Elsevier

Brain Research

Volume 849, Issues 1–2, 4 December 1999, Pages 139-146
Brain Research

Research report
Re-entrant activity in a presubiculum–subiculum circuit generates epileptiform activity in vitro

https://doi.org/10.1016/S0006-8993(99)02045-4Get rights and content

Abstract

The retrohippocampal cortices form the transition between neocortex and the hippocampus. Area CA3 of the hippocampus and the entorhinal cortex (EC) of the retrohippocampal region are established as brain regions that generate epileptiform activity. Interictal activity generated in EC consists of a primary population burst followed by multiple afterdischarges. The presubiculum is similar to EC in its six-layered structure, but lacks a columnar circuitry that the EC possesses. Isolated presubicular tissue cannot generate afterdischarges and isolated subicular tissue generates no spontaneous activity under some conditions. We report epileptiform activity in combined presubiculum–subiculum slices that consists of synchronous population bursts and multiple afterdischarges. Intracellular and field potential recordings reveal two re-entrant paths for interaction of presubicular and subicular neurons. We demonstrate a deep presubicular input to subiculum and separate return paths from subicular bursting neurons onto deep and superficial layer pre-/parasubicular neurons. Recordings from subicular cell apical dendrites showed repetitive burst firing during sustained depolarizing current injection. We conclude that re-entrant activity in a presubiculum–subiculum circuit generates epileptiform activity in both regions. Presubicular inputs to subiculum depolarize apical dendrites which can then burst repetitively. These bursts are transmitted back to the presubiculum. We suggest that iterations on this circuit act to prolong the dendritic depolarization of subicular bursting neurons and to entrain the activity across subicular cells resulting in multiple afterdischarges.

Introduction

The entorhinal cortex (EC) has been shown to generate ictal-like and interictal-like activity in intact brains 4, 16, 22 and brain slices 6, 10, 11, 12, 17, 27. This activity can be independent of activity in the hippocampus [6] or it can be synchronous with hippocampal activity as a result of EC inputs to the hippocampus and hippocampal inputs to the EC 1, 15.

In the hippocampus, epileptiform activity has been shown to depend upon recurrent excitatory connections among CA3 neurons 24, 25, 26. In retrohippocampal regions such as the EC, excitatory collaterals appear to exist among deep layer 6, 11 and superficial layer [7] neurons. Differences in the activity generated by the two regions imply differences in their circuitry.

Located between the EC and the hippocampus are the presubiculum and parasubiculum 13, 14, 28. These regions are similar in many ways to the EC, but there are differences. One difference is the form of interictal discharges generated by the isolated regions. Isolated pieces of pre- and parasubicular tissue generate epileptiform events when exposed to picrotoxin, which consist of a single burst. Each event in isolated pieces of entorhinal tissue, by contrast, consists of a primary burst followed by multiple ADs [6].

The second difference, we have hypothesized, is related to the first. The EC, but not pre- or parasubiculum, contains an intracortical “columnar” circuit that includes projections from deep layer neurons onto superficial layer neurons, and a return projection 6, 9, 14. A deep to superficial projection is absent from pre- and parasubiculum [6], although connections of superficial and deep layer cells with cells of the adjacent subiculum or EC form more extensive circuits.

Here, we report activity in an isolated, combined presubiculum–subiculum piece, cut from horizontal slices of the rat hippocampal formation. The timing of events recorded at different locations suggests that the epileptiform activity is generated by re-entrant circuits involving superficial and deep layer presubicular cells and the bursting neurons of subiculum.

Section snippets

Materials and methods

Our methods have been published in detail elsewhere 5, 6, 19.

Somatic intracellular and field potential recordings

Field potential recordings were taken from at least one location in every slice. Typically this was layer V of presubiculum. Single or simultaneous paired intracellular recordings were taken to examine the temporal relations between cells in different regions. A total of 88 cells were recorded with the following distribution: subiculum, 48; deep pre-/parasubiculum, 25; superficial pre-/parasubiculum, 15. Paired intracellular recordings (39 pairs) from this set were as follows: subiculum — deep

Discussion

We describe epileptiform activity in combined presubiculum–subiculum slices that results from reantrant activity in circuits joining these regions. We present electrophysiological evidence for subicular inputs to superficial and deep layer cells of pre- and parasubiculum and a deep layer presubicular projection to subiculum. Subicular stimuli elicited bursts in subicular cells with the shortest latency whereas deep layer presubicular cells responded earliest when stimuli were applied to layer V

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