Potentiation In Hippocampal CA1 Region Research Articles

Effects of exposure to extremely low frequency electromagnetic fields on hippocampal long-term potentiation in hippocampal CA1 region

Exposure to environmental electromagnetic fields, especially to the extremely low-frequency (ELF < 300 Hz) electromagnetic fields (EMFs) might produce modulation effects on neuronal activity. Long-term changes in synaptic plasticity such as long-term potentiation (LTP) involved in learning and memory may have contributions to a number of neurological diseases. However, the modulation effects of ELF-EMFs on LTP are not yet fully understood. In our present study, we aimed to evaluate the effects of exposure to ELF-EMFs on LTP in hippocampal CA1 region in rats. Hippocampal slices were exposed to magnetic fields generated by sXcELF system with different frequencies (15, 50, and 100 Hz [Hz]), intensities (0.5, 1, and 2 mT [mT]), and duration (10 s [s], 20 s, 40 s, 60 s, and 5 min), then the baseline signal recordings for 20 min and the evoked field excitatory postsynaptic potentials (fEPSPs) were recorded. We found that the LTP amplitudes decreased after magnetic field exposure, and the LTP amplitudes decreased in proportion to exposure doses and durations, suggesting ELF-EMFs may have dose and duration-dependent inhibition effects. Among multiple exposure duration and doses combinations, upon 5 min magnetic field exposure, 15 Hz/2 mT maximally inhibited LTP. Under 15 Hz/2 mT ELF-EMFs, LTP amplitude decreases in proportion to the length of exposure durations within 5 min time frame. Our findings illustrated the potential effects of ELF-EMFs on synaptic plasticity and will lead to better understanding of the influence on learning and memory.

Levothyroxine rescues the lead-induced hypothyroidism and impairment of long-term potentiation in hippocampal CA1 region of the developmental rats

Lead (Pb) exposure during development has been associated with impaired long-term potentiation (LTP). Hypothyroidism happening upon subjects with occupational exposure to Pb is suggestive of an adverse effect of Pb on thyroid homeostasis, leading to the hypothesis that Pb exposure may alter thyroid hormone homeostasis. Hippocampus is one of the targets of Pb exposure, and is sensitive to and dependent on thyroid hormones, leading us to explore whether levothyroxine (L-T 4) administration could alter the thyroid disequilibrium and impairment of LTP in rat hippocampus caused by Pb exposure. Our results show that Pb exposure caused a decrease in triiodothyronine (T 3) and tetraiodothyronine (T 4) levels accompanied by a dramatic decrease of TSH and application of L-T 4 restored these changes to about control levels. Hippocampal and blood Pb concentration were significantly reduced following L-T 4 treatment. L-T 4 treatment rescued the impairment of LTP induced by the Pb exposure. These results suggest that Pb exposure may lead to thyroid dysfunction and induce hypothyroidism and provide a direct electrophysiological proof that L-T 4 relieves chronic Pb exposure-induced impairment of synaptic plasticity.

Impairment of spatial learning and memory in transgenic mice overexpressing human fibroblast growth factor-23

Fibroblast growth factor-23 (FGF-23) is a potent circulating phosphaturic factor associated with renal phosphate wasting. Effects of FGF-23 on skeleton, phosphate homeostasis, and cardiovascular system have been investigated; however, the effect of FGF-23 on the central nervous system (CNS) is unknown. To assess whether FGF-23 influences the function and structure of the CNS and whether the effect of FGF-23 on the CNS is mediated by FGF receptors directly or by hypophosphatemia indirectly, FGF-23 transgenic mice and their wild-type littermates were fed a normal diet or a high-phosphate diet containing a normal diet plus 1.25% phosphate in drinking water from weaning for 5 weeks and the phenotypes of the CNS were compared between FGF-23 transgenic mice and their wild-type littermates on the same diet. At the end of this time period, transgenic animals on the normal diet showed impaired spatial learning and memory. Furthermore, these mice exhibited the impairment of long-term potentiation in hippocampal CA1 region, and the reduction of hippocampal adenosine-triphosphate content and of choline acetyltransferase-positive neurons in basal forebrain, possibly as pathogenetic factors contributing to the cognitive deficit. The central nervous phenotypes of transgenic mice were rescued following improved hypophosphatemia by the high-phosphate diet intake. This study demonstrates that FGF-23 overexpression can result in abnormalities in the CNS mediated by the secondary severe hypophosphatemia.

Cerebroside-A provides potent neuroprotection after cerebral ischaemia through reducing glutamate release and Ca2+ influx of NMDA receptors

Excessive presynaptic glutamate release after cerebral ischaemia leads to neuronal death mainly through excessive calcium entry of N-methyl-D-aspartate receptors (NMDARs). Our recent study reported that cerebroside can open large-conductance Ca²⁺-activated K⁺ (BKCa) channels. The present study evaluated the effects of cerebroside-A (CS-A), a single molecule isolated from an edible mushroom, on brain injury after focal or global ischaemia in adult male mice and rats. We herein report that treatment with CS-A after 60-min middle cerebral artery occlusion dose-dependently reduced the cerebral infarction with at least a 6-h efficacious time-window, which was partially blocked by the BKCa channel blocker charybdotoxin (CTX). Treatment with CS-A after 20 min global cerebral ischaemia (four-vessel occlusion) significantly attenuated the death of pyramidal cells in hippocampal CA1 area, which was also sensitive to CTX. CS-A, by opening the BKCa channel, could prevent excessive glutamate release after oxygen-glucose deprivation (OGD). In addition, CS-A could inhibit NMDAR Ca²⁺ influx, which did not require the activation of the BKCa channel. Furthermore, CS-A blocked the OGD-induced NMDAR-dependent long-term potentiation in hippocampal CA1 region. These findings indicate that treatment with CS-A after stroke exerts potent neuroprotection through prevention of excessive glutamate release and reduction of Ca²⁺ influx through NMDARs.

Amyloid β-protein fragment 31–35 suppresses long-term potentiation in hippocampal CA1 region of rats in vivo

Effects of fragment 31-35 of amyloid beta-protein (AbetaP31-35) on the baseline synaptic transmission, shown as fEPSPs, and the long-term potentiation (LTP) induced by high-frequency stimuli (HFS) were investigated in vivo in the hippocampal CA1 region of rats; a longer fragment of AbetaP, i.e., AbetaP25-35, which had been generally accepted as the active center in AbetaP, was also tested comparatively along with AbetaP31-35. The results showed that: (1) the baseline fEPSPs induced by test stimuli were not changed by i.c.v. injection of AbetaP31-35, while application of either AbetaP31-35 or AbetaP25-35 with the same molar concentration (50 nmol) significantly and similarly suppressed the HFS-induced LTP; (2) higher concentration of AbetaP31-35 or longer time of AbetaP exposure exhibited stronger suppression on LTP, indicating a dose- and time-dependent trends; (3) no significant effects could be found on the paired-pulse facilitation (PPF) following AbetaP31-35 injection; (4) pretreatment with verapamil (2.5 mg/kg, i.p., 1 h prior to HFS), a blocker of L-type Ca2+ channels, did not affect the baseline fEPSPs, while it exhibited a significant suppression on LTP induced by HFS; and (5) surprisingly enough, coapplication with verapamil and AbetaP31-35 exhibited a similar suppression on LTP just as both of these two agents were used alone. These results indicate that: (1) AbetaP31-35, similar to AbetaP25-35, possesses potent suppressive effects on hippocampal LTP in vivo, supporting our proposal that the fragment AbetaP31-35 might be to date the shortest active sequence in full-length of AbetaP molecule; (2) AbetaP31-35-induced LTP suppression is not mediated by affecting the presynaptic processes; and (3) L-type Ca2+ channels might be one of the main pathways by which AbetaP31-35 insults LTP.

1S,3R-ACPD dose-dependently induces a slow-onset potentiation in the rat hippocampal CA1 region in vivo

It has been reported that application of 1 S,3 R-1-aminocyclopentane 1,3-dicarboxylic acid (ACPD) in vitro triggers a slow-onset potentiation in the hippocampal CA1 region. This study examined the effect of ACPD in the CA1 of freely moving rats. No effect on fEPSP baseline recordings occurred at 40 and 400 μM/5 μ1, however at 4 mM/5 μ1 ACPD induced a slow-onset potentiation. MCPG (200 mM/5 μ1) completely inhibited this ACPD effect. These results indicate that slow-onset potentiation in the CA1 region, also occurs in vivo.

Prolonged enhancement of transmitter release accompanying long-term potentiation in hippocampal CA1 region

Prolonged enhancement of transmitter release accompanying long-term potentiation in hippocampal CA1 region