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Perfusing rat hippocampal slices with high-K+ (7.5 mM) saline induced brief population bursts originating in CA3 at 0.5-1 Hz and spreading synaptically into CA1. In 42% of the slices the brief bursts evoked in CA1 gave way every 0.5-2 s to sustained ictal (or seizure) episode with tonic and clonic components. Paired intra- and extracellular recordings in the CA1 pyramidal layer were used to characterize the synaptic and nonsynaptic mechanisms generating the brief and sustained epileptiform events. The interictal, tonic, or clonic primary burst response in CA1 comprised a spindle-shaped, tight cluster (170-180 Hz) of five to seven population spikes. Bursts evoked between sequential seizures (interictal bursts) were initially small and progressively increased in size. Concurrently, basal extracellular K+ concentration ([K+]o] increased from 6.5 to 7.5 mM. The tonic event emanated from a large primary burst and comprised prolonged (> 1 s), self-sustained afterdischarge, associated with a rise in [K+]o to 12 mM. Bursts generated during the subsequent [K+]o decline (clonic bursts) also were large and followed by some afterdischarge. They became small during [K+]o undershoot to 6.5 mM. Intrinsically burst firing pyramidal cells (PCs) were recruited before or at the very onset of the primary population burst and fired repetitively during its course. Nonbursters were recruited > or = 10 ms after the beginning of the primary burst and fired, on average, only one spike. The PCs depolarized during the primary burst and subsequent afterdischarge. The primary depolarizing shift was larger in bursters than in nonbursters. Both bursters and nonbursters fired repetitively, albeit intermittently, during tonic and clonic afterdischarge. Throughout the interictal-ictal cycle intracellular spikes were time-locked to population spikes, indicating that PCs fire in tight synchrony. Differential recording of transmembrane potentials unmasked rapid (4-7 ms) transmembrane depolarizing potentials of up to 10 mV, coincident with population spikes. We conclude that in the high-K+ model of hippocampal epilepsy, the local generation of population bursts in CA1 is led by intrinsic bursters, which recruit and synchronize other PCs by synaptic, electrical, and K(+)-mediated excitatory interactions. The cycling between interictal, tonic, and clonic events appears to result from feedback interactions between neuronal discharge and [K+]o.

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N-methyl-d-aspartate receptors (NMDARs) are known for their role in the induction of long-term potentiation (LTP). Here we start by reviewing the early evidence for their role in LTP at CA1 synapses in the hippocampus. We then discuss more recent evidence that NMDAR dependent synaptic plasticity at these synapses can be separated into mechanistically distinct components. An initial phase of the synaptic potentiation, which is generally termed short-term potentiation (STP), decays in an activity-dependent manner and comprises two components that differ in their kinetics and NMDAR subtype dependence. The faster component involves activation of GluN2A and GluN2B subunits whereas the slower component involves activation of GluN2B and GluN2D subunits. The stable phase of potentiation, commonly referred to as LTP, requires activation of primarily triheteromeric NMDARs containing both GluN2A and GluN2B subunits. In new work, we compare STP with a rebound potentiation (RP) that is induced by NMDA application and conclude that they are different phenomena. We also report that NMDAR dependent long-term depression (NMDAR-LTD) is sensitive to a glycine site NMDAR antagonist. We conclude that NMDARs are not synonymous for either LTP or memory. Whilst important for the induction of LTP at many synapses in the CNS, not all forms of LTP require the activation of NMDARs. Furthermore, NMDARs mediate the induction of other forms of synaptic plasticity and are important for synaptic transmission. It is, therefore, not possible to equate NMDARs with LTP though they are intimately linked.This article is part of a Special Issue entitled SI: Brain and Memory.