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 21205.
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