Intracellular tetanization with hyperpolarizing currents potentiates synapses formed by mossy fibers on pyramidal cells in hippocampal field CA3 in rats.

Studies on living rat hippocampal slices using point recording in the whole cell configuration addressed the efficiency of the synaptic responses of pyramidal neurons in field CA3 in conditions of minimal stimulation of mossy fibers. Paired-pulse responses were recorded before and after intracellular tetanizing hyperpolarization of pyramidal neurons. In these conditions, potentiation of excitatory synaptic transmission lasting at least 20 min was seen. This phenomenon, termed hyperpolarizing tetanization-induced long-term potentiation, could arise without simultaneous mossy fiber stimulation and showed signs of having a presynaptic origin. Administration of a Ca2+ chelator into pyramidal neurons completely suppressed this potentiation. The results obtained from these experiments suggest that induction of long-term potentiation evoked by hyperpolarizing tetanization was postsynaptic, while its expression appeared to be presynaptic. These results provide evidence of the importance of gamma-rhythm hyperpolarizing oscillations in altering the efficiency of synaptic inputs and the role of its network organization in the mechanisms of cellular plasticity.

[Intracellular tetanization by the hyperpolarizing current potentiates synapses formed by mossy fibers on the pyramidal cells of the CA3 hyppocampal area of the rat].

Whole-cell recordings of excitatory postsynaptic potentials evoked by the minimum stimulation of mossy fiber inputs were performed in CA3pyramidal neurons in rat hippocampal slices. Paired responses were recorded before and after intracellular hyperpolarization tetanization. This procedure produced an increase in excitatory postsynaptic potentials at least for 20-min recording period. The effect, referred to as hyperpolarization-tetanization-induced long-term potentiation, could arise without simultaneous mossy fiber stimulation and revealed signs ofpresynaptic origin. Loading Ca2+ chelator BAPTA into the postsynaptic neuron completely prevented this form oflong-term potentiation. The findings suggest that whereas the induction of hyperpolarization-tetanization-induced long-term potentiation was postsynaptic, its expression was presumably presynaptic. The results show the significance ofgamma-rhythmical hyperpolarizing oscillations for changes in synaptic input efficacy and the role ofa network in cellular mechanisms of plasticity.

Studies of the synaptic plasticity of field CA3 of the hippocampus during tetanization of the perforant path.

Studies on living slices of hippocampus-entorhinal cortex formation from adult rats were performed to investigate changes in responses in field CA3 to stimulation of mossy fibers in conditions of perforant path tetanization with different parameters. Tetanization of the perforant path at frequencies of 10 and 100 Hz induced depression of responses in CA3 on testing of this same path. Tetanization of the perforant path at a frequency of 10 Hz and an amplitude subthreshold for potentiating mossy fiber synapses in CA3 became threshold if preceded by tetanization of the perforant path at a frequency of 100 Hz. Tetanization of mossy fibers at 10 Hz resulted in potentiation of the input to CA3, while tetanization at 100 Hz induced depression. High-frequency tetanization of the perforant path (100 Hz) delivered in trains following at the frequency of the theta rhythm, led mainly to depression of field CA3 responses to stimulation of mossy fibers.

[Study of giant depolarizing activity in the neonatal hippocampal neurones]. / Issledovanie mekhanizma vozniknoveniya gigantskikh depoliariziruiushchikh potentsialov v neironakh gippokampa novorozhdennykh krys.

Spontaneous oscillatory activity is a general feature of developing neural networks. Early in postnatal development, spontaneous network-driven events, termed giant depolarizing potentials (GDPs), occur synchronously over the entire hippocampus. By performing simulation of hippocampal network with using physiology parameters of the neurons and its network from the present experiments and literature dates, we investigated the participation of the different components of network in the generation of GDPs. Comparing the results of the model and in vitro experiments we conclude that are necessary for the GDP generation involvement the activation of GABAergic, glutamatergic inputs and perhaps gap junction.

[Study of synaptic plasticity of hippocampal CA3 area as a result of tetanization of perforant path]. / Issledovanie sinapticheskoi plastichnosti oblasti CA3 gippokampa pri tetanizatsii perforantnogo puti.

Evoked responses in CA3 area to the mossy fibers stimulation were studied after low and high frequency tetanizations of the perforant path. Stimulations of perforant path with 10 and 100 Hz frequencies inducted depression testing through the same path. Subthreshold for potentiation of the mossy fibers inputs to the CA3 tetanization of the perforant path with 10 Hz frequency transformed to threshold one after previous tetanization of the perforant path with 100 Hz frequency. Tetanization of the mossy inputs to the CA3 with 10 Hz frequency leaded to potentiation whereas tetanization with frequency 100 Hz depressed the same inputs. High frequency tetanizations (100 Hz) of the perforant path with theta-rithm frequency stimulation basically depressed of the CA3 evoked responces to the mossy fiber stimulation.

Stimulation of the lateral hypothalamus provokes the initiation of robust long-term potentiation of the thalamo-cortical input to the barrel field of the adult, freely moving rat.

Long-term potentiation in the thalamo-cortical input to the somatosensory cortex barrel field has been reported to be inducible in vitro only during a narrow critical period of the first postnatal week. Here we explored whether this is due to inability of adult synapses to express LTP or lack of appropriate conditions for LTP induction in slice preparations. We recorded thalamo-cortical field potentials (FPs) from the barrel field of chronically prepared adult rats. In the first series, several parameters of conditioning tetanization of thalamus (T) have been tried. Statistically significant LTP of 135-150% relative to the baseline was observed only in rare cases (3/18) so that the mean changes were not statistically significant. In the second series, five trains of 100 Hz stimulation of T were paired with a "reinforcing" stimulation of the lateral hypothalamus (LH). In most cases (9/13), thalamo-cortical FPs were potentiated. The mean post-tetanic amplitude was 238 +/- 42% (+/- SEM) relative to the baseline (n = 13). The potentiation persisted for >1 h and typically even further increased when tested 24-48 h later. LTP magnitude strongly correlated with the initial paired-pulse ratio (PPR, coefficient of correlation r = 0.98) so that the LTP magnitude was larger (333 +/- 107, n = 6) in cases with PPR > 1.3. The mean PPR tended to decrease after LTP (from 2.05 to 1.65). Altogether the results suggest that LTP is inducible in the thalamo-cortical input to the barrel field of normal adult rats. The dependence of the LTP magnitude upon the initial PPR suggests that inputs with low initial release probability undergo larger LTP. Together with the tendency to a decrease in the PPR this suggests an involvement of presynaptic mechanisms in the maintenance of neocortical LTP.

Stimulation of the lateral hypothalamus provokes the initiation of robust long-term potentiation of the thalamo-cortical input to the barrel field of the adult, freely moving rat.

Long-term potentiation in the thalamo-cortical input to the somatosensory cortex barrel field has been reported to be inducible in vitro only during a narrow critical period of the first postnatal week. Here we explored whether this is due to inability of adult synapses to express LTP or lack of appropriate conditions for LTP induction in slice preparations. We recorded thalamo-cortical field potentials (FPs) from the barrel field of chronically prepared adult rats. In the first series, several parameters of conditioning tetanization of thalamus (T) have been tried. Statistically significant LTP of 135-150% relative to the baseline was observed only in rare cases (3/18) so that the mean changes were not statistically significant. In the second series, five trains of 100 Hz stimulation of T were paired with a "reinforcing" stimulation of the lateral hypothalamus (LH). In most cases (9/13) thalamo-cortical FPs were potentiated. The mean post-tetanic amplitude was 238 +/- 42% (+/- SEM) relative to the baseline (n = 13). The potentiation persisted for > > 1 hr and typically even further increased when tested 24-48 hr later. LTP magnitude strongly correlated with the initial paired-pulse ratio (PPR, coefficient of correlation r = 0.98) so that LTP magnitude was larger (333 +/- 107, n = 6) in cases with PPR > 1.3. The mean PPR tended to decrease after LTP (from 2.05 to 1.65). Altogether the results suggest that LTP is inducible in the thalamo-cortical input to the barrel field of normal adult rats. The dependence of LTP magnitude upon the initial PPR suggests that inputs with low initial release probability undergo larger LTP. Together with the tendency to a decrease in the PPR this suggests an involvement of presynaptic mechanisms in the maintenance of neocortical LTP.

[Modulating influence of adenosine triphosphate on the oscillating properties of hippocampal neurons during early ontogenesis]. / Moduliruiushchee vliianie adenozintrifosfata na ostsiliatornye svoistva gippokampal'nykh neironov v rannem ontogeneze.

Extracellular ATP was used to test the involvement of purinergic P2 receptors in the modulation of GAB Aergic giant depolarizing potentials (GDPs) in rat neonatal hippocampus. Bath application of ATP reduced the GDP frequency in a concentration-dependent manner. The inhibitory effect of ATP persisted in the presence of adenosine P1 receptor antagonist DPCPX indicating the action of ATP on GDPs. It was suggested that, during development, ATP can modulate network-driven activity in the neonatal hippocampus through the activation of purinergic P2 receptors.

Reverberation of excitation in living "hippocampal formation-entorhinal cortex" slices from rats. Optical recording.

A vital potential-dependent dye was used to conduct optical recording of the electrical activity of the hippocampal formation in living slices of the rat brain including the hippocampal formation and the entorhinal cortex. These studies showed that single electrical stimuli applied to the entorhinal cortex, subiculum. and dentate gyrus produced responses in which waves of excitation passed across the hippocampal formation sequentially from the dentate gyrus, through CA3, to the CA1 field of the hippocampus. When GABAergic inhibition was partially blocked with picrotoxin, the first wave of excitation was immediately followed by several further waves in all zones of the hippocampal formation, with a constant shift in latency, which increased from the dentate gyrus to CA3 and CA1. Reverberation of excitation in the "hippocampal formation-entorhinal cortex" structure is regarded as the most probable cause for the appearance of these sequences of waves.

Restoration of decaying long-term potentiation in the hippocampal formation by stimulation of neuromodulatory nuclei in freely moving rats.

Induction of long-term potentiation within the hippocampal formation can be modulated by afferent influences from a number of subcortical structures known to be involved in hippocampal-dependent learning and memory. This study performed on freely moving rats investigated the effects of stimulation of the noradrenergic locus coeruleus nucleus and the serotonergic dorsal raphe nucleus on spontaneously decaying posttetanic long-term potentiation in the dentate gyrus and the hippocampal CA1 area, respectively. High-frequency electrical stimulation of the locus coeruleus or the dorsal raphe elicited a well-expressed behavioural reaction of exploratory or defensive type, respectively, but did not significantly alter transmission at perforant path-dentate gyrus or Schaffer collateral-CA synapses, when delivered either before tetanic stimulation of the perforant path or the Schaffer collaterals or long (hours and days) after previously induced long-term potentiation had completely decayed. However, when locus coeruleus or dorsal raphe stimulation was delivered with the same parameters during a limited time (minutes and hours) after marked or even complete decay of tetanus-induced long-term potentiation at perforant path-dentate gyrus or Schaffer collateral-CA1 synapses, the potentiation was partially or entirely restored but never increased beyond the initial level of potentiation. In CA1, stimulation of ipsilateral and contralateral Schaffer collaterals demonstrated that the restoration of previously existing long-term potentiation by dorsal raphe stimulation was input-specific, occurring, like tetanus-induced potentiation, only in the pathway which had previously been tetanized. These findings suggest that the noradrenergic locus coeruleus and the serotonergic dorsal raphe can influence not only induction, but also spontaneous decay of long-term potentiation in the hippocampal formation. Since hippocampal long-term potentiation is thought to play a role in certain kinds of learning and memory, and association of tetanic stimulation with activation of ascending neuromodulatory systems is required for full expression of long-term potentiation, the restoration of hippocampal long-term potentiation by activation of a neuromodulatory system alone may serve as a mechanism of associative reminder which may underlie facilitation of memory retrieval after a period of forgetting, as has been observed in trained rats under similar conditions.

[The generation of action potentials in the terminals of the Schaffer collaterals during long-term potentiation in the CA1 region of the hippocampus]. / Generatsiia potentsialov deistviia v okonchaniiakh kollateralei Shaffera vo vremia dlitel'noi potentsiatsii v oblasti CA1 gippokampa.

Experiments were performed in rat hippocampal slices. Activity of individual CA3 pyramidal neurons and field potentials in the CA1 areas were recorded extracellularly. The collision technique was applied to detect the antidromic origin of the background action potentials in the somata of CA3 neurons. Threshold stimulation of terminals of the Schaffer collaterals in the stratum radiatum of the CA1 area was applied to study their excitability during the CA1 long-term potentiation. During the long-term potentiation, antidromic action potentials appeared in the somata of the CA3 neurons. The obtained evidence suggests that the synaptic potentiation is accompanied by an enhancement of axon terminal excitability resulting in generation of the action potentials.

Triggering action potentials in an axo-dendritic inhibitory synaptic terminal.

Intracellular activity of the slow adapting neurone (SAN) was recorded together with extracellular action potentials (APs) of SAN, fast adapting neurone and inhibitory fibre in the isolated stretch receptor of the moulting crayfish. Following strychnine application, spontaneous APs and seizure-like AP trains were observed. A delay of the inhibitory fibre APs relative to SAN inhibitory postsynaptic potential, their waveforms and their initiation by intracellular SAN hyperpolarization indicate that their generation was close to the inhibitory nerve terminal. Such antidromic (ectopic) APs assert their postsynaptic action on both receptor neurones via the axon reflex. The findings provide first evidence of antidromic APs generated in the vicinity of inhibitory terminals, their direct and axon reflex-mediated action on target neurones and support a hypothesis that increased terminal excitability contributes to seizure activity.

Identification of a latent state arising in the hippocampus following the cessation of long-term potentiation.

The possibility of the restoration of long-term potentiation in the CA1 region and the dentate gyrus of the hippocampus during stimulation respectively of the dorsal raphé nuclei and locus coeruleus, with stimulus parameters inducing behavioral reactions, was investigated in freely-behaving rats. It was demonstrated that stimulation of the locus coeruleus, which was ineffective prior to the tetanization of the perforant path, led to the restoration of extinguished long-term posttetanic potentiation in the dentate gyrus of the hippocampus induced by tetanization of the perforant path. Stimulation of the dorsal raphé nucleus, which was ineffective prior to the tetanization of the Schaffer collaterals, led to the restoration of long-term posttetanic potentiation in the CA1 region of the hippocampus induced by tetanization of the Schaffer collaterals. A mathematical model is proposed which has made it possible to describe the restoration of long-term posttetanic potentiation on the basis of the notion of the existence of several states of calcium/calmodulin-dependent protein kinase. The restoration of long-term potentiation during stimulation of emotiogenic zones was examined as a model of the phenomenon of emotional reminding.

[The detection of a latent state occurring in the hippocampus after the cessation of long-term potentiation]. / Vyiavlenie skrytogo sostoianiia, voznikaiushchego v gippokampe posle prekrashcheniia dlitel'noi potentsiatsii.

The possibility of restoration of long-term potentiation (LTP) due to stimulation of the locus coeruleus and the dorsal raphe nucleus was investigated in the dentate gyrus and the area CA1 of the hippocampus correspondingly. The stimulation parameters were sufficient to evoke behavioral reactions of the freely moving rats. It was shown that the stimulation of the locus coeruleus non-effective before tetanization of the perforant path restored the already ceased LTP in the dentate gyrus evoked by tetanization of the perforant path. Also, the stimulation of the dorsal raphe nucleus non-effective before tetanization of the Schaffer collaterals restored the already ceased LTP in the area CA1 evoked by tetanization of the Schaffer collaterals. The mathematical model of LTP restoration is presented based on the existence of several forms of calcium/calmodulin-dependent protein kinase. LTP restoration due to stimulation of the emotiogenic brain structures is considered as a model of emotional reminder phenomenon.

[Localization of sources of thalamic inputs into the sensomotor area of the cerebral cortex of the rabbit using the technic of retrograde axonal transport of horseradish peroxidase]. / Lokalizatsiia istochnikov talamicheskikh vkhodov v sensomotornuiu oblast' kory mozga krolika s ispol'zovaniem metoda retrogradnogo aksonnogo transporta peroksidazy khrena.

A horseradish peroxidase study has shown that the rabbit sensorimotor cortex received afferent fibres from the neurons, located in specific, nonspecific and associative thalamic nuclei. The location, form and size of the somata of relay cells were analyzed in these nuclei. The total number of cells of the origin of thalamo-sensorimotor-cortical fibres was calculated and the coordinates of the loci with maximal density were determined. Among the relay cells the most abundant ones appeared to be multipolar neurons (12-20 micron in size) and stellate cells (10-15 micron). Among the specific nuclei most of afferent fibres originated from n. ventralis lateralis, n. ventralis anterior and n. anterior ventralis; a comparable number of fibres originated from n. medialis dorsalis and n. paracentralis that had much more labelled cells than other associative and nonspecific nuclei, respectively. It is supposed that the afferentation from many thalamic nuclei is essential for the sensorimotor cortex to participate in thalamocortical interactions.

[Callosal neurons: monosynaptic connection between them and their descending projections]. / Kallozal'nye neirony: monosinapticheskaia sviaz' mezhdu nimi i ikh niskhodiashchie proektsii.

Antidromic and monosynaptic unit responses to the stimulation of the corpus callosum and the symmetrical cortical area as well as antidromic responses to pyramidal tract and thalamic nuclei stimulation were recorded in the sensorimotor cortex of unanaesthetized rabbits. Out of 182 callosal neurones 13 exhibited transcallosal monosynaptic responses. 8 out of 56 callosal units responded antidromically to pyramidal tract or thalamic stimulation. Thus callosal neurones may be monosynaptically excited by callosal units via the corpus callosum and by the pyramidal tract units. It was also found that a pyramidal tract neurone may send a collateral through the corpus callosum and at the same time have a transcallosal monosynaptic input. The role of monosynaptic transcallosal excitation of callosal neurones is discussed.

[Characteristics of monosynaptic connections between neurons of the callosal system and specific thalamic nuclei]. / Kharakteristika monosinapticheskikh sviazei mezhdu neironami kallozal'noi sistemy i spetsificheskimi iadrami talamusa.

In the sensorimotor cortex of awake rabbits monosynaptic afferent and efferent connections of callosal neurons (CN) with ipsilateral specific thalamic nuclei (ventral posterolateral, ventral posteromedial, ventral lateral and anteroventral nuclei) were analyzed by electrophysiological method and compared with those of target-units of callosal fibres (TU). It was demonstrated that CN and TU differed in their monosynaptic inputs from the thalamus and in their axons projecting to these structures and/or being a part of the pyramidal tract. These differences were the following: a greater portion of TU had the descending projections (54%) as compared with CN (14%); 22% of TU responded by monosynaptic action potentials to the stimulation of specific thalamic nuclei, while CN never manifested such responses. TU could project to the thalamus through the main axon stem as well as through the collaterals of the pyramidal tract axons. It is supposed that the discovered differences evidence for the much greater convergence of the thalamic relay neuron effect on TU, thus revealing the mechanism underlying the differences both in receptive field properties and in the background and evoked activity of CN and neurons synaptically excited in response to the transcallosal stimulation.