The Journal of Neurophysiology Vol. 85 No. 1 January 2001, pp. 384-390
Copyright ©2001 by the American Physiological Society
Attenuated LTP in Hippocampal Dentate Gyrus Neurons of Mice
Deficient in the PAF Receptor
Chu
Chen,
Jeffrey C.
Magee,
Victor
Marcheselli,
Mattie
Hardy, and
Nicolas
G.
Bazan
Neuroscience Center, Louisiana State University Health Sciences
Center, New Orleans, Louisiana 70112
Chen, Chu,
Jeffrey C. Magee,
Victor Marcheselli,
Mattie Hardy, and
Nicolas
G. Bazan.
Attenuated LTP in Hippocampal Dentate Gyrus Neurons of Mice
Deficient in the PAF Receptor. J. Neurophysiol. 85: 384-390, 2001. Platelet-activating factor (PAF), a
bioactive lipid
(1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) derived
from phospholipase A2 and other pathways, has
been implicated in neural plasticity and memory formation. Long-term
potentiation (LTP) can be induced by the application of PAF and blocked
by a PAF receptor (PAF-R) inhibitor in the hippocampal CA1 and dentate
gyrus. To further investigate the role of PAF in synaptic plasticity,
we compared LTP in dentate granule cells from hippocampal slices of
adult mice deficient in the PAF-R and their age-matched wild-type
littermates. Whole cell patch-clamp recordings were made in the
current-clamp mode. LTP in the perforant path was induced by a
high-frequency stimulation (HFS) and defined as >20% increase above
baseline of the amplitude of excitatory postsynaptic potentials (EPSPs) from 26 to 30 min after HFS. HFS-induced enhancement of the EPSP amplitude was attenuated in cells from the PAF-R-deficient mice (163 ± 14%, mean ± SE; n = 32)
when compared with that in wild-type mice (219 ± 17%,
n = 32). The incidence of LTP induction was also lower
in the cells from the deficient mice (72%, 23 of 32 cells) than in the
wild-type mice (91%, 29 of 32 cells). Using paired-pulse facilitation
as a synaptic pathway discrimination, it appeared that there were
differences in LTP magnitudes in the lateral perforant path but not in
the medial perforant path between the two groups. BN52021 (5 µM), a
PAF synaptosomal receptor antagonist, reduced LTP in the lateral path
in the wild-type mice. However, neither BN52021, nor BN50730 (5 µM),
a microsomal PAF-R antagonist, reduced LTP in the lateral perforant
path in the receptor-deficient mice. These data provide evidence that
PAF-R-deficient mice are a useful model to study LTP in the dentate
gyrus and support the notion that PAF actively participates in
hippocampal synaptic plasticity.
