title: Developmental changes of GABA synaptic transient in cerebellar granule cells.
abstract: The time course of synaptic currents is largely determined by the microscopic gating of the postsynaptic receptors and the temporal profile of the synaptic neurotransmitter concentration. Although several lines of evidence indicate that developmental changes of GABAergic synaptic current time course are clearly correlated with a switch in postsynaptic receptors, much less is known about the modification of GABA release during development. To address this issue, we studied the sensitivity of miniature inhibitory postsynaptic currents (mIPSCs) to a quickly dissociating competitive antagonist, 1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid (TPMPA), in neurons cultured for 6 to 8 days in vitro (DIV) ("young") and for 12 to 14 DIV ("old"). mIPSCs recorded in young neurons were significantly more resistant to the block by TPMPA. This observation was interpreted as a consequence of a more efficient displacement of TPMPA from GABA(A) receptors caused by a stronger GABA release in young neurons. The change in mIPSC sensitivity to TPMPA during development was not affected by the deletion of alpha(1) subunit, supporting its presynaptic origin. The effects of a second quickly dissociating antagonist, SR-95103 [2-(carboxy-3'-propyl)-3-amino-4-methyl-6-phenylpyridazinium chloride], on young, old, and alpha(1) -/- neurons were qualitatively the same as those obtained with TPMPA. Moreover, the analysis of current responses to ultrafast GABA applications showed that the unbinding rates of TPMPA in DIV 6 to 8 and in DIV 12 to 14 neurons are not significantly different, ruling out the postsynaptic mechanism of differential TPMPA action. Thus, we provide evidence that presynaptic GABA uniquantal release is developmentally regulated.
authors.affiliation: Department of Physiology and Biophysics, Georgetown University School of Medicine, 225 Basic Research Bldg. 3900 Reservoir Road NW, Washington, DC 20007, USA. barberis@sissa.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Barberis
authors.forename: Congyi
authors.initials: C
authors.lastname: Lu
authors.forename: Stefano
authors.initials: S
authors.lastname: Vicini
authors.forename: Jerzy W
authors.initials: JW
authors.lastname: Mozrzymas
mesh_terms: D000367:Age Factors; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010721:Phosphinic Acids / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C101879:(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid; D010721:Phosphinic Acids; D011725:Pyridines; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid