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NMDA-receptor independent LTP
Neurochem. Int. Vol. 20, No. 4, pp. 461~,62, 1992
0197-0186/9255.00+0.00 Copyright© 1992PergamonPressLtd
Printed in Great Britain.All rights reserved
CRITIQUE N M D A - R E C E P T O R I N D E P E N D E N T LTP DANIEL JOHNSTON Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, U.S.A.
Dr Bramham's review is a valuable and timely con- inhibition is blocked (Derrick et al., 1991 ; S. Williams tribution to the rapidly changing field of long-term and D. Johnston, unpublished). These results, if subpotentiation or LTP. Although it has been known for stantiated, completely change the focus of invessome time that LTP in the hippocampus could be tigation for opioid action from interneurons to that subdivided into NMDA-receptor dependent and of either the excitatory synapses or the pyramidal NMDA-receptor independent forms (at least), the neurons themselves. A similar analysis obviously NMDA-receptor independent variety has received needs to be done for the lateral perforant path. much less attention because it appeared to be found A second question is whether NMDA-receptor only at mossy fiber synapses. Through the recent work independent LTP at other synapses (e.g. Schaffer colof Dr Bramham and others (cf. Aniksztejn and Ben- laterals) is affected by naloxone. In other words, how Ari, 1991 ; Grover and Teyler, 1990)NMDA-receptor general (outside of the lateral perforant path and independent LTP has now been demonstrated at mossy fibers) is the involvement of opioid peptides in most of the excitatory pathways in the hippocampus the induction of NMDA-receptor independent LTP? (mossy fibers, lateral perforant path, and Schaffer And third, is "opioid LTP" at the lateral perforant collaterals). path Hebbian? Considerable interest has been focused On the basis of his work at the lateral perforant on Hebbian mechanisms for synaptic plasticity. With path, Dr Bramham suggests that NMDA-receptor NMDA-receptor dependent LTP, concomitant activindependent LTP may in fact be opioid dependent. ity of the pre- and postsynaptic neuron appears to be This is an intriguing possibility for which a number required for its induction (Kelso et al., 1986). We of questions immediately spring to mind. The first have recently demonstrated that the induction of relates to the hypothesis that the action of the opioids mossy fiber LTP, an NMDA-receptor independent is to cause disinhibition. Does this hypothesis imply variety, also follows a Hebbian rule (Jaffe and Johnthat LTP at the lateral perforant path normally ston, 1990). requires disinhibition for its induction, as suggested We found that hyperpolarization of the postfor LTP at the Schaffer collaterals and perforant path synaptic neuron during high-frequency stimulation (Davies et al., 1991; Mott and Lewis, 1991)? Can blocks the induction of mossy fiber LTP while deLTP at the lateral perforant path be elicited under polarization during high-frequency stimulation disinhibited conditions? And, does naloxone inhibit enhances the induction (and magnitude) of LTP. With the induction of LTP at the lateral perforant path in the previous results of Williams and Johnston (Wilthe presence of G A B A antagonists? The results of liams and Johnston, 1989), in which mossy fiber LTP such experiments would have important implications was blocked by the postsynaptic injection of calcium for mechanisms of LTP. For example, the mossy fibers chelators, there is now strong support for postsynaptic also release opioids that affect the induction of LTP control over the induction of mossy fiber LTP. A (Martin, 1983). It now appears that the effects of question then for Dr Bramham is whether LTP at endogenous opioids on mossy fiber LTP may be inde- the lateral perforant path is also Hebbian and under pendent of any actions on interneurons. Two groups control of the postsynaptic neuron or is this where have preliminary evidence that naloxone inhibits the similarities between the mossy fibers and lateral perinduction of mossy fiber LTP when GABA-mediated forant path end? 461
462
Critique
Another interesting finding from our work on the mossy fibers is that mossy fiber LTP appears to require some level of high-frequency stimulation for its induction (Jaffe and Johnston, 1990). We found that pairing postsynaptic depolarization with single mossy fiber EPSPs was not sufficient for the induction of LTP. This is quite unlike that of N M D A - r e c e p t o r dependent LTP where such pairing paradigms are quite effective for eliciting LTP. Our results at mossy fibers lead to the speculation that something is released under conditions of high-frequency stimulation that is either requircd for, or at least facilitates, the induction of this form of N M D A - r e c e p t o r independent LTP. It would be interesting to compare this finding with the results of similar experiments at the lateral perforant path. I believe that the issues outlined above (and others) will be fruitful areas of further investigations, and Dr Bramham's review is very stimulating in this regard. Much needs to be learned about LTP in different pathways and especially about the role of neuropcptides as modulators of synaptic transmission. The possible co-release of neuropeptides only under conditions of high-frequency activity makes them particularly well suited for playing a role in various forms of activity-dependent synaptic plasticity.
REFEREN( ES
Anikszlejn L. and Ben-Ari Y. (199l) Novel form of longterm potentiation produced by a K ~ channel blocker in the hippocampus. Nature 349, 67 69. Davies C. H.. Starkey S. J., Pozza M. F. and Collingridgc G. L. ( 1991 ) GABAR auto, receptors regulate the induction of LTP. Nature 349, 6(19 61 I. Derrick B. E., Weinbergcr S. B. and Martinez J. L. (1991) Opioid receptors are involved in an NMDA receptorindependent mechanism of LTP induction at hippocampal mossy fiber-CA3 synapses. Brain Res. Bull. 27, 219 223. (trover L. M. and Teyler T. J. (1990) Two components of long-term potentiation iqduced by different palterns of afferent activation. Nature 347, 477 479. Jaffe D. and Johnston D. (1990) The induction of longterm potentiation at hippocampal mossy fibers follows a Itebbian rule. J. Neurophysiol. 64, 948 960. Kelso S. R., Ganong A. H. and Brown T. H. (1986) Hebbian synapses in hippocampus. Proc. Jlatu Acad. Sci., U.S.A. 83, 5326 5330. Martin M. R. (1983) Naloxone and long term potentiation of hippocampal CA3 feld potentials in Htro. Neurop~Ttides 4, 45 50. MoU D. D. and Lewis D, V. ([991) Facilitation of the induction of long-term potentiation by GABAB receptors, Science 252, 1718 1720. Williams S. and Johnston D, (1989) Long-term potentiation of hippocampal mossy tibcr synapses is blocked by postsynaptic injection of calcium chelators. Neuron 3, 583 588.
0197-0186/9255.00+0.00 Copyright© 1992PergamonPressLtd
Printed in Great Britain.All rights reserved
CRITIQUE N M D A - R E C E P T O R I N D E P E N D E N T LTP DANIEL JOHNSTON Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, U.S.A.
Dr Bramham's review is a valuable and timely con- inhibition is blocked (Derrick et al., 1991 ; S. Williams tribution to the rapidly changing field of long-term and D. Johnston, unpublished). These results, if subpotentiation or LTP. Although it has been known for stantiated, completely change the focus of invessome time that LTP in the hippocampus could be tigation for opioid action from interneurons to that subdivided into NMDA-receptor dependent and of either the excitatory synapses or the pyramidal NMDA-receptor independent forms (at least), the neurons themselves. A similar analysis obviously NMDA-receptor independent variety has received needs to be done for the lateral perforant path. much less attention because it appeared to be found A second question is whether NMDA-receptor only at mossy fiber synapses. Through the recent work independent LTP at other synapses (e.g. Schaffer colof Dr Bramham and others (cf. Aniksztejn and Ben- laterals) is affected by naloxone. In other words, how Ari, 1991 ; Grover and Teyler, 1990)NMDA-receptor general (outside of the lateral perforant path and independent LTP has now been demonstrated at mossy fibers) is the involvement of opioid peptides in most of the excitatory pathways in the hippocampus the induction of NMDA-receptor independent LTP? (mossy fibers, lateral perforant path, and Schaffer And third, is "opioid LTP" at the lateral perforant collaterals). path Hebbian? Considerable interest has been focused On the basis of his work at the lateral perforant on Hebbian mechanisms for synaptic plasticity. With path, Dr Bramham suggests that NMDA-receptor NMDA-receptor dependent LTP, concomitant activindependent LTP may in fact be opioid dependent. ity of the pre- and postsynaptic neuron appears to be This is an intriguing possibility for which a number required for its induction (Kelso et al., 1986). We of questions immediately spring to mind. The first have recently demonstrated that the induction of relates to the hypothesis that the action of the opioids mossy fiber LTP, an NMDA-receptor independent is to cause disinhibition. Does this hypothesis imply variety, also follows a Hebbian rule (Jaffe and Johnthat LTP at the lateral perforant path normally ston, 1990). requires disinhibition for its induction, as suggested We found that hyperpolarization of the postfor LTP at the Schaffer collaterals and perforant path synaptic neuron during high-frequency stimulation (Davies et al., 1991; Mott and Lewis, 1991)? Can blocks the induction of mossy fiber LTP while deLTP at the lateral perforant path be elicited under polarization during high-frequency stimulation disinhibited conditions? And, does naloxone inhibit enhances the induction (and magnitude) of LTP. With the induction of LTP at the lateral perforant path in the previous results of Williams and Johnston (Wilthe presence of G A B A antagonists? The results of liams and Johnston, 1989), in which mossy fiber LTP such experiments would have important implications was blocked by the postsynaptic injection of calcium for mechanisms of LTP. For example, the mossy fibers chelators, there is now strong support for postsynaptic also release opioids that affect the induction of LTP control over the induction of mossy fiber LTP. A (Martin, 1983). It now appears that the effects of question then for Dr Bramham is whether LTP at endogenous opioids on mossy fiber LTP may be inde- the lateral perforant path is also Hebbian and under pendent of any actions on interneurons. Two groups control of the postsynaptic neuron or is this where have preliminary evidence that naloxone inhibits the similarities between the mossy fibers and lateral perinduction of mossy fiber LTP when GABA-mediated forant path end? 461
462
Critique
Another interesting finding from our work on the mossy fibers is that mossy fiber LTP appears to require some level of high-frequency stimulation for its induction (Jaffe and Johnston, 1990). We found that pairing postsynaptic depolarization with single mossy fiber EPSPs was not sufficient for the induction of LTP. This is quite unlike that of N M D A - r e c e p t o r dependent LTP where such pairing paradigms are quite effective for eliciting LTP. Our results at mossy fibers lead to the speculation that something is released under conditions of high-frequency stimulation that is either requircd for, or at least facilitates, the induction of this form of N M D A - r e c e p t o r independent LTP. It would be interesting to compare this finding with the results of similar experiments at the lateral perforant path. I believe that the issues outlined above (and others) will be fruitful areas of further investigations, and Dr Bramham's review is very stimulating in this regard. Much needs to be learned about LTP in different pathways and especially about the role of neuropcptides as modulators of synaptic transmission. The possible co-release of neuropeptides only under conditions of high-frequency activity makes them particularly well suited for playing a role in various forms of activity-dependent synaptic plasticity.
REFEREN( ES
Anikszlejn L. and Ben-Ari Y. (199l) Novel form of longterm potentiation produced by a K ~ channel blocker in the hippocampus. Nature 349, 67 69. Davies C. H.. Starkey S. J., Pozza M. F. and Collingridgc G. L. ( 1991 ) GABAR auto, receptors regulate the induction of LTP. Nature 349, 6(19 61 I. Derrick B. E., Weinbergcr S. B. and Martinez J. L. (1991) Opioid receptors are involved in an NMDA receptorindependent mechanism of LTP induction at hippocampal mossy fiber-CA3 synapses. Brain Res. Bull. 27, 219 223. (trover L. M. and Teyler T. J. (1990) Two components of long-term potentiation iqduced by different palterns of afferent activation. Nature 347, 477 479. Jaffe D. and Johnston D. (1990) The induction of longterm potentiation at hippocampal mossy fibers follows a Itebbian rule. J. Neurophysiol. 64, 948 960. Kelso S. R., Ganong A. H. and Brown T. H. (1986) Hebbian synapses in hippocampus. Proc. Jlatu Acad. Sci., U.S.A. 83, 5326 5330. Martin M. R. (1983) Naloxone and long term potentiation of hippocampal CA3 feld potentials in Htro. Neurop~Ttides 4, 45 50. MoU D. D. and Lewis D, V. ([991) Facilitation of the induction of long-term potentiation by GABAB receptors, Science 252, 1718 1720. Williams S. and Johnston D, (1989) Long-term potentiation of hippocampal mossy tibcr synapses is blocked by postsynaptic injection of calcium chelators. Neuron 3, 583 588.