Development of "Pinceaux" formations and dendritic translocation of climbing fibers during the acquisition of the balance between glutamatergic and gamma-aminobutyric acidergic inputs in developing Purkinje cells.
The acquisition of the dynamic balance between excitation and inhibition in developing Purkinje cells, necessary for their proper function, is analyzed. Newborn (P0) mouse cerebellum contains glutamatergic (VGLUT2-IR) and gamma-aminobutyric acid (GABA)-ergic (VIAAT-IR) axons. The former prevail and belong to climbing fibers, whereas the latter neither colabel with calbindin-expressing fibers nor belong to axons of the cortical GABAergic interneurons. During the first postnatal week, VIAAT-IR axons in the Purkinje cell neighborhood remains very low, and the first synapses with basket fibers are formed at P7, when climbing fibers have already established dense pericellular nets. The descending basket fibers reach the Purkinje cell axon initial segment by P9, immediately establishing axoaxonic synapses. The pinceaux appear as primitive vortex-like arrangements by P12, and by P20 interbasket fiber septate-like junctions, typical of fully mature pinceaux, are still missing. The climbing fiber's somatodendritic translocation occurs later than expected, after the regression of the multiple innervation, and follows the ascending collaterals of the basket axons, which are apparently the optimal substrate for the proper subcellular targeting of the climbing fibers. These results emphasize that chemical transmission in the axon initial segment precedes the electrical inhibition generated by field effects. In addition, GABAergic Purkinje cells, as opposed to glutamatergic projection neurons in other cortical structures, do not begin to receive their excitation to inhibition balance until the end of the first postnatal week, despite the early presence of potentially functional GABAergic axons that possess the required vesicular transport system.
Sotelo
Constantino
C
Cátedra de Neurobiología del Desarrollo "Remedios Caro Almela," Instituto de Neurociencias de Alicante, Universidad Miguel Hernández y CSIC, Sant Joan d'Alacant, 03550 Alicante, Spain. sotelo@umh.es
D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009412:Nerve Fibers / Q000502:physiology* / Q000648:ultrastructure; D051762:PAX2 Transcription Factor / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D011247:Pregnancy; D011689:Purkinje Cells / Q000166:cytology* / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D051762:PAX2 Transcription Factor; D010320:Parvalbumins; C497319:Pax2 protein, mouse; C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2