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Volume 17, Number 16,
Issue of August 15, 1997
pp. 6470-6477
Copyright ©1997 Society for Neuroscience
Stimulation on the Positive Phase of Hippocampal Theta Rhythm
Induces Long-Term Potentiation That Can Be Depotentiated by Stimulation
on the Negative Phase in Area CA1 In Vivo
Received March 12, 1997; revised May 22, 1997; accepted June 6, 1997.
Christian Hölscher1,
Roger Anwyl2, and
Michael
J. Rowan1
Departments of 1 Pharmacology and Therapeutics and
2 Physiology, Trinity College Dublin, Dublin 2, Ireland
Long-term potentiation (LTP) of synaptic transmission induced by
high-frequency stimulation (HFS) is considered to be a model for
learning processes; however, standard HFS protocols consisting of long
trains of HFS are very different from the patterns of spike firing in
freely behaving animals. We have investigated the ability of brief
bursts of HFS triggered at different phases of background theta rhythm
to mimic more natural activity patterns. We show that a single burst of
five pulses at 200 Hz given on the positive phase of tail
pinch-triggered theta rhythm reliably induced LTP in the stratum
radiatum of the hippocampus of urethane-anesthetized rats. Three of
these bursts saturated LTP, and 10 bursts occluded the induction of LTP
by long trains of HFS. Burst stimulation on the negative phase or at
zero phase of theta did not induce LTP or long-term depression. In
addition, stimulation with 10 bursts on the negative phase of theta
reversed previously established LTP. The results show that the phase of
sensory-evoked theta rhythm powerfully regulates the ability of brief
HFS bursts to elicit either LTP or depotentiation of synaptic
transmission. Furthermore, because complex spike activity of
approximately five pulses on the positive phase of theta rhythm can be
observed in freely moving rats, LTP induced by the present
theta-triggered stimulation protocol might model putative synaptic
plastic changes during learning more closely than standard HFS-induced
LTP.
Key words:
hippocampus;
CA1;
long-term potentiation (LTP);
depotentiation;
long-term depression (LTD);
theta rhythm;
rhythmic slow
activity;
learning and memory
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