Desynchronization of epileptiform activity by extracellular current pulses in rat hippocampal slices.

1. A single cathodic current pulse applied in the somatic CA1 region of the hippocampus was found to induce a large decrease in the amplitude of the population spike. 2. Intracellular recordings showed intense cellular firing suggesting the amplitude decrease could not be attributed to a decrease in neuronal firing. 3. Simultaneous intracellular and extracellular potentials were recorded to analyse the synchronization of neuronal firing in the CA1 region. Action potentials were synchronized with the first population spike but this synchronization decreased with subsequent spikes. Histograms of the phase of the action potentials displayed a normal distribution. 4. Histograms of the phases of the action potentials following the application of the ‘singular stimulus’ (one producing a singular response) revealed a uniform distribution of the phases suggesting that the neuronal population was desynchronized. 5. This desynchronization effect of the singular stimulus was verified by double intracellular recordings. The simultaneous firing of two neurons could be desynchronized by the application of the singular stimulus. 6. These findings indicate that it is possible to desynchronize a neuronal pool with the application of a single current pulse. In addition, the results show that it is possible for a neuronal population to fire a large number of action potentials with no resulting evoked potentials in the extracellular space.

[1]  H. Haas,et al.  Synchronized bursting of CA1 hippocampal pyramidal cells in the absence of synaptic transmission , 1982, Nature.

[2]  W. R. Adey,et al.  Comparison between the effects of extracellular direct and sinusoidal currents on excitability in hippocampal slices , 1986, Brain Research.

[3]  F. Dudek,et al.  Coupling in rat hippocampal slices: Dye transfer between CA1 pyramidal cells , 1982, Brain Research Bulletin.

[4]  A. Winfree.  Phase control of neural pacemakers. , 1977, Science.

[5]  F. Dudek,et al.  Role of electrical interactions in synchronization of epileptiform bursts. , 1986, Advances in neurology.

[6]  F. Dudek,et al.  Electrotonic coupling between pyramidal cells: a direct demonstration in rat hippocampal slices. , 1981, Science.

[7]  A. Winfree,et al.  Sudden Cardiac Death: A Problem in Topology , 1983 .

[8]  R. Miles,et al.  Single neurones can initiate synchronized population discharge in the hippocampus , 1983, Nature.

[9]  C. Antzelevitch,et al.  Phase resetting and annihilation of pacemaker activity in cardiac tissue. , 1979, Science.

[10]  Robert S. Fisher,et al.  Animal models of the epilepsies , 1989, Brain Research Reviews.

[11]  D. Durand,et al.  Suppression of spontaneous epileptiform activity with applied currents , 1991, Brain Research.

[12]  F. Dudek,et al.  Synchronous epileptiform bursts without chemical transmission in CA2, CA3 and dentate areas of the hippocampus , 1984, Brain Research.

[13]  C. Nicholson,et al.  A model for the polarization of neurons by extrinsically applied electric fields. , 1986, Biophysical journal.

[14]  Charles H. Altshuler.  Excitability of the Heart , 1956 .

[15]  C. Nicholson,et al.  Theoretical analysis of field potentials in anisotropic ensembles of neuronal elements. , 1973, IEEE transactions on bio-medical engineering.

[16]  R. W. Turner,et al.  Extracellular fields influence transmembrane potentials and synchronization of hippocampal neuronal activity , 1984, Brain Research.

[17]  D. Prince,et al.  Penicillin‐induced epileptiform activity in the hippocampal in vitro preparation , 1977, Annals of neurology.

[18]  D. Prince,et al.  Cellular and field potential properties of epileptogenic hippocampal slices , 1978, Brain Research.

[19]  F. Dudek,et al.  Synchronous neural afterdischarges in rat hippocampal slices without active chemical synapses. , 1982, Science.

[20]  W Buño,et al.  Modulation of pacemaker activity by IPSP and brief length perturbations in the crayfish stretch receptor. , 1987, Journal of neurophysiology.

[21]  J. Jefferys,et al.  Influence of electric fields on the excitability of granule cells in guinea‐pig hippocampal slices. , 1981, The Journal of physiology.

[22]  R. Dingledine,et al.  Potassium-induced spontaneous electrographic seizures in the rat hippocampal slice. , 1988, Journal of neurophysiology.

[23]  D. Durand,et al.  Effects of applied currents on epileptiform bursts in vitro , 1991, Experimental Neurology.

[24]  W. W. Anderson,et al.  NMDA antagonists differentiate epileptogenesis from seizure expression in an in vitro model. , 1989, Science.

[25]  C. Nicholson,et al.  Modulation by applied electric fields of Purkinje and stellate cell activity in the isolated turtle cerebellum. , 1986, The Journal of physiology.

[26]  H. Pinsker.  Aplysia bursting neurons as endogenous oscillators. I. Phase-response curves for pulsed inhibitory synaptic input. , 1977, Journal of neurophysiology.

[27]  Desynchronization of epileptiform activity by phase resetting , 1989, Images of the Twenty-First Century. Proceedings of the Annual International Engineering in Medicine and Biology Society,.

[28]  D Paydarfar,et al.  Resetting of mammalian respiratory rhythm: existence of a phase singularity. , 1986, The American journal of physiology.

[29]  R. Andrew,et al.  Osmotic effects upon excitability in rat neocortical slices , 1990, Neuroscience.

[30]  S J Korn,et al.  Epileptiform burst activity induced by potassium in the hippocampus and its regulation by GABA-mediated inhibition. , 1987, Journal of neurophysiology.

[31]  D. Prince,et al.  Cellular Mechanisms of Interictal-Ictal Transitions , 1988 .

[32]  D. Durand,et al.  Electrical stimulation can inhibit synchronized neuronal activity , 1986, Brain Research.

[33]  A. Winfree.  When time breaks down , 1987 .

[34]  O. Creutzfeldt,et al.  Influence of transcortical d-c currents on cortical neuronal activity. , 1962, Experimental neurology.