Studies of human and monkey “Epileptic” neocortex in the in vitro slice preparation

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.

Excitatory synaptic potentials in kainic acid-denervated rat CA1 pyramidal neurons

“…At low levels of stimulation, the subthreshold EPSP often was much longer in duration than those recorded from unlesioned slices, as shown in Table 1. The graded bursts closely resembled those recorded in human epileptic cortex (Schwartzkroin et al, 1983; Schwartz- Figure 2. A series of responses to increasing stratum radiatum stimulation, showing the progressive recruitment of a graded burst of action potentials evoked by the EPSP.…”

“…The study of chronic animal models of epilepsy and human brain tissue slices (Lothman and Collins, 198 1;Pumain, 198 1;Wheal, 1982, 1984;Schwartzkroin et al, 1983;Schwartzkroin and Knowles, 1984;Ashwood et al, 1986;Ashwood and Wheal, 1987;Avoli and Olivier, 1987;Mody and Heinemann, 1987;Franck et al, 1988;Nakajima et al, 199 1;Sloviter, 1991) has revealed new physiological mechanisms underlying bursting activity that were not observed in in vitro models generated by acute convulsants, such as penicillin and bicucilline, which block inhibitory processes (Dingledine and Gjerstad, 1980;Johnston and Brown, 198 1;Wheal et al, 1984). The chronic animal models and abnormal human tissue show less structured and more graded bursting activity than the acute convulsant models.…”

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

“…Means ± SEM of six experiments. studies using microelectrode recordings (Schwartzkroin et al, 1983;Koch et al, 2005). In most studied pyramidal neurons, hyperpolarizing current injections elicited depolarizing potential sags, and rebound action potentials appeared after the hyperpolarizing currents (Figure 1d).…”

Synaptic Depolarizing GABA Response in Adults Is Excitatory and Proconvulsive When GABAB Receptors Are Blocked

“…GABA B receptor knockout mice have epilepsy, but slices from these mice do not show epileptiform activity without the addition of 4-AP or some other convulsant (Brown et al 2003). Likewise, areas of brain expressing seizure discharges in humans do not necessarily show epileptiform events when excised and cut into slices (Hwa et al 1991;Schwartzkroin et al 1983). Studies examining epileptiform activity in human tissue from epilepsy patients typically use 4-AP, bicuculline, or low Mg 2ϩ to elicit the activity (e.g., Avoli et al 1987;D'Antuono et al 2004;Tasker et al 1992).…”