VDCCs and NMDARs underlie two forms of LTP in CA1 hippocampus in vivo.
Animals; Calcium Channel Blockers/*pharmacology; Dizocilpine Maleate/pharmacology; Excitatory Amino Acid Antagonists/*pharmacology; Excitatory Postsynaptic Potentials/drug effects; Hippocampus/*drug effects; Long-Evans; Long-Term Potentiation/*drug effects; Male; Membrane Potentials/physiology; N-Methyl-D-Aspartate/*antagonists & inhibitors; Rats; Receptors; Verapamil/pharmacology
N-methyl-D-aspartate receptor/channel (NMDAR) and voltage-dependent calcium channel (VDCC) antagonists applied independently reduce the magnitude of long-term potentiation (LTP) in area CA1 of the hippocampal slice preparation. When used in combination, the antagonists completely block the induction of LTP. In urethan-anesthetized rats we examined the effect of the NMDAR blocker MK-801 (0.1 mg/kg) and the VDCC blocker Verapamil (10 mg/kg) on LTP induction in area CA1. Extracellular recordings were obtained from stratum radiatum following stimulation of Schaffer collaterals. LTP was induced by a 200-Hz/100-ms tetanus repeated 10 times (2 s isi). Tetanus was given in the presence of intraperitoneal saline, MK-801, Verapamil, or both Verapamil and MK-801. When given separately, Verapamil and MK-801 both significantly reduced the magnitude of LTP as compared with control animals. When given together, the drugs blocked the induction of LTP completely. We conclude that like LTP in vitro, VDCCs and NMDAR underlie two forms of LTP in vivo.
Morgan S L; Teyler T J
Journal of neurophysiology
1999
1999-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jn.1999.82.2.736" target="_blank" rel="noreferrer noopener">10.1152/jn.1999.82.2.736</a>
Synaptic plasticity and secondary epileptogenesis.
Animals; Epilepsy/etiology/*physiopathology; Humans; Long-Term Potentiation/physiology; Neuronal Plasticity/*physiology; Synapses/*physiology
Teyler T J; Morgan S L; Russell R N; Woodside B L
International review of neurobiology
2001
1905-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0074-7742(01)45014-8" target="_blank" rel="noreferrer noopener">10.1016/s0074-7742(01)45014-8</a>
Epileptic-like activity induces multiple forms of plasticity in hippocampal area CA1.
*Neuronal Plasticity; Animals; Calcium Channels; Electrophysiology; Epilepsy/chemically induced/*physiopathology; Hippocampus/*physiopathology; Ion Channels/physiology; L-Type/physiology; Long-Evans; Long-Term Potentiation/physiology; N-Methyl-D-Aspartate/metabolism; Potassium Chloride; Rats; Receptors; Synapses/physiology
Mesial temporal lobe epilepsy is a relatively common form of epilepsy that afflicts many thousands of people. It has been suggested that the development of primary and secondary foci may involve mechanisms similar to long-term potentiation (LTP). In vitro seizure models typically involve an increase in spontaneous asynchronous bursting activity (epileptiform activity) induced either by increasing excitation or decreasing inhibition. Previous experiments have indicated that these models often generate bursting activity that closely resembles epileptic activity. LTP is often observed following epileptiform activity. In area CA1 of the hippocampus two forms of LTP that are dependent on the activation of either the L-type voltage dependent calcium channel (vdccLTP) or the N-methyl-D-aspartate receptor/channel (nmdaLTP) have been described. It is unclear from previous experiments which type of LTP results from epileptiform activity. Recent evidence indicates that nmdaLTP is most likely a short-term type of plasticity while vdccLTP may be a long-lasting form of synaptic plasticity. Given the characteristics of vdccLTP it is a likely candidate mechanism to underlie the development and formation of secondary seizure foci. We have therefore tested the ability of epileptiform activity induced by elevated potassium chloride to induce multiple forms of LTP in area CA1 of the rat hippocampus. Elevation of extracellular potassium chloride resulted in spontaneous asynchronous bursting. The net result of the spontaneous asynchronous bursting was to induce a compoundLTP consisting of nmdaLTP and vdccLTP components.
Morgan S L; Teyler T J
Brain research
2001
2001-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0006-8993(01)02913-4" target="_blank" rel="noreferrer noopener">10.1016/s0006-8993(01)02913-4</a>
Electrical stimuli patterned after the theta-rhythm induce multiple forms of LTP.
*Theta Rhythm; 2-Amino-5-phosphonovalerate/pharmacology; Animals; Calcium Channel Blockers/pharmacology; Calcium Channels/physiology; Excitatory Amino Acid Agonists/pharmacology; Excitatory Amino Acid Antagonists/pharmacology; Excitatory Postsynaptic Potentials/drug effects/physiology; Long-Evans; Long-Term Potentiation/drug effects/*physiology; Male; N-Methyl-D-Aspartate/physiology; N-Methylaspartate/pharmacology; Neuronal Plasticity/drug effects/*physiology; Nifedipine/pharmacology; Organ Culture Techniques; Rats; Receptors
The induction of long-term potentiation (LTP) by high-frequency stimulation is considered an acceptable model for the study of learning and memory. In area CA1 calcium influx through N-methyl-D-aspartate receptors (NMDARs; nmdaLTP) and/or
Morgan S L; Teyler T J
Journal of neurophysiology
2001
2001-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jn.2001.86.3.1289" target="_blank" rel="noreferrer noopener">10.1152/jn.2001.86.3.1289</a>
Depotentiation of vdccLTP requires NMDAR activation.
2-Amino-5-phosphonovalerate/pharmacology; Animals; Calcium Channel Blockers/*pharmacology; Calcium Channels/drug effects/*physiology; Electric Stimulation; Electrophysiology; Hippocampus/*physiology; Long-Evans; Long-Term Potentiation/*physiology; Male; N-Methyl-D-Aspartate/drug effects/*physiology; Nifedipine/*pharmacology; Organ Culture Techniques; Rats; Receptors; Synaptic Transmission/*physiology
Long-term potentiation is an enduring increase in synaptic efficacy following repeated stimulation of afferent fibers that is thought to underlie memory. In area CA1 of the hippocampus at least two forms of synaptic potentiation coexist at the same synapses; nmdaLTP and vdccLTP. NmdaLTP is induced by Ca2+ entry through NMDARs and is dependent on serine/threonine kinase activation, while vdccLTP is induced through Ca2+ entry through VDCCs and is dependent on tyrosine kinase activation. Depotentiation is a mechanism known to reverse nmdaLTP through phosphatase activation. The depotentiation of vdccLTP has not been previously investigated. We used hippocampal slices (area CA1) from male Long-Evans rats to induce vdccLTP with a 200-Hz tetanus in the presence of 50 microM APV. The 200-Hz tetanus resulted in a slowly developing vdccLTP that remained stable for at least 30 min. Thirty minutes after vdccLTP was induced, a low-frequency tetanus (3, 10, 20, 30, or 40 Hz) was applied in the presence of APV in an attempt to depotentiate vdccLTP. The 3- and 10-Hz low-frequency tetani resulted in no depotentiation. The 20- and 30-Hz tetani partially depotentiated vdccLTP (by approximately 13%), whereas the 40-Hz tetanus resulted in further potentiation. When APV was washed out prior to the 3-Hz low-frequency tetanus, the vdccLTP was completely depotentiated–presumably by NMDAR mechanisms. Our results indicate that vdccLTP is resistant to depotentiation under low-frequency stimulation conditions that readily depotentiate nmdaLTP. As tetanus frequencies are increased a small depotentiation is observed, suggesting that vdccLTP can be depotentiated to a small extent. When NMDARs are unblocked, vdccLTP can be completely depotentiated by a 3-Hz low-frequency tetanus, suggesting that vdccLTP can be depotentiated via activation of NMDAR mechanisms.
Morgan S L; Coussens C M; Teyler T J
Neurobiology of learning and memory
2001
2001-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1006/nlme.2001.4016" target="_blank" rel="noreferrer noopener">10.1006/nlme.2001.4016</a>