Modulation of GABA- and Glycine-Activated Ionic Currents with Semax in Isolated Cerebral Neurons.

The concentration-clamp experiments with neurons isolated from the rat brain showed that nootropic and neuroprotective drug Semax added to perfusion solution at concentration of 1 μM augmented the amplitude of GABA-activated ionic currents in cerebellum Purkinje cells by 147±13%. In addition, Semax in perfusion solution (0.1 and 1 μM) diminished the amplitude of glycine-activated chloride currents in hippocampal pyramidal neurons down to 68 and 43% control level, respectively.

Nootropic dipeptide noopept enhances inhibitory synaptic transmission in the hippocampus.

Application of nootropic agent Noopept on hippocampal slices from Wistar rats enhanced the inhibitory component of total current induced by stimulation of Shaffer collaterals in CA1 pyramidal neurons, but did not affect the excitatory component. A direct correlation between the increase in the amplitude of inhibitory current and agent concentration was found. The substance did not affect the release of inhibitory transmitters from terminals in the pyramidal neurons, which indicated changes in GABAergic interneurons.

[The fundaments of neuronal plasticity].

Plasticity of the nervous system is determined by the modification of efficacy ofsynaptic transmission: long-term potentiation and long-term depression. Different modern technical approaches such as: registration of ionic currents in single neuron, molecular-genetic analysis, neurovisualization, and others reveal the molecular mechanisms of synaptic plasticity. The understanding of these mechanisms, in its turn, stimulates the development of methods of pharmacological correction of different forms of brain pathology such as Alzheimer disease, parkinsonism, alcoholism, aging and others.

[Peptidergic modulation of the hippocampus synaptic activity].

Effects of two newly synthesized nootropic and anxiolytic dipeptides: Noopept and Selank on inhibitory synaptic transmission in hippocampal CA1 pyramidal cells were investigated using patch-clamp technique in whole-cell configuration. Bath application of Noopept (1 microM) or Selank (2 microM) significantly increased the frequency of spike-dependent spontaneous m1PSCs, whereas spike-independent mlPSCs remained unchanged. It was suggested that both peptides mediated their effect sue to activation of inhibitory interneurons terminating on CA1 pyramidal cells.

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.

Interaction of acetylcholinesterase inhibitor donepezil with ionic channels of the neuronal membrane.

The effects of donepezil on voltage-dependent Ca(2+)- and low-threshold K(+)-current were studied on isolated molluscan neurons using two-electrode voltage clamp technique. Donepezil reduced the amplitude of voltage-dependent Ca(2+)-current (IC(50)=7.9 microM) and shifted the current-voltage relationships toward hyperpolarization.

Potentiation of GABA-activated currents by imidazobenzoimidazole derivative RU-353 in isolated cerebellum Purkinje cells.

Voltage clamp and concentration jump experiments performed on Purkinje cells isolated from rat cerebellum showed that novel imidazobenzoimidazole derivative RU-353 increased the amplitude of GABA-activated chlorine current in a dose-dependent manner (EC50=15 microM for the currents activated by 1 microM GABA). RU-353 shifted the GABA dose-response curve to the left, but produced no effect on the maximum response (EC50 in control and in the presence of 30 microM RU-353 were 6.9 and 2.

Pyroglutamyl-asparagine amide normalizes long-term potentiation in rat hippocampal slices.

Preapplication of peptide piracetam analogue pyroglutamyl-asparagine amide to rat hippocampal slices facilitates long-term potentiation of focal responses in the CA1 field after weak tetanization of the synaptic input (30 pulses, 100 Hz). This treatment normalized the development of long-term potentiation after standard tetanization (100 pulses, 100 Hz) impaired by ethanol.

Comenic acid prevents post-stress enhancement of long-term potentiation in rat hippocampus.

In experiments on hippocampal slices from young rats subjected to immobilization-cold stress we observed a pronounced increase in the amplitude of long-term potentiation of focal responses in CA1 area. Daily injections of comenic acid during stress exposure normalized parameters of long-term potentiation in the hippocampus.

[Memory and potassium channels].

The K(+)-channels of the surface membrane play a crucial role in the generation of electrical activity of a neuron. There is a large diversity of the K(+)-channels that depends on a great number (over 200) of genes encoding channels proteins. An evolutionary conservation of channel's proteins is determined.

Effect of pyroglutamylasparagine amide on plastic characteristics of synaptic transmission in the hippocampus.

Preincubation of rat hippocampal slices with 0.05-0.5 microM pyroglutamylasparagine amide improved characteristics of long-term potentiation of focal responses in the synaptic system of Schaffer collaterals-CA1 field pyramids facilitating LTP development and increasing its amplitude and duration.

Arginine vasopressin fragment AVP(4-9)facilitates induction of long-term potentiation in the hippocampus.

Long-term potentiation of CA1 field potentials was induced by weak tetanic orthodromic stimulation of the Schaffer collateral/commissural fibers in isolated hippocampal slices perfused with a medium containing arginine vasopressin fragment AVP(4-9)in micromolar concentrations. It is hypothesized that AVP(4-9)affects induction of long-term potentiation at the intracellular level.

[Synaptic plasticity in learning and memory].

Pavlovian conditioning has been considered as one of the principal experimental approaches to understanding such complex brain functions as learning and memory. Use-dependent alterations in synaptic efficacy are believed to form the basis for these functions. The algorithm of synapse modification proposed by D.

[Induction of a delayed cyclic AMP-sensitive sodium current in mollusk neurons by G-protein activators].

The experiments have been carried out with isolated Helix pomatia neurons by the method of two-microelectrode voltage clamping. cAMP and the activators of G-proteins, F-, GTP and Gpp (NH)p, were injected via ionophoresis into the neurons using a seven-channel microelectrode. It is found that the G-protein activators induce both input and output currents in the neurons where slow sodium current can be activated by cAMP.

[Frequency potentiation mechanisms of cyclic AMP-dependent responses of snail neurons].

Intracellular injection of cAMP with the help of microiontophoresis (5-40 nA, 1-10 s) into land snail neurons induces rapid membrane depolarization. Action potentials have not influence on the following cAMP-responses. When the intervals between cAMP-injections are less than 5 minutes the effect of frequency potentiation of cAMP-responses is obtained.

[Preservation of plastic properties of synaptic transmission in long-lasting hippocampal slices under the effects of a peptide analog of piracetam, L-pGlu-D-Ala-NH2].

The tetanic stimulation of the Schaffer collaterals (SC) in rat hippocamp slices after 6 hrs in vitro conditions did not produce long-term potentiation (LTP) of the field response amplitude in the CA1 pyramidal cell layer. In contrast, LTP after the late tetanization was well preserved in the slices that were perfused for 20 minutes with 0.5 mkM L-pGlu-D-Ala-NH2 (PGAA) after 4-4.

[Tetrodotoxin--a sensitive component of the depolarizing response to GABA administration to the pyramidal neuron dendrites of the CA1 field of the hippocampus].

The intracellular recording of CA1 neurons in mouse hippocampal slice preparation was used to study the properties of depolarizing responses to iontophoretically applied GABA to their apical dendrites. Reversal potential of depolarizing responses was dependent on parameters of injecting current. It was about -60 mV and - (45-55) mV when iontophoretic currents 40-60 nA and 8-20 nA were used respectively.

[Effects of polymethylene derivatives of 4-aminopyridine on functional properties of hippocampal neurons].

The effects of amiridin (9-amino-2,3,5,6,7,8-hexahydro-IH-cyclopenta(b) quinoline) and tacrine (1,2,3,4-tetrahydro-9-aminoacridine) on Schaffer collaterals--CAI field potentials were compared in rat hippocampal slice preparations. Similar dose-dependent increase in pop-spike amplitude was observed during slice perfusion with low concentrations of amiridin (5-50 microM) or tacrine (0.5-10 microM).

[Effect of the beta-carboline derivative FG 7142 on inhibition in hippocampal sections].

The action of anxiogenetic derivative of beta-carboline FG7142 on evoked activity of neurons in hippocampal sections was investigated using extra- and intracellular recordings. The activity in CAI area was registered upon stimulation of Schaffer's collaterals (SC). Excitatory effect of FG7142 (5 microM) on population spike (PS) was blocked by simultaneous diazepam (5 microM) or RO15-1788 (5 microM) application.