Target-cell-specific facilitation and depression in neocortical circuits

Article metrics

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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.

References

  1. 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).

  2. 2

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

  3. 3

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

  4. 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).

  5. 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).

  6. 6

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

  7. 7

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

  8. 8

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

  9. 9

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

  10. 10

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

  11. 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).

  12. 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).

  13. 13

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

  14. 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).

  15. 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).

  16. 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).

  17. 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).

  18. 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).

  19. 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).

  20. 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).

  21. 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).

  22. 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).

  23. 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).

  24. 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).

  25. 25

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

  26. 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).

  27. 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).

  28. 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).

  29. 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).

  30. 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).

  31. 31

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

  32. 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).

  33. 33

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

  34. 34

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

  35. 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).

  36. 36

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

  37. 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).

  38. 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).

  39. 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).

  40. 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).

  41. 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).

  42. 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).

  43. 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).

Download references

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.

Author information

Correspondence to R. Lujan.

Rights and permissions

Reprints and Permissions

About this article

Further reading