Elsevier

Neuroscience

Volume 76, Issue 4, 15 January 1997, Pages 1187-1203
Neuroscience

Epileptic afterdischarge in the hippocampal–entorhinal system: current source density and unit studies

https://doi.org/10.1016/S0306-4522(96)00446-0Get rights and content

Abstract

The contribution of the various hippocampal regions to the maintenance of epileptic activity, induced by stimulation of the perforant path or commissural system, was examined in the awake rat. Combination of multiple-site recordings with silicon probes, current source density analysis and unit recordings allowed for a high spatial resolution of the field events. Following perforant path stimulation, seizures began in the dentate gyrus, followed by events in the CA3–CA1 regions. After commissural stimulation, rhythmic bursts in the CA3–CA1 circuitry preceded the activation of the dentate gyrus. Correlation of events in the different subregions indicated that the sustained rhythmic afterdischarge (2–6 Hz) could not be explained by a cycle-by-cycle excitation of principal cell populations in the hippocampal–entorhinal loop. The primary afterdischarge always terminated in the CA1 region, followed by the dentate gyrus, CA3 region and the entorhinal cortex. The duration and pattern of the hippocampal afterdischarge was essentially unaffected by removal of the entorhinal cortex. The emergence of large population spike bursts coincided with a decreased discharge of interneurons in both CA1 and hilar regions. The majority of hilar interneurons displayed a strong amplitude decrement prior to the onset of population spike phase of the afterdischarge.

These findings suggest that (i) afterdischarges can independently arise in the CA3–CA1 and entorhinal–dentate gyrus circuitries, (ii) reverberation of excitation in the hippocampal–entorhinal loop is not critical for the maintenance of afterdischarges and (iii) decreased activity of the interneuronal network may release population bursting of principal cells.

Section snippets

Surgery

Twenty-four male and female Sprague–Dawley rats (Hilltop, PA, U.S.A.; 300–450 g) were used in this study. The rats were anaesthetized with a mixture (4 ml/kg) of ketamine (25 mg/ml), xylazine (1.3 mg/ml) and acepromazine (0.25 mg/ml). Pairs of stainless steel wires (100 μm in diameter) with 0.5 mm vertical tip separation were placed in the angular bundle on the right or both sides to stimulate the medial PP afferents to the hippocampus (AP=−7.0 mm from bregma, L=3.5 mm from midline and V=−3.0 mm).

Results

In agreement with previous studies on stimulus-induced afterdischarges in the rat, several distinctive epochs could be recognized9, 29 that included (i) a 20 to 60 s long pAD of slow (2–12 Hz), fast (30–120 Hz) and ultrafast (200–400 Hz) oscillations, (ii) a silent period (1–4 min) and (iii) a secondary afterdischarge. The animal sat or stood still throughout these events with occasional “wet-dog” shakes occurring during the secondary afterdischarge and, rarely, during the later part of pAD. After

Discussion

The principal findings of the present experiments are that: (i) sustained rhythmicity of the pAD can not be explained by serial excitation of principal cell populations within the hippocampal–entorhinal loop, (ii) afterdischarges can independently arise in the CA3–CA1 and entorhinal–dentate gyrus circuitries and (iii) decreased activity of the interneuronal network may be causally related to the population bursting of principal cells.

Acknowledgements

We thank K. Wise and J. Hetke for providing us the silicon probes, J. J. Chrobak, S. L-W. Leung, G. G. Somjen and R. D. Traub for their comments on the manuscript. This work was supported by NINDS (NS34994; 1P41RR09754; NS33310) and the Whitehall Foundation. M. Penttonen was a visiting scholar at Rutgers University, supported by the Finnish Academy of Sciences and the A. I. Virtanen Institute.

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    1

    Permanent address: Institute of Theoretical and Experimental Biophysics, Puschino, Russia.

    2

    Permanent address: A. I. Virtanen Institute, University of Kuopio, PO Box 1627, FIN-70211, Kuopio, Finland.

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