Postsynaptic Mechanisms Underlying Long-Term Depression of GABAergic
Transmission in Neurons of the Deep Cerebellar Nuclei.
Morishita, W. and B. R. Sastry.
Neuroscience Research Laboratory, Department of Pharmacology and
Therapeutics, The University of British Columbia, 2176 Health Sciences Mall,
Vancouver, Canada, V6T 1Z3.
APStracts 3:0018N, 1996.
SUMMARY AND CONCLUSIONS
1. The mechanisms underlying long-term depression (LTD) of GABA A receptor-
mediated synaptic transmission induced by 10 Hz stimulation of the inhibitory
afferents were investigated using perforated and whole-cell voltage-clamp
recordings from neurons of the deep cerebellar nuclei (DCN). 2. LTD of
inhibitory postsynaptic currents (IPSCs) was reliably induced when the 10 Hz
stimulation was delivered under current-clamp conditions where the
postsynaptic neuronal membrane was allowed to depolarize. 3. Currents elicited
by local applications of the GABA A receptor agonist, 4,5,6,7-
tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride (THIP) were also
depressed during LTD. 4. LTD could be induced heterosynaptically and did not
require the activation of GABA A receptors during the 10 Hz stimulation. 5. In
cells loaded with QX-314 and superfused with media containing 6-cyano-7-
nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonovaleric acid (APV), a
series of depolarizing pulses (50 mV, 200 ms) induced a sustained depression
of the IPSC. However, this was not observed in cells recorded with high BAPTA-
containing pipette solutions or when they were exposed to the L-type Ca 2+
channel antagonist, nitrendipine. 6. The 10 Hz-induced LTD was also inhibited
by BAPTA and was significantly reduced when DCN cells were loaded with
microcystin LR or treated with okadaic acid, both inhibitors of protein
phosphatases. 7. These results indicate that increases in postsynaptic [Ca 2+
] and phosphatase activity can reduce the efficacy of GABA A receptor-mediated
Received 14 November 1995; accepted in final form 2 January 1996.
APS Manuscript Number J768-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96