Abstract
The simultaneous discharge of hippocampal CA3 pyramidal cells is a widely studied in vitro model of physiological and pathological network synchronization. This network is rapidly activated because of extensive positive feedback mediated by recurrent axon collaterals. Here we show that population-burst duration is limited by depletion of the releasable glutamate pool at these recurrent synapses. Postsynaptic inhibitory conductances further limit burst duration but are not necessary for burst termination. The interval between bursts in vitro depends on the rate of replenishment of releasable glutamate vesicles and the probability of release of those vesicles at recurrent synapses. Therefore presynaptic factors controlling glutamate release at recurrent synapses regulate the probability and duration of synchronous discharges of the CA3 network.
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References
Li, X.G., Somogyi, P., Ylinen, A. & Buzsaki, G. The hippocampal CA3 network: an in vivo intracellular labeling study. J. Comp. Neurol. 339, 181–208 ( 1994).
MacVicar, B.A. & Dudek, F.E. Local circuit interactions in rat hippocampus: interactions between pyramidal cells. Brain Res. 242, 341–344 (1982).
Miles, R. & Wong, R.K.S. Single neurones can initiate synchronized population discharge in the hippocampus. Nature 306 , 371–373 (1983).
Buzsaki, G. Hippocampal sharp waves: their origin and significance. Brain Res. 398:242–252 (1986).
Chrobak, J.J. & Buzsaki, G. High-frequency oscillations in the output networks of the hippocampal-entorhinal axis of the freely behaving rat. J. Neurosci. 16, 3056– 3066 (1996).
Traub, R.D. & Miles, R. in Neuronal networks of the hippocampus Ch. 6 (Cambridge Univ. Press, 1991).
Traub, R.D., Knowles, W.D., Miles, R. & Wong, R.K.S. Synchronized afterdischarges in the hippocampus: simulation studies of the cellular mechanism. Neuroscience 12, 1191–1200 (1984).
Jefferys, J.G.R. in The Epilepsies, 4th edn (eds Laidlaw, J., Richens, A. & Chadwick, D.W.) 241–276 (Edinburgh, Churchill Livingstone, 1993).
Wong, R.K.S. & Prince, D.A. Afterpotential generation in hippocampal pyramidal cells. J. Neurophysiol. 45, 86 –97 (1981).
Bush, P.C. & Sejnowski, T.J. Effects of inhibition and dendritic saturation in simulated neocortical pyramidal cells. J. Neurophysiol. 71, 2183–2193 ( 1994).
Miles, R., Wong, R.K.S. & Traub, R.D. Synchronized afterdischarges in the hippocampus: contribution of local synaptic interactions. Nature Neuroscience 12, 1179– 1189 (1984).
Rutecki, P.A., Lebeda, F.J. & Johnston, D. Epileptiform activity in the hippocampus produced by tetraethylammonium . J. Neurophysiol. 64, 1077– 1088 (1990).
Mueller, A.L. & Dunwiddie, T.V. Anticonvulsant and proconvulsant actions of alpha- and beta-noradrenergic agonists on epileptiform activity in rat hippocampus in vitro. Epilepsia 24, 57–64 (1983).
Chamberlin, N.L. & Dingledine, R. Control of epileptiform burst rate by CA3 hippocampal cell afterhyperpolarizations. Brain Res . 492, 337–346 ( 1989).
Mayr, O. The origins of feedback control (MIT Press, Cambridge, Massachusetts, 1970).
Martina, M. & Jonas, P. Functional differences in Na+ channel gating between fast-spiking interneurones and principal neurones of rat hippocampus . J. Physiol. 505, 593– 603 (1997).
Scanziani, M. et al. Use-dependent increases in glutamate concentration activate presynaptic metabotropic glutamate receptors. Nature 385, 630– 634 (1997).
Otis, T., Zhang, S. & Trussell, L.O. Direct measurement of AMPA receptor desensitization induced by glutamatergic synaptic transmission. J. Neurosci. 16, 7496–7504 (1996).
von Gersdorff, H., Schneggenburger, R., Weis, S. & Neher, E. Presynaptic depression at a calyx synapse: the small contribution of metabotropic glutamate receptors. J. Neurosci. 17, 8137 –8146 (1997).
Dobrunz, L.E. & Stevens, C.F. Heterogeneity of release probability, facilitation, and depletion at central synapses. Neuron 18, 995–1008 (1997).
Harris, K.M. & Sultan, P. Variation in the number, location, and size of synaptic vesicles provides an anatomical basis for the nonuniform probability of release at hippocampal CA1 synapses. Neuropharmacology 34, 1387–1395 ( 1995).
Schikorski, T. & Stevens, C.F. Quantitative ultrastructural analysis of hippocampal excitatory synapses. J. Neurosci. 17 , 5858–5867 (1997).
Liu, G. & Tsien, R.W. Properties of synaptic transmission at single hippocampal synaptic boutons. Nature 375, 404–408 (1995).
Stevens, C.F. & Tsujimoto, T. Estimates for the pool size of releasable quanta at a single central synapse and for the time required to fill the pool. Proc. Natl Acad. Sci. USA 92, 846–849 (1995).
Murthy, V.N., Sejnowski, T.J. & Stevens, C.F. Heterogenous release properties of visualized individual hippocampal synapses. Neuron 18, 599– 612 (1997).
Madison, D.V. & Nicoll, R.A. Noradrenaline blocks accommodation of pyramidal cell discharge in the hippocampus. Nature 299, 636–638 (1986).
Stevens, C.F. Quantal release of neurotransmitter and long-term potentiation. Neuron 10(suppl), 55–63 (1996).
Patneau D.K., Vyklicky L. Jr & Mayer M.L. Hippocampal neurons exhibit cyclothiazide-sensitive rapidly desensitizing responses to kainate. J Neurosci. 13, 3496–3509 (1993).
Chamberlin, N.L., Traub, R.D. & Dingledine R. Role of EPSPs in initiation of spontaneous synchronized burst firing in rat hippocampal neurons bathed in high potassium. J. Neurophysiol. 64, 1000–1008 (1990).
Fatt, P. & Katz, B. Spontaneous subthreshold activity at motor nerve endings. J. Physiol. 117, 109– 128 (1952).
Manabe T., Renner, P. & Nicoll, R.A. Postsynaptic contribution to long-term potentiation revealed by the analysis of miniature synaptic currents. Nature 355, 50–55 (1992).
Rosenmund, C. & Stevens, C.F. Definition of the readily releasable pool of vesicles at hippocampal synapses. Neuron 16 , 1197–1207 (1996).
Capogna, M., Gähwiler, B.H. & Thompson, S.M. Presynaptic inhibition of calcium-dependent and independent release elicited with ionmycin, gadolinium, and α-latrotoxin in the hippocampus. J. Neurophysiol. 75, 2017– 2028 (1996).
Dunwiddie, T.V. Endogenously released adenosine regulates excitability in the in vitro hippocampus. Epilepsia 21, 541–548 ( 1980).
Swartzwelder, H.S., Lewis, D.V., Anderson, W.W. & Wilson, W.A. Seizure-like events in brain slices: suppression by interictal activity. Brain Res. 410, 362–366 (1987).
Thompson, S.M. & Gähwiler, B.H. Activity-dependent disinhibition. II.effects of extracellular potassium, furosemide, and membrane potential on ECl in hippocampal CA3 neurons. J. Neurophysiol. 61, 512–523 (1989).
Anderson, C.M. & Jefferys, J.G.R. Ventral CA3 exhibits a lower threshold to disinhibition than dorsal hippocampus. Epilepsia 38(Supp 8), 16 (1997).
Korn, S.J., Giacchino, J.L., Chamberlin, N.L. & Dingledine, R. Epileptiform burst activity induced by potassium in the hippocampus and its regulation by GABA-mediated inhibition. J. Neurophysiol. 57, 325–340 (1987).
Scharfman, H.E. EPSPs of dentate gyrus granule cells during epileptiform bursts of dentate hilar "mossy" cells and area CA3 pyramidal cells in disinhibited rat hippocampal slices . J. Neurosci. 14, 6041– 6057 (1994).
Whittington, M.A. & Jefferys, J.G.R. Epileptic activity outlasts disinhibition after intrahippocampal tetanus toxin in the rat. J. Physiol. 481, 593–604 (1994).
Tanaka, K. et al. Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science 276, 1699– 1702 (1997).
Barbarosie, M. & Avoli, M. CA3-driven hippocampal-entorhinal loop controls rather than sustains in vitro limbic seizures. J. Neurosci. 17, 9308–9314 (1997).
Stasheff, S.F., Anderson, W.W., Clark, S. & Wilson, W.A. NMDA antagonists differentiate epileptogenesis from seizure expression in an in vitro model. Science 245, 648– 651 (1989).
Rafiq, A., DeLorenzo, R.J. & Coulter, D.A. Generation and propagation of epileptiform discharges in a combined entorhinal cortex/hippocampal slice. J. Neurophysiol. 70, 1962–1974 ( 1993).
Traub, R.D., Borck, C., Colling, S.B. & Jefferys J.G. On the structure of ictal events in vitro. Epilepsia 37, 879–891 (1996).
Taylor, G.W., Merlin, L.R. & Wong, R.K. Synchronized oscillations in hippocampal CA3 neurons induced by metabotropic glutamate receptor activation. J. Neurosci. 15, 8039–8052 (1995).
Traub R.D., Miles, R. & Jefferys, J.G. Synaptic and intrinsic conductances shape picrotoxin-induced synchronized after-discharges in the guinea-pig hippocampal slice. J Physiol. (Lond.) 461, 525–547 (1993).
Ylinen, A. et al. Intracellular correlates of hippocampal theta rhythm in identified pyramidal cells, granule cells, and basket cells. Hippocampus 5, 78–90 (1995).
Kim, U., Sanchez-Vives, M.V. & McCormick, D.A. Functional dynamics of GABAergic inhibition in the thalamus . Science 278, 130–134 (1997).
Staley, K.J., Soldo, B. & Proctor W. Ionic mechanisms of neuronal excitation by inhibitory GABAA receptors. Science 269, 977–981 ( 1995).
Acknowledgements
We thank Thomas Dunwiddie, Darrell Lewis, Charles Stevens, and Roger Traub for comments and discussions. This work was supported by the NIH and the Epilepsy Foundation of America.
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Staley, K., Longacher, M., Bains, J. et al. Presynaptic modulation of CA3 network activity. Nat Neurosci 1, 201–209 (1998). https://doi.org/10.1038/651
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DOI: https://doi.org/10.1038/651
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