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Target-cell-specific facilitation and depression in neocortical circuits

Abstract

In neocortical circuits, repetitively active neurons evoke unitary postsynaptic potentials (PSPs) whose peak amplitudes either increase (facilitate) or decrease (depress) progressively. To examine the basis for these different synaptic responses, we made simultaneous recordings from three classes of neurons in cortical layer 2/3. We induced repetitive action potentials in pyramidal cells and recorded the evoked unitary excitatory (E)PSPs in two classes of GABAergic neurons. We observed facilitation of EPSPs in bitufted GABAergic interneurons, many of which expressed somatostatin immunoreactivity. EPSPs recorded from multipolar interneurons, however, showed depression. Some of these neurons were immunopositive for parvalbumin. Unitary inhibitory (I)PSPs evoked by repetitive stimulation of a bitufted neuron also showed a less pronounced but significant difference between the two target neurons. Facilitation and depression involve presynaptic mechanisms, and because a single neuron can express both behaviors simultaneously, we infer that local differences in the molecular structure of presynaptic nerve terminals are induced by retrograde signals from different classes of target neurons. Because bitufted and multipolar neurons both formed reciprocal inhibitory connections with pyramidal cells, the results imply that the balance of activation between two recurrent inhibitory pathways in the neocortex depends on the frequency of action potentials in pyramidal cells.

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Figure 1: Selection of three classes of neurons in layer 2/3.
Figure 2: Anatomical and immunocytochemical identification of layer 2/3 neurons.
Figure 3: Frequency-dependent, short-term modification of glutamatergic excitatory postsynaptic potentials evoked in two classes of neurons.
Figure 4: Frequency-dependent short-term modification of GABAergic inhibitory postsynaptic potentials in two classes of interneurons.
Figure 6: Reciprocal excitatory and inhibitory connections between pyramidal and nonpyramidal cells.
Figure 5: Release mechanisms in presynaptic terminals underlie frequency-dependent short-term modification.

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References

  1. Thomson, A. M., Deuchars, J. & West, D. C. Single axon excitatory postsynaptic potentials in neocortical interneurons exhibit pronounced paired pulse facilitation. Neuroscience 54, 347–360 (1993).

    Article  CAS  Google Scholar 

  2. Thomson, A. M. & Deuchars, J. Synaptic interactions in neocortical local circuits: dual intracellular recordings in vitro. Cereb. Cortex. 7, 510–522 (1997).

    Article  CAS  Google Scholar 

  3. Markram, H. & Tsodyks, M. Redistribution of synaptic efficacy between neocortical pyramidal neurons. Nature 382, 807–810 (1996).

    Article  CAS  Google Scholar 

  4. Thomson, A. M. Activity-dependent properties of synaptic transmission at two classes of connections made by rat neocortical pyramid axons in vitro. J. Physiol. (Lond.) . 502, 131–147 ( 1997).

    Article  CAS  Google Scholar 

  5. Buhl, E. H. et al. Effect, number and location of synapses made by single pyramidal cells onto aspiny interneurones of cat visual cortex. J. Physiol. (Lond.) 500, 689–713 ( 1997).

    Article  CAS  Google Scholar 

  6. Del Castillo, J. & Katz, B. Statistical factors involved in neuromuscular facilitation and depression. J. Physiol. (Lond.) 124 , 574–585 (1954).

    Article  CAS  Google Scholar 

  7. Katz, B. & Miledi, R. The role of calcium in neuromuscular facilitation . J. Physiol. (Lond.) 195, 481– 492 (1968).

    Article  CAS  Google Scholar 

  8. Rahamimoff, R. A dual effect of calcium ions on neuromuscular facilitation. J. Physiol. (Lond.) 195, 471–480 ( 1968).

    Article  CAS  Google Scholar 

  9. Betz, W.J. Depression of transmitter release at the neuromuscular junction of the frog. J. Physiol. (Lond.) 206, 629–644 (1970).

    Article  CAS  Google Scholar 

  10. Zucker, R.S. Short-term synaptic plasticity. Annu. Rev. Neurosci. 12, 13–31 (1989).

    Article  CAS  Google Scholar 

  11. Winslow, J.L, Duffy, S.N. & Charlton, M.P. Homosynaptic facilitation of transmitter release in crayfish is not affected by mobile calcium chelators: Implications for the residual ionized calcium hypothesis from electrophysiological and computational analyses . J. Neurophysiol. 72, 1769– 1793 (1994).

    Article  CAS  Google Scholar 

  12. Atluri, P.P. & Regehr, W.G. Determinants of the time course of facilitation at the granule cell to Purkinje cell synapses. J. Neurosci. 16, 5661–5671 (1996).

    Article  CAS  Google Scholar 

  13. Zucker, R.S. Exocytosis: a molecular and physiological perspective. Neuron 17 , 1049–1055 (1996).

    Article  CAS  Google Scholar 

  14. Frank, E. Matching of facilitation at the neuromuscular junction of the lobster: a possible case for influence of muscle on nerve. J. Physiol. (Lond.) 233, 635–658 (1973).

    Article  CAS  Google Scholar 

  15. Muller, K.J. & Nicholls, J.G. Different properties of synapses between a single sensory neuron and two different motor cells in the leech CNS. J. Physiol. (Lond.) 238, 357– 369 (1974).

    Article  CAS  Google Scholar 

  16. Koerber, H.R. & Mendell, L.M. Modulation of synaptic transmission at Ia-afferent fiber connections on motoneurons during high-frequency stimulation: Role of postsynaptic target. J. Neurophysiol. 65, 590–597 (1991).

    Article  CAS  Google Scholar 

  17. Davis, G.W. & Murphey, R.K. A role for postsynaptic neurons in determining presynaptic release properties in the cricket CNS: Evidence for retrograde control of facilitation. J. Neurosci. 13, 3827–3838 (1993).

    Article  CAS  Google Scholar 

  18. Katz, P.S., Kirk, M.D. & Govind, C.K. Facilitation and depression at different branches of the same motor axon: Evidence for presynaptic differences in release. J. Neurosci. 13, 3075–3089 (1993).

    Article  CAS  Google Scholar 

  19. Brodin, L., Shupliakov, O., Pieribone, V.A., Hellgren, J. & Hill, R.H. The reticulospinal glutamate synapse in lamprey: Plasticity and presynaptic variability. J. Neurophysiol. 72, 592–604 (1994).

    Article  CAS  Google Scholar 

  20. Davis, G.W. & Murphey, R.K. Long-term regulation of short-term transmitter release properties: retrograde signaling and synaptic development . Trends Neurosci. 17, 9– 13 (1994).

    Article  CAS  Google Scholar 

  21. Mennerick, S. & Zorumski, C.F. Paired-pulse modulation of fast excitatory synaptic currents in microcultures of rat hippocampal neurons. J. Physiol. (Lond.) 488, 85–101 (1995).

    Article  CAS  Google Scholar 

  22. Ali, A.B. & Thomson, A.M. Brief train depression and facilitation at pyramid-interneurone connections in slices of rat hippocampus; paired recordings with biocytin filling. J. Physiol. (Lond.) 501, 9P (1997).

    Google Scholar 

  23. Ali, A.B. & Thomson, A.M. Facilitating pyramid to horizontal oriens-alveus interneurone inputs: dual intracellular recordings in slices of rat hippocampus. J. Physiol. (Lond.) 507, 185–199 (1998).

    Article  CAS  Google Scholar 

  24. Ali, A.B., Deuchars J., Pawelzik H. & Thomson, A.M. CA1 pyramidal to basket and bistratified cell EPSPs: dual intracellular recordings in rat hippocampal slices. J. Physiol. (Lond.) 507, 201–217 (1998).

    Article  CAS  Google Scholar 

  25. Atwood, H.L. & Bittner, G.D. Matching of excitatory and inhibitory inputs to crustacean muscle fibers. J. Neurophysiol. 34, 157–170 (1970).

    Article  Google Scholar 

  26. Bower, J.M. & Haberly, L.B. Facilitating and nonfacilitating synapses on pyramidal cells: A correlation between physiology and morphology . Proc. Natl. Acad. Sci. USA 83, 1115– 1119 (1986).

    Article  CAS  Google Scholar 

  27. Stratford, K.J., Tarczy-Hornoch, K., Martin, K.A.C., Bannister, N.J. & Jack, J.J.B. Excitatory synaptic inputs to spiny stellate cells in cat visual cortex. Nature 382, 258–261 (1996).

    Article  CAS  Google Scholar 

  28. Mason, A., Nicoll A. & Stratford, K. Synaptic transmission between individual pyramidal neurons of the rat visual cortex in vitro J. Neurosci.. 11, 72– 84 (1991).

    Article  CAS  Google Scholar 

  29. Schröder, R. & Luhmann, H.J. Morphology, electrophysiology and pathophysiology of supragranular neurons in rat primary somatosensory cortex. Eur. J. Neurosci. 9, 163– 176 (1997).

    Article  Google Scholar 

  30. Somogyi, P., Tamas, G., Lujan R. & Buhl, E.H. Salient features of synaptic organization in the cerebral cortex. Brain Res. Rev. 26, 113–135 ( 1998).

    Article  CAS  Google Scholar 

  31. Kawaguchi, Y. & Kubota, Y. GABAergic cell subtypes and their synaptic connections in rat frontal cortex. Cereb. Cortex, 7, 476–486 (1997).

    Article  CAS  Google Scholar 

  32. Somogyi, P. et al. Different populations of GABAergic neurons in the visual cortex and hippocampus of cat contain somatostatin- or cholecystokinin-immunoreactive material. J. Neurosci. 4, 2590–2603 (1984).

    Article  CAS  Google Scholar 

  33. Faber, D.S. & Korn, H. Applicability of the coefficient of variation method for analyzing synaptic plasticity. Biophys. J. 60, 1288–1294 ( 1991).

    Article  CAS  Google Scholar 

  34. Gil, Z., Connors I.W. & Amitai, Y. Differential regulation of neocortical synapses by neuromodulators and activity . Neuron 19, 679–686 (1997).

    Article  CAS  Google Scholar 

  35. Glitsch M ., Llano I. & Marty, A. Glutamate as a candidate retrograde messenger at interneurone-Purkinje cell synapses of rat cerebellum. J. Physiol. (Lond.) 497 , 531–537 (1996).

    Article  CAS  Google Scholar 

  36. Shigemoto, R. et al. Target-cell-specific concentration of a metabotropic glutamate receptor in the presynaptic active zone. Nature 381, 523–525 (1996).

    Article  CAS  Google Scholar 

  37. Baude, A. et al. The metabotropic glutamate receptor (mGluR1α) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron 11, 771–787 ( 1993).

    Article  CAS  Google Scholar 

  38. Blasco-Ibanez, J.M. & Freund, T.F. Synaptic input of horizontal interneurons in stratum oriens of the hippocampal CA1 subfield: Structural basis of feed-back activation. Eur. J. Neurosci. 7, 2170– 2180 (1995).

    Article  CAS  Google Scholar 

  39. Han, Z.-H., Buhl, E.H., Lörinczi Z. & Somogyi, P. A high degree of spatial selectivity in the axonal and dendritic domains of physiologically identified local-circuit neurons in the dentate gyrus of the rat hippocampus . Eur. J. Neurosci. 5, 395– 410 (1993).

    Article  CAS  Google Scholar 

  40. Maccaferri, G. & McBain, C.J. Passive propagation of LTD to stratum oriens-alveus inhibitory neurons modulates the temporoammonic input to the hippocampal CA1 region. Neuron 15, 137– 145 (1995).

    Article  CAS  Google Scholar 

  41. Stuart, G.J., Dodt, H.U. & Sakmann, B. Patch clamp recordings from the soma and dendrites of neurones in brain slices using infrared video microscopy. Pflügers Arch. 423, 511–518 (1993).

    Article  CAS  Google Scholar 

  42. Markram, H., Lübke, J., Frotscher, M., Roth, A. & Sakmann, B. Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex. J. Physiol. (Lond.) 500, 409–440 (1997).

    Article  CAS  Google Scholar 

  43. Vincent S.R., McIntosh, C.H., Buchan, A.M. & Brown, J.C. Central somatostatin systems revealed with monoclonal antibodies. J. Comp. Neurol. 238, 169–186 (1985).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank E. Neher, B. Katz and G. Borst for their comments on the manuscript and B. Katz for suggesting the term 'local release fraction' of vesicles. We also thank J. C. Brown, at the MRC of Canada Group on Regulatory Peptides, Vancouver, for the gift of monoclonal antibodies to somatostatin, Z. Nusser and J. D. B. Roberts for assistance with digital micrography and Z. Ahmad for excellent technical assistance.

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Reyes, A., Lujan, R., Rozov, A. et al. Target-cell-specific facilitation and depression in neocortical circuits . Nat Neurosci 1, 279–285 (1998). https://doi.org/10.1038/1092

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