Suppression of the glutamate receptor [delta] 2 subunit produces a specific
impairment in cerebellar long-term depression.
Jeromin, Andreas, Richard L. Huganir and David J. Linden.
Howard Hughes Medical Institute, Department of Neuroscience, Johns Hopkins
University School of Medicine, 725 North Wolfe Street, Baltimore, MD
APStracts 3:0165N, 1996.
SUMMARY AND CONCLUSIONS
1. The role of the glutamate receptor subunit d2 in the induction of
cerebellar long-term depression (LTD) was investigated by application of
antisense oligonucleotides. The d2 subunit is selectively localized to
Purkinje cells (PCs), with the highest levels being in the PC dendritic
spines, where parallel fibers are received and where cerebellar LTD is
expressed. 2. Immunocytochemical analysis of calbindin-positive Purkinje cells
revealed that both the dendritic and somatic expression of [delta] 2 was
reduced in antisense but not in sense treated cultures. An antisense
oligonucleotide directed against the related subunit [delta] 1 did not affect
the expression of [delta] 2 in Purkinje cells. 3. Cerebellar LTD may be
reliably induced in a preparation of cultured embryonic cerebellar neurons
from the mouse when parallel and climbing fiber stimulation are replaced by
brief glutamate pulses and strong, direct depolarization of the PC,
respectively. Application of an antisense oligonucleotide directed against d2
completely blocked the induction of LTD produced by glutamate/depolarization
conjunctive stimulation. A [delta] 2 sense oligonucleotide or an antisense
oligonucleotide directed against the related [delta] 1 subunit had no effect.
4. The effect of the [delta] 2 antisense oligonucleotide was not related to
attenuation of Ca influx via voltage-gated channels or Ca mobilization via
metabotropic glutamate receptors, as assessed with fura-2 microfluorimetry.
Current flow through AMPA receptor-associated ion channels also appeared
unaltered. All three of these processes have previously been shown to be
required for cerebellar LTD induction. These observations, that [delta] 2 is
involved in a metabotropic-glutamate receptor-independent signaling pathway
which is required for LTD induction, supports the view that d2 participates in
the formation of a novel postsynaptic receptor complex.
Received 11 July 1996; accepted in final form 2 August 1996.
APS Manuscript Number J544-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996