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The Journal of Neurophysiology Vol. 86 No. 1 July 2001, pp. 492-502
Copyright ©2001 by the American Physiological Society
1Department of Physiology and Center for Neuroscience, University of Wisconsin Medical School, Madison, Wisconsin 53706; and 2Institute of Neuroinformatics, University of Zürich and Federal Institute of Technology, CH-8057 Zurich, Switzerland
Gao, Bao-Xi,
Christian Stricker, and
Lea Ziskind-Conhaim.
Transition From GABAergic to Glycinergic Synaptic
Transmission in Newly Formed Spinal Networks. J. Neurophysiol. 86: 492-502, 2001. The role of glycinergic and
GABAergic systems in mediating spontaneous synaptic transmission in
newly formed neural networks was examined in motoneurons in the
developing rat spinal cord. Properties of action potential-independent
miniature inhibitory postsynaptic currents (mIPSCs) mediated by glycine
and GABAA receptors (GlyR and
GABAAR) were studied in spinal cord slices of 17- to 18-day-old embryos (E17-18) and 1- to 3-day-old
postnatal rats (P1-3). mIPSC frequency and amplitude
significantly increased after birth, while their decay time decreased.
To determine the contribution of glycinergic and GABAergic synapses to
those changes, GlyR- and GABAAR-mediated mIPSCs
were isolated based on their pharmacological properties. Two
populations of pharmacologically distinct mIPSCs were recorded in the
presence of glycine or GABAA receptors
antagonists: bicuculline-resistant, fast-decaying GlyR-mediated mIPSCs,
and strychnine-resistant, slow-decaying
GABAAR-mediated mIPSCs. The frequency of
GABAAR-mediated mIPSCs was fourfold higher than
that of GlyR-mediated mIPSCs at E17-18, indicating that
GABAergic synaptic sites were functionally dominant at early stages of
neural network formation. Properties of
GABAAR-mediated mIPSC amplitude fluctuations
changed from primarily unimodal skewed distribution at
E17-18 to Gaussian mixtures with two to three discrete
components at P1-3. A developmental shift from primarily
long-duration GABAergic mIPSCs to short-duration glycinergic mIPSCs was
evident after birth, when the frequency of GlyR-mediated mIPSCs
increased 10-fold. This finding suggested that either the number of
glycinergic synapses or the probability of vesicular glycine release
increased during the period studied. The increased frequency of
GlyR-mediated mIPSCs was associated with more than a twofold increase
in their mean amplitude, and in the number of motoneurons in which
mIPSC amplitude fluctuations were best fitted by multi-component
Gaussian curves. A third subpopulation of mIPSCs was apparent in the
absence of glycine and GABAA receptor
antagonists: mIPSCs with both fast and slow decaying components. Based
on their dual-component decay time and their suppression by either
strychnine or bicuculline, we assumed that these were generated by the
activation of co-localized postsynaptic glycine and
GABAA receptors. The contribution of mixed
glycine-GABA synaptic sites to the generation of mIPSCs did not change
after birth. The developmental switch from predominantly long-duration
GABAergic inhibitory synaptic currents to short-duration glycinergic
currents might serve as a mechanism regulating neuronal excitation in
the developing spinal networks.
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