title: LTP in hippocampal area CA1 is induced by burst stimulation over a broad frequency range centered around delta.
abstract: Long-term potentiation (LTP) is typically studied using either continuous high-frequency stimulation or theta burst stimulation. Previous studies emphasized the physiological relevance of theta frequency; however, synchronized hippocampal activity occurs over a broader frequency range. We therefore tested burst stimulation at intervals from 100 msec to 20 sec (10 Hz to 0.05 Hz). LTP at Schaffer collateral-CA1 synapses was obtained at intervals from 100 msec to 5 sec, with maximal LTP at 350-500 msec (2-3 Hz, delta frequency). In addition, a short-duration potentiation was present over the entire range of burst intervals. We found that N-methyl-d-aspartic acid (NMDA) receptors were more important for LTP induction by burst stimulation, but L-type calcium channels were more important for LTP induction by continuous high-frequency stimulation. NMDA receptors were even more critical for short-duration potentiation than they were for LTP. We also compared repeated burst stimulation with a single primed burst. In contrast to results from repeated burst stimulation, primed burst potentiation was greater when a 200-msec interval (theta frequency) was used, and a 500-msec interval was ineffective. Whole-cell recordings of postsynaptic membrane potential during burst stimulation revealed two factors that may determine the interval dependence of LTP. First, excitatory postsynaptic potentials facilitated across bursts at 500-msec intervals but not 200-msec or 1-sec intervals. Second, synaptic inhibition was suppressed by burst stimulation at intervals between 200 msec and 1 sec. Our data show that CA1 synapses are more broadly tuned for potentiation than previously appreciated.
authors.affiliation: Department of Pharmacology, Physiology and Toxicology, Marshall University, School of Medicine, Huntington, West Virginia 25755, USA. grover@marshall.edu
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Grover
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Kim
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Cooke
authors.forename: William R
authors.initials: WR
authors.lastname: Holmes
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002555:Cerebrospinal Fluid; D003700:Delta Rhythm; D004121:Dimethyl Sulfoxide; D004558:Electric Stimulation; D004569:Electroencephalography; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D015763:2-Amino-5-phosphonovalerate; D009543:Nifedipine; D004121:Dimethyl Sulfoxide