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GABAergic synaptogenesis marks the onset of differentiation of basket and stellate cells in mouse cerebellum.
Eur J Neurosci 2007; 26(8):2239-56EJ

Abstract

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 gamma-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 alpha1 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.

Authors+Show Affiliations

Institute of Pharmacology and Toxicology, University of Zurich, CH-8057 Zurich, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17892480

Citation

Simat, Marija, et al. "GABAergic Synaptogenesis Marks the Onset of Differentiation of Basket and Stellate Cells in Mouse Cerebellum." The European Journal of Neuroscience, vol. 26, no. 8, 2007, pp. 2239-56.
Simat M, Ambrosetti L, Lardi-Studler B, et al. GABAergic synaptogenesis marks the onset of differentiation of basket and stellate cells in mouse cerebellum. Eur J Neurosci. 2007;26(8):2239-56.
Simat, M., Ambrosetti, L., Lardi-Studler, B., & Fritschy, J. M. (2007). GABAergic synaptogenesis marks the onset of differentiation of basket and stellate cells in mouse cerebellum. The European Journal of Neuroscience, 26(8), pp. 2239-56.
Simat M, et al. GABAergic Synaptogenesis Marks the Onset of Differentiation of Basket and Stellate Cells in Mouse Cerebellum. Eur J Neurosci. 2007;26(8):2239-56. PubMed PMID: 17892480.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GABAergic synaptogenesis marks the onset of differentiation of basket and stellate cells in mouse cerebellum. AU - Simat,Marija, AU - Ambrosetti,Lisa, AU - Lardi-Studler,Barbara, AU - Fritschy,Jean-Marc, Y1 - 2007/09/24/ PY - 2007/9/26/pubmed PY - 2008/2/2/medline PY - 2007/9/26/entrez SP - 2239 EP - 56 JF - The European journal of neuroscience JO - Eur. J. Neurosci. VL - 26 IS - 8 N2 - 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 gamma-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 alpha1 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. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/17892480/GABAergic_synaptogenesis_marks_the_onset_of_differentiation_of_basket_and_stellate_cells_in_mouse_cerebellum_ L2 - https://doi.org/10.1111/j.1460-9568.2007.05846.x DB - PRIME DP - Unbound Medicine ER -