Long-term Post-tetanic Potentiation Research Articles

Hippocampus-Dependent Learning Deficit Does Not Correlate with Suppression of Long-Term Post-Tetanic Potentiation by Systemic Blockade of NMDA Receptors

Hippocampus-Dependent Learning Deficit Does Not Correlate with Suppression of Long-Term Post-Tetanic Potentiation by Systemic Blockade of NMDA Receptors

Effect of Cryopreservation Time on the Activity of Ionotropic Glutamatergic Mechanisms: An in vitro Study

The effects of cryopreservation for different periods of time on the amplitudes of AMPA (α‑amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and NMDA (N-methyl-D-aspartate) glutamatergic ionotropic mechanisms and the action potential of the lateral olfactory tract (AP LOT) at –20°C and subsequent warming to 37°C was studied. Experiments were performed on brain slices of 22 nonhibernating animals—Wistar rats. After cryopreservation, the glutamatergic ionotropic mechanisms were preserved and restored using electrophysiological recording of the AMPA and NMDA potentials and the total AP LOT. The AMPA-dependent mechanisms and the activity of conductive LOT fibers were restored to the normothermal values; the recovery of the NMDA-dependent mechanisms was incomplete and averaged 34% compared with the normothermal values; the long-term post-tetanic potentiation was not restored after cryopreservation.

A Study of Synaptic Plasticity in the Rat Hippocampal Field CA1 in Conditions of Deficiency of Acetylcholine and Other Neurotransmitters

Experiments showed that high-amplitude, long-lasting tetanic potentiation could be induced in synaptic terminals formed by Schaffer collaterals on field CA1 pyramidal cells in rat hippocampal slices in which acetylcholine deficiency was modeled by application of the choline reuptake inhibitor hemicholine and the vesicular acetylcholine uptake inhibitor vesamicol. Deficiencies of different neurotransmitters were modeled by 5-min incubation of slices in solution containing an elevated potassium concentration, which led, as demonstrated previously, to depletion of the release of these neurotransmitters from nerve endings. The result of this procedure was that synapses formed by Schaffer collaterals developed long-term potentiation. Long-term post-tetanic potentiation was also induced in slices on this background in the model of neurotransmitter deficiency. Its amplitude was not significantly different from the amplitude of long-term potentiation in controls but was less than that obtained using vesamicol or hemicholine. As deficiency of serotonin, noradrenaline, and dopamine is known to be able to decrease the extent of long-term potentiation of synaptic transmission between fields CA3 and CA1, these result points to the possibility that acetylcholine deficiency partially compensates for this decrease. Considering known data on the locations of different types of nicotinic and muscarinic cholinoreceptors both on pyramidal cells and on inhibitory interneurons, the possible effects of acetylcholine on the efficiency of the inputs formed by Schaffer collaterals were studied. This analysis and consideration of the data obtained here led to the hypothesis that in conditions of acetylcholine deficiency, the main influence on the efficiency of excitation of pyramidal cells in field CA1 by field CA3 is exerted by disinhibition via a network of interacting interneurons.

Effect of Interleukin-10 on Localization of AMPA Receptors in Synapses during Long-Term Posttetanic Potentiation in Cultured Hippocampal Slices.

The effect of the anti-inflammatory cytokine IL-10 on the ultrastructural distribution of AMPA receptor GluR1 subunit in CA1 field of cultured hippocampal slices was studied by using immunohistochemical technique. It was found that long-term posttetanic potentiation increased the content of GluR1 in the postsynaptic density of the axo-spinous synapse. Addition of IL-10 in concentrations of 1 and 10 ng/ml to the medium facilitated long-term posttetanic potentiation thereby changing the distribution of GluR1 in the spine: the number of receptors increased in the cytoplasm and decreased in the postsynaptic density. It is assumed that activation of neuronal IL-10 receptors affects the distribution of AMPA receptors in axo-spinous synapses of hippocampal field CA1 through interplay of intracellular signaling pathways, thereby participating in the mechanisms of synaptic plasticity under normal conditions.

Effect of TGF-beta1 on long-term synaptic plasticity and distribution of AMPA receptors in the CA1 field of the hippocampus

Using the methods of electrophysiology and immunohistochemistry, the effect of the transforming factor beta-1(TGF-β1), an anti-inflammatory cytokine, on the long-term post-tetanic potentiation (LTP) in CA1 field hippocampal slices and the distribution of the GluR1 subunit of the AMPA receptor has been studied.It was shown that TGF-β1 at a concentration of 10 ng/ml did not significantly affect the initial stage of LTP and substantially changed the distribution of synaptic AMPA receptors in response to tetanic stimulation. Twenty five minutes after the tetanization, the main pool of AMPA receptors (90%) was due to the postsynaptic density (PSD). By contrast, LTP in the presence of TGF-β1 was accompanied by less pronounced changes in the distribution of AMPA receptors. Their localization in both pre- and postsynaptic regions remained nearly the same as that in the control. It may be suggested that the normal distribution of AMPA receptors in spinous synapses promotes the stabilization of potentiated synapses, thereby retaining LTP for longer terms.

Pre- and Postsynaptic Mechanisms of the Deprivation Potentiation of Neuron Population Responses in Rat Hippocampal Field CA1

Studies using in vitro rat hippocampal slices addressed the mechanism of deprivation potentiation (DeP) of neuron population responses in field CA1 developing as a result of prolonged (60 or 120 min) cessation of rare (0.05 Hz) test stimuli of Schaffer collaterals (SC). The development of DeP was found to involve two independent mechanisms: pre- and postsynaptic, responsible for induction of the short-term and long-term components of DeP, respectively. These studies showed that the interaction of DeP and long-term post-tetanic potentiation (LTP) is competitive in nature, providing evidence of similarity in the mechanisms of the long-term phase of DeP and the phase of LTP associated with protein phosphorylation. Our investigation showed that the Ca2+-dependent mechanism of induction of the postsynaptic component of DeP does not involve NMDA receptors, but does involve purine P2 receptors. A common curve for the relationship between the efficiency of synaptic transmission and the use/non-use of synapses including DeP, long-term depression (LTD), and LTP zones is presented.

Regulation of S100B Expression in Long-Term Potentiation

In this study, contributions of intracellular regulatory cascades in the induction of S100B expression in rat hippocampal CA1 area during long term posttetanic potentiation (LTP) were estimated. The activation of transcription factor p53 (positive regulator of S100B transcription) by nutlin-3 increased the basal content of S100B mRNA up to 151% of the control level, which was significantly lower than its content in tetanized slices (280%). Therefore, p53 seems to be not unique transcription factor upregulating S100B expression during LTP. The inhibitor of Ca2+/calmodulin-dependent kinases (CaMKs) KN-93 fully blocked the increase of S100B mRNA after tetanization, while KN-92 (inactive analogue of KN-93) was ineffective. The inhibitor of CaMKII and receptor tyrosine kinases K-252a essentially suppressed S100B expression during LTP, the inhibition of MAPK p38 or RSK2 moderately decreased, and the inhibition of MEK1 did not influence S100B mRNA content. Thus, CaMKs play a key role in the induction of S100B expression during LTP.

Mdm2-dependent regulation of p53 expression during long-term potentiation.

Induction of long-term posttetanic potentiation in rat hippocampal CA1 filed was followed by a decrease in the content of transcription factor p53 against the background of unchanged level of p53 mRNA, which implies activation of negative regulators of p53. Mdm2 is an important regulator of p53. We studied the effects of Mdm2 inhibitor nutlin-3 on p53 expression during generation of long-term posttetanic potentiation. Mdm2 inhibition completely prevented tetanization-induced decrease in the content of p53 protein; the level of p53 mRNA tended to increase in 30 min after tetanization. Thus, Mdm2 contributes to the maintenance of constant level of mRNA and plays a pivotal role in the decrease in the level of p53 protein during induction of long-term potentiation.

Recovery of Long-Term Post-Tetanic Potentiation in Conditions of Food Deprivation

The possibility of restoring decayed long-term potentiation of projections of Schaffer collaterals was studied in food-deprived rats on delivery of small food portions. Food delivery was found to produce partial recovery of the amplitude of the population spike of the first response in paired responses in field CA1. Population spike amplitude for the second response showed complete recovery. Food delivery in the control group of deprived rats without prior induction of potentiation did not change responses in field CA1. Recovery of potentiation in these experiments was linked with a defined level of emotional tension in the animal. In natural conditions, recovery of potentiation may be needed to solve tasks directed to satisfying needs of importance to the animal.

Induction of S100B Gene Expression in Long-Term Potentiation in the Hippocampal CA1 Field Depends on Activity of NMDA Receptors

The effects of NMDA receptor blocker MK-801 on the increase in S100B protein mRNA content induced by long-term posttetanic potentiation in the hippocampal sections were studied. The level of S100B mRNA after 30-min tetanization in the presence of 10 μM MK-801 constituted 132% of the basal level, which was significantly (226%) lower than the control level. Hence, gene expression, induced by long-term posttetanic potentiation, in the glial cells (similarly as in the neurons) depended significantly on NMDA receptors.

In vivo injected mitochondria-targeted plastoquinone antioxidant SkQR1 prevents β-amyloid-induced decay of long-term potentiation in rat hippocampal slices

Addition of 200 nM β-amyloid 1-42 (Abeta) to a rat hippocampal slice impairs the induction of a long-term post-tetanic potentiation (LTP) of population spike (PS) in pyramidal neurons of the CA1 field of hippocampus. Intraperitoneal injection into the rat of the mitochondria-targeted plastoquinone derivative SkQR1 (1 µmol/kg of weight given 24 h before the slices were made) abolishes the deleterious effect of Abeta on LTP. These data demonstrate that SkQR1 therapy is able to compensate the Abeta-induced impairments of long-term synaptic plasticity in the hippocampus, which are the main cause of loss of memory and other cognitive functions associated with Alzheimer's disease.

Influences of Hippocampal Field CA1 on Theta Activity in Urethane-Anesthetized Rats

We report results from studies of the influences of hippocampal field CA1 on the generation of theta activity in urethane-anesthetized rats in relation to the efficiency of its synaptic inputs. Long-term post-tetanic potentiation of the projections of Schaffer collaterals increased the theta power peak in the spectrum of the hippocampal EEG, without altering the theta frequency. A strong correlations between increases in the amplitude of focal potentials and increases in the expression of theta activity was seen in long-term posttetanic potentiation. The mechanisms and possible functional significance of this relationship between potentiation and theta activity are discussed.

Age-Specific Peculiarities of Formation of Long-Term Posttetanic Potentiation in OXYS Rats

OXYS rats with hereditary hyperproduction of active oxidative radicals and early disorders in the mitochondrial structure and functions are an interesting model for studies of age-specific features of synaptic plasticity. The formation of long-term posttetanic potentiation in the mossy fibers-CA3 pyramidal neuron system were studied in hippocampal slices from Wistar and OXYS rats aged 3 and 4.5 months (young), 11 (middle-aged), and 18 months (old). No appreciable age-related differences were detected in the amplitudes and latencies of stimulatory postsynaptic summary potentials of the mossy synapses evoked by test stimuli in Wistar and OXYS rat groups of different age and between the two strains. The capacity to induction and formation of long-term posttetanic potentiation and its value decreased in 18-month-old Wistar rats, which attested to disorders in synaptic plasticity of old animals. The capacity to induction and formation of long-term posttetanic potentiation and its value in OXYS were lower than Wistar rats of the same age in all the studied groups.

Donepezil Eliminates Suppressive Effects of β-Amyloid Peptide (1-42) on Long-Term Potentiation in the Hippocampus

β-Amyloid peptide 1-42 in a concentration of 200 nM impairs induction of long-term posttetanic potentiation of population spike in CA1 pyramidal neurons in rat hippocampal slices. Application of donepezil, a drug used for the treatment of Alzheimer disease, in a concentration of 1 μM eliminates the suppressive effect of β-amyloid peptide 1-42 on long-term posttenanic potentiation in the hippocampus.

Time Course of Expression of “Early” Genes during Long-Term Posttetanic Potentiation in Rat Hippocampal CA1 Field

The expression of egr-1, junB, c-jun, and c-fos genes in rat hippocampal CA1 field was studied by the real-time PCR 30, 60, and 120 min after induction of long-term posttetanic potentiation. The content of egr-1, junB, and c-jun mRNA gradually increased and doubled 120 min after tetanization. The increase in c-jun mRNA level lagged behind the increment of egr-1 and junB. The level of c-fos mRNA increased 30 min after tetanization, returned to the initial level by min 60, and again increased 120 min after induction of long-term posttetanic potentiation.

Expression of S100B and S100A6 Genes during Long-Term Posttetanic Potentiation in the Hippocampus

The expression of S100B and S100A6 mRNA in CA1 region of rat hippocampal sections was studied after tetanizing stimulation. The level of S100B expression increased 2-4-fold in comparison with the control after 30 min and gradually returned to the basal level 120 min after tetanization. The level of S100A6 mRNA was very low and did not change after tetanization.

Neurotropic effect of exogenous L-carnosine in cultured slices of the olfactory cortex from rat brain

Incubation of cultured slices of the olfactory cortex from rat brain with L-carnosine in concentrations of 50, 250, and 500 M induced activation of glutamatergic and GABAB-ergic mechanisms and facilitated long-term posttetanic potentiation. The effect of L-carnosine is mediated by its effect on AMPA- and NMDA-related glutamatergic receptors and on inhibitory GABAB receptors.

Effect of hypobaric hypoxia on the development of long-term posttetanic potentiation in slices of rat olfactory cortex: Correction with hypoxic preconditioning

We studied the effect of in vivo hypobaric hypoxia on the development (after 3 h) of in vitro long-term posttetanic potentiation in Wistar rats. Severe hypoxia suppressed induction of posttetanic potentiation in slices of the olfactory cortex. Preconditioning exposure (moderate hypobaric hypoxia) prevented inhibition of posttetanic potentiation induced by severe hypoxia.

Activity of Acetylcholinesterase in Olfactory Bulb of the Pike Esox lucius and Its Role in Development of Long-Term Posttetanic Potentiation

A complex electrophysiological, biochemical, and histochemical study is carried out for determination of activity and distribution of acetylcholinesterase (AChE) in olfactory bulb (OB) of the pike during long-term posttetanic potentiation (PTP). Between the 30th and 60th min after tetanus, a stable increase of enzymatic activity in parallel with a rise of potentiation is observed. Sixty min after tetanus, at the point of maximal development of long-term PTP (the potentiation value is 170%), the specific activity of AChE rises by 89%. This increase was found to be due to synthesis of the enzyme de novo, with involvement of the majority of mitral cells and a significant part of granular cells.

Effects of Cholinergic Substances on Plasticity of Synapses in Olfactory Bulb of the Pike Esox lucius

An electrophysiological and morphometric study of effects of cholinergic substances on orthodromic potential (OP), induction of long-term post-tetanic potentiation (PTP), and potentiated OP in olfactory bulb (OB) of intact pike was carried out. The final effect of endogenous ACh on relay neurons of the OB was found to be inhibitory. Activation of M1-like cholinoreceptors (ChR) was shown to play the key role in induction of long-term PTP. In response to tetanization of olfactory nerve (ON) after pirenzepine-induced inhibition of M1-like ChR, no potentiation appears and the length of cross-section of axo-dendritic synapse active zone (AZ) does not change in the OB glomerular neuropil. Tetanization of ON after inhibition of M2-like ChR by gallamine leads to the appearance of short-term PTP transformed later into long-term PTP accompanied by a significant decrease of length of cross-sections of axo-dendritic synapse AZ. Effects of both increase of endogenous ACh concentration by eserine (0.1 μM) and blockade of M2-like ChR by gallamine (10 μM) on potentiated OP were manifested as a decrease of its amplitude to control level. The obtained data allow considering that endogenous ACh in the pike OB has a pronounced effect on induction, development, and stabilization of the long-term PTP. This holds equally true to both functional and morphological manifestations of plasticity of axo-dendritic synapses of the glomerular neuropil.