Segregated expression of AMPA-type glutamate receptors and glutamate transporters defines distinct astrocyte populations in the mouse hippocampus.
Recent data have suggested the existence of direct signaling pathways between glial cells and neurons. Here we report the coexistence of distinct types of cells expressing astrocyte-specific markers within the hippocampus that display diverse morphological, molecular, and functional profiles. Usage of transgenic mice with GFAP promoter-controlled enhanced green fluorescent protein (EGFP) expression allowed the identification of astroglial cells after fresh isolation or in brain slices. Combining patch-clamp recordings and single-cell reverse transcription-PCR, we distinguished two morphologically distinct types of EGFP-positive cells, one expressing glutamate transporters and the other expressing ionotropic glutamate receptors. None of the EGFP-positive cells coexpressed glutamate receptors and transporters. Subpopulations of glutamate receptor-bearing EGFP-positive cells expressed AN2, the mouse homolog of the rat NG2 proteoglycan or transcripts for excitatory amino acid carrier 1, a neuronal glutamate transporter. Our data demonstrate the presence of distinct, independent populations of cells with astroglial properties in the developing hippocampus that can differently modulate neuronal signaling pathways. The observed heterogeneity of cells with GFAP promoter-regulated EGFP expression and S100beta/GFAP immunoreactivity challenges the hitherto accepted definition of astrocytes.
Matthias
Katja
K
Experimental Neurobiology, Department of Neurosurgery, University of Bonn, 53105 Bonn, Germany.
Kirchhoff
Frank
F
Seifert
Gerald
G
Hüttmann
Kerstin
K
Matyash
Marina
M
Kettenmann
Helmut
H
Steinhäuser
Christian
C
D027322:Amino Acid Transport System X-AG / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D000941:Antigens / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D027341:Excitatory Amino Acid Transporter 1 / Q000096:biosynthesis / Q000235:genetics; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D050491:Glutamate Plasma Membrane Transport Proteins; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D011401:Promoter Regions, Genetic; D011509:Proteoglycans / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D018091:Receptors, AMPA / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics; D000099216:Chondroitin Sulfate Proteoglycan 4
D027322:Amino Acid Transport System X-AG; D000941:Antigens; D000943:Antigens, Differentiation; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D005904:Glial Fibrillary Acidic Protein; D050491:Glutamate Plasma Membrane Transport Proteins; D008164:Luminescent Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D018091:Receptors, AMPA; D027981:Symporters; D000099216:Chondroitin Sulfate Proteoglycan 4