Skip to main content
Log in

A Possible Mechanism for the Effect of Neuromodulators and Modifiable Inhibition on Long-Term Potentiation and Depression of the Excitatory Inputs to Hippocampal Principal Cells

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

Abstract

A postsynaptic mechanism for the influences of various neuromodulators and modifiable disynaptic inhibition on long-term potentiation and depression of the excitatory inputs to granule and pyramidal neurons in the hippocampus is described. According to this mechanism, facilitation of the induction of long-term depression/potentiation at the excitatory input to the inhibitory interneuron induced by the action of a neuromodulator on a receptor bound to a Gi/0/(Gs or Gq/11) protein can lead to decreases/increases in GABA release, weakening/strengthening of the inhibitory action on the target cell, and improvement in the conditions for induction of long-term potentiation/depression of the excitatory input to this cell. In the absence of inhibition, the same neuromodulator, activating the same type of receptors on the target cell, would facilitate induction of long-term depression/potentiation in that cell. The resultant effect of the action of the neuromodulator on the target cell depends on the ratio of the “strengths” of the excitatory and inhibitory inputs to the cell, on the presence on the interneuron and the target cell of the same or different types of receptors sensitive to this neurumodulator, and on the concentration of the neurumodulator, because of its different affinities for the receptors through which its differently directed effects on postsynaptic processes are mediated. Predictions based on this mechanism are in agreement with known experimental data.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. O. S. Vinogradova, “Neuroscience at the end of the second millennium: a paradigm shift,” Zh. Vyssh. Nerv. Deyat., 50, No. 5, 743–774 (2000).

    Google Scholar 

  2. N. A. Otmakhov, “The neural network of the hippocampus: morphological analysis,” Usp. Fiziol. Nauk, 24, No. 4, 79–101 (1993).

    Google Scholar 

  3. I. G. Sil'kis, “General principles of synaptic plasticity in the neocortex, hippocampus, and cerebellum,” Zh. Vyssh. Nerv. Deyat., 47, No. 2, 374–392 (1997).

    Google Scholar 

  4. V. G. Skrebitskii and A. N. Chepkova, “Synaptic plasticity in learning and memory,” Usp. Fiziol. Nauk, 30, No. 1, 3–13 (1999).

    Google Scholar 

  5. J. A. Arias-Montano, D. Martinez-Fong, and J. Aceves, “Glutamate stimulation of tyrosine hydroxylase is mediated by NMDA receptors in the rat striatum,” Brain Res., 569, No. 2, 317–322 (1992).

    Google Scholar 

  6. J. M. Auerbach and M. Segal, “Muscarinic receptors mediating depression and long-term potentiation in rat hippocampus,” J. Physiol. (England), 492, No. 2, 479–493 (1996).

    Google Scholar 

  7. J. Berzhanskaya, N. N. Urban, and G. Barrionuevo, “Electrophysiological and pharmacological characterization of the direct perforant path input to the hippocampal area CA3,” J. Neurophys., 79, No. 4, 2111–2118 (1998).

    Google Scholar 

  8. J. M. Blasco-Ibanez and T. F. Freund, “Synaptic input of horizontal interneurons in stratum oriens of the hippocampal CA1 subfield: structural basis of feed-back activation,” Eur. J. Neurosci., 7, No. 10, 2170–2180 (1995).

    Google Scholar 

  9. J. M. Blasco-Ibanez, F. J. Marinez-Guijarro, and T. F. Freund, “Enkephalin-containing interneurons are specialized to innervate other interneurons in the hippocampal CA1 region of the rat and guinea-pig,” Eur. J. Neurosci., 10, No. 5, 1784–1795 (1998).

    Google Scholar 

  10. C. R. Bramham, K. Bacher-Svedsen, and J. M. Sarvey, “LTP in the lateral perforant path is beta-adrenergic receptor-dependent,” NeuroReport, 8, No. 3, 719–724 (1997).

    Google Scholar 

  11. F. H. Brucato, E. D. Levin, D. D. Mott, et al., “Hippocampal long-term potentiation and spatial learning in the rat: effects of GABAB receptor blockade,” Neurosci., 74, No. 2, 331–339 (1996).

    Google Scholar 

  12. E. C. Burgard, T. E. Cote, and J. M. Sarvey, “Muscarinic depression of synaptic transmission and blockade of norepinephrine-induced long-lasting potentiation in the dentate gyrus,” Neurosci., 54, No. 2, 377–389 (1993).

    Google Scholar 

  13. E. C. Burgard and J. M. Sarvey, “Muscarinic receptor activation facilitates the induction of long-term potentiation (LTP) in the rat dentate gyrus,” Neurosci. Lett., 116, No. 1-2, 34–39 (1990).

    Google Scholar 

  14. E. C. Burgard and J. M. Sarvey, “Long-lasting potentiation and epileptiform activity produced by GABAB receptor activation in the dentate gyrus of rat hippocampal slice,” J. Neurosci., 11, No. 5, 1198–1209 (1991).

    Google Scholar 

  15. Z. Chen, K. Ito, S. Fujii, et al., “Roles of dopamine receptors in long-term depression: enhancement via D1 receptor and inhibition via D2 receptors,” Receptors Channels, 4, No. 1, 1–8 (1996).

    Google Scholar 

  16. C. M. Colbert and W. B. Levy, “Electrophysiological and pharmacological characterization of perforant path synapses in CA1: mediation by glutamate receptors,” J. Neurophysiol., 68, No. 1, 1–8 (1992).

    Google Scholar 

  17. K. G. Commons and T. A. Milber, “Localization of delta opioid receptor immunoreactivity in interneurons and pyramidal cells in the rat hippocampus,” J. Comp. Neurol., 381, No. 3, 373–387 (1997).

    Google Scholar 

  18. R. A. Cunha, B. Johansson, and I. Van der Ploeg, “Evidence for functionally important adenosine A2a receptors in the rat hippocampus,” Brain Res., 649, No. 1-2, 208–216 (1994).

    Google Scholar 

  19. D. Dahl and J. M. Sarvey, “Beta-adrenergic agonist-induced longlasting synaptic modifications in hippocampal dentate gyrus require activation of NMDA receptors, but not electrical activation of afferents,” Brain Res., 526, No. 2, 347–350 (1990).

    Google Scholar 

  20. A. de Mendonca, T. Almeida, Z. I. Bashir, and J. A. Ribeiro, “Endogenous adenosine attenuates long-term depression and depotentiation in the CA1 region of the rat hippocampus,” Neuropharmacology, 36, No. 2, 161–167 (1997).

    Google Scholar 

  21. B. E. Derrick and L. J. Martinez, Jr., “Opioid receptor activation is one factor underlying the frequency dependence of mossy fiber LTP induction,” J. Neurosci., 14, No. 7, 4359–4367 (1994).

    Google Scholar 

  22. H. Dvorak-Carbone and E. M. Schuman, “Long-term depression of temporoammonic-CA1 hippocampal synaptic transmission,” J. Neurophysiol., 81, No. 3, 1036–1044 (1999).

    Google Scholar 

  23. R. M. Empson and U. Heinemann, “The perforant path projection to hippocampal area CA1 in the rat hippocampal-entorhinal cortex combined slice,” J. Physiol. (England), 484, No. 3, 707–720 (1995).

    Google Scholar 

  24. R. Forghani and K. Krnjevic, “Adenosine antagonists have differential effects on induction of long-term potentiation in hippocampal slices,” Hippocampus, 5, No. 1, 71–77 (1995).

    Google Scholar 

  25. T. F. Freund, A. I. Gulyas, and L. Acsady, “Serotonergic control of the hippocampus via local inhibitory interneurons,” Proc. Natl. Acad. Sci. USA, 87, No. 21, 8501–8505 (1990).

    Google Scholar 

  26. M. Frotscher, E. Soriano, and C. Leranth, “Cholinergic and GABAergic neurotransmission in the fascia dentata: electron microscopic immunocytochemical studies in rodents and primates,” Epilepsy Res., 7, Supplement, 65–78 (1992).

    Google Scholar 

  27. S. K. Goldsmith and J. N. Joyce, “Dopamine D2 receptor expression in hippocampus and parahippocampal cortex of rat, cat, and human in relation to tyrosine hydroxylase-immunoreactive fibers,” Hippocampus, 4, No. 3, 354–373 (1994).

    Google Scholar 

  28. H. C. Grunze, D. G. Rainnie, M. E. Hasselmo, et al., “NMDAdependent modification of CA1 local circuit inhibition,” J. Neurosci., 16, No. 6, 2034–2043 (1996).

    Google Scholar 

  29. W. Jin and C. Chavkin, “Mu opioids enhance mossy fiber synaptic transmission indirectly by reducing GABAB receptor activation,” Brain Res., 821, No. 2, 286–293 (1999).

    Google Scholar 

  30. S. Kaneko, T. Maeda, and M. Satoh, “Cognitive enhancers and hippocampal long-term potentiation in vitro,” Behav. Brain Res., 83, No. 1-2, 45–49 (1997).

    Google Scholar 

  31. I. Katona, L. Acsady, and T. F. Freund, “Postsynaptic targets of somatostatin-immunoreactive interneurons in the rat hippocampus,” Neurosci., 88, No. 1, 37–55 (1999).

    Google Scholar 

  32. K. Kawa, “Distribution and functional properties of 5-HT3 receptors in the rat hippocampal dentate gyrus: a patch-clamp study,” J. Neurophysiol., 71, No. 5, 1935–1947 (1994).

    Google Scholar 

  33. M. Kouznetsova and A. Nistri, “Modulation by substance P of synaptic transmission in the mouse hippocampal slice,” Eur. J. Neurosci., 10, No. 10, 3076–3084 (1998).

    Google Scholar 

  34. M. Kouznetsova and A. Nistri, “Facilitation of cholinergic transmission by substance P methyl ester in the mouse hippocampal slice preparation,” Eur. J. Neurosci., 12, No. 2, 585–594 (2000).

    Google Scholar 

  35. Y. Levkovitz and M. Segal, “Serotonin 5-HT1A receptors modulate hippocampal reactivity to afferent stimulation,” J. Neurosci., 17, No. 14, 5591–5598 (1997).

    Google Scholar 

  36. W. B. Levy, N. L. Desmond, and D. X. Zhang, “Perforant path activation modulates the induction of long-term potentiation of Schaffer collateral - hippocampal CA1 response: theoretical and experimental analysis,” Learn. Mem., 4, No. 6, 510–518 (1998).

    Google Scholar 

  37. H. Liu, A. M. Mazarati, H. Katsumori, et al., “Substance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus,” Proc. Natl. Acad. Sci. USA, 96, No. 9, 5286–5291 (1999).

    Google Scholar 

  38. C. R. Lupica, “Delta and mu enkephalins inhibit spontaneous GABA-mediated IPSPs via a cyclic AMP-independent mechanism in rat hippocampus,” J. Neurosci., 15, No. 3, 737–749 (1995).

    Google Scholar 

  39. T. Maeda, S. Kaneko, and M. Satoh, “Bidirectional modulation of long-term potentiation by carbachol via M1 and M2 muscarinic receptors in guinea pig hippocampal mossy fiber-CA3 synapses,” Brain Res., 619, No. 1-2, 324–330 (1993).

    Google Scholar 

  40. C. J. McBain, T. J. di Chiara, and J. A. Kauer, “Activation of metabotropic glutamate receptors differentially affects two classes of hippocampal interneurons and potentiates excitatory synaptic transmission,” J. Neurosci., 14, No. 7, 4433–4445 (1994).

    Google Scholar 

  41. A. R. McQuiston and D. V. Madison, “Muscarinic receptor activity induces an afterdepolarization in a subpopulation of hippocampal CA1 interneurons,” J. Neurosci., 19, No. 14, 5703–5710 (1999).

    Google Scholar 

  42. T. Melander, W. A. Staines, and A. Rokaeus, “Galanin-like immunoreactivity in hippocampal afferents in the rat, with special reference to cholinergic and noradrenergic inputs,” Neurosci., 19, No. 1, 223–240 (1986).

    Google Scholar 

  43. R. Miettinen and T. F. Freund, “Neuropeotide Y-containing interneurons in the hippocampus receive synaptic input from median raphe and GABAergic septal afferents,” Neuropeptides, 22, No. 3, 185–193 (1992).

    Google Scholar 

  44. D. D. Mott and D. V. Lewis, “The pharmacology and function of central GABAB receptors,” Int. Rev. Neurobiol., 36, 97–223 (1994).

    Google Scholar 

  45. D. D. Mott, Q. Li, M. M. Okazaki, et al., “GABAB receptor-mediated currents in interneurons of the dentate-hilus border,” J. Neurophysiol., 82, No. 3, 1438–1450 (1999).

    Google Scholar 

  46. N. A. Otmakhova and J. E. Lisman, “D1/D5 dopamine receptor activation increases the magnitude of early long-term potentiation at CA1 hippocampal synapses,” J. Neurosci., 16, No. 23, 7478–7486 (1996).

    Google Scholar 

  47. N. A. Otmakhova and J. E. Lisman “Dopamine selectively inhibits the direct cortical pathway to the CA1 hippocampal region,” J. Neurosci., 19, No. 4, 1437–1445 (1999).

    Google Scholar 

  48. P. Parra, A. I. Gulyas, and R. Miles, “How many subtypes of inhibitory cells in the hippocampus?” Neuron, 20, No. 5, 983–993 (1998).

    Google Scholar 

  49. P. Piguet and R. A. North, “Opioid actions at mu and delta receptors in rat dentate gyrus in vitro,” J. Pharmacol. Exptl. Ther., 266, 1139–1146 (1993).

    Google Scholar 

  50. N. Ropert and N. Guy, “Serotonin facilitates GABAergic transmission in the CA1 region of rat hippocampus in vitro,” J. Physiol. (England), 441, 121–136 (1991).

    Google Scholar 

  51. S. T. Rouse, M. J. Marino, L. T. Potter, et al., “Muscarinic receptor subtypes involved in hippocampal circuits,” Life Sci., 64, No. 6-7, 501–509 (1999).

    Google Scholar 

  52. S. Sagratella, R. Longo, and M. R. Domenici, “Selective opposite modulation of dentate granule cells excitability by mu and kappa opioids in rat hippocampal slices,” Neurosci. Lett., 205, No. 1, 53–56 (1996).

    Google Scholar 

  53. S. Schmitz, R. M. Empson, and U. Heinemann, “Serotonin reduces inhibition via 5-HT1A receptors in area CA1 of rat hippocampal slices in vitro,” J. Neurosci., 15, No. 11, 7217–7225 (1995).

    Google Scholar 

  54. M. Segal and J. M. Auerbach, “Muscarinic receptors involved in hippocampal plasticity,” Life Sci., 60, No. 13-14, 1085–1091 (1997).

    Google Scholar 

  55. O. Selbach, R. E. Brown, and H. L. Haas, “Long-term increase of hippocampal excitability by histamine and cyclic AMP,” Neuropharmacology, 36, No. 11-12, 1539–1548 (1997).

    Google Scholar 

  56. Y. Shimoshige, T. Maeda, S. Kaneko, et al., “Involvement of M2 receptor in an enhancement of long-term potentiation by carbachol in Schaffer collateral-CA1 synapses of hippocampal slices,” Neurosci. Res., 27, No. 2, 175–180 (1997).

    Google Scholar 

  57. I. Silkis, “The unitary modification rules for neural networks with excitatory and inhibitory synaptic plasticity,” BioSystems, 48, No. 1-3, 205–213 (1998).

    Google Scholar 

  58. I. Silkis, “Synaptic plasticity in the cortico-basal ganglia-thalamocortical circuit. I. Modification rules for excitatory and inhibitory synapses in the striatum,” BioSystems, 57, No. 3, 187–196 (2000).

    Google Scholar 

  59. M. L. Simmons and C. Chavkin, “Endogenous opioid regulation of hippocampal function,” Int. Rev. Neurobiol., 39, 145–196 (1996).

    Google Scholar 

  60. P. M. Steele and M. D. Mauk, “Inhibitory control of LTP and LTD: stability of synaptic strength,” J. Neurophysiol., 81, No. 4, 1559–1566 (1999).

    Google Scholar 

  61. A. Stelzer and H. Shi, “Impairment of GABAA receptor function by N-methyl-D-aspartate-mediated calcium influx in isolated CA1 pyramidal cells,” Neurosci., 62, No. 3, 813–828 (1994).

    Google Scholar 

  62. K. R. Svoboda, C. E. Adams, and C. R. Lupica, “Opioid receptor subtype expression defines morphologically distinct classes of hippocampal interneurons,” J. Neurosci., 19, No. 1, 85–95 (1999).

    Google Scholar 

  63. G. W. Terman, C. T. Drake, M. L. Simmons, et al., “Opioid modulation of recurrent excitation in the hippocampal dentate gyrus,” J. Neurosci., 20, No. 12, 4379–4388 (2000).

    Google Scholar 

  64. K. Toth, T. F. Freund, and R. Miles, “Disinhibition of rat hippocampal pyramidal cells by GABAergic afferents from the septum,” J. Physiol. (England), 500, No. 2, 463–474 (1997).

    Google Scholar 

  65. K. Toth, G. Suares, J. J. Lawrence, et al., “Differential mechanisms of transmission at three types of mossy fiber synapse,” J. Neurosci., 20, No. 22, 8279–8289 (2000).

    Google Scholar 

  66. K. Tsou, K. Mackie, M. C. Sanudo-Pena, and J. M. Walker, “Cannabinoid CB1 receptors are localized primarily on cholecystokinin-containing GABAergic interneurons in the rat hippocampal formation,” Neurosci., 93, No. 3, 969–975 (1999).

    Google Scholar 

  67. R. Y. Wang and V. L. Arvanov, “M100907, a highly selective 5-HT2A receptor antagonist and a potential atypical antipsychotic drug, facilitates induction of long-term potentiation in area CA1 of the rat hippocampal slice,” Brain Res., 779, No. 1-2, 309–313 (1998).

    Google Scholar 

  68. J. H. Wang and A. Stelzer, “Shared calcium signaling pathways in the induction of long-term potentiation and synaptic disinhibition in CA1 pyramidal cell dendrites,” J. Neurophysiol., 75, No. 4, 1687–1702 (1996).

    Google Scholar 

  69. Y. Yanovsky and H. L. Haas, “Long-term suppression of synaptic transmission by tetanization of a single pyramidal cell in the mouse hippocampus in vitro,” J. Physiol. (England), 515, No. 3, 757–767 (1999).

    Google Scholar 

  70. Y. Yanovsky, O. A. Sergeeva, T. F. Freund, and H. L. Haas, “Activation of interneurons at the stratum oriens/alveus border suppresses excitatory transmission to apical dendrites in the CA1 area of the mouse hippocampus,” Neurosci., 77, No. 1, 87–96 (1997).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sil'kis, I.G. A Possible Mechanism for the Effect of Neuromodulators and Modifiable Inhibition on Long-Term Potentiation and Depression of the Excitatory Inputs to Hippocampal Principal Cells. Neurosci Behav Physiol 33, 529–541 (2003). https://doi.org/10.1023/A:1023960402109

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1023960402109

Navigation