Tp. Hicks et Ki. Ito, THE EFFECTS OF D-ALPHA-AMINOADIPIC ACID ON LONG-TERM POTENTIATION IN THE HIPPOCAMPUS OF THE RAT IN-VITRO, Neuroscience research, 24(2), 1996, pp. 139-150
Many studies on long-term potentiation (LTP) in hippocampal region CA1
focus on receptor-mediated events that are often presumed to be linke
d to postsynaptic processes. Whereas it is now well-known that LTP con
sists of multiple components involving increases in postsynaptic respo
nsiveness as well as enhanced presynaptic release of transmitter, litt
le specific information has accrued on the nature of the presynaptic r
eceptor-linked events. In the course of a series of experiments examin
ing the actions of several antagonists of N-methyl-D-aspartate (NMDA)
receptors on LTP, we made certain observations that suggested the role
of a novel type of amino acid receptor which possibly was located pre
synaptically and that seemed to contribute to the induction of LTP. LT
P evoked in region CA1 following high frequency stimulation (HFS) of t
he Schaffer collateral-commissural pathway measured 20-30 min after HF
S always was attenuated incompletely when induced during administratio
n of D alpha AA at doses ranging from 50 mu M to as high as 1000 mu M,
whereas 2-amino-5-phosphonopropionate (AP5), at a concentration of 30
mu M, always abolished the process completely. 6,7-Dinitroquinoxaline
-2,3-dione (DNQX) (10 mu M) administered alone also did not block LTP
completely unless delivered in combination with D alpha AA. These non-
APS-like effects of D alpha AA could not be attributed to incomplete a
ntagonism of postsynaptic NMDA receptors, since D alpha AA (200 mu M)
completely and reversibly blocked the membrane depolarising effects of
NMDA, as assessed through intracellular recording. Furthermore, the p
harmacologically isolated NMDA-receptor-mediated component of the low-
frequency, stimulus-evoked synaptic response was always abolished reve
rsibly by D alpha AA (200 mu M). The most parsimonious explanation of
these data is that a receptor which is only activated during HFS, is s
ensitive to the antagonising actions of AP5 and possibly also to DNQX
but not to D alpha AA, and which could conceivably exist on terminals
of the Schaffer collateral-commissural fibres, makes a significant con
tribution to LTP.