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Journal of Neuroscience, Vol 14, 2098-2105, Copyright © 1994 by Society for Neuroscience
Enhanced activation of NMDA receptor responses at the immature retinogeniculate synapse
AS Ramoa and DA McCormick
Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510.
The maturation of retinogeniculate excitatory transmission and
intrathalamic inhibition was studied in slices of the dorsal LGN obtained
from ferrets during the first 2 postnatal months. Response to optic tract
stimulation at neonatal ages consisted of slow EPSPs lasting several
hundred milliseconds. Application of the NMDA receptor antagonist
D-(-)-2-amino-5-phosphonovaleric acid (D-APV) during the first 2 postnatal
weeks resulted in EPSPs that were reduced in peak amplitude and
dramatically curtailed in duration, indicating that NMDA receptors
participate strongly in retinogeniculate transmission at the immature
synapse. Gradually, EPSPs became shorter in duration such that after the
second postnatal week, the retinogeniculate EPSPs were only a few
milliseconds in duration. At this late stage of development responses were
remarkably less affected by application of D-APV. These changes in
contribution of NMDA receptors to retinogeniculate transmission were found
to be due to the development of strong IPSPs, the result of gradual
maturation of activation of GABAergic inhibition. Indeed, application of
bicuculline methiodide to block GABAA receptor- mediated IPSPs strongly
enhanced the NMDA component of the EPSPs in more mature cells. The voltage
dependence and kinetics of NMDA-induced excitatory postsynaptic currents
(NMDA EPSCs) were characterized by voltage-clamp recordings after blocking
AMPA/kainate receptors with 6- cyano-7-nitroquinoxaline-2,3-dione and GABAA
receptors wit' bicuculline methiodide. The voltage dependence of the NMDA
EPSCs remained unaltered with age. During the first postnatal month the
kinetic properties of the NMDA EPSCs also remained unaltered, but a
reduction in EPSC duration was observed within the following weeks, well
after the critical period of anatomical reorganization.(ABSTRACT TRUNCATED
AT 250 WORDS)
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