Epileptogenesis in chronically injured cortex: in vitro studies

Abstract

1. Field potentials and intracellular activities were examined in neocortical slices obtained through areas of chronic cortical injury produced by cortical undercutting and transcortical lesions made in vivo 7-122 days before the terminal in vitro slice experiment. 2. Abnormal field potentials characterized by long- and variable-latency multiphasic events could be evoked by layer VI-white matter or subpial stimulation in 9 of 15 animals that had adequate partial cortical isolations. These "epileptiform" field potentials were recorded in layers II-V and propagated across the cortex. They appeared at threshold in an all-or-none fashion and, in most slices, could be blocked by increasing stimulus intensity. In one slice, spontaneous epileptiform events occurred that were similar to those evoked by extracellular stimulation. 3. Intracellular activities during the epileptiform field potentials consisted of polyphasic synaptic events that were predominantly depolarizing and that could last < or = 400-500 ms, synchronous with the field potential activities. A variety of observations suggested that the neuronal activities underlying epileptiform field potentials were relatively asynchronous and much less intense than those previously found in chemically induced epileptogenesis within the neocortex. 4. Inhibitory postsynaptic potentials (IPSPs) were not prominent in neurons when threshold stimuli evoked epileptiform events; however, suprathreshold stimuli could elicit biphasic IPSPs and block the long-latency polysynaptic activity and abnormal field potential in most slices. Depolarizing components of the polysynaptic activity had the appearance of excitatory postsynaptic potentials in terms of their responses to alterations in membrane potential. 5. Comparison of spike parameters in layer V neurons of epileptogenic slices with those in control layer V neurons showed no significant differences in spike height, threshold, duration, or rise time. Resting membrane potentials were also not significantly different. 6. There was a highly significant difference in input resistance (RN) between layer V neurons in control and injured slices; the mean value for neurons in lesioned cortex was 68.1 M omega, whereas that in control cells was 30.5 M omega. There was also a significant prolongation of the slow membrane time constant in neurons of injured cortex (19.4 ms) as opposed to that in control cells (12.2 ms), suggesting that a change in specific resistivity or capacitance contributed to the higher RNS. 7. The relationship between adapted spike frequency and applied current (f-I slope) was steeper in layer V neurons from injured cortical slices (44.3 Hz/nA) than in normal layer V cells (28.2 Hz/nA).(ABSTRACT TRUNCATED AT 400 WORDS)

Synaptic Strength Modulation after Cortical Trauma: A Role in Epileptogenesis

“…Therefore, additional factors should have been responsible for the increased amplitude of averaged postsynaptic responses in the undercut cortex. We found that neuronal input resistance in chronic conditions was increased, confirming previous findings obtained in vitro from chronically deafferented cortical neurons (Prince and Tseng, 1993;Tseng and Prince, 1996). In addition, we observed an increased number of spikes and instantaneous firing rate of neurons located in the traumatized cortex, supporting the hyperactivity of these neurons.…”

“…In agreement with a previous study (Prince and Tseng, 1993), the firing threshold of neurons in chronic undercut cortex was not different from control (data not shown).…”

“…In addition, we observed an increased number of spikes and instantaneous firing rate of neurons located in the traumatized cortex, supporting the hyperactivity of these neurons. Our results are also sustained by in vitro undercut models and by studies done in axotomized corticospinal neurons illustrating a steeper relationship between applied current and adapted spike firing frequency ( f-I slope); therefore, for the same inward current, neurons would generate more action potentials (Prince and Tseng, 1993;Tseng and Prince, 1996). We assume that the increased neuronal firing in chronic conditions was a reflection of the increased input resistance, which would make these neurons more responsive to excitatory events (Prince and Tseng, 1993;Jacobs et al, 2000), because we found no differences of action potential threshold, as also reported previously in the in vitro undercut model (Prince and Tseng, 1993).…”

“…Partially isolated neocortex is a well established model of epileptogenesis after cortical trauma (Prince and Tseng, 1993;Hoffman et al, 1994;Jacobs et al, 2000;Topolnik et al, 2003b;Nita et al, 2007). The undercut cortex becomes increasingly hyperexcitable over a few weeks and progressively generates paroxysmal activity, both in vivo (Nita et al, 2006(Nita et al, , 2007 and in vitro (Prince and Tseng, 1993;Salin et al, 1995).…”

“…The undercut cortex becomes increasingly hyperexcitable over a few weeks and progressively generates paroxysmal activity, both in vivo (Nita et al, 2006(Nita et al, , 2007 and in vitro (Prince and Tseng, 1993;Salin et al, 1995). Several mechanisms may contribute to the development of hyperexcitability after cortical injury, including changes in intrinsic neuronal properties (Esplin et al, 1994;Topolnik et al, 2003a), selective loss of inhibitory synapses (Ribak and Reiffenstein, 1982), increase of both inhibition and excitation (Bush et al, 1999), and axonal sprouting (Salin et al, 1995).…”