[Caspase-3 activity in the rat hippocampal slices reflects changes in synaptic plasticity].

Considering the involvement of caspase-3 in neuronal plasticity, we studied caspase-3 activity in the rat hippocampal slices, and electrophysiological characteristics of extracellular responses to paired-pulse stimulation of Schaffer's collaterals in the CA1 subfield of hippocampus. Caspase-3 activity was measured after electrophysiological recording in each slice separately. Maximal caspase-3 activity was observed in the slices with low responsiveness to single afferent stimulation indicative of decreased efficacy of interneuronal interaction. This phenomenon is unrelated to depression of neuronal excitability since paired-pulse stimulation increases the synaptic efficacy to second stimulus thus restoring population spike amplitudes to normal values. In "damaged" slices with impaired spike generation up to disappearing spikes to both stimuli, caspase-3 activity was close to the normal level of the "healthy" slices. The activity of another proteinase, cathepsin B, was increased in the "damaged" slices, no correlation with the modifications of electrophysiological indices being detected. Our data suggest that high caspase-3 activity in hippocampal slices is involved in maintenance of synaptic plasticity but not necessarily related to apoptosis.

[Developmental caspase-3 activation in the rat hippocampus is involved in the maturation of instrumental behavior].

Previously the developmental switch to caspase-3 activation in the rat hippocampus has been shown during the third week of life. The goal of this study was to explore effects of caspase-3 inhibition during this period on learning in a two-way avoidance paradigm. On postnatal day 18, the pups were intracerebroventricularly administered with caspase-3 inhibitor Z-DEVD-FMK. Control groups were injected with either the control peptide Z-FA-FMK or saline. Caspase-3 inhibition, naturally activated in this critical period, was found to disturb the maturation of instrumental behavior. In particular, the young adult rats of Z-DEVD-FMK group displayed less effective elaboration of escape and active avoidance reactions in two-way avoidance paradigm, accompanied with a decrease in inter-trial crossings. However, associative components of the learning did not change after caspase-3 inhibition. Conditioned emotional behavior was, in general, similar in all groups, and the number of responses related to conditioned stimulus exploration did not differ in Z-DEVD-FMK and Z-FA-FMK groups. In spite of the deficit in active avoidance conditioning in Z-DEVD-FMK group, a significant increase in incomplete or preparatory reactions to conditioned stimulus was demonstrated suggesting that the association between predictive conditioned stimulus and possibility of crossing can be elaborated. The change of exploratory behavior is unlikely to be specific for caspase-3 inhibition, being similar in Z-DEVD-FMK and Z-FA-FMK groups.

[Kindling during early postnatal development: the effects on the maturation of the hippocampal electrophysiological characteristics].

The effect of repeated pentylentetrazole (PTZ) administration on the postnatal development of hippocampal electrophysiological indices has been studied. Contrary to adult rats, repeated PTZ injections did not intensify convulsive activity in rat pups (from postnatal day 14). We did not observe any between-group differences in population spike amplitudes and paired pulse facilitation (PPF) ratio at 70 ms interpulse interval during early period of postnatal development, PPF suppression at short interlulse interval (15 ms) only was significantly less in PTZ group as compared with saline-injected controls, but the effect of saline injections has developed in the same directio However PTZ resulted in the modification of developmental profile. Besides the change of paired-pulse inhibition (15 ms), in the slices of young rats (27-48 postnatal days) the input-output curve was specifically modified and the intensity-dependent increase in population spike amplitudes was less expressed than in the slices of young control rats repeatedly subjected to saline injection, while PPF ratio of both groups was significantly decreased in a similar way, as compared with passive controls. In addition, LTP magnitude in the slices of PTZ group was also suppressed. These modifications did not correlate with convulsive activity. A significant correlation with convulsive activity was found only for population spike amplitudes evoked by low, near-threshold stimuli.

[Prenatal experience and postnatal development of the rat hippocampus: sleep deprivation of pregnant rats].

The effects of sleep deprivation in pregnancy on the development of hippocampal function of the offspring have been investigated. For this purpose we compared electrophysiological characteristics in the hippocampal slices of 15-20-old-day rats of the control and two experimental groups. In the first experimental group the pups were taken from mother for weighting three times during the first postnatal week and then weekly. Another experimental group was brought up without handling. We found that CA1 population spikes developed to significantly less amplitude in experimental groups of rat pups. This phenomenon was observed at higher intensity of monosynaptic activation, although near-threshold stimuli didn't reveal any differences among groups. However, under paired-pulse stimulation (70 ms inter-pulse interval) small amplitudes in the hippocampal slices of experimental animals could facilitate up to control value, and second in pair responses didn't differ from corresponding control. Our data doesn't confirm the hypothesis about decreased connectivity in the hippocampus of experimental rats, but the efficacy of CA3-CA1 inputs seems to be lower. Besides excitatory transmission, the effectiveness of inhibition of paired-pulse facilitation at 15 ms inter-pulse interval was also significantly decreased. The observed effects of prenatal influences seem to develop under postnatal experience. We observed significant trend to more pronounced modifications upon age especially in the case of early handling and testing.

[Effects of intracerebroventricular administration of a caspase-3 inhibitor Z-DEVD-FMK on behavior of rats].

Rats received intracerebroventricular injections of z-DEVD-FMK (caspase-3 inhibitor) or z-FA-FMK (control peptide) in a dose of 3 nmol. Administration of z-DEVD-FMK significantly decreased the number of avoidance reactions in some blocks of trials in active avoidance (shuttle box) learning. However, only slight effect of the caspase inhibitor across the session was found. Z-DEVD-FMK impaired development of some essential components of the two-way active avoidance performance, such as escape reaction, conditioned fear reaction, and inter-trial crossings. Z-DEVD-FMK did not impair working memory in the spontaneous alternation behavior paradigm. Z-DEVD-FMK affected neither emotionality nor locomotor activity in the open-field test. It also did not influence behavior in the light-dark chamber. Measurement of caspase-3 activity in rat brain regions involved in active avoidance learning revealed z-DEVD-FMK-related inhibition of the enzyme activity most pronounced (about 30%) in the fronto-parietal cortex; a similar effect was close to significant in the hippocampus. The results suggest the involvement of brain caspase-3 in selected forms of learning.

[Effects of caspase-3 inhibition on long-term potentiation in the hippocampus: analysis of paired pulse facilitation].

Incubation of the rat hippocampal slices with caspase-3 inhibitor Z-DEVD-FMK resulted in a time-dependent decrease in long-term potentiation (LTP) magnitude. Analysis of paired pulse facilitation at a 70-msec interval revealed that, after caspase-3 inhibition, the increase in the amplitude of the second response in the pair during LTP that was characteristic for control slices, did not occur. In this situation, the LTP magnitude depended on differences in the amplitudes of the first and second responses before the LTP induction. LTP was absent in slices with initially high efficacy of the afferent stimulation and respective low paired pulse facilitation. The Caspase inhibition seems to prevent structural reorganization during the LTP related to involvement into the response of new synapses and neurons.

[Postnatal development of conditioned reflex behavior: comparison of the periods related to the onset of the different forms of hippocampal plasticity in rats]. / Postnatal'noe razvitie uslovnoreflektornogo povedeniia: sravnenie periodov sozrevaniia plasticheskikh protsessov v gippokampe krys.

Fear conditioning, escape and active avoidance reactions in two-way avoidance paradigm were compared in rats of different ages. Fear conditioning, but not escape and active avoidance reactions could be acquired on the 16-17th postnatal days, and the acquisition was more effective than in adults. Escape behavior matured beginning from the 18th postnatal day reaching the adult level within the 3d-4th postnatal weeks. Maturation of the mechanisms of Pavlovian (fear reaction) and instrumental (escape reaction) conditioning did not facilitate the acquisition of two-way avoidance until the 4th postnatal week, young animals displayed low acquisition in this period. The maturation of these memory processes is proposed to be related to developmental stages of different mechanisms of hippocampal plasticity.

[Caspase-3 inhibition blocks long-term potentiation in hippocampal slices]. / Ingibirovanie kaspazy-3 blokiruet dlitel'nuiu potentsiatsiiu v srezakh gippokampa.

Incubation of hippocampal slices with Z-DEVD-FMK, a specific inhibitor of caspase-3, elicits a time dependent decrease in long-term potentiation (LTP). After 4 hours or later after the incubation with Z-DEVD-FMK the tetanization fails to induce LTP. However, Z-DEVD-FMK does not affect basal indices of synaptic plasticity and short-term plasticity (population spike amplitudes and paired pulse facilitation). The results are the first evidence for the involvement of caspase-3-mediated mechanisms in long-term potentiation phenomenon.

[Age-related changes in characteristics of evoked responses in the CA1 area of hippocampal slices after forelimb deafferentation]. / Vozrastnye izmeneniia kharakteristik vyzvannykh otvetov v pole CA1 v srezakh gippokampa krys posle deafferentatsii perednei konechnosti.

The effect of forelimb deafferentation (median nerve transection) on postnatal development of hippocampal synaptic transmission was studied. Paired-pulse paradigm was applied to determine the properties of short-term plasticity, such as paired-pulse facilitation (PPT) in hippocampal slices. Significant changes in the time course of the PPT development were observed after the forelimb deafferentation. It was shown that the earlier described decrease in a population spike amplitude can be related not only to modification of synaptic efficacy but to some destructive processes, i.e., elimination of synapses and neurons. It was followed by the period by intensive formation of new synapses. The data suggest that there is no acceleration or delay in hippocampal development after the forelimb deafferentation but new intrahippocampal networks are formed.

[Change in the signal properties of a conditioned stimulus during two-way avoidance conditioning in rats]. / Izmenenie signal'nogo znacheniia uslovnogo stimula pri vyrabotke uslovnogo refleksa dvustoronnego izbeganiia u krys.

Acquisition of two components of conditioned active avoidance behavior by rats was studied. First presentations of electroshock evoked a number of different behavioral reactions. However, after five trials many rats learned to escape punishment running away to another part of a shuttle-box. The efficiency of the avoidance reaction conditioning significantly depended on the ability of an animal to learn the correct escape reaction to the unconditioned stimulus. However, some animals were incapable for acquisition of the conditioned reaction despite their high level of successful escapes. Increase in the number of negative reactions to the conditioned stimulus (light) at the next stage of learning suggests that the conditioned stimulus becomes the signal of forthcoming punishment. The ability of an animal to identify the conditioned stimulus as a signal significantly affected the efficiency of conditioned avoidance acquisition.

[Reactions of hippocampal neurons at different stages of rat avoidance conditioning]. / Reaktsii neironov gippokampa na paznykh stadiiakh vyrabotki uslovnoreflektornogo izbeganiia u krys.

The electrophysiological responses of neurons were compared in hippocampal slices from rats acquired and not acquired the passive avoidance reaction after the same conditioning procedure. Associative conditioning was accompanied by a gradual increase in the amplitude of the population spike evoked in CA1 area by stimulation of Schaffer collaterals. However, after reaching the learning criterion, the population spike significantly decreased. These phenomena were observed only at low (not maximal) intensities of test stimuli. After reaching the learning criterion, the paired-pulse facilitation was significantly higher in the slices prepared from the well-learned animals as compared with other groups (those having not reached the learning criterion, passive and active control). The obtained evidence validates the hypothesis that the observed intergroup differences stem from modifications of synaptic efficacy and suggests that after behavioral acquisition, plasticity induced by associative learning was substituted by other mechanisms probably related with declarative memory formation.

[Effect of isatin on the electrical activity in the rat hippocampus cells]. / Vliianie izatina na élektricheskuiu aktivnost' kletok gippokampa krys.

In vitro superfusion of rat hippocampal slices with isatin changed the population spikes. Isatin perfusion produced two clear effects. 50 microM isatin it increased the amplitude of the population spike in the CA1 evoked by stimulation of stratum radiatum. This effect was readily reversible. 100 microM isatin decreased the population spike amplitude with minimal effect on its latency. High initial response were more suppressed. This effect on the population spike amplitude was not eliminated even after 1 h of washing with saline. The data obtained suggest that isatin-induced electrophysiological changes are involved into the anticonvulsant effect of isatin.

[Effect of deafferentation of the forelimb on the postnatal development of the synaptic plasticity in the hippocampus]. / Vliianie deafferentatsii perednei konechnosti na postnatal'noe razvitie sinapticheskoi plastichnosti v gippokampe.

The postnatal development of LTP in CA1 area of hippocampus was studied in hippocampal slices from 13-20-day-old intact rats, after unilateral resection of n. medianus on the 13th day, and sham-operated animals. In slices from the intact rats prepared on the 15th-16th-day of postnatal development, the LTP magnitude and duration were significantly larger than in adult animals. Partial deafferentation eliminated this overshoot. However, a less pronounced increase in synaptic plasticity was observed in operated animals on the 17th day. The LTP suppression in the experimental animals may be explained by a decrease in the NMDA receptor activity due to enhanced synaptic activity in the hippocampus. We think that the limited sensory inflow from the partially deafferented forelimb to the hippocampus via the entorhinal cortex may be compensated by activation of other inputs from specific or/and nonspecific pathways. In contrast, the LTP magnitude and duration were significantly increased in slices from the sham-operated rats. This increase may be explained by a decline of synaptic activation of the hippocampus under anesthesia.

[The effect of forelimb deafferentation in early postnatal ontogeny on the development of synaptic transmission in the hippocampus]. / Vliianie deafferentatsii perednei konechnosti v rannem postnatal'nom ontogeneze na formirovanie sinapticheskoi peredachi v gippokampe.

Hippocampal slices from 15-20-day-old Wistar rats were used to study the development of some features of synaptic transmission in hippocampus and the influence of partial limitation of the sensory inflow in the early ontogeny of this transmission. The dynamics of population spike changes was observed in the CA1 hippocampal field in response to stimulation of Schaffer collaterals. The early ontogenetic limitation of the sensory inflow was accomplished by cutting n. medianus on the 13th day. Between the 15th and 20th days, the dynamics of the population spike amplitude increase in the control and experimental animals was similar, however, the response amplitude of the control rats remained higher than in the experimental animals throughout the whole period of observation. It is suggested that the partial limitation of sensory inflow from a forelimb at the early stages of the ontogeny alters the formation of synaptic transmission in hippocampus.

[The effect of vasopressin on hippocampal slices from trained rats]. / Vliianie vazopressina na srezy gippokampa obuchennykh krys.

Vasopressin effects were compared in hippocampal slices of control and conditioned rats. Continuous presentation both of paired and unpaired conditioned and unconditioned stimuli induced an increase in sensitivity of hippocampal neurons to vasopressin. This effect consisted in a complex biphasic reaction (excitatory-inhibitory modulation of population spike amplitude) to peptide application similar to the reaction of the control slices to the increased peptide concentration. The excitatory increased with the number of stimuli presentations and did not depend on the factor of learning. The inhibitory phase increased to a greater extent with the number of paired stimulations. It is suggested that the enhancement of depression by vasopressin in the trained animals in comparison with the active control most probably results from intracellular Ca2+ accumulation during conditioning.

Sensory information--the major factor of ontogeny.

On the basis of their own data authors postulate that the increase in sensory input during early ontogeny results in a delay in the development of the sensory systems formed earlier. In connection with this, the sensory basis of behavioral patterns becomes ineffective, causing their reorganization and the appearance of new forms of behavior. Limitation of sensory input during during the critical periods of development stimulates the accelerated manifestation of behavioral patterns. However, this acceleration also has long-lasting negative effects - alterations in the process of learning and memory in adult animals.

[Sensory information--an important factor in ontogeny]. / Sensornaia informatsiia--vazhnyi faktor ontogeneza.

Ontogenetic process reveals a row of consecutive stages characterized by the gradual increase in complexity and by the changing specificity of sensory mechanisms basic for the adaptive behavior of the young. The study examines the mechanisms of interaction among different sensory systems during the formation of early behavioral patterns and analyzes why, at a certain stage of development, a particular sensory stimulus loses its efficacy in the organization of a given behavior and is substituted by another one, previously ineffective. A special attention is paid to formation of behavior based on sensory information within the limits of ontogenetically fixed developmental critical periods and to the role of the early sensory experience in learning in adult animals.