We describe here the ionic changes which occur during repetitive stimulation of a type which will induce long-term potentiation and kindling plasticity. The causes of these ionic changes, particularly of changes in [Ca 2+ ] o , are discussed. Evidence will be presented which shows that only a fraction of the decreases in [Ca 2+ ] o is due to movement through N -methyl-d-aspartate (NMDA)-operated channels. Since NMDA-receptor activation is critical in many synapses for induction of long-term potentiation (LTP) and since the initial response to a stimulus in hippocampus is a long-lasting slow inhibitory postsynaptic potential (IPSP), mechanisms must be defined which ultimately permit activation of NMDA receptors. We conclude that increases in [K + ] o and reductions in [Ca 2+ ] o and [Mg 2+ ] o , together with a K + -dependent reduction of slow IPSP promote the activation of NMDA receptors during a stimulus train and help to overcome the blocking effect which the long-lasting hyperpolarizations exert on NMDA receptors. Preliminary evidence derived from analysis of quisqualate and NMDA-induced changes in [Ca 2+ ] o suggests that NMDA-receptor activation slows the extrusion of Ca 2+ from cells. This mechanism may be important for induction of long-term changes. Finally, we document that a number of long-term changes in neuronal excitability are associated with alterations of stimulus and excitatory amino acid (EAA)-induced changes in the ionic microenvironment, which give some insight into the mechanisms underlying stimulus-induced plasticity and, perhaps, progression of temporal lobe epilepsy.

Activity-dependent ionic changes and neuronal plasticity in rat hippocampus

https://pure.uva.nl/ws/files/977360/1149_030645229400587U_main.pdf

Potassium currents in isolated CA1 neurons of the rat after kindling epileptogenesis

The entorhinal cortex- hippocampus complex has particular features not only with respect to synaptic plasticity but also with respect to the readiness to develop progressive epilepsy. It might well be that this particular feature depends on the impressive plastic properties of the involved structures. A model for the progression of epilepsy is the kindling epilepsy. It is caused by stimuli (1 s, 50 Hz) of a type which also elicits long term potentiation [1]. Such stimulation induces generalized seizures when the stimuli are repeated in daily intervals [4]. The number of stimulations required to induce the kindling epilepsy is dependent on structure and varies between roughly 20 and more than 100.

Changes in Synaptic Transmission in the Kindled Hippocampus

Daily repeated tetanic stimulation of mild physiological intensity leads, in many parts of the brain, to the gradual development of an epileptogenic focus. This treatment (kindling) may finally even result in generalized tonic clonic convulsions. Since its first description in 1969 by Goddard [7], this experimental model of epilepsy has drawn considerable attention as one of the few models of permanent plasticity in the adult vertebrate brain. Much work has been devoted to defining optimal parameters for stimulation, to determine the sensitivity for kindling of different regions of the brain in a variety of species, and to exclude the phenomenon from being an implantation artifact (reviews are given by Racine [29] and McNamara et al. [20]. Despite the fact that a lot of knowledge has been acquired in this way, still little is known about the cellular mechanisms that underlie kindling epilepsy. Changes in polarity of epileptiform transients recorded in vivo during kindling epileptogenesis suggested that some dendritic process might be involved [16, 32]. Furthermore, it is known from several other models of epilepsy that variations in the concentrations of calcium and potassium in the extracellular space play an important role in the stability of neuronal circuits and that the concentrations of these ions can vary considerably during epileptiform activity [10,13, 23, 24–26, 31, 33]. In order to investigate the underlying mechanisms of kindling in more detail at a cellular level, we combined the in vivo model of kindling with the in vitro method of hippocampal slices [3,11,18]. The in vitro technique enabled us to record accurately, in tissue obtained from kindled rats, the laminar profiles of changes in extracellular potassium [K+]O and extracellular calcium [Ca2+]O induced by different methods.

W. J. Wadman

Papers

Laminar Profiles of [K+]O and [Ca2+]O in Region CA1 of the Hippocampus of Kindled Rats