No abstract

The in vitro slice technique was used to study neuronal activity in human cortical tissue removed during neurosurgical procedures for intractable epilepsy and in monkey neocortex rendered epileptogenic by injection of alumina gel. In both cases, biopsies were guided by electrocorticographic signs of epileptiform activity. Intracellular recordings were made from 167 neurons in human tissue and from 73 neurons in monkey tissue samples. There was little spontaneous activity in these biopsies and no indication of spontaneous cellular bursting. Stimulation at the pial surface or in white matter evoked synaptically driven activity that was primarily excitatory. Graded bursts of activity could be elicited from some cells, but no all-or-none paroxysmal depolarization shifts were recorded. Inhibitory postsynaptic potentials were relatively rare. Intracellular injections of dye in a small number of neurons revealed no obvious differences between bursting and nonbursting neurons. These in vitro studies of chronic epileptic cortex have thus far provided few clear insights into the basic mechanisms of epilepsy.

Intracellular recordings were performed in the CA1 region of the rat hippocampus following an ipsilateral intraventricular injection of kainic acid. Seven days postlesion, graded bursts of up to four action potentials could be evoked by stimulation of the stratum radiatum. The evoked EPSPs underlying these bursts showed a prolonged 10–90% rise time and half-width compared to control EPSPs, an absence of a significant inhibitory phase, and an increase in magnitude and duration at depolarized resting levels. The evoked EPSPs also exhibited a significant decrease in amplitude and time course in response to D-APV (D-2-amino-5-phosphonovaleric acid; 1–20 microM), though this effect was variable from cell to cell. The prolonged time course, voltage sensitivity, and response to a selective NMDA antagonist confirmed that the major component of the EPSP in neurons from lesioned slices was mediated by NMDA receptors. The partial denervation of the CA1 area induced by the kainic acid led to both an enhanced NMDA-mediated excitatory phase and a decrease in postsynaptic inhibition, resulting in the pronounced hyperexcitability noted in the lesioned slices.

SUMMARY1. The patterns of inhibition in the CAI region of the rat hippocampus were evaluated by focal proximal and distal stratum radiatum stimulation, during intracellular recording. The characteristics of isolated inhibitory responses and the interactions of excitatory and inhibitory potentials were analysed.2. The amplitude of minimal inhibitory postsynaptic potentials (IPSPs) evoked by both proximal and distal stimulation averaged -0-51 + 0-24 mV (mean +S.D.; n = 32). These responses demonstrated little variability from trial to trial and showed no net trends in amplitude at a stimulation rate of 1 Hz.3. Minimal IPSPs demonstrated a short latency to onset (2-90 + 1-58 ms for proximal and 3-64 + 1-39 ms for distal) at stimulation levels which were insufficient to evoke an extracellular field potential. Thus, minimal IPSPs were recruited through feed-forward circuitry, based on the rapid onset and the lack of activation of recurrent collaterals.4. The minimal IPSPs showed a similar 10-90 % rise time for proximal and distal responses. However, the half-width and decay time constant (from the peak) were more prolonged for the distal stimulation, indicating that a late IPSP component was evoked primarily by the distal stimulation. This late component was not observed in isolation at low stimulation intensities.5. The conductance transient underlying the IPSPs was calculated using a neurone cable model. The proximal IPSP responses were simulated by an a input function (at the soma) with a peak conductance in the range of 25-45 nS (a = 1-75; reversal potential -1-0 to -10 mV). The distal IPSP shape was only partially reproduced by a longer single transient (a = 1P25), suggesting the presence of a second, slower component. However, insufficient data on this slower component precluded a more exact simulation of the distal IPSP response.6. Analysis of interactions between minimal excitatory postsynaptic potentials (EPSPs) and IPSPs showed that often the rising as well as the falling phase of the EPSP could be affected by the IPSP. At small stimulation levels, minimal EPSPs and IPSPs were closely overlapping, but the IPSPs were of significantly longer duration than EPSP responses.7. The composite EPSP waveform shape became progressively truncated with increasing afferent stimulation. Feed-forward inhibition limited the time course of excitation to a narrow window, approximately 3-5 ms wide. Feed-forward postsynaptic inhibition significantly limited both the duration and the overall efficacy of small EPSPs in CAl pyramidal neurones.