Comment on "On the origin of interictal activity in human temporal lobe epilepsy in vitro".

For more than a decade, there has been extensive discussion about whether hippocampal sclerosis causes enhanced neuronal excitability as a prerequisite for seizure generation. The disorder known as Ammon’s horn sclerosis (AHS) is characterized by pronounced cell loss and gliosis in various regions of the hippocampal formation, leaving the subiculum generally intact (1, 2). Given the hypothesis that epileptic activity is generated within the hippocampal formation when the CA3 and CA1 regions are damaged or even absent, it is feasible that the adjacent subiculum is uniquely responsible for the generation of limbic seizures. Using multielectrode recordings in hippocampal brain slices of patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis, Cohen et al. (3) detected spontaneous, rhythmic spikes in the subiculum—but rarely in the CA3 or CA1 regions. This activity closely resembled the discharges seen on the electroencephalograms (EEGs) of these patients. Cohen et al. (3) therefore concluded that in patients with AHS, deafferentation of the subiculum initiates an epileptogenic plasticity that includes changes in glutamatergic or -aminobutyric acid (GABA)-ergic signaling. We find that even in nonsclerotic hippocampal tissue, as graded by Wyler (4), the subiculum shows cellular and synaptic changes which suffice to generate an epileptic focus. To elucidate this issue further, we investigated the contribution of subicular cells to interictal activity recorded in EEGs of TLE patients with (AHS, Wyler score W3, W4; n 7) and without hippocampal sclerosis (non-AHS, W0-W2;