Abstracts

The hypothalamic hamartoma (HH) represents a rare but important model of subcortical epileptogenesis. Clinical studies, based primarily on intracranial electrode recordings have established that the HH itself is epileptogenic, but the mechanisms are unknown. In the present study, we examined the network properties of surgically-resected human HH tissue using a planar multielectrode array recording system., HH tissue was obtained with patient consent and upon resection was immediately submerged in ACSF bubbled with 95% O[sub]2[/sub]/5% CO[sub]2[/sub]. Tissue slices (400 [mu]m) were placed in a microelectrode dish (Alpha Med Systems, Osaka, Japan) and perfused with warmed (35[deg]C) oxygenated ACSF. The electrodes were arranged in an 8x8 grid with 150 [mu]m separation. Slices were arbitrarily placed over the entire electrode grid., Paired-pulse stimulation (50 ms interval) to random points within the tissue elicited small negative field potentials and stimulation-evoked single unit firing within specific regions of the tissue. A 5-20% paired-pulse depression of the field potential was evident in most areas, and was converted to a similar magnitude of paired-pulse facilitation by picrotoxin (100 [mu]M) suggesting the presence of both excitatory and inhibitory synaptic components. Furthermore, the stimulation-evoked single unit firing increased ([sim]4-fold) with the second pulse consistent with paired-pulse facilitation of an excitatory component. Picrotoxin substantially increased evoked unit firing suggesting that endogenous GABAergic neuron activity is present normally, and inhibition or shunting of an excitatory component is prominent. In addition, we recorded spontaneous single unit firing of individual cells from multiple electrodes with frequencies ranging from 1-14 Hz and spontaneous negative slow wave activity with amplitudes ranging from 5-300 mV. Interestingly, the frequency of spontaneous slow wave activity decreased with application of picrotoxin and increased with muscimol (30 [mu]M)., Our observations indicate that HH tissue is composed of neurons that are strongly modulated by GABA[sub]A[/sub] receptor-mediated mechanisms. This is consistent with earlier observations demonstrating positive immunoreactivity of HH tissue to glutamic acid decarboxylase (GAD65/67). A novel finding in this study is that populations of neurons also give rise to spontaneous slow wave discharges. It is of interest to determine if the spontaneous activity will become synchronous across the tissue and develop into epileptiform activity in response to provocation. Future studies will characterize the spontaneous activity and the functional architecture of HH tissue., (Supported by NIH and the Barrow Neurological Foundation.)