The Journal of Neurophysiology Vol. 84 No. 5 November 2000, pp. 2484-2493
Copyright ©2000 by the American Physiological Society
Differential Maintenance and Frequency-Dependent Tuning of LTP at
Hippocampal Synapses of Specific Strains of Inbred Mice
Peter V.
Nguyen,1,2
Steven N.
Duffy,1,2 and
Jennie Z.
Young2
1Department of Physiology and
2Division of Neuroscience, University
of Alberta School of Medicine, Edmonton, Alberta T6G 2H7, Canada
Nguyen, Peter V.,
Steven N. Duffy, and
Jennie Z. Young.
Differential Maintenance and Frequency-Dependent Tuning of LTP at
Hippocampal Synapses of Specific Strains of Inbred Mice. J. Neurophysiol. 84: 2484-2493, 2000. Transgenic and knockout mice are used extensively to elucidate
the molecular mechanisms of hippocampal synaptic plasticity. However,
genetic and phenotypic variations between inbred mouse strains that are
used to construct genetic models may confound the interpretation of
cellular neurophysiological data derived from these models. Using in
vitro slice stimulation and recording methods, we compared the membrane
biophysical, cellular electrophysiological, and synaptoplastic
properties of hippocampal CA1 neurons in four specific strains of
inbred mice: C57BL/6J, CBA/J, DBA/2J, and 129/SvEms/J. Hippocampal
long-term potentiation (LTP) induced by theta-pattern stimulation, and
by repeated multi-burst 100-Hz stimulation at various interburst
intervals, was better maintained in area CA1 of slices from BL/6J mice
than in slices from CBA and DBA mice. At an interburst interval
of 20 s, maintenance of LTP was impaired in CBA and DBA slices, as
compared with BL/6J slices. When the interburst interval was reduced to
3 s, induction of LTP was significantly enhanced in129/SvEms
slices, but not in DBA and CBA slices. Long-term depression (LTD) was
not significantly different between slices from these four strains. For
the four strains examined, CA1 pyramidal neurons showed no significant differences in spike-frequency accommodation, membrane input
resistance, and number of spikes elicited by current injection.
Synaptically-evoked glutamatergic postsynaptic currents did not
significantly differ among CA1 pyramidal neurons in these four strains.
Since the observed LTP deficits resembled those previously seen in
transgenic mice with reduced hippocampal cAMP-dependent protein kinase
(PKA) activity, we searched for possible strain-dependent differences
in cAMP-dependent synaptic facilitation induced by forskolin (an
activator of adenylate cyclase) and IBMX (a phosphodiesterase
inhibitor). We found that forskolin/IBMX-induced synaptic facilitation
was deficient in area CA1 of DBA/2J and CBA/J slices, but not in BL/6J
and 129/SvEms/J slices. These defects in cAMP-induced synaptic
facilitation may underlie the deficits in memory, observed in CBA/J and
DBA/2J mice, that have been previously reported. We conclude
that hippocampal LTP is influenced by genetic background and by the
temporal characteristics of the stimulation protocol. The plasticity of
hippocampal synapses in some inbred mouse strains may be "tuned" to
particular temporal patterns of synaptic activity. From
a broader perspective, our data support the notion that
strain-dependent variation in genetic background is an important factor
that can influence the synaptoplastic phenotypes observed in studies
that use genetically modified mice to explore the molecular bases of
synaptic plasticity.
