Effects of hippocampal high‐frequency electrical stimulation in memory formation and their association with amino acid tissue content and release in normal rats

Abstract

Hippocampal high frequency electrical stimulation (HFS) at 130 Hz has been proposed as a therapeutical strategy to control neurological disorders such as intractable temporal lobe epilepsy (TLE). This study was carried out to determine the effects of hippocampal HFS on the memory process and the probable involvement of amino acids. Using the autoshaping task, we found that animals receiving hippocampal HFS showed augmented short-term, but not long-term memory formation, an effect blocked by bicuculline pretreatment and associated with enhanced tissue levels of amino acids in hippocampus. In addition, microdialysis experiments revealed high extracellular levels of glutamate, aspartate, glycine, taurine, and alanine during the application of hippocampal HFS. In contrast, GABA release augmented during HFS and remained elevated for more than 1 h after the stimulation was ended. HFS had minimal effects on glutamine release. The present results suggest that HFS has an activating effect on specific amino acids in normal hippocampus that may be involved in the enhanced short-term memory formation. These data further provide experimental support for the concept that hippocampus may be a promising target for focal stimulation to treat intractable seizures in humans.

GABAA Receptor and Glycine Receptor Activation by Paracrine/Autocrine Release of Endogenous Agonists: More Than a Simple Communication Pathway

“…An increase in the extracellular glycine concentration measured by microdialysis has been described in the substantia nigra pars compacta of the rat following calciumdependent high potassium-mediated depolarization [106]), as well as following the application of high-frequency electrical stimulations in the hippocampus [112]. These experiments suggest that the fluctuations of the extracellular levels of glycine in these areas depend on the electrical activity of the network and could be calcium-dependent.…”

“…The hypothesis of the presence of a significant amount of glycine in the extracellular space was strengthened by data showing that a proportion of strychnine-sensitive GlyRs are continuously active in resting CA1 pyramidal neurons of the hippocampus, creating a state of tonic inhibition that "shunts" EPSPs evoked by shocking the Schaffer collaterals [111]. Finally, microdialysis experiments also revealed a functionally significant extracellular concentration of glycine in the hippocampus during high-frequency electrical stimulations [112]. There is also evidence that Bergmann glia can release glycine [113], and we recently showed that radial cells in the embryonic spinal cord can release glycine as well, thereby modulating the early electrical activity of the developing neuronal network [9].…”

Seizure Suppression by High Frequency Optogenetic Stimulation Using In Vitro and In Vivo Animal Models of Epilepsy

“…However, a different optogenetic strategy for seizure suppression that mimics electrical HFS protocols by activating neurons can also effective. Electrical HFS has been thought to suppress seizures by generating a depolarization block related to the inactivation of sodium channels (10, 11) or driving GABA release during stimulation (24, 25). In the present study, histological analyses show that mostly interneurons express ChR2 in the Thy1-ChR2 mice and thus GABA release could be enhanced by optical stimulation together with the activation of some pyramidal cells.…”

Improvements in Memory after Medial Septum Stimulation Are Associated with Changes in Hippocampal Cholinergic Activity and Neurogenesis

“…Furthermore, stimulation of the entorhinal region was found to enhance memory for spatial information when applied during learning [6]. In animal studies, high frequency stimulation activates specific amino acids in the hippocampus that may be involved in the enhancement of short-term memory formation [7]. Also, formation of water maze memory is facilitated after bilateral stimulation of the entorhinal cortex [8].…”