Paired pulse suppression and facilitation in human epileptogenic hippocampal formation

Wilson, Charles L.; Khan, S; Engel, J; Isokawa, Masako; Babb, Thomas L.; Behnke, Eric

doi:10.1016/s0920-1211(98)00063-1

Cited by 92 publications

(72 citation statements)

References 64 publications

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“…The finding that granule cells always became less, rather than more, excitable over time is consistent with physiological studies in epileptic patients that indicate chronic hippocampal hyperinhibition (Cherlow et al, 1977;Colder et al, 1996;Wilson et al, 1998). The mechanism by which initial granule cell hyperexcitability is gradually reversed remains unclear, and could conceivably involve a wide variety of mechanisms, including changes in GABA A receptor dynamics (Coulter, 2000;Cohen et al, 2003;Goodkin et al, 2005).…”

Section: Possible Functional Implicationssupporting

confidence: 81%

Kainic acid‐induced recurrent mossy fiber innervation of dentate gyrus inhibitory interneurons: Possible anatomical substrate of granule cell hyperinhibition in chronically epileptic rats

Sloviter

Zappone

Harvey

et al. 2005

J of Comparative Neurology

141

110

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Kainic acid-induced neuron loss in the hippocampal dentate gyrus may cause epileptogenic hyperexcitability by triggering the formation of recurrent excitatory connections among normally unconnected granule cells. We tested this hypothesis by assessing granule cell excitability repeatedly within the same awake rats at different stages of the synaptic reorganization process initiated by kainate-induced status epilepticus (SE). Granule cells were maximally hyperexcitable to afferent stimulation immediately after SE, and became gradually less excitable during the first month post-SE. The chronic epileptic state was characterized by granule cell hyperinhibition, i.e. abnormally increased paired-pulse suppression and an abnormally high resistance to generating epileptiform discharges in response to afferent stimulation. Focal application of the GABA A receptor antagonist bicuculline methiodide within the dentate gyrus abolished the abnormally increased paired-pulse suppression recorded in chronically hyperinhibited rats. Combined Timm staining and parvalbumin immunocytochemistry revealed dense innervation of dentate inhibitory interneurons by newly-formed, Timm-positive, mossy fiber terminals. Ultrastructural analysis by conventional-and post-embedding GABA immunocytochemical electron microscopy confirmed that abnormal mossy fiber terminals of the dentate inner molecular layer formed frequent asymmetrical synapses with inhibitory interneurons and with GABA-immunopositive dendrites, as well as with GABA-immunonegative dendrites of presumed granule cells. These results in chronically epileptic rats demonstrate that dentate granule cells are maximally hyperexcitable immediately after SE, prior to mossy fiber sprouting, and that synaptic reorganization following kainate-induced injury is temporally associated with GABA A receptor-dependent granule cell hyperinhibition, rather than an hypothesized progressive hyperexcitability. The anatomical data provide evidence of a possible anatomical substrate for the chronically hyperinhibited state.

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Section: Possible Functional Implicationssupporting

confidence: 81%

Kainic acid‐induced recurrent mossy fiber innervation of dentate gyrus inhibitory interneurons: Possible anatomical substrate of granule cell hyperinhibition in chronically epileptic rats

Sloviter

Zappone

Harvey

et al. 2005

J of Comparative Neurology

141

110

View full text Add to dashboard Cite

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“…The relative silence of the DG has not been addressed in our study. Because granule cells in epileptic tissue show a high resting membrane potential (Urban et al, 1993;Williamson et al, 1993;Franck et al, 1995), display reduced calcium influx (Nägerl et al, 2000), and still receive inhibitory input (Mathern et al, 1995;Patrylo et al, 1999b;Magló czky et al, 2000;Wittner et al, 2001) evident as strong orthodromically evoked paired-pulse depression (present investigation; Swanson et al, 1998;Wilson et al, 1998), it might be understandable that we had to depolarize the granule cells and to increase synaptic cooperation by high K ϩ to evoke epileptiform activity.…”

Section: Discussionmentioning

confidence: 89%

Stimulus and Potassium-Induced Epileptiform Activity in the Human Dentate Gyrus from Patients with and without Hippocampal Sclerosis

Gabriel¹,

Njunting²,

Pomper³

et al. 2004

J. Neurosci.

154

102

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Hippocampal specimens resected to cure medically intractable temporal lobe epilepsy (TLE) provide a unique possibility to study functional consequences of morphological alterations. One intriguing alteration predominantly observed in cases of hippocampal sclerosis is an uncommon network of granule cells monosynaptically interconnected via aberrant supragranular mossy fibers. We investigated whether granule cell populations in slices from sclerotic and nonsclerotic hippocampi would develop ictaform activity when challenged by low-frequency hilar stimulation in the presence of elevated extracellular potassium concentration (10 and 12 mM) and whether the experimental activity differs according to the presence of aberrant mossy fibers.We found that ictaform activity could be evoked in slices from sclerotic and nonsclerotic hippocampi (27 of 40 slices, 14 of 20 patients; and 11 of 22 slices, 6 of 12 patients, respectively). However, the two patient groups differed with respect to the pattern of ictaform discharges and the potassium concentration mandatory for its induction. Seizure-like events were already induced with 10 mM K ϩ . They exclusively occurred in slices from sclerotic hippocampi, of which 80% displayed stimulus-induced oscillatory population responses (250 -300 Hz). In slices from nonsclerotic hippocampi, atypical negative field potential shifts were predominantly evoked with 12 mM K ϩ . In both groups, the ictaform activity was sensitive to ionotropic glutamate receptor antagonists and lowering of [Ca 2ϩ ] o . Our results show that, in granule cell populations of hippocampal slices from TLE patients, high K ϩ -induced seizure-like activity and ictal spiking coincide with basic electrophysiological abnormalities, hippocampal sclerosis, and mossy fiber sprouting, suggesting that network reorganization could play a crucial role in determining type and threshold of such activity.

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“…The resolution of our ability to locate microelectrode tips in patients made it impossible for us to determine whether any of them may have actually been in the dentate gyrus. Whereas inhibitory mechanisms may be increased interictally in the epileptic hippocampus (Wilson et al, 1993(Wilson et al, , 1998, there is loss of paired-pulse suppression within discrete areas generating fast ripples (Bragin et al, 2002b). It is possible, therefore, that loss of critical inhibitory influences in these localized epileptogenic regions could mediate the transition of normal ripples to pathological fast ripples.…”

Section: Discussionmentioning

confidence: 99%

Cell Type-Specific Firing during Ripple Oscillations in the Hippocampal Formation of Humans

Quyen¹,

Bragin²,

Staba³

et al. 2008

Journal of Neuroscience

149

123

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High-frequency field ripples occur in the rodent hippocampal formation and are assumed to depend on interneuron type-specific firing patterns, structuring the activity of pyramidal cells. Ripples with similar characteristics are also present in humans, yet their underlying cellular correlates are still unknown. By in vivo recording interneurons and pyramidal cells in the human hippocampal formation, we find that cell type-specific firing patterns and phase-locking on a millisecond timescale can be distinguished during ripples. In particular, pyramidal cells fired preferentially at the highest amplitude of the ripple, but interneurons began to discharge earlier than pyramidal cells. Furthermore, a large fraction of cells were phase-locked to the ripple cycle, but the preferred phase of discharge of interneurons followed the maximum discharge probability of pyramidal neurons. These relationships between human ripples and unit activity are qualitatively similar to that observed in vivo in the rodents, suggesting that their underlying mechanisms are similar.

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Paired pulse suppression and facilitation in human epileptogenic hippocampal formation

Cited by 92 publications

References 64 publications

Kainic acid‐induced recurrent mossy fiber innervation of dentate gyrus inhibitory interneurons: Possible anatomical substrate of granule cell hyperinhibition in chronically epileptic rats

Kainic acid‐induced recurrent mossy fiber innervation of dentate gyrus inhibitory interneurons: Possible anatomical substrate of granule cell hyperinhibition in chronically epileptic rats

Stimulus and Potassium-Induced Epileptiform Activity in the Human Dentate Gyrus from Patients with and without Hippocampal Sclerosis

Cell Type-Specific Firing during Ripple Oscillations in the Hippocampal Formation of Humans

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