Intracellular and extracellular recordings were made from pyramidal neurons in hippocampal slices in order to study spontaneous paroxysmal bursting induced by raising the extracellular potassium concentration from 3.5 to 8.5 mM. Extracellular recordings from all hippocampal subfields indicated that spontaneous bursts appeared to originate in region CA3c or CA3b as judged by burst onset. Burst intensity was also greatest in regions CA3b and CA3c and became progressively less toward region CA2. Intracellular recordings indicated that in 8.5 mM potassium, large spontaneous excitatory postsynaptic potentials (EPSPs), large burst afterhyperpolarizations, and rhythmic hyperpolarizing-depolarizing waves of membrane potential were invariably present in CA3c neurons. High potassium (8.5 mM) induced a positive shift (+9 mV) in the reversal potential of GABAergic inhibitory postsynaptic potentials (IPSPs) in CA3c neurons without changing input resistance or resting potential. This resulted in a drastic reduction in amplitude of the IPSP. Reduction of IPSP amplitude occurred before the onset of spontaneous bursting and was reversible upon return to normal potassium. A new technique to quantify the relative intensity of interictal-like burst discharges is described. Pentobarbital, diazepam, and GABA uptake inhibitors, which enhance GABA-mediated synaptic inhibition, reduced the intensity of potassium-induced bursts, whereas the GABA antagonist bicuculline increased burst intensity. Diphenylhydantoin and phenobarbital, anticonvulsants that have little effect on GABAergic inhibition, were without effect on spontaneous bursts. Burst frequency was reduced by bicuculline and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol but was unaffected by other drugs. Reduction of slice temperature from 35 to 19 degrees C dramatically reduced burst intensity but did not markedly affect burst frequency. We hypothesize that high potassium induces a rise in intracellular chloride concentration, possibly by activating an inward KCl pump or by a passive Donnan effect, which results in a decreased IPSP amplitude. With inhibition suppressed, the large spontaneous EPSPs that appear in high potassium cause individual CA3c neurons to fire. A combination of synaptic and electrical interactions among CA3c cells then synchronizes discharges into interictal spike bursts.

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The concentration of potassium ([K+]o) and of calcium ([Ca2+]o) in interstitial fluid of the hippocampal formation of rats anesthetized with urethan was recorded with double-barreled ion-selective microelectrodes. The ipsilateral angular bundle was stimulated with trains of repetitive pulses. [K+]o increased during angular bundle stimulation in both dendritic and cell body layers of the fascia dentata. When stimulation was frequent and intense enough to provoke intercurrent paroxysmal discharge (IPaD), [K+]o in the granule cell body layer rose much above the level it attained during previous, nonparoxysmal activation. No similar excess increase of [K+]o related to paroxysmal firing was observed in the dendritic layer. It is concluded that tonic paroxysmal discharge of the granule cells is associated with an outflow of K ions from the cell somata, but not the dendrites. Extracellular sustained potential (SP) shifts and responses of [K+]o associated with paroxysmal firing showed no consistent correlation in fascia dentata. It is concluded that paroxysmal SP shifts in fascia dentata (unlike in spinal cord and cerebral neocortex) are dominated by the extracellular currents generated by granule cells, not by neuroglia. In the postparoxysmal phase, however, a small residual SP shift was observed in both soma and dendrite layers, which had characteristics compatible with its being generated by glial cells. Responses of [Ca2+]o varied from rat to rat. During nonparoxysmal excitation [Ca2+]o increased, decreased, or remained unchanged. During paroxysmal firing [Ca2+]o always decreased in the granule cell body layer, but the magnitude of the response varied greatly. In the dendritic layer a similar but smaller decrease was observed in some but not all cases. Probable reasons for the unpredictability of the responses of [Ca2+]o are discussed. The responses of [Ca2+]o recorded in fascia dentata of urethan-anesthetized rats that have previously been kindled were not detectably different from those of control animals. Leão's spreading depression (LD) was associated with large increase of [K+]o, decrease of [Ca2+ )o, and intense negative SP shift in both dendritic and cell body layers of fascia dentata, as well as in CA1 zone of hippocampus. It is concluded that LD in hippocampal formation is associated with more widespread depolarization of pyramidal and granule cells than in cerebral neocortex and cerebellar cortex where changes of [K+]o are limited to the more superficial layers.

To determine if electrophysiological properties of hippocampal pathways are altered in kindled rats, extracellular recordings were made from hippocampal slices of rats kindled in the lateral entorhinal cortex and compared with those from implanted but unstimulated controls. Studies were made either 24 h or 28 days after the last kindled seizure and done in normal (3.5 mM) or elevated (7 mM) K+. The preparation of slices, data accumulation, and data analyses were done blind. One day or 28 days after the last kindled seizure, the proportion of slices with spontaneous epileptiform bursts recorded from the CA2/3 region in elevated K+ was significantly (P less than 0.001) increased in the kindled animals. The frequency of spontaneous burst firing was also increased and reached significance (P less than 0.02) at 28 days following the last kindling stimulus. One day after the last kindling stimulus, paired-pulse (GABAergic) inhibition in the CA1 region was decreased (P less than 0.001). Several measures suggested an increased synaptic inhibition in the dentate gyrus of slices from the kindled groups 1 day after kindling. Paired-pulse inhibition was increased (P less than 0.01), the current required to evoke a near-threshold population spike was increased (P less than 0.05), and the population spike amplitude was reduced for a given field excitatory postsynaptic potential (EPSP) (P less than 0.01). Twenty-eight days after the last kindling stimulus, however, paired-pulse inhibition in the dentate was slightly less in slices from kindled rats (P less than 0.005). In other respects the CA1 and dentate regions did not differ between kindled and control groups within 24 h of the last stage V seizure. Thus the maximum amplitudes of presynaptic fiber volley, population spike, and field-excitatory postsynaptic potential (EPSP) slope, and the number of population spikes evoked by a near-maximally effective afferent stimulus, were unchanged. In the CA1 region the input-output curve of field EPSP versus population spike, and the current intensity required to evoke a near-threshold population spike were also unchanged. In addition, no spontaneous bursts were recorded from CA1 in 3.5 mM K+. We conclude that either synapses or neurons intrinsic to the hippocampus are altered by kindling stimuli applied outside this brain area. The transient increase in inhibition in the dentate gyrus suggests that it may reflect a compensatory reaction to kindled seizures. In contrast, the long-lasting (at least 28 days) increase in burst firing in CA2/3 may represent a mechanism for the initiation or propagation of kindled seizures.(ABSTRACT TRUNCATED AT 400 WORDS)