogenesis marks the onset of differentiation of basket and stellate cells in mouse cerebellum
Author(s) -
Simat Marija,
Ambrosetti Lisa,
LardiStudler Barbara,
Fritschy JeanMarc
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05846.x
Subject(s) - gabaergic , synaptogenesis , microbiology and biotechnology , interneuron , biology , granule cell , cerebellum , golgi apparatus , hepatic stellate cell , glycine receptor , parvalbumin , neuroscience , inhibitory postsynaptic potential , biochemistry , dentate gyrus , endocrinology , central nervous system , glycine , amino acid , endoplasmic reticulum
Type 2 glycine transporter (GlyT2) mediates intracellular glycine transport and is expressed selectively in glycinergic neurons. Expression of GlyT2 gene promoter‐driven enhanced green fluorescent protein (eGFP) in BAC transgenic mice allows selective visualization of glycinergic neurons by fluorescence microscopy. Here, we show that cerebellar interneuron precursors identified by the transcription factor Pax2, including γ‐aminobutyric acid (GABA)ergic interneurons of the molecular layer (ML; basket and stellate cells), transiently express GlyT2‐eGFP during development. In contrast, expression of endogenous GlyT2 is restricted to glycinergic Golgi cells. Comparison with knock‐in mice expressing eGFP in GABAergic neurons [glutamic acid decarboxylase (GAD)67‐eGFP] revealed that GlyT2‐eGFP expression often precedes GAD67‐eGFP and is therefore a marker of immature GABAergic interneurons. In the internal granule cell layer, GABAergic Golgi cells differentiated shortly after birth, prior to glycinergic Golgi cells. In the ML, GlyT2‐eGFP‐positive precursor cells migrated until the boundary with the external granule cell layer, forming an inside‐out maturation gradient that determined the final position of interneurons in the ML. After migration, GlyT2‐eGFP gradually disappeared, while interneurons differentiated morphologically and became immunoreactive for parvalbumin, the GABA A receptor α1 subunit, and the K + Cl – exchanger KCC2 (K + Cl – cotransporter type 2). Numerous presumptive GABAergic synaptic terminals were seen on immature ML interneurons as early as P4, preceding the expression of these neurochemical markers. These results suggest that GABAergic synaptogenesis marks the onset of differentiation of basket and stellate cells in the mouse cerebellum, and that GABAergic synaptic function might contribute to the differentiation of interneurons in the cerebellar cortex.