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. The experiments with cAMP-injection from two different barrels of multibarreled microelectrode show that a change of the microelectrode barrels during repetitive injections causes an abolition of the frequency potentiation effect of cAMP-responses. The results suggest that the frequency potentiation effect of cAMP-responses may be explained by peculiarities of microiontophoresis.

Animals↗

PubMed1990

[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 4-4.5 hrs in vitro. There were no significant reactivity changes during the perfusion of the slices with this drug concentration. Two other drugs with nootropic activity, piracetam (100 mkM) and gamma-hydroxybutyrate (100 mkM, Na-salt) did not prevent the disappearance of LTP in the late period in vitro, while enhanced the reactivity during perfusion period. The maintenance of the plastic properties of the SC-CA1 synaptic transmission under the influence of PGAA is thought to be the result of some specific interaction of the drug with LTP induction mechanisms. LTP damaged in the late period in vitro might be a new model of memory disturbances and this model can turn out to be useful for the comparative estimation of the effectiveness of the drugs with proposed nootropic activity and for the analysis of the possible mechanisms of their action.

Animals↗

PubMed1990

[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. Application of tetrodotoxin (0.1-0.5 microM) resulted in decrease in amplitude of depolarizing responses evoked by weak currents, increase in slope of plot, reflecting relationship between response amplitude and membrane potential, and hyperpolarizing shift of reversal potential. Blocking++ of synaptic transmission with low calcium solution did not produce such changes. These results suggest that GABA depolarizing responses have a potential-sensitive component due to activation of sodium channels.

Action Potentials↗

PubMed1989

[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). This facilitation was not always fully reversible. The effect was accompanied by slight decrease in pop-EPSP amplitude suggesting membrane depolarization as a possible mechanism of pop-spike facilitation. Further increase in drug concentrations led to the depression and full blockade of pop-spike, that was associated with significant decrease in the pop-EPSP and fiber potential amplitudes. In contrast structurally related 4-aminopyridine evoked dose-dependent increase in both pop-EPSP and pop-spike amplitudes with all the concentrations tested (0.05-1000 microM), this facilitation was transformed into epileptiform response with 4-aminopyridine concentration about 500 microM. Possible mechanisms of drug actions on hippocampal neuron reactivity are discussed. It is suggested that amiridin might turn to be as effective as tacrine in symptomatic treatment of Alzheimer disease.

4-Aminopyridine↗

PubMed1985

[Dynamic changes in the response of molluscan neurons to cyclic AMP with repeated injections].

Microiontophoretic injection of cAMP (but not of non-cyclic AMP) into Helix snail neurons induces rapid reversible membrane depolarization. The reversa potential of the cAMP response varies between +10 and -30 mV in different cells. The amplitude of the responses gradually increases (15 experiments), decreases (4 experiments) or remains unchanged (40 experiments) when the interval between the injections is less than 5 minutes. The identified neurons of the different preparations exhibit different types of dynamic changes in the amplitude of the responses to repeated cAMP injections. The possible role of the retaining current in the origin of the potentiation of cAMP responses was investigated. Potentiation of cAMP responses was preserved after the retaining current was switched off only in cases with no membrane depolarization due to spontaneous leakage of the substance from the microelectrode. It is suggested that potentiation or depression of cell responses to repeated cAMP injections is caused by dynamic changes in the cell cAMP system.

Animals↗

PubMed1985

[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. This suggests that FG7142 action is mediated by benzodiazepine receptors. To evaluate the action of FG7142 on hippocampal inhibitory processes paired-pulse stimulation of SC was used. It was shown that FG7142 (5 microM) increased 4-5 times the amplitude of the second PS, the amplitude of the first one being much less augmented (10-20%). Such an effect may probably be associated with specific action of GABA inhibition. The following application of diazepam (5 microM) partially reversed disinhibitory effect of FG7142. The main intracellular change observed was the appearance of the local depolarization following the single action potential (AP). With the application continued, this depolarization gave rise to the second AP. The data suggest that suppression of hippocampal inhibitory circuits may contribute to the development of the anxiety feeling.

Animals↗

PubMed1985

[Characteristics of the electrical activity in hippocampal slices in mice with Corazol kindling].

It has been shown in experiments on hippocampal slices of (CBA X C57BL/6)F1 mice with corazol kindling that the threshold of the appearance of the induced seizure discharge (ISD) in the area CA1 was decreased by stimulation of Schaffer collaterals. Diazepam provoked an increase in seizure susceptibility to corazol and penicillin and reduction of the ISD. The data suggest that alterations in neuronal reactivity, which follow kindling, can be found in an individual hippocampal segment, thus making it possible to investigate this phenomenon at the synaptic and molecular levels.

Animals↗

PubMed1984

[Prolonged potentiation of responses of the neocortex of the intact brain and in vitro cortical slices].

The field potentials (FPs) and neuronal responses evoked by stimulation of subcortical white matter were recorded in the sensorimotor cortex of intact brain in alert rabbits and in cortical slices. After a few short (500 msec) tetanizations (200 Hz) delivered via the stimulating electrodes, a long-term (several hours) increase of short-latency (1-3 msec) FP amplitude occurred in the brain as well as an increase of the same FP components in cortical slices. The probability of short-latency (up to 1.8 msec) unit discharges increased after the tetanization. Repetition of tetanic stimulation in the same experiment increased and prolonged potentiation in vivo though it had an opposite effect in vitro. The long-term potentiation of neocortical FP seems to be due to the potentiation in monosynaptic pathways.

Animals↗

PubMed1984

[Action of beta-carboline derivatives on the evoked activity of hippocampal neurons].

The effects of tetrahydro-beta-carboline-3-carbonic acid methyl ester (I), 1-phenyl-tetrahydro-beta-carboline-3-carbonic acid methyl ester (II), tetrahydro-beta-carboline-3-carbonic acid methylamide, and beta-carboline-3-carbonic acid methylamide on evoked potentials (EP) of neurons were investigated in experiments with hippocampal slices. Each compound was tested in 5 experiments. These derivatives applied in a concentration 4 M had the following features in common: 1) a 10-20% augmentation of the amplitude of the population spike (PS) evoked in the CAI area by Schaffer collaterals stimulation; 2) appearance of additional PSs; 3) potentiation of the substance effect after beginning of washing; 4) poor washing (incomplete recovery of EP after 40-60 min of washing). In one of five experiments, I administration led to a decrease in the PS amplitude (by 15%). A similar effect was observed in one of five experiments during perfusion of II. The authors assume that there are hippocampal mechanisms responsible for realization of opposite effects associated with occupation of benzodiazepine receptors by ligands.

Animals↗

PubMed1983

[Effect of a specific benzodiazepine antagonist RO 15-1788 on phenazepam-induced inhibition of the evoked potentials in hippocampal neurons].

It is suggested that the inhibitory action of phenazepam on the evoked potential (EP) in the CA1 area of the hippocamp in response to the stimulation of Schaffer's collaterals is mediated by phenazepam interaction with a specific benzodiazepine receptor (BR). Experiments were made to study the action of a specific benzodiazepine antagonist RO15-1788 on the phenazepam-induced inhibition in the hippocamp. After RO15-1788 administration (4 microM) the phenazepam-induced (2 microM) inhibition of evoked activity of hippocampal neurons was attenuated. The inhibition provoked by hexenal (2 microM) was not affected by antagonist administration. It is concluded that phenazepam effect on the EP is related to the interaction with BR. In most cases, RO15-1788 (4 microM) had an insignificant inhibitory effect on the EP. However, in individual experiments, it produced an opposite action, i. e. raised the evoked activity of neurons.

Animals↗

PubMed1982

[Effect of diazepam on reactivity of hippocampal neurons during blocking of GABA-ergic system].

It was suggested that diazepam action is mediated by the GABA-ergic system. This suggestion was controlled in vitro experiments with hippocampal slices. The GABA-ergic system was blocked by bicuculline and picrotoxin. The influence of diazepam (1 X 10(-6) M) on the population spikes (PS) evoked in the CA1 area by Schaffer's collaterals stimulation manifested itself in a reversible decrease. Bicuculline (1 X 10(-7) M) and picrotoxin (1 X 10(-6) M) induced an increase in the PS amplitude and appearance of additional PS. Diazepam was normally ineffective when applied in conjunction with bicuculline or picrotoxin. The data indicate that the action of diazepam is really mediated by the GABA-ergic system.

Action Potentials↗

PubMed1982

[Effect of diazepam on the evoked response of the neurons in hippocampal slices].

Influence of diazepam on the amplitude of the population spikes (PS) evoked in CA1 area by Schaffer collateral stimulation in hippocampal slices was analyzed. Diazepam was diluted in Hanks solution used for slice incubation. Introduction of diazepam (3.96 X 10-6 M) into the medium led to a significant decrease in the PS amplitude. higher concentrations (3.96 X 10-5 M) resulted in augmentation of the population EPSP and in disappearance of the PS. The effects were reversible. It is concluded that diazepam inhibits the discharges of the population of CAl neurones.

Animals↗

PubMed1981

[Comparative sensitivity of surviving sections of hippocampus to corticosteroids and angiotensin II].

Sensitivity of CA3 field neurones to hydrocortisone hemisuccinate, sodium dexamethasone-21-phosphate and angiotensin II was studied in experiments on surviving sections of the mouse hippocampus. High sensitivity of the neurones of surviving sections of the hippocampus to the steroid hormones (hydrocortisone and dexamethasone) and virtually complete absence of responses to angiotensin II were demonstrated.

Angiotensin II↗