The Journal of Neuroscience, December 15, 2002, 22(24):10948-10957
Depression of Fast Excitatory Synaptic Transmission in Large
Aspiny Neurons of the Neostriatum after Transient Forebrain
Ischemia
Zhi-Ping
Pang,
Ping
Deng,
Yi-Wen
Ruan, and
Zao C.
Xu
Department of Anatomy and Cell Biology, Indiana University School
of Medicine, Indianapolis, Indiana 46202
Spiny neurons in the neostriatum die within 24 hr after transient
global ischemia, whereas large aspiny (LA) neurons remain intact. To
reveal the mechanisms of such selective cell death after ischemia,
excitatory neurotransmission was studied in LA neurons before and after
ischemia. The intrastriatally evoked fast EPSCs in LA neurons were
depressed
24 hr after ischemia. The concentration-response curves
generated by application of exogenous glutamate in these neurons were
approximately the same before and after ischemia. A train of five
stimuli (100 Hz) induced progressively smaller EPSCs, but the
proportion of decrease in EPSC amplitude at 4 hr after ischemia was
significantly smaller compared with control and at 24 hr after
ischemia. Parallel depression of NMDA receptor and AMPA
receptor-mediated EPSCs was also observed after ischemia, supporting
the involvement of presynaptic mechanisms. The adenosine A1 receptor
antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked the inhibition of
evoked EPSCs at 4 hr after ischemia but not at 24 hr after ischemia.
Electron microscopic studies demonstrated that the most presynaptic
terminals in the striatum had a normal appearance at 4 hr after
ischemia but showed degenerating signs at 24 hr after ischemia. These
results indicated that the excitatory neurotransmission in LA neurons
was depressed after ischemia via presynaptic mechanisms. The depression
of EPSCs shortly after ischemia might be attributable to the
enhanced adenosine A1 receptor function on synaptic transmission, and
the depression at late time points might result from the degeneration
of presynaptic terminals.
Key words:
ischemia; excitotoxicity; AMPA; neuronal death; striatum; interneurons; excitatory synaptic transmission
Copyright © 2002 Society for Neuroscience 0270-6474/02/222410948-10$05.00/0