Inhibitory effects of N-valproyl-l-tryptophan on high potassium, low calcium and low magnesium-induced CA1 hippocampal epileptiform bursting activity in rat brain slices

N-valproyl-l-tryptophan (VPA-Tryp), new antiepileptic drug, was tested on CA1 hippocampal epileptiform bursting activity obtained by increasing potassium and lowering calcium and magnesium concentrations in the fluid perfusing rat brain slices. Each slice was treated with a single concentration (0.2, 0.5, 1 or 2?mM) of Valproate (VPA) or VPA-Tryp. Both burst duration and interburst frequency during and after treatment were off-line compared with baseline values. For both parameters, the latency and the length of statistically significant response periods as well as the magnitude of drug-induced responses were calculated. VPA-Tryp evoked fewer and weaker early excitatory effects than VPA on bursting activity. On the contrary, VPA-Tryp induced powerful and long-lasting inhibitory effects on epileptiform discharge in a significantly higher number of slices than VPA. In fact, greater length and magnitude of VPA-Tryp-induced inhibition on both interburst frequency and burst duration were observed. Furthermore, VPA-Tryp showed antiepileptic activity at lower concentration than VPA and, when testing both drugs at analogue concentrations, VPA-Tryp evoked responses with either shorter latency or greater effect length and magnitude than VPA.     

Background potassium concentrations and epileptiform discharges. I. Electrophysiological characteristics of neuronal activity

Intra- and extracellular recording techniques were used to study the epileptiform activity generated by guinea pig hippocampal slices perfused with free-magnesium artificial cerebrospinal fluid in the presence of physiologic (4 mM), reduced (2 mM) or elevated (8 mM) extracellular potassium concentrations ([K(+)](o)). Extracellular field potentials along with intracellular recordings were recorded in CA1 or CA3 region. Reduction of [K(+)](o) significantly increased the latency of epileptiform field potential (EFP) appearance as well as burst discharge duration and decreased EFP repetition rate. Depending on different background [K(+)](o), epileptiform burst discharges appeared in different patterns including varied types of paroxysmal depolarisation shifts and burst activity in CA1 and CA3 subfields. Comparison with physiological and increased [K(+)](o,) reduction of [K(+)](o) significantly increased the mean duration of bursts, mean amplitude of depolarisation, mean after-hyperpolarisation duration, and inter-spike intervals in both CA1 and CA3 areas. Three distinct patterns were distinguished on the basis of their evoked firing pattern in response to application of depolarising current pulses in the interval of epileptiform burst discharges. Neurons superfused with 2 mM [K(+)](o) presented fast adapting pattern while cells washed with 4 or 8 mM [K(+)](o) exhibited intrinsically bursting or slow adapting patterns. Comparing the groups with different background [K(+)](o), there is a more severe form of discharges in low K(+) and a subtle difference between 4 and 8 mM K(+). The data indicate the importance of background [K(+)](o) on epileptiform burst discharge pattern and characteristics.     

The influence of dopamine of epileptiform burst activity in hippocampal pyramidal neurons

Dopamine (DA) application to guinea pig hippocampal CA1 neurons in vitro causes hyperpolarization of the resting potential, increase in conductance, and increase in amplitude and duration of the afterhyperpolarization (AHP). Since these changes could influence repetitive firing, we performed experiments to determine whether DA-induced effects would suppress epileptogenesis in the hippocampus. Epileptiform bursts were induced by adding penicillin (3.4 mM) to the perfusion medium. Focal application of DA (40-160 microns) onto CA1 cells (n = 15) produced a hyperpolarization averaging 4.5 mV beginning in 5-20 s and lasting up to 3 min. DA also caused an increase in the amplitude and duration of slow AHPs. The frequency of spontaneous epileptiform events however was not affected. CA3 neurons (n = 6) responded to DA application with an initial 1-3 mV depolarization beginning within 5-30 s and lasting 1-2 min. In 3 cases a small hyperpolarization lasting several minutes subsequently developed. AHP duration increased 70% and amplitude increased 35% (n = 4). Along with these membrane changes the frequency of epileptiform bursting in CA3 cells slowed for 1-3 min. We added DA (10-80 microM) to the perfusion medium to see whether a significant decrease in epileptiform burst frequency might occur in the follower CA1 region if greater numbers of pacemaker CA2 and CA3 cells were exposed to DA. Spontaneous CA1 bursting was reversibly slowed, the interburst interval became variable and increased from a mean of 4 to a mean of 5-7 s (n = 6). These results suggest that DA may play a role in decreasing the incidence or frequency of epileptogenic discharges in vivo.     

低镁诱发急性海马切片高兴奋性的多电极记录

目的 多电极记录技术在脑片研究的应用已经远远超过了10年,然而该技术却没有广泛地用于癫痫领域的研究。用经典的致痫剂低镁人工脑脊液灌流大鼠急性海马切片,诱导产生癫痫样电活动并用多电极记录技术对其放电特征及内部传导方式进行分析。 方法 用多电极阵列持续记录灌流低镁人工脑脊液后海马各区域的放电情况,并比较切断CA3与CA1区域间的Schaffer氏纤维后各区的放电情况。 结果 在急性海马切片上诱导出自发、同步、癫痫样电活动;CA3区神经元簇发放电持续时间及簇发放电内动作电位的个数与CA1及DG区相比有显著的统计学差异;剪断CA3与CA1间的Schaffer氏纤维后,CA1区的电活动消失,CA3区仍有同步放电,且其自发同步放电的频率与对照组相比无显着改变,但其簇发放电持续时间及簇发放电内动作电位的个数明显降低（P<0.05）。 结论 成功地在多电极上记录到急性海马切片自发、同步、癫痫样电活动;其中CA3区神经元兴奋性最高;在低镁灌流下自发癫痫样电活动起源于CA3区,在剪断Schaffer氏侧支后CA3区神经元群体同步放电的频率的频率没有显着变化。     

The variability of basal action potential firing is positively correlated with bursting in hypothalamic oxytocin neurones

Magnocellular oxytocin neurones are proposed as a suitable system for studying the mechanisms involved in the regulation of neuronal bursting activity. They display high frequency (50 sp./s) bursts of spikes (approximately every 300 s), in response to specific stimuli, which are superimposed on a variable level of basal activity and are tightly co-ordinated as a result of network interactions. The relationship between the strength of the bursting activity (as quantified by burst amplitude and interburst interval) and the characteristics of the interburst basal activity were assessed. During control conditions, mean basal activity and variability of firing increased just before bursts. During experimental conditions leading to burst facilitation, burst amplitude increased and interburst interval decreased while a sustained increase in mean firing rate occurred. Variability of firing (measured by both the standard deviation of firing rate, and the index of dispersion which corrected this standard deviation for differences in mean firing rate), increased demonstrating an increase in spike clustering greater than expected as a result of increased basal activity. When bursting was restrained (i.e. interburst interval increased), mean basal activity increased substantially, but index of dispersion decreased. A narrowing of the interspike interval distribution occurred, indicating increased regularity of firing. The aspect of basal activity most strongly correlated with bursting was variability of firing rate. The strongest correlate of burst amplitude was the standard deviation of mean firing rate, whereas the strongest and most consistent correlate of interburst interval was the index of dispersion. In conclusion, bursting behaviour is most strongly related to the irregularity rather than the level of basal activity.     

低镁诱发急性海马切片高兴奋性的多电极记录

目的 多电极记录技术在脑片研究的应用已经远远超过了10年,然而该技术却没有广泛地用于癫痫领域的研究。用经典的致痫剂低镁人工脑脊液灌流大鼠急性海马切片,诱导产生癫痫样电活动并用多电极记录技术对其放电特征及内部传导方式进行分析。 方法 用多电极阵列持续记录灌流低镁人工脑脊液后海马各区域的放电情况,并比较切断CA3与CA1区域间的Schaffer氏纤维后各区的放电情况。 结果 在急性海马切片上诱导出自发、同步、癫痫样电活动;CA3区神经元簇发放电持续时间及簇发放电内动作电位的个数与CA1及DG区相比有显著的统计学差异;剪断CA3与CA1间的Schaffer氏纤维后,CA1区的电活动消失,CA3区仍有同步放电,且其自发同步放电的频率与对照组相比无显着改变,但其簇发放电持续时间及簇发放电内动作电位的个数明显降低（P<0.05）。 结论 成功地在多电极上记录到急性海马切片自发、同步、癫痫样电活动;其中CA3区神经元兴奋性最高;在低镁灌流下自发癫痫样电活动起源于CA3区,在剪断Schaffer氏侧支后CA3区神经元群体同步放电的频率的频率没有显着变化。     

Spontaneous epileptiform bursts and long-term potentiation in rat CA3 hippocampal slices induced by chaotic stimulation of mossy fibers

The relation between long-term potentiation (LTP) and spontaneous rhythm in CA3 was investigated using rat hippocampal slices. Field potential response of CA3 to mossy fiber stimulation consisted of a mono-synaptic positive potential and subsequent poly-synaptic negative potentials. LTP of both field potentials was induced by chaotic mossy fiber stimulation. Although CA3 did not show any spontaneous rhythm before LTP induction in a normal perfusing medium, CA3 spontaneously caused epileptiform bursts after LTP induction by chaotic mossy fiber stimulation. The amplitude of those epileptiform bursts and the inter-burst interval were not uniform. After LTP induction, the cross-correlation function of spontaneous field potentials simultaneously recorded at two sites approximately 300 μm apart in CA3 showed a large central peak. This indicates that neuronal activity at two sites is synchronized. These results suggest that epileptiform bursts in CA3 are caused by synchronization of spontaneous CA3 pyramidal cell activity due to LTP induced by chaotic burst stimulation.     

Potassium, Pentylenetetrazol, and Anticonvulsants in Mouse Hippocampal Slices

We studied the effect of varying potassium (K+) concentrations on spontaneous and pentylenetetrazol (PTZ)-induced population burst discharges in mouse hippocampal slices. Standard techniques were used to obtain extracellular recordings in the CA3 region of hippocampal slices from Swiss-Webster mice (21-28 days old). No spontaneous burst discharges occurred at 3.25 mM K+, but population bursts were observed in 20 and 90% of the slices at 6.25 and 9.25 mM K+, respectively. In the presence of 3.25 mM K+, PTZ produced bursts in 12% of the slices at a concentration of 200 micrograms/ml, in 36% at 300 micrograms/ml, and in 40% at 400 micrograms/ml. Slices exhibiting no burst discharges in the presence of 6.25 mM K+ could be induced to do so with the addition of PTZ; bursts were produced in 11% of these slices at a PTZ concentration of 100 micrograms/ml, in 65% at 150 micrograms/ml, and in 87% at 200 micrograms/ml. The PTZ-induced bursting activity was reversible. Clonazepam abolished the bursting elicited with 200 micrograms/ml PTZ at 6.25 mM K+, and phenytoin reduced, but did not stop, bursting activity. Ethosuximide (ETH) was ineffective in stopping or reducing the burst discharges at a concentration of 125 micrograms/ml ETH was there a consistent reduction in the frequency of population bursts. The induction of PTZ discharges in the hippocampal in vitro preparation offers the advantage of a simplified model for studying the pharmacology of antiepileptic drugs.     

Spontaneous firing patterns of identified spiny neurons in the rat neostriatum

Spontaneous firing patterns of 94 unidentified neurons and 34 identified spiny neurons were compared in the neostriatum of locally anesthetized immobilized rats. Intracellular and extracellular recordings were analyzed using first order interval histograms and autocorrelograms, and neurons were identified by their somatodendritic morphology after intracellular injection of horseradish peroxidase. All neostriatal neurons tended to fire in irregular phasic bursts of activity. Considerable variation in mean firing rate, burst duration, interburst interval and the occurrence and rate of firing between bursts was apparent in both groups of neurons. There was no apparent difference between spiny neurons and the sample of unidentified extracellularly recorded neurons along any of these firing pattern parameters. Intracellular recordings from identified spiny neurons revealed noisy irregular periods of maintained 5–20 mV membrane depolarizations which corresponded to the occurrence of bursts of firing in spontaneously active neurons. These depolarizations occurred in neostriatal neurons exhibiting no spontaneous activity but were of insufficient amplitude to trigger impulse activity.     

Adenosine-mediated synaptic inhibition: partial blockade by barium does not prevent anti-epileptiform activity.

Adenosine-induced inhibition of evoked postsynaptic potentials (PSPs) and epileptiform burst firing in the CA1 subfield of rat hippocampal slices was studied with intracellular recordings in vitro. Adenosine (50 microM) caused a membrane hyperpolarization which was abolished during superfusion with 2 mM Ba2+. The adenosine-induced inhibition of the PSPs was still evident, although the magnitude of the effect was significantly reduced. Adenosine also reduced Ba(2+)-induced burst firing, but less effectively than it did bursts evoked by TEA (5 mM). The results suggest that adenosine inhibits synaptic transmission and epileptiform activity by at least 2 mechanisms: a postsynaptic barium-sensitive increase in gK and a presynaptic effect independent of this adenosine-evoked outward potassium conductance.     

Synchronization of GABAergic interneuronal networks during seizure-like activity in the rat horizontal hippocampal slice

We studied the contribution of GABAergic (gamma-aminobutyric acid) neurotransmission to epileptiform activity using the horizontal hippocampal rat brain slice. Seizure-like (ictal) activity was evoked in the CA1 area by applying high-frequency trains (80 Hz for 2 s) to the Schaffer collaterals. Whole-cell recordings from stratum oriens-alveus interneurons revealed burst firing with superimposed high-frequency spiking which was synchronous with field events and pyramidal cell firing during ictal activity. On the other hand, interictal interneuronal bursts were synchronous with large-amplitude inhibitory postsynaptic potentials (IPSPs) in pyramidal cells. Excitatory and inhibitory postsynaptic potentials were simultaneously received by pyramidal neurons during the ictal afterdischarge, and were synchronous with interneuronal bursting and field potential ictal events. The GABAA receptor antagonist bicuculline greatly reduced the duration of the ictal activity in the CA1 layer, and evoked rhythmic interictal synchronous bursting of interneurons and pyramidal cells. With intact GABAergic transmission, interictal field potential events were synchronous with large amplitude IPSPs (9.8 +/- 2.4 mV) in CA1 pyramidal cells, and with interneuronal bursting. Simultaneous dual recordings revealed synchronous IPSPs received by widely separated pyramidal neurons during ictal and interictal periods, indicative of widespread interneuronal firing synchrony throughout the hippocampus. CA3 pyramidal neurons fired in synchrony with interictal field potential events recorded in the CA1 layer, and glutamate receptor antagonists abolished interictal interneuronal firing and synchronous large amplitude IPSPs received by CA1 pyramidal cells. These observations provide evidence that the interneuronal network may be entrained in hyperexcitable states by GABAergic and glutamatergic mechanisms.     

Topological organization of CA3‐to‐CA1 excitation

The CA1‐projecting axons of CA3 pyramidal cells, called Schaffer collaterals, constitute one of the major information flow routes in the hippocampal formation. Recent anatomical studies have revealed the non‐random structural connectivity between CA3 and CA1, but little is known regarding the functional connectivity (i.e. how CA3 network activity is functionally transmitted downstream to the CA1 network). Using functional multi‐neuron calcium imaging of rat hippocampal slices, we monitored the spatiotemporal patterns of spontaneous CA3 and CA1 burst activity under pharmacological GABAergic blockade. We found that spatially clustered CA3 activity patterns were transformed into layered CA1 activity sequences. Specifically, synchronized bursts initiated from multiple hot spots in CA3 ensembles, and CA1 neurons located deeper in the pyramidal cell layer were recruited during earlier phases of the burst events. The order of these sequential activations was maintained across the bursts, but the sequence velocity varied depending on the inter‐burst intervals. Thus, CA3 axons innervate CA1 neurons in a highly topographical fashion.     

Single neuron burst firing in the human hippocampus during sleep

Although there are numerous non-primate studies of the single neuron correlates of sleep-related hippocampal EEG patterns, very limited hippocampal neuronal data are available for correlation with human sleep. We recorded human hippocampal single neuron activity in subjects implanted with depth electrodes required for medical diagnosis and quantitatively evaluated discharge activity from each neuron during episodes of wakefulness (Aw), combined stage 3 and 4 slow-wave sleep (SWS), and rapid eye movement (REM) sleep. The mean firing rate of the population of single neurons was significantly higher during SWS and Aw compared with REM sleep (p = 0.002; p < 0.0001). In addition, burst firing was significantly greater during SWS compared with Aw (p = 0.001) and REM sleep (p < 0.0001). The synchronized state of SWS and associated high-frequency burst discharge found in human hippocampus may subserve functions similar to those reported in non-primate hippocampus that require burst firing to induce synaptic modifications in hippocampal circuitry and in hippocampal projections to neocortical targets that participate in memory consolidation.     

Differences in Penicillin-Induced Synchronous Bursts in the CA1 and CA3 Regions of the Hippocampus

Epileptiform field potentials were compared in the CA3 and CA1 regions of penicillin-treated hippocampal slices. The CA3 field bursts usually began with decrementing spike patterns similar to reported single-unit bursts, whereas spike amplitude gradually increased in spontaneous and long-latency CA1 bursts. Stimuli close to CA1 recording sites also evoked short-latency, decrementing CA1 responses. We postulate that these patterns reflect a more rapid recruitment of CA3 neurons into synchronous bursts and a gradual sequential activation of the CA1 neurons by Schaffer collateral input from CA3. Stimulation of stratum radiatum close to CA1 also produced long-latency "all-or-none" bursts in CA3 and then CA1, identical to spontaneous bursts and those produced by stimulation remote from CA1. At threshold, 76% of the latency to the CA1 burst occurred between the stimulus and the onset of the CA3 burst. The latency to the CA3 burst decreased with increasing stimulus intensity but the intervals from CA3 to CA1 bursts remained constant. Thus, long-latency CA1 bursts appear to be due to antidromic activation of CA3 followed by reexcitation of CA1.     

Suppression of spontaneous epileptiform activity with applied currents.

It has been well established that both applied and endogenous electric fields can modulate neuronal activity in various preparations. In this paper, we present the effects of applied currents on spontaneous epileptiform activity in the CA1 region of the rat hippocampus. A computer-controlled system was designed to detect the spontaneous abnormal activity and then apply current pulses of programmable amplitude with monopolar electrodes in the stratum pyramidale. The epileptiform activity was generated by subperfusion of the neural tissue with an elevated potassium artificial cerebrospinal fluid (CSF) solution. Extracellular recordings showed that the interictal bursts could be fully suppressed in 90% of the slices by subthreshold currents with an average amplitude of 12.5 microA. Intracellular recordings showed that the anodic currents generated hyperpolarization of the somatic membrane thereby suppressing neuronal firing. This inhibitory effect of applied current pulses is important for the understanding of electric field effects on abnormal neuronal activity and could be an effective means of preventing the spread of epileptiform activity.     

Electrophysiology of neural units in goldfish optic tectum

Axons of retinal ganglion cells showed responses not previously emphasized: (a) many tonic units discharged oscillations, 2--12 spikes per burst, interburst intervals 20--300 msec; (b) phasic units showed concentric or flanking ON and OFF fields, response frequency depended on balance of retinal excitation and inhibition; (c) directional sensitivity was maximal for retinal stimuli moving in naso-temporal direction; (d) in anterior tectum deep afferent layer (DAL) provides for deep electrical sink, fibers of DAL have small fields, mostly in front of fish; (e) color-opponent units are prevalent in the superficial terminal layers, color is spatially and temporally represented. Tectal cell responses were distinguished by large visual fields, spontaneity, multiple spikes and long latencies to optic nerve stimulation, failure to follow above 60 per sec, plasticity of response. Tectal neurons of three classes included (a) cells of one type in upper layers were inhibited in ongoing activity by visual input, receptive fields exceeded 100 degrees, were often oblong, responses did not habituate; (b) cells of second type were excited by visual stimuli, became unresponsive (habituated) or responsive only to stimuli in different position or direction (newness cells); lability precluded field mapping and dishabituation was produced by change in background, extraneous stimulation, and spontaneous firing; (c) pyriform cells in periventricular layer were abundant, difficult to isolate electrically, discharged spontaneously in bursts at intervals of several seconds and responded to visual input by interruption of firing. Some tectal cells responded to non-visual stimuli as well.     

Hyperexcitability of CA3 pyramidal cells in mice lacking the potassium channel subunit Kv1.1

PURPOSE: To investigate further the membrane properties and postsynaptic potentials of the CA3 pyramidal cells in mice that display spontaneous seizures because of a targeted deletion of the Kcna1 potassium channel gene (encoding the Kv1.1 protein subunit). METHODS: Intracellular recordings were obtained from CA3 pyramidal cells in hippocampal slices prepared from Kcna1-null and control littermates. CA3 pyramidal cells were activated: orthodromically, by stimulating mossy fibers; antidromically, by activating Schaffer collaterals; and by injecting intracellular pulses of current. Responses evoked under these conditions were compared in both genotypes in normal extracellular medium (containing 3 mM potassium) and in medium containing 6 mM potassium. RESULTS: Recordings from CA3 pyramidal cells in Kcna1-null and littermate control slices showed similar membrane and action-potential properties. However, in 33% of cells studied in Kcna1-null slices bathed in normal extracellular medium, orthodromic stimulation evoked synaptically driven bursts of action potentials that followed a short-latency excitatory postsynaptic potential (EPSP)-inhibitory PSP (IPSP) sequence. Such bursts were not seen in cells from control slices. The short-latency gamma-aminobutyric acid (GABA)A-mediated IPSP event appeared similar in null and control slices. When extracellular potassium was elevated and excitatory synaptic transmission was blocked, antidromic activation or short pulses of intracellular depolarizing current evoked voltage-dependent bursts of action potentials in the majority of cells recorded in Kcna1 null slices, but only single spikes in control slices. CONCLUSIONS: Lack of Kv1.1 potassium channel subunits in CA3 pyramidal cells leads to synaptic hyperexcitability, as reflected in the propensity of these cells to generate multiple action potentials. The action-potential burst did not appear to result from loss of GABAA receptor-mediated inhibition. This property of CA3 neurons, seen particularly when tissue conditions become abnormal (e.g., elevated extracellular potassium), helps to explain the high seizure susceptibility of Kcna1-null mice.     

Evidence for two types of firing pattern during the sleep-waking cycle in the reticular thalamic nucleus of the cat

The activity of 23 neurons was recorded extracellularly in the nucleus reticularis thalami (RT) of four chronically implanted cats. Patterns of discharge were studied and their relationship to wakefulness (W), slow-wave sleep (SS), and paradoxical sleep (PS) were examined. The firing pattern was analyzed using zero-order (firing rate), first-order (interspike interval histogram), and second-order (joint interval histogram and autocorrelogram histogram) statistics. The SS bursting pattern was investigated taking into account the duration of the intervals between the bursts, the number of spikes per burst, and the duration of the bursts. Zero- and first-order characterizations during W and PS were found to be comparable. However, the joint interval histogram revealed a state-specific pattern during W for 74% of the cells. This pattern was characterized by a nonrandom occurrence of some categories of adjacent intervals. This was not found during PS. Two-thirds of the cells recorded, called “fast” neurons, exhibited firing rates higher than 15 spikes/s during W and PS. Those remaining, called “slow” neurons, showed a mean discharge rate lower than 10 spikes/s. In SS “fast” neurons fired long-duration bursts with interburst intervals generally shorter than 1 s. Conversely, “slow” neurons discharged shortduration bursts interrupted by long interburst intervals (greater than 1 s). Nevertheless, both types of cells had the same number of spikes within the burst and a similar intraburst pattern. Approximately half of the cells studied depicted a “slow rhythm” in the autocorrelogram histogram. Its periodicity was independent of firing rates and behavioral states.     

Comparison between the effects of extracellular direct and sinusoidal currents on excitability in hippocampal slices

The amplitude of population spikes in the CA1 cell layer of rat hippocampal slices was transiently altered during stimulation of the tissue with DC and sinusoidal extracellular electric fields parallel to the dendrosomatic axis of the CA1 pyramidal neurons. Field threshold was about 50 mV/cm in the tissue. Independently, long-lasting (min) increases in population spike amplitude followed sinusoidal fields as low as 7 mV/cm parallel or perpendicular to the cell axis.     

Sustained hyperexcitability elicited by repetitive electric stimulation of organotypic hippocampal explants

Sustained or complex evoked extracellular slow-wave field potentials were recorded in the CA3/2 areas of organotypic hippocampal explants following stimulation of the dentate area. After repetitive electric stimulation, these discharges became more complex and/or self-sustaining. Self-sustaining discharges continued to occur for the duration of the experiment (15 min-10 h). These slow-wave discharges were evoked (or occurred spontaneously) over a wide range of extracellular K+ concentrations (3-9 mM) without addition of pharmacologic inhibitory antagonists, whereas in some explants raising extracellular K+ from 5.9 to 8-9 mM resulted in spontaneous discharges. The observation that epileptiform discharges in hippocampal explants often occurred spontaneously, were elicited by repetitive electric stimulation, and were recorded at K+ levels which are generally ineffective in acute adult hippocampal slices, indicates that excitability of these CNS explants may be significantly increased following altered neuronal and synaptic development (and/or reorganization) under isolated conditions in culture.