Summary: Purpose:In limbic or mesial temporal lobe epilepsy, much attention has been given to specific regions or cell populations (e.g., the hippocampus or dentate granule cells). Epileptic seizures may involve broader changes in neural circuits, and evidence suggests that subcortical regions may play a role. In this study we examined the midline thalamic regions for involvement in limbic seizures, changes in anatomy and physiology, and the potential role for this region in limbic seizures and epilepsy Methods: Using two rat models for limbic epilepsy (hippocampal kindled and chronic spontaneous limbic epilepsy) we examined the midline thalamus for evidence of involvement in seizure activity, alterations in structure, changes in the basic in vitro physiology of the thalamic neurons. We also explored how this region may influence limbic seizures. Results:The midline thalamus was consistently involved with seizure activity from the onset, and there was significant neuronal loss in the medial dorsal and reuniens/rhomboid nuclei. In addition, thalamic neurons had changes in synaptically mediated and voltage-gated responses. Infusion of lidocaine into the midline thalamus significantly shortened afterdischarge duration.Conclusions: These observations suggest that this thalamic region is part of the neural circuitry of limbic epilepsy and may play a significant role in seizure modulation. Local neuronal changes can enhance the excitability of the thalamolimbic circuits.

The goal of the present study was to identify and characterize, at the electron microscopic level, the synapses formed by entorhinal cortical (EC) axons in the hippocampal CA1 stratum lacunosum-moleculare of the adult rat. Phaseolus vulgaris leucoagglutinin was ionotophoresed at various loci throughout the mediolateral and dorsoventral extent of the EC to label EC-CA1 synapses. Virtually all labeled synapses were asymmetric and axospinous. EC axons did not preferentially synapse with any particular type of dendritic spine; rather, EC axons formed synapses with the range of dendritic spine morphologies observed in CA1 s. lacunosum-moleculare. Spines with either perforated or nonperforated postsynaptic densities were contacted by EC axons. Occasionally both a labeled and an unlabeled axon synapsed on a single dendritic spine head. The data are discussed in relation to the morphology of other afferent systems synapsing in s. lacunosum-moleculare and to the physiology of the EC-CA1 system.

Summary:Purpose: The focus of research in limbic epilepsy has been the hippocampus because of its well-known pathology of hippocampal atrophy and sclerosis as well as the strong propensity for this structure to seize under a variety of circumstances. There is ample evidence, however, for pathological alterations in other regions of the limbic system in limbic/ mesial temporal lobe epilepsy, including the amygdala, the entorhinal cortex, and, in some cases, the thalamus. In this preliminary evaluation of the pathological substrate for limbic epilepsy, we wished to determine if there was consistent anatomic change at extrahippocampal sites.Methods: We compared paraffin sections of brains from rats with chronic spontaneous limbic epilepsy and age-matched controls to determine the consistency of the pathology at five sites: the hippocampus, amygdala, entorhinal cortex, piriform cortex, and medial dorsal thalamus.Results: In a qualitative evaluation of these sections taken from standardized positions, we found that the medial dorsal thalamic nucleus in the epileptic animals was the site that was consistently involved with neuronal loss. With all other sites, at least several animals had qualitatively normal tissue.Conclusions: This finding suggests that neuronal loss in the medial dorsal thalamus may be the consistent pathology in limbic epilepsy, at least in an animal model of the disorder. The presence of a structurally abnormal subcortical region with broad connections to the limbic sites involved with chronic epilepsy may have implications for our understanding of the pathophysiology of this disorder. Key Words: EpilepsyPathology-Thalamus-Hippocampus-Limbic.The mesial temporal lobe epilepsy syndrome has been associated with hippocampal pathology for many decades, and these changes of regional neuronal loss and gliosis, called hippocampal sclerosis, have become the pathognomonic finding for this condition. However, there have also been numerous observations of pathology in the adjacent regions of the amygdala, entorhinal cortex, and thalamus (1-4). A few reports have suggested that in some instances the extrahippocampal pathology is the primary change in selected patients with the mesial temporal lobe epilepsy syndrome (3). These observations indicate that the syndrome encompasses a more widespread pathology and that there may be more variability in the pathology from case to case. Understanding the nature and distribution of the pathology is a major component of developing a conceptual framework for this syndrome. There have been other observations made by a number of investigators that suggest that the pathological basis and pathophysiology are not confined to the hippocampus. One such observation is that the pattern of electrographic seizure onset is often regional, with the seizure beginning at multiple points within the temporal lobe at one time (5,6). A similar finding is that it is necessary to resect multiple structures in the mesial temporal region to effect a significant reduction in seizure frequency (7...

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