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Single granule cells reliably discharge targets in the hippocampal CA3 network in vivo

Abstract

Processing of neuronal information depends on interactions between the anatomical connectivity and cellular properties of single cells. We examined how these computational building blocks work together in the intact rat hippocampus. Single spikes in dentate granule cells, controlled intracellularly, generally failed to discharge either interneurons or CA3 pyramidal cells. In contrast, trains of spikes effectively discharged both CA3 cell types. Increasing the discharge rate of the granule cell increased the discharge probability of its target neuron and decreased the delay between the onset of a granule cell train and evoked firing in postsynaptic targets. Thus, we conclude that the granule cell to CA3 synapses are 'conditional detonators,' dependent on granule cell firing pattern. In addition, we suggest that information in single granule cells is converted into a temporal delay code in target CA3 pyramidal cells and interneurons. These data demonstrate how a neural circuit of the CNS may process information.

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Figure 1: Classification of extracellular units.
Figure 2: Spike transmission between a granule cell and its interneuron and pyramidal cell targets in CA3c.
Figure 3: Spike transmission dynamics.
Figure 4: Frequency dependence of granule cell–CA3 spike transmission.
Figure 5: Spike transmission from a granule cell to CA3c during physiological granule cell firing patterns.

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References

  1. Collier, T.J., Miller, J.S., Travis, J. & Routtenberg, A. Dentate gyrus granule cells and memory: electrical stimulation disrupts memory for places rewarded. Behav. Neural Biol. 34, 227–239 (1982).

    Article  CAS  Google Scholar 

  2. Jung, M.W. & McNaughton, B.L. Spatial selectivity of unit activity in the hippocampal granular layer. Hippocampus 3, 165–182 (1993).

    Article  CAS  Google Scholar 

  3. Rolls, E.T. . in Neural Models of Plasticity (eds. Byrne, J. H. & Berry, W. O.) 240–265 (Academic, San Diego, 1989).

    Book  Google Scholar 

  4. Sloviter, R.S. The functional organization of the hippocampal dentate gyrus and its relevance to the pathogenesis of temporal lobe epilepsy. Ann. Neurol. 35, 640–654 (1994).

    Article  CAS  Google Scholar 

  5. Mody, I., Lambert, J.D. & Heinemann, U. Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices. J. Neurophysiol. 57, 869–888 (1987).

    Article  CAS  Google Scholar 

  6. Lothman, E.W., Stringer, J.L. & Bertram, E.H. . in The Dentate Gyrus and its Role in Seizures (eds. Ribak, C. E., Gall, C. M. & Mody, I.) 301–313 (Elsevier, Amsterdam, 1992).

    Google Scholar 

  7. Boss, B.D., Peterson, G.M. & Cowan, W.M. On the number of neurons in the dentate gyrus of the rat. Brain Res. 338, 144–150 (1985).

    Article  CAS  Google Scholar 

  8. Amaral, D.G., Ishizuka, N. & Claiborne, B. Neurons, numbers and the hippocampal network. Prog. Brain Res. 83, 1–11 (1990).

    Article  CAS  Google Scholar 

  9. Amaral, D.G. & Dent, J.A. Development of the mossy fibers of the dentate gyrus: I. A light and electron microscopic study of the mossy fibers and their expansions. J. Comp. Neurol. 195, 51–86 (1981).

    Article  CAS  Google Scholar 

  10. Frotscher, M., Soriano, E. & Misgeld, U. Divergence of hippocampal mossy fibers. Synapse 16, 148–160 (1994).

    Article  CAS  Google Scholar 

  11. Acsady, L., Kamondi, A., Sik, A., Freund, T. & Buzsáki, G. GABAergic cells are the major postsynaptic targets of mossy fibers in the rat hippocampus. J. Neurosci. 18, 3386–3403 (1998).

    Article  CAS  Google Scholar 

  12. Maccaferri, G., Toth, K. & McBain, C.J. Target-specific expression of presynaptic mossy fiber plasticity. Science 279, 1368–1370 (1998).

    Article  CAS  Google Scholar 

  13. Toth, K., Suares, G., Lawrence, J.J., Philips-Tansey, E. & McBain, C.J. Differential mechanisms of transmission at three types of mossy fiber synapse. J. Neurosci. 20, 8279–8289 (2000).

    Article  CAS  Google Scholar 

  14. McNaughton, B.L. & Morris, R.G.M. Hippocampal synaptic enhancement and information storage within a distributed memory system. Trends Neurosci. 10, 408–415 (1987).

    Article  Google Scholar 

  15. Markram, H., Lubke, J., Frotscher, M. & Sakmann, B. Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science 275, 213–215 (1997).

    Article  CAS  Google Scholar 

  16. Magee, J.C. & Johnston, D. A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons. Science 275, 209–213 (1997).

    Article  CAS  Google Scholar 

  17. Henze, D.A., Urban, N.N. & Barrionuevo, G. The multifarious hippocampal mossy fiber pathway: a review. Neuroscience 98, 407–427 (2000).

    Article  CAS  Google Scholar 

  18. Henze, D.A. et al. Intracellular features predicted by extracellular recordings in the hippocampus in vivo. J. Neurophysiol. 84, 390–400 (2000).

    Article  CAS  Google Scholar 

  19. Csicsvari, J., Hirase, H., Czurko, A. & Buzsáki, G. Reliability and state dependence of pyramidal cell-interneuron synapses in the hippocampus: an ensemble approach in the behaving rat. Neuron 21, 179–189 (1998).

    Article  CAS  Google Scholar 

  20. Ranck, J.B. Jr. Studies on single neurons in dorsal hippocampal formation and septum in unrestrained rats. I. Behavioral correlates and firing repertoires. Exp. Neurol. 41, 461–531 (1973).

    Article  Google Scholar 

  21. Galarreta, M. & Hestrin, S. Spike transmission and synchrony detection in networks of GABAergic interneurons. Science 292, 2295–2299 (2001).

    Article  CAS  Google Scholar 

  22. Skaggs, W.E., McNaughton, B.L., Wilson, M.A. & Barnes, C.A. Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences. Hippocampus 6, 149–172 (1996).

    Article  CAS  Google Scholar 

  23. Rolls, E.T. . in The Computing Neuron (eds. Durbin, R., Miall, C. & Mitchison, G.) 125–159 (Addison-Wesley, Wokingham, 1989).

    Google Scholar 

  24. Lisman, J.E. Relating hippocampal circuitry to function: recall of memory sequences by reciprocal dentate-CA3 interactions. Neuron 22, 233–242 (1999).

    Article  CAS  Google Scholar 

  25. Paulsen, O. & Sejnowski, T.J. Natural patterns of activity and long-term synaptic plasticity. Curr. Opin. Neurobiol. 10, 172–179 (2000).

    Article  CAS  Google Scholar 

  26. Buzsáki, G. Two-stage model of memory trace formation: a role for “noisy” brain states. Neurosci. 31, 551–570 (1989).

    Article  Google Scholar 

  27. Chattarji, S., Stanton, P.K. & Sejnowski, T.J. Commissural synapses, but not mossy fiber synapses, in hippocampal field CA3 exhibit associative long-term potentiation and depression. Brain Res. 495, 145–150 (1989).

    Article  CAS  Google Scholar 

  28. Salin, P.A., Scanziani, M., Malenka, R.C. & Nicoll, R.A. Distinct short-term plasticity at two excitatory synapses in the hippocampus. Proc. Natl. Acad. Sci. USA 93, 13304–13309 (1996).

    Article  CAS  Google Scholar 

  29. Alle, H., Jonas, P. & Geiger, J.R. PTP and LTP at a hippocampal mossy fiber-interneuron synapse. Proc. Natl. Acad. Sci. USA 98, 14708–14713 (2001).

    Article  CAS  Google Scholar 

  30. Doherty, J. & Dingledine, R. Reduced excitatory drive onto interneurons in the dentate gyrus after status epilepticus. J. Neurosci. 21, 2048–2057 (2001).

    Article  CAS  Google Scholar 

  31. Scharfman, H.E., Kunkel, D.D. & Schwartzkroin, P.A. Synaptic connections of dentate granule cells and hilar neurons: results of paired intracellular recordings and intracellular horseradish peroxidase injections. Neuroscience 37, 693–707 (1990).

    Article  CAS  Google Scholar 

  32. Urban, N.N., Henze, D.A. & Barrionuevo, G. Revisiting the role of the hippocampal mossy fiber synapse. Hippocampus 11, 408–417 (2001).

    Article  CAS  Google Scholar 

  33. Marshall, L. et al. Hippocampal pyramidal cell-interneuron spike transmission is frequency dependent and responsible for place modulation of interneuron discharge. J. Neurosci. 22, RC197 (2002).

  34. Lorincz, A. & Buzsáki, G. Two-phase computational model training long-term memories in the entorhinal-hippocampal region. Ann. NY Acad. Sci. 911, 83–111 (2000).

    Article  CAS  Google Scholar 

  35. Tank, D.W. & Hopfield, J.J. Neural computation by concentrating information in time. Proc. Natl. Acad. Sci. USA 84, 1896–1900 (1987).

    Article  CAS  Google Scholar 

  36. Bi, G.Q. & Poo, M.M. Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type. J. Neurosci. 18, 10464–10472 (1998).

    Article  CAS  Google Scholar 

  37. O'Keefe, J. & Recce, M.L. Phase relationship between hippocampal place units and the EEG theta rhythm. Hippocampus 3, 317–330 (1993).

    Article  CAS  Google Scholar 

  38. Harris, K.D. et al. Spike train dynamics predicts theta-related phase precession in hippocampal pyramidal cells. Nature (in press).

  39. Vanderwolf, C.H. Cerebral activity and behavior: control by central cholinergic and serotonergic systems. Int. Rev. Neurobiol. 30, 225–340 (1988).

    Article  CAS  Google Scholar 

  40. Ylinen, A. et al. Sharp wave-associated high-frequency oscillation (200 Hz) in the intact hippocampus: network and intracellular mechanisms. J. Neurosci. 15, 30–46 (1995).

    Article  CAS  Google Scholar 

  41. Hara, K. & Harris, R.A. The anesthetic mechanism of urethane: the effects on neurotransmitter-gated ion channels. Anesth. Analg. 94, 313–318 (2002).

    CAS  PubMed  Google Scholar 

  42. Harris, K.D., Henze, D.A., Csicsvari, J., Hirase, H. & Buzsáki, G. Accuracy of tetrode spike separation as determined by simultaneous intracellular and extracellular measurements. J. Neurophysiol. 84, 401–414 (2000).

    Article  CAS  Google Scholar 

  43. O'Keefe, J. & Dostrovsky, J. The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res. 34, 171–175 (1971).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the National Institutes of Health (NS34994, MH54671, MH12403, NS43157, 5P41RR009754).

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Correspondence to György Buzsáki.

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Henze, D., Wittner, L. & Buzsáki, G. Single granule cells reliably discharge targets in the hippocampal CA3 network in vivo. Nat Neurosci 5, 790–795 (2002). https://doi.org/10.1038/nn887

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