NMDA or 5-HT receptor antagonists impair memory reconsolidation and induce various types of amnesia.

Elucidation of amnesia mechanisms is one of the central problems in neuroscience with immense practical application. Previously, we found that conditioned food presentation combined with injection of a neurotransmitter receptor antagonist or protein synthesis inhibitor led to amnesia induction. In the present study, we investigated the time course and features of two amnesias: induced by impairment of memory reconsolidation using an NMDA glutamate receptor antagonist (MK-801) and a serotonin receptor antagonist (methiothepin, MET) on snails trained with food aversion conditioning. During the early period of amnesia (<10th day), the unpaired presentation of conditioned stimuli (CS) or unconditioned stimuli (US) in the same training context did not have an effect on both types of amnesia. Retraining an on 1st or 3rd day of amnesia induction facilitated memory formation, i.e. the number of CS + US pairings was lower than at initial training. On the 10th or 30th day after the MET/reminder, the number of CS + US pairings did not change between initial training and retraining. Retraining on the 10th or 30th day following the MK-801/reminder in the same or a new context of learning resulted in short, but not long-term, memory, and the number of CS + US pairings was higher than at the initial training. This type of amnesia was specific to the CS we used at initial training, since long-term memory for another kind of CS could be formed in the same snails. The attained results suggest that disruption of memory reconsolidation using antagonists of serotonin or NMDA glutamate receptors induced amnesias with different abilities to form long-term memory during the late period of development.

Specific changes in c-fos expression and colocalization with DNA in identified neuronal nuclei of edible snail following neurotransmitter application.

The effects of serotonin and glutamate on c-fos expression and c-Fos colocalization with DNA were immunohistochemically studied in defense behavior command neurons R-LPa2-3 in snail Helix lucorum. Simultaneous neurotransmitter application resulted in increased c-Fos-immunoreactivity and colocalization with DNA-specific stain Hoechst 33342 in LPa2 and RPa2 neurons with specific dynamics for each identified cell. In the nuclei of LPa3 and RPa3 neurons, neurotransmitter application did not significant change the c-Fos level. These findings are indicative of specific spatiotemporal changes in c-fos expression and c-Fos colocalization with DNA in investigated neurons of edible snail under the influence of neurotransmitters.

Intravital investigation of the effects of serotonin and glutamate on the dynamics of DNA activity in L-RPl1 neurons of edible snail.

Microloci of varying size with increased fluorescence were observed in L-RPl1 neuronal nuclei of snails using DNA-selective dye SYTO16. Application of serotonin and glutamate increased the number of small (<1 micro in diameter) microloci, while the number of medium and large (1-3 micro) loci decreased. Combined application of neurotransmitters produced more pronounced changes in the number of microloci compared to individual administration. RNA synthesis inhibitors abolished the effects of the transmitters. We hypothesized that the revealed small microloci of fluorescence are "active" DNA zones, where transcription of new genes are initiated.

Effects of protein synthesis inhibitors during reactivation of associative memory in the common snail induces reversible and irreversible amnesia.

The effects of protein synthesis inhibitors on the reactivation of an associative skill consisting of refusing a particular food by common snails were studied. Animals were given single injections of a protein synthesis inhibitor (cycloheximide at 0.6 mg/snail or anisomycin at 0.4 mg) 24 h after three days of training, and were then presented with a "reminding" stimulus (the "conditioned reflex" food-banana) and tested for retention of the skill. Observations revealed an impairment of reproduction of the acquired skill 2.5 h after the "reminder," with spontaneous restoration at 4.5-5.5 h. Other snails were given single 1.8-mg doses of cycloheximide or three 0.6-mg doses with intervals of 2 h. "Reminders" were presented after each injection. In these conditions, impairment of reproduction of the conditioned reflex also appeared 2.5 h after the first "reminder," though amnesia lasted at least 30 days and repeat training of the animals produced only partial recovery of the skill. Thus, we have provided the first demonstration that recovery of a long-term memory "trace" on exposure to relatively low doses of protein synthesis inhibitors produces transient and short-lived amnesia, lasting 2-3 h, while long-term, irreversible amnesia occurs after longer-lasting or more profound suppression of protein synthesis. These results suggest that the "reminding" process induces reconsolidation of the " initial" memory, suppression of which by protein synthesis inhibitors leads to "erasure" of the memory "trace" and impairs consolidation on repeat training.

[Inhibition of protein synthesis during associative memory reactivation produces reversible or irreversible amnesia in the snail Helix lucorum].

Effects of protein synthesis inhibitors on reactivation processes of food aversion conditioning were inverstigated in snail Helix lucorum. Protein synthesis inhibitor (PSI, anisomycin, 0.4 mg, or cycloheximede, 0.6 mg) was injected into snail body cavity 24 hours after 3-day training; then conditioned stimulus (banana) was presented and memory was tested. It was found that 2.5-3 hours after first reminding, associative food conditioning was suppressed, recovering of the conditioning was observed 4.5-5.5 hours after first reminding. In other group of snails, PSI injections were single (1.8 mg) or triple (0.6 mg with 2-hour interval). Reminding stimulus was presented after each injection. In this case, suppression of food aversion conditioning was also observed 2.5-3 hours after first reminding, while amnesia in this case lasted over 30 days. Repeated training of the group of snails recovered the food aversion conditioning only partially. In control snails (saline instead of PSI or 3 injections of PSI without reminding), foot aversion conditioning was detected 30 days after first training. Thus we found that PSI effects during reminding of food aversion conditioning produced two phases amnesia: (1) the easily suppressed by PSI transient phase lasted 2-3 hours, and (2) irreversible phase, its suppression by high doses of PSI-initiated amnesia lasting over 1 month. Second phase of amnesia was not recovered after repeated training. It was suggested that reminding induced reconsolidation of initial memory. Its suppression by protein synthesis inhibitors results in erasing of memory trace and disturbs repeated consolidation.

In vivo investigation of genome activity and synaptic plasticity of neurons in snails during learning.

The present report describes in vivo investigations of genome activity and its role in the mechanisms forming long-term synaptic plasticity in defensive behavior command neuron LPl1 during the acquisition of nociceptive sensitization by common snails. Transcription processes were recorded using SYTO 16, a specific fluorescent indicator of DNA activity, along with in vivo computer image analysis. Studies in control snails showed that application of nociceptive stimuli to the head led to biphasic changes in the bioelectrical responses of neurons to tactile and chemical stimulation--depression of responses in the short-term stage (during the 1 h after training) and their facilitation during the long-term stage of sensitization (more than 24 h). There were marked increases in fluorescence over the nucleus of the command neuron stained with SYTO 16 at 15-20 min from the start of training, this lasting 4-5 h. Acquisition of sensitization in the presence of the RNA synthesis inhibitor actinomycin D (20 microM) to the neuron led to the complete elimination of changes in fluorescence and synaptic facilitation in the responses of LPl1 to sensory stimulation in the long-term stage of sensitization but had no effect during the short-term stage of sensitization. Actinomycin D given 30 min after the end of acquisition of sensitization (1 h after the start) had no effect on the dynamics of fluorescence or synaptic facilitation. Thus, the acquisition of nociceptive sensitization is accompanied by a rapid (within 15-20 min) activation of the DNA of neuron LPl1 and subsequent (about 1 h) display of long-term synaptic facilitation. Induction of both processes was suppressed by the RNA synthesis inhibitor over a relatively short time period--1 h from the moment at which training started.

Inactivation of C/EBP transcription factors specifically affects the synaptic plasticity of a common snail neuron.

Our previous studies showed that the acquisition of nociceptive sensitization in common snails is accompanied by long-term facilitation of synaptic transmission in defensive behavior command neuron LP11, this being dependent on translation and transcription processes. The characteristics of the neurochemical mechanisms of plasticity in the different sensory inputs of this nerve cell were identified. The mechanisms of induction of synaptic facilitation of the responses of neuron LP11 to chemical sensory stimulation of the snail's head involved NMDA glutamate receptors, serotonin receptors, cAMP, and serotonin-modulated transcription-regulating protein SMP-69. The mechanisms of induction of synaptic facilitation of another sensory input of the neuron--from tactile receptors on the head - involved protein kinase C. The present study addresses the involvement of C/EBP transcription factors (CCAAT-enhancer-binding protein) in the processes of synapse-specific plasticity of neuron LP11 during the acquisition of sensitization in snails. C/EBP was inactivated using oligonucleotides specifically binding to these proteins. The results showed that acquisition of sensitization during intracellular administration of oligonucleotides led to the selective suppression of synaptic facilitation in the responses of neuron LP11 to chemical sensory stimulation of the snail's head. Synaptic facilitation in the responses to tactile stimulation of the head or foot developed as in neurons in control sensitized snails. It is suggested that C/EBP transcription factor is selectively involved in the mechanisms of synapse-specific plasticity of the sensory input of neuron LP11 from chemoreceptors on the head during the acquisition of sensitization in snails.

[Transcription factors C/EBP inhibition specifically affects synaptic plasticity in the snail's neuron]. / Inaktivatsiia transkriptsionnykh faktorov C/EBP spetsificheski vliiaet na sinapticheskuiu plastichnost' neirona vinogradnoi ulitki.

In our previous investigations it was found that nociceptive sensitization is followed by a long-term facilitation of synaptic transmission in command neuron of defence behavior. The facilitation is translation- and transcription-dependent. Features of plasticity neurochemical mechanisms of different sensory inputs in the neural cells were determined. NMDA glutamate receptors, serotonin receptors, cAMP as well as serotonin-modulated protein SMP-69 are involved in mechanisms of induction of neural response facilitation in LPl 1 neuron evoked by chemical sensory stimulation of snail head. Protein kinase C is involved in synaptic facilitation-induction mechanisms from other sensory neural input--tactile receptors of snail "head". In this work, participation of C/EBP (CCAAT-enhancing-binding protein) immediate early gene transcription factor was established in mechanisms of synapse-specific plasticity during sensitization in LPl 1 neuron in snail Helix lucorum. Specific binding with C/EBP oligonucleotides were used as C/EBP inhibitors. It was found that sensitization during intracellular oligonucleotide injection selectively suppressed synaptic facilitation in LPl 1 neuron responses evoked by chemical sensory stimulation of snail "head". At the same time, development of synaptic facilitation of the neuron responses evoked by tactile stimulation of snail head or foot was the same as in control sensitized snails. It seems that C/EBP transcription factor is selectively involved in mechanisms of synapse-specific plasticity of sensory input in LPl 1 neuron from snail head chemoreceptors.

[Vital investigation of the genome activity and neuronal synaptic plasticity in snail in the course of learning]. / Prizhiznennoe isledovanie aktivnosti genoma i sinapticheskoi plastichnosti neironov ulitki pri obuchenii.

Vital investigation of genome activity and its role in mechanisms of long-term synaptic plasticity formation were studied in LP11 neuron (command neurone of defence behaviour) during sensitisation (simple form of learning) in semi-intact preparation of snail Helix lucorum. Genome activity was investigate by means of specific fluorescent dye SYTO 16 and image analysis system. It was found that application of sensitizing stimulation (10% quinine solution) onto the snail head initiate two-phase changes in neural responses evoked by tactile or chemical stimulation. Depression of neural responses was obtained during short-term phase (during 1 hour after sensitization) and facilitation of neural responses--during long-term phases (over 1 hour). At the same time (15-20 min after learning), a significant increase in SYTO 16 fluorescent level was found in nucleus site LP11 neurone. Initial SYTO 16 fluorescence level was registered in 4-5 hours after sensitization. If the sensitization was produced during actinomycin D application (inhibitor of RNA synthesis, 20 microM) then facilitation of neural responses evoked by sensory stimulation were suppressed during long-term phase of sensitization and was the same as in control sensitized snails during short-term phase of learning. Increase in SYTO 16 fluorescence level in nucleus region site of LP11 neurone was completely prevented in sensitization during actinomycin D application. If actinomycin D was applied 30 min after sensitization (1 hour after first sensitizing stimulation) then synaptic facilitation and fluorescent dynamics was the same as in control sensitized snails. Our experimental data showed that nociceptive sensitization development was followed by quick (15-20 min) DNA activation and long-term synaptic facilitation (1 hour after sensitization), while induction of the processes was suppressed by inhibitor of RNA synthesis during short time interval (during 1 hour of learning).

The selective action of opioid peptides on excitability and the various sensory inputs of defensive behavior command neurons LPl1 and RPl1 of the common snail.

The nature of the effects of opioid peptides on the properties of electrogenic membranes and the responses of defensive behavior command neurons LPl1 and RPl1, evoked by sensory stimuli of different modalities and application sites was studied in semi-intact preparations from common snails. Application of met-enkephalin (10 microM) to the snail CNS produced increases in membrane excitability along with facilitation of responses to application of dilute quinine solution to the animal's head and depression of responses to tactile stimulation of the head. Met-enkephalin (0.1 microM) produced only depression of responses to tactile stimulation of the head. Application of leu-enkephalin (10 microM) was accompanied by depression of responses to tactile stimulation of the head. Membrane excitability and responses to chemical sensory stimulation during application showed no change during application of this peptide. These effects of both peptides appeared 10-20 min from the start of application and lasted 15-30 min after washing was started. In addition, facilitation of the responses of neurons to chemical sensory stimulation was seen 30-50 min after the start of leu-enkephalin application. The responses of neurons to tactile stimulation of the snail's foot were not altered by application of peptides. The neuronal effects of peptides were suppressed by simultaneous application of naloxone (50 microM). Thus, we observed the selective action of opioid peptides on the synaptic plasticity of neurons LPl1 and RPl1, both in relation to the location of sensory stimulation and in relation to sensory modality.

Selective effects of an NMDA glutamate receptor antagonist on the sensory input from chemoreceptors in the snail's head during acquisition of nociceptive sensitization.

Experiments on semi-intact preparations from common snails were used to study the characteristics of the actions of MK-801, an antagonist of NMDA glutamate receptors, on the plasticity of various sensory inputs to defensive behavior command neurons LP11 and RP11 during acquisition of nociceptive sensitization. Application of sensitizing stimuli to the head or foot of control snails led to depression of neuron responses to tactile and chemical sensory stimulation during the short-term stage and marked facilitation of these responses during the long-term stage of sensitization. Application of sensitizing stimuli to the snail's head during administration of MK-801 led to marked depression of responses to chemical stimulation of the head in both the short-term and long-term stages of sensitization. In addition, blockade of NMDA receptors during application of sensitizing stimuli to the foot or head had no effect on changes in neuron responses elicited by chemical stimulation of the snail's foot and by tactile stimulation of the foot or head. It is suggested that NMDA-like glutamate receptors are selectively involved in the mechanism of induction of plasticity of synaptic inputs to command neurons LP11 and RP11, excited by chemical sensory stimulation of the head--a skin receptor zone specific for these neurons.

[Selectivity of opioid peptide effects on excitability and various sensory inputs in LPl1 and PPl1 command neurons participating in defensive behavior of the snail Helix lucorum]. / Izbiratel'noe deistvie opioidnykh peptidov na vozbudimost' i razlichnye sensornye vkhody kommandnykh neironov oboronitel'nogo povedeniia LPl1 i PPl1 vinogradnoi ulitki.

Opioid peptides effects on neural membrane as well as neural responses evoked by sensory stimuli with different modality and site of application, were investigated in L-RPII command neurones of defensive behaviour of semi-intact preparation in the land snail Helix lucorum. Met-enkephalin (10 uM) application onto the snail CNS increases membrane excitability and produces facilitation of neural responses evoked by quinine solution (0.5%) application onto snail head and depression of reactions evoked by tactile stimulation of the head. Met-enkephalin in dose of 0.1 uM initiates only a depression of neural responses evoked by tactile stimulation of the head. Leu-enkephalin (10 uM) application suppresses neural reactions evoked by tactile stimulation of the head. Membrane excitability and neural responses evoked by quinine application onto the snail head do not change after leu-enkephalin administration. Effects appear 10-20 min after initiation of the peptide application. Initial neural responses were observed 15-30 min after CNS washing with Ringer solution. In addition, facilitation of neural responses evoked by chemical stimulation of the snail head was found 30-50 min after leu-enkephalin washing. Peptides do not change neural responses evoked by tactile stimulation of the snail foot. Neural effects of peptides were prevented by simultaneous naloxon administration (50 uM). Experimental results show selective opioid peptides' effects on excitability and plasticity of L-RPII neural inputs with site- and modality-specifics.

The effects of antibodies against proteins of the s100 group on neuron plasticity in sensitized and non-sensitized snails.

The effects of antibodies to a total fraction of s100 proteins and protein s100b on the activity of defensive behavior command neurons LP11 and RP11 were studied in common snails, using non-sensitized animals and animals which had acquired nociceptive sensitization. In non-sensitized snails, application of antibodies against s100 or s100b (0.1 mg/ml) induced membrane depolarization, increased membrane permeability, and suppressed slow excitatory postsynaptic potentials in the responses of neurons to sensory stimulation. Acquisition of sensitization in snails in the presence of antibodies to s100 or s100b (0.1 mg/ml) led to significantly less marked facilitation of synaptic transmission and smaller increases in neuron membrane excitability than in cells of control sensitized animals. The difference in synaptic facilitation in the neurons of control sensitized snails and neurons in sensitized snails given antibody was comparable with the magnitude of synaptic depression due to antibody in non-sensitized animals. At a dose of 0.01 mg/ml, antibody had no effect on these measures of neuron activity. It is suggested that s100 proteins, particularly s100b, are involved in the mechanisms regulating excitability, the membrane potential, and synaptic transmission in command neurons in untrained snails, as well as in the mechanism of plasticity of the electrogenic membranes of nerve cells during the acquisition of nociceptive sensitization.

[The selective effect of NMDA glutamate receptor antagonist on plasticity of sensory inputs from chemoreceptors of snail head during nociceptive sensitization]. / Izbiratel'noe vliianie antagonista NMDA-retseptora glutamata na plastichnost' sensornogo vkhoda ot khemoretseptorov golovy ulitki pri vyrabotke notsitseptivnoi sensitizatsii.

The effects of N-methyl-D-aspartate (NMDA) glutamate receptor antagonist (+)-MK-801 hydrogen maleate (MR801) on plasticity of different sensory inputs of the L-RPl1 command neurons were studied in Helix lucorum snail during nociceptive sensitization. Application of sensitizing stimulation onto the snail head or foot in the control semi-intact preparation initiated depression of neural responses evoked by tactile or chemical sensory stimulation during the short-term period of sensitization and significant facilitation of neural responses during the long-period of sensitization. Sensitizing stimulation of snail head against the background of MK-801 application (10-30 microM) produced a pronounced depression of neural responses to chemical stimulation of the head both in the short- and long-term sensitization periods. At the same time, sensitizing stimulation of the foot or head during the MK-801 application produced the same changes in neural responses to chemical stimulation of the foot and tactile stimulation of the foot or head as in the control preparation. It can be suggested that NMDA-like glutamate receptors are selectively involved in the mechanisms of plasticity induction in the synaptic inputs of the command LPl1 and RPl1 neurons, which process the information resulting from chemical excitation of the snail head (a specific receptor skin site for these neurons in Helix lucorum).

NMDA glutamate receptor antagonists selectively affect the synaptic mechanisms of nociceptive sensitization in snails.

Defensive behavior command neurons LP11 and RP11 were studied in semi-intact snail preparations to investigate the effects of N-methyl-D-aspartate (NMDA) receptor antagonists on the mechanisms of nociceptive sensitization. Application of sensitizing stimuli to the heads of control snails led to membrane depolarization and increased excitability, and also depressed the responses of neurons to tactile and chemical sensory stimuli in the short-term stage and facilitated responses in the long-term stage of sensitization. Development of sensitization in conditions of exposure to the NMDA receptor antagonists AP5 or MK-801 produced changes in the membrane potential and membrane excitability of command neurons similar to those seen in neurons of control sensitized snails. In addition, changes in the responses of command neurons to tactile stimulation of the head and foot and chemical stimulation of the foot in these conditions were also similar to those seen in neurons of control animals. Acquisition of sensitization during administration of NMDA receptor antagonists led to pronounced depression of responses to chemical test sensory stimulation of the snails' heads in both the short-term and long-term stages of sensitization. Thus. in sensitized snails. NMDA glutamate receptor antagonists selectively acted on the mechanisms of induction of plasticity the synaptic "inputs" of command neurons mediating excitation from chemical sensory stimuli from the animal's head.

[Effect of antibodies against S100 proteins on neural plasticity in sensitized and naive snails]. / Vliianie antitel protiv belkov gruppy S100 na plastichnost' neironov u sensitizirovannykh i nesensitizirovannykh ulitok.

The influence of antibodies against total S100 protein fraction (AB-S100) and S100b protein (AB-S100b) on the activity of LP11 and RP11 neurons were studied in naive snails and during the nociceptive sensitization. Application of AB-S100 or AB-S100b (0.1 mg/ml) initiated membrane depolarization, increase in its excitability, and depression of neural responses to sensory stimulation in nonsensitized snails. The sensitization produced facilitation of neural transmission and increase in membrane excitability. Exposure to AB-S100 or AB-S100b (0.1 mg/ml) during sensitization substantially reduced its effects on neural transmission and membrane excitability. The difference between the extent of synaptic facilitation in neurons of sensitized snails and neurons of snails sensitized under conditions of AB-S100 or AB-S100b application was comparable with synaptic depression in neurons of naive snails produced by the isolated application of AB-S100 or AB-S100b. Application of AB-S100 of AB-S100b in the dose of 0.01 mg/ml did not change the parameters of neural activity. The obtained evidence suggest that S100 proteins (in particular, S100b) in L-RP11 neurons are involved in the mechanisms of membrane excitability, regulation of membrane potential and synaptic transmission in naive snails and in the mechanisms of membrane plasticity in the neurons during development of nociceptive sensitization.

[Antagonists of NMDA glutamate receptors selectively affect synaptic mechanisms of the nociceptive sensitization in the snail]. / Antagonisty NMDA-retseptorov glutamata izbiratel'no vliiaiut na sinapticheskie mekhanizmy notsitseptivnoi sensitizatsii u ulitki.

The effects of N-methyl-D-aspartate (NMDA) glutamate receptor antagonists on the mechanisms of nociceptive sensitization were studied in LPl1 and RPl1 neurons of the semiintact preparation of a Helix lucorum snail. Application of sensitizing stimuli on the head part of the control preparation led to a depolarization of the membrane and increase in its excitability. A depression of responses of neurons evoked by tactile or chemical sensory stimulation during the short-term period and significant facilitation of responses during the long-term period of sensitization were observed. Sensitization performed under conditions of application of NMDA antagonists (AP5 or MK801) produced similar changes in membrane potential, membrane excitability, and neuronal responses evoked by tactile stimulation of the head or foot. However, the chemical stimulation of the head under these conditions evoked a significant depression of responses during the short- and long-term sensitization periods. The results suggest that the NMDA glutamate receptor antagonists selectively affect the plasticity induction mechanisms of the command neuron synaptic inputs, which mediate the chemical sensory stimulation from the snail's head.

Serotonin imitates several of the neuronal effects of nociceptive sensitization in the common snail.

Experiments on defensive behavior command neurons in common snails showed that synaptic facilitation in the responses of nerve cells to sensory stimulation occurs 50-60 min after the onset of application of serotonin (10 microM) to the CNS. The properties of neuron electrogenic membranes (membrane potential, membrane excitability) did not change after exposure to serotonin. Along with synaptic facilitation, serotonin (100 microM) increased the excitability and produced minimal depolarization of the membranes of command neurons. Serotonin had selective effects on the reactions of neurons to different sensory stimuli: facilitation of neuron responses to tactile stimulation of the head lasted 1 h, while responses to application of dilute quinine solution lasted 2-3 h; serotonin facilitated neuron responses to tactile stimulation only of the snail's head, and did not alter the responses to stimulation of the foot or the mantle ridge. The time course of the electrophysiological effects of serotonin coincided with changes in bound calcium (Cab) levels in command neurons. This set of serotonin-induced neurophysiological effects is similar to the effects resulting from the development of nociceptive sensitization. It is suggested that serotonin is involved in the mechanisms of transient changes and consolidation of long-term plastic rearrangements in command neurons which underlie sensitization.

[Serotonin simulates the neuronal effects of nociceptive sensitization in the snail]. / Serotonin imitiruet nekotorye neironal'nye éffekty notsitseptivnoi sensitizatsii u vinogradnoi ulitki.

Serotonin (5-HT) application (10 mcM) onto L-PPl1 neurons of the pleural ganglia of land snail Helix lucorum produced the synaptic facilitation of the neuronal response evoked by sensory stimulation. At the same time, it did not change the parameters of the neuronal membrane (resting potential and membrane excitability). In addition to synaptic facilitation, the higher 5-HT concentration (100 mcM) produced an increase in membrane excitability and a slight membrane depolarization. The 5-HT effects were modality-dependent: the duration of facilitation of the response evoked by tactile stimulation of the snail head was about 1 h while that of the response evoked by quinine application (0.3% solution) onto the snail lip was 2-3 h. The 5-HT effects were site-specific: its application facilitated only the neuronal responses evoked by tactile stimulation of the snail head but not other body sites. The dynamics of the electrophysiological effects and the level of bound calcium were similar in L-PPl1 neurons. The described neuronal effects resemble those observed after the nociceptive sensitization of these neurons. The data obtained suggest the 5-HT involvement in the mechanisms of short-term changes and consolidation of long-term plasticity underlying the sensitization in Helix L-PPl1 neurons.

[Protein-synthesis blockers reproduce the effect of nociceptive sensitization on the defense and food reactions in the snail]. / Blokatory sinteza belka vosproizvodiat vliianie notsitseptivnoi sensitizatsii na oboronitel'nye i pishchevye reaktsii u vinogradnoi ulitki.

Effects of translation inhibitors on defence and feeding behaviour and command neurons of defence behaviour (L-RPl1) were studied in Helix lucorum snail. It was found that anisomycin and cycloheximide facilitated defence reactions and neuronal responses evoked by tactile or chemical stimuli 60-80 min after inhibitor application. At the same time feeding behaviour and neuronal responses (L-RMtc1 neurons) evoked by a food stimulus were suppressed. Effects of inhibitors were obtained within 30 min of their application or single injection in intact snail. Effects of inhibitors were absent after continuous application or double injection with 50 min interval. Duration of the inhibitor effects depended on modality of a sensory stimulus. In particular, inhibitor effects on behavioural and neuronal responses evoked by tactile stimuli lasted 1 h., by weak quinine solution--2-3 h., and by a food stimulus--1.5 h. Cycloheximide suppressed only appetitive phase of feeding behaviour but did not affect consummatory phase of feeding behavior. Some parameters of the behavioural and neuronal effects were similar to those obtained during sensitization development. It was suggested that translation inhibitors induced activation of synthesis of protein molecules with a short lifetime, functions of which consisted in selective regulation of synaptic transmission.