Effects of Specific Inhibitor of Phosphodiesterase 7 at the Late Stage of Long-Term Potentiation in Murine Hippocampal Slices.

Second messengers cAMP and cGMP play an important role in synaptic plasticity and memory consolidation. The inhibitors of phosphodiesterases, enzymes hydrolyzing these cyclic nucleotides, are actively studied as potential drugs for the treatment of various cognitive disorders and depression. We studied the effects of a new inhibitor of phosphodiesterase 7 AGF2.20 on the formation of long-term potentiation in hippocampal slices. Administration of AGF2.20 (10 nM) in 90 min after weak tetanization prevented a decrease in the amplitude of excitatory post-synaptic potentials and stabilized long-term potentiation. These data attest to the involvement of phosphodiesterase 7 in the development of synaptic plasticity in the hippocampus. The inhibitor AGF2.20 is considered for the further analysis as a promising substance for the treatment of cognitive impairments.

Long-term sensitization in the common snail: electrophysiological correlates in the defense behavior command neurons.

It was found that an increase in the excitability of command neurons of the reflex takes place during long-term sensitization (LTS). It was demonstrated that two factors are the cause of the increase in excitability: a depolarizational shift of the membrane potential of these cells (both a decrease in the initial resting potential and an accumulation of depolarization in the course of tactile stimulation), and a decrease in the threshold of generation of the action potentials. Injection of amphetamine leads to the appearance of sensitization, but its mechanisms only partially coincide with those in the case of LTS.

Effect of antibodies to morphine in ultralow doses on induction of long-term potentiation in hippocampal slices from rats with chronic morphine dependence.

Antibodies to morphine produced after its chronic administration can contribute to changes in the central nervous system during opiate abuse. Facilitation of long-term posttetanic potentiation in mossy fibers of the hippocampus in rats with chronic morphine dependence can be reproduced in hippocampal slices from normal animals treated with antibodies to morphine. Incubation of hippocampal slices with ultralow doses of antibodies to morphine had no effect on control rats, but reduced facilitation of long-term potentiation in hippocampal slices from animals with chronic morphine dependence. This confirms the possibility of using ultralow doses of antibodies to morphine for therapeutic correction of mechanisms underlying the formation of drug abuse.

In vitro effects of bipathic treatment with antibodies in ultralow doses during long-term post-tetanic potentiation.

We studied the effects of individual or combination treatment with monoclonal antibodies 5F5-B6 in ultralow doses specifically marking mossy fibers in rat hippocampus and antibodies to S100 protein during long-term post-tetanic potentiation in hippocampal slices. The possible mechanisms of changes produced by therapeutic administration of antibodies in ultralow doses were revealed.

[Mathematical modeling of calcium incurrent flow in a somatic membrane during an action potential]. / Matematicheskoe modelirovanie kal'tsievogo vkhodiashchego toka v somaticheskoi membrane vo vremia potentsiala deistviia.

The application of modified Hodgkin -- Huxley equations to the description of transmembrane ionic currents when the action potential is generated in the somatic membrane of mullusc giant neurons is described. The input currents were divided on sodium and calcium components. The results of calculations were compared with the experimental data. An observed discrepancy between predicted and experimental action potentials is explained. Using the corrections proposed the results of calculations well agree with the experimental results.

[Long-term sensitization in the snail: the electrophysiological correlates in the command neurons of defensive behavior]. / Dolgovremennaia sensitizatsiia u vinogradnoi ulitki: élektrofiziologicheskie korreliaty v komandnykh neironakh oboronitel'nogo povedeniia.

The long-term sensitization of defensive reflex led to an increase of excitability of the command neurons LPa3 and RPa3, controlling the defensive pneumostome contraction reaction due to a depolarization shift of the membrane potential and a decrease of the threshold potential. Depletion of dopamine by amphetamine injection also led to an increase of excitability in these command neurons mainly due to a decrease of the threshold potential. Sensitization of animals after amphetamine treatment resulted in a partial summation of effects--a reliable decrease of the threshold potential in comparison with the sensitized snails and amphetamine-treated ones. It was concluded that the increases of excitability during the long-term sensitization and amphetamine treatment were underlain by different mechanisms.

[Behavioral changes during the acquisition of long-term sensitization of the defensive reflex in the edible snail]. / Izmenenie povedeniia pri vyrabotke dolgovremennoi sensitizatsii oboronitel'nogo refleksa u vinogradnoi ulitki.

Reaction of long-term sensitization (LTS) of defensive reflex was elaborated in the snail. It was accompanied by a considerable increase of the time of closing of pneumostome. The results show that LTS is preserved for more than two week and may be a model of long-term memory.

[Electrophysiological and neurochemical study of long-term sensitization in the snail]. / Elektrofiziologicheskoe i neirokhimicheskoe issledovanie dolgovremennoi sensitizatsii u vinogradnoi ulitki.

The long-term sensitization of avoidance reflex was produced in snail Helix pomatia, which led to the remarkable increase in the pneumostome closures period. The formation of long-term sensitization is also accompanied by increase in excitability of command neurons of this reflex. One of the possible mechanisms of this phenomenon is the depolarization of these cells. The quantitative redistribution of water-soluble proteins with relative mobility 0.54 0.42 0.40 was also observed in the identified neurons, both included in the avoidance reflex (command neurons) and non-included (bursting neurons, nerve cells of pool D). The protein with the relative mobility of 0.75 was unique for the nerve cells of neurosecretory pool D in sensitized snails, and was never found in control animals.

Effect of antibodies to morphine on synaptic plasticity of the hippocampus.

Incubation of hippocampal slices with antibodies to morphine did not change the total excitatory postsynaptic potential of mossy fibers, but markedly facilitated long-term posttetanic potentiation. Culturing of the organotypic hippocampal culture in the presence of 10 microM morphine increased the total excitatory postsynaptic potential of mossy fibers and reduced the probability of long-term posttetanic potentiation.