Brain Advance Access originally published online on December 14, 2007
Brain 2008 131(2):485-499; doi:10.1093/brain/awm297
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Properties of in vivo interictal spike generation in the human subiculum
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cs21Institute for Psychology, Hungarian Academy of Sciences, 2National Institute of Psychiatry and Neurology, Epilepsy Centre, 3Institute of Experimental Medicine, Hungarian Academy of Sciences, 4National Institute of Neurosurgery, 5Szent István Hospital, Department of Neurology, Budapest, Hungary, 6University of California, San Diego, Departments of Radiology, Neuroscience and Psychiatry, La Jolla, California, USA and 7Pázmány Péter Catholic University, Department of Information Technology, Budapest, Hungary
Correspondence to: István Ulbert, Institute for Psychology, Hungarian Academy of Sciences, 1068 Budapest, Szondi u. 83-85, Hungary E-mail: ulbert{at}cogpsyphy.hu
A large proportion of hippocampal afferents and efferents are relayed through the subiculum. It is also thought to be a key structure in the generation and maintenance of epileptic activity; rhythmic interictal-like discharges were recorded in previous studies of subicular slices excised from temporal lobe epilepsy patients. In order to investigate if and how the subiculum is involved in the generation of epileptic discharges in vivo, subicular and lateral temporal lobe electrical activity were recorded under anesthesia in 11 drug-resistant epilepsy patients undergoing temporal lobectomy. Based on laminar field potential gradient, current source density, multiple unit activity (MUA) and spectral analyses, two types of interictal spikes were distinguished in the subiculum. The more frequently occurring spike started with an initial excitatory current (current source density sink) in the pyramidal cell layer associated with increased MUA in the same location, followed by later inhibitory currents (current source density source) and decreased MUA. In the other spike type, the initial excitation was confined to the apical dendritic region and it was associated with a less-prominent increase in MUA. Interictal spikes were highly synchronized at spatially distinct locations of the subiculum. Laminar data showed that the peak of the initial excitation occurred within 0–4 ms at subicular sites separated by 6 mm at the anterior–posterior axis. In addition, initial spike peak amplitudes were highly correlated in most recordings. A subset of subicular and temporal lobe spikes were also highly synchronous, in one case the subicular spikes reliably preceded the temporal lobe discharges. Our results indicate that multiple spike generator mechanisms exist in the human epileptic subiculum suggesting a complex network interplay between medial and lateral temporal structures during interictal epileptic activity. The observed widespread intra-subicular synchrony may reflect both of its intrinsic and extrinsically triggered activity supporting the hypothesis that subiculum may also play an active role in the distribution of epileptiform activity to other brain regions. Limited data suggest that subiculum might even play a pacemaker role in the generation of paroxysmal discharges.
Key Words: epilepsy; hippocampus; current source density; multiple unit activity; laminar recording
Abbreviations: CSD, current source density; EC, entorhinal cortex; FPG, field potential gradient; MUA, multiple unit activity
Received September 21, 2007. Revised October 28, 2007. Accepted November 16, 2007.
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