Research reportRe-entrant activity in a presubiculum–subiculum circuit generates epileptiform activity in vitro
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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2015, NeuroscienceCitation Excerpt :The distinct spatial distribution of BS and RS cells in the proximo-to-distal and deep-to-superficial axes of the subiculum (Greene and Totterdell, 1997; Staff et al., 2000; Menendez de la Prida et al., 2003) and the topography of subicular efferents suggest that bursting and regular-firing cells may target different brain structures in rodents (Naber and Witter, 1998; Ishizuka, 2001). In particular, the subiculum is connected bi-directionally with the entorhinal cortex (EC) and the presubiculum and there is evidence that subicular RS cells interact predominantly with the lateral EC while BS cells project to the medial EC and presubiculum (Köhler, 1986; Stewart, 1997; Funahashi et al., 1999; Kim and Spruston, 2012). Experimental models and studies in humans suggest that seizures go along with disturbances in the adrenergic system (Trottier et al., 1981; Yu et al., 2009).
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