The entorhinal cortex (EC) provides the predominant excitatory drive to the hippocampal CA1 and subicular neurones in chronic epilepsy. Here we analysed the effects of one-sided lateral EC (LEC) and temporoammonic (alvear) path lesion on the development and properties of 4-aminopyridine-induced seizures. Electroencephalography (EEG) analysis of freely moving rats identified that the lesion increased the latency of the hippocampal seizure significantly and decreased the number of brief convulsions. Seizure-induced neuronal c-fos expression was reduced in every hippocampal area following LEC lesion. Immunocytochemical analysis 40 days after the ablation of the LEC identified sprouting of cholinergic and calretinin-containing axons into the dentate molecular layer. Region and subunit specific changes in the expression of ionotropic glutamate receptors (iGluRs) were identified. Although the total amount of AMPA receptor subunits remained unchanged, GluR1 flop displayed a significant decrease in the CA1 region. An increase in NR1 and NR2B N-methyl-Daspartate (NMDA) receptor subunits and KA-2 kainate receptor subunit was identified in the deafferented layers of the hippocampus. These results further emphasize the importance of the lateral entorhinal area in the spread and regulation of hippocampal seizures and highlight the potential role of the rewiring of afferents and rearrangement of iGluRs in the dentate gyrus in hippocampal convulsive activity.

BackgroundStereotactic targets for thalamotomy are usually derived from population-based coordinates. Individual anatomy is used only to scale the coordinates based on the location of some internal guide points. While on conventional MR imaging the thalamic nuclei are indistinguishable, recently it has become possible to identify individual thalamic nuclei using different connectivity profiles, as defined by MR diffusion tractography.Methodology and Principal FindingsHere we investigated the inter-individual variation of the location of target nuclei for thalamotomy: the putative ventralis oralis posterior (Vop) and the ventral intermedius (Vim) nucleus as defined by probabilistic tractography. We showed that the mean inter-individual distance of the peak Vop location is 7.33 mm and 7.42 mm for Vim. The mean overlap between individual Vop nuclei was 40.2% and it was 31.8% for Vim nuclei. As a proof of concept, we also present a patient who underwent Vop thalamotomy for untreatable tremor caused by traumatic brain injury and another patient who underwent Vim thalamotomy for essential tremor. The probabilistic tractography indicated that the successful tremor control was achieved with lesions in the Vop and Vim respectively.ConclusionsOur data call attention to the need for a better appreciation of the individual anatomy when planning stereotactic functional neurosurgery.

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The effect of acute brief seizures on neocortical c-fos expression was investigated in rats injected with 5 mg/kg 4-aminopyridine. Electroencephalography in freely moving animals with implanted neocortical electrodes detected an average of 2.67 tonic-clonic convulsions within 1 h following the 4-AP treatment. Tissue samples of the somatosensory neocortex were collected at 30 min, 1 h, 3 h, 5 h and 8 h following the treatment for PCR and immunohistochemistry. The c-fos mRNA displayed the first significant rise at 1 h, and remained significantly higher through 3 h. The number of c-fos protein immunoreactive cells was significantly elevated already at 30 min, peaked at 1 h, and declined by 5 h. We conclude that in repetitive, brief seizures, the first convulsion does not increase c-fos RNA transcription, whilst the second causes a long-lasting gene expression and a large increase of c-fos protein synthesis. The phenomenon may have implications in the pathogenesis of human and animal epilepsies.