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First published on January 5, 2005; DOI: 10.1124/mol.104.006437

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Received for publication August 20, 2004.
Revised January 5, 2005.
Accepted for publication January 5, 2005.

Developmental Changes of GABA Synaptic Transient in Cerebellar Granule Cells

Andrea Barberis 1*, Congyi Lu 1, Stefano Vicini 2, Jerzy W Mozrzymas 1

1 Dept Physiology Georgetown University 2 Dept PhysiologyGeorgetown University

* Address correspondence to: E-mail: barberis{at}sissa.it

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. While several lines of evidence indicate that developmental changes of GABAergic synaptic currents 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 mIPSCs to a quickly dissociating competitive antagonist, TPMPA, in neurons cultured for 6-8 days in vitro 6-8, young and for 12-14 days in vitro, 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 GABAA receptors due to a stronger GABA release in young neurons. The change of mIPSCs 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, 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 days in vitro 6-8 and in days in vitro 12-14 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.


Key words: GABAA, GABAC, Single channel kinetics, Synaptic plasticity


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