Epilepsia, 46(Suppl. 5):17–21, 2005 Blackwell Publishing, Inc. C  International League Against Epilepsy The Subiculum: A Potential Site of Ictogenesis in Human Temporal Lobe Epilepsy Christian Wozny, Andreas Knopp, Thomas-Nicolas Lehmann, Uwe Heinemann, and Joachim Behr Neuroscience Research Center of the Charit´ e, Humboldt University Berlin, Berlin, Germany Summary: Purpose: This study determines synaptic and intrin- sic alterations of subicular pyramidal cells that are associated with activity recorded in patients suffering from temporal lobe epilepsy. Methods: Electroencephalograms with sphenoidal electrodes were correlated with in vitro single cell recordings of subicular pyramidal cells from the corresponding resected epileptic tissue. We determined alterations of synaptic and intrinsic properties of subicular pyramidal cells that accompany spontaneous rhythmic activity in human sclerotic and nonsclerotic epileptic tissue. Results: We found that in sclerotic, but also in nonsclerotic hippocampal tissue, the subiculum showed cellular and synap- tic changes that were associated with spontaneous rhythmic ac- tivity correlated to the occurrence and frequency of interictal discharges recorded in the electroencephalograms of the corre- sponding patients. Conclusions: Even though Ammon’s horn sclerosis (AHS) in resected hippocampi from patients suffering from temporal lobe epilepsy has important prognostic implications for freedom from seizures postoperatively, we report here that both synaptic and in- trinsic alterations enhance seizure susceptibility of the subiculum also in the absence of classical AHS. Key Words: Subiculum— Temporal lobe epilepsy—Ammon’s horn sclerosis—Interictal activity. Ammon’s horn sclerosis (AHS) is the neuropathologi- cal hallmark of many patients with temporal lobe epilepsy (TLE); it is characterized by pronounced cell loss and gliosis in various regions of the hippocampal formation, while the subiculum generally remains intact (1). Given that epileptic activity is generated within the hippocampal formation with CA3 and CA1 damaged or even absent, it is feasible that the subiculum is a critical factor for the gen- eration of hippocampal seizures. Using multi-electrode recordings in hippocampal brain slices of patients with TLE and AHS, Cohen et al. (2) recently detected sponta- neous, rhythmic activity in the subiculum but never in CA3 or CA1. As the synchronous activity persisted in the iso- lated human subiculum, an epileptogenic plasticity down- stream of the sclerotic CA1 region appeared to under- lie its generation. The authors concluded that, in patients with AHS, deafferentation of the subiculum initiates an epileptogenic plasticity, including changes in GABAergic signaling. We found that, even in nonsclerotic hippocam- pal tissue, the subiculum generates spontaneous rhythmic activity that correlates with the occurrence of interictal activity recorded in electroencephalograms of the corre- sponding TLE patients (3). To elucidate the underlying Address correspondence and reprint requests to Dr. J. Behr at Neuroscience Research Center of the Charit´ e, Humboldt Univer- sity Berlin, Schumannstr. 20/21, 10117 Berlin, Germany. E-mail: joachim.behr@charite.de mechanisms, we determined alterations of synaptic and in- trinsic properties in sclerotic and nonsclerotic hippocam- pal tissue. METHODS AND MATERIALS Electroencephalograms with sphenoidal electrodes were correlated with spontaneous activity recorded in subicular neurons of the resected epileptic tissue. The study was approved by the local ethics committee and each patient gave informed consent to the studies on the removed tissue. Patients were between 20 and 67 years of age in the AHSgroup (34 ± 6) and had suffered from TLE for 21 ± 4 years (n = 7). In the non-AHS group, patients ranged from 15 to 46 years (28 ± 5; p > 0.4), with a seizure history of 13 ± 5 years (n = 6; p > 0.2). The hippocampal specimen (5–8 mm of the hippocampal body) was ob- tained in the operation theater and immediately incubated in a cold (4 ◦ C) carbogenated solution containing (in mM): KCl, 3; NaH 2 PO 4 , 1.25; glucose, 10; MgSO 4 , 2; MgCl 2 , 2; CaCl 2 , 1.6; NaHCO 3 , 21; sucrose, 200; α-tocopherol, 0.1; pH 7.4, osmolarity 300 mOsmol/l. Sodium chloride was reduced to prevent hypoxia-induced sodium influx into neurons, while α-tocopherol was added as a scavenger of free radicals. The tissue was transported in a cooling re- ceiver filled with the chilled carbogenated transport solu- tion. Transport from the operating theater to the laboratory 17