Impairing of Serotonin Synthesis by P-Chlorphenylanine Prevents the Forgetting of Contextual Memory After Reminder and the Protein Synthesis Inhibition

HIGHLIGHTSThe injection of p-chlorophenylalanine, specific blocker of 5-HT synthesis 3 days before reminder with anisomycin administration prevented forgetting.It is known that the reminder cause reactivation of the long-term memory and it leads to reconsolidation of memory. We showed earlier that the disruption of the reconsolidation of contextual memory in terrestrial snail was caused by anisomycin, the inhibitor of protein syntheses (Gainutdinova et al., 2005; Balaban et al., 2014). In this paper we investigated the possible changes of the memory reconsolidation under the conditions of serotonin deficit, caused by administration of p-chlorophenylalanine, the inhibitor of tryptophan hydroxylase synthesis (intermediate stage of the synthesis of serotonin). It was shown that the forgetting process for contextual memory after reminder and inhibition of protein synthesis did not occur if the serotonin transmission in nervous system was impaired. This effect was significantly different from the direct action of anisomycin, which blocked the reconsolidation of contextual memory. We concluded that the serotonin system was included to the process of memory reconsolidation

Reconsolidation of a context long-term memory in the terrestrial snail requires protein synthesis

We investigated the influence of the protein synthesis blocker anisomycin on contextual memory in the terrestrial snail Helix. Prior to the training session, the behavioral responses in two contexts were similar. Two days after a session of electric shocks (5 d) in one context only, the context conditioning was observed as the significant difference of behavioral response amplitudes in two contexts. On the day following testing of context learning, a session of “reminding” was performed, immediately after which the snails were injected with anisomycin or vehicle. Testing of long-term context memory has shown that only anisomycin injections impaired the context conditioning. In control series, the snails were injected after the training session with anisomycin/saline without reminding, and no impairment of the long-term context memory was observed, while injection of anisomycin during the training session completely abolished the long-term memory. No effects of anisomycin on the short-term memory were observed. Surprisingly, injection of anisomycin after the reminding combined with reinforcing stimuli elicited no effect on the context memory. Differences between single-trial and multisession learning are discussed

Responses of Withdrawal Interneurons to Serotonin Applications in Naïve and Learned Snails Are Different

Long-term changes in membrane potential after associative training were described previously in identified premotor interneurons for withdrawal of the terrestrial snail Helix. Serotonin was shown to be a major transmitter involved in triggering the long-term changes in mollusks. In the present study we compared the changes in electrophysiological characteristics of identifiable premotor interneurons for withdrawal in response to bath applications of serotonin (5-HT) or serotonin precursor 5-hydroxytryptophan (5-HTP) in preparations from naïve, neurotoxin-injected or associatively trained snails. It was found that 5-HT or 5-HTP applications caused a significant decrease of membrane potential in premotor interneurons of naïve snails, associatively trained snails and snails with impaired serotonergic system by injection of a selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) 1 week before the experiments. Applications of 5-HT or 5-HTP did not cause significant changes in the action potential (AP) threshold potential of these neurons in naïve snails. Conversely, applications of 5-HT or 5-HTP to the premotor interneurons of previously trained or 5,7-DHT-injected snails caused a significant increase in the firing threshold potential in spite of a depolarizing shift of the resting membrane potential. Results demonstrate that responsiveness of premotor interneurons to extracellularly applied 5-HT or 5-HTP changes for days after the associative training or serotonin depletion. Similarity of the effects in trained and 5,7-DHT-injected animals may be due to massive release of serotonin elicited by 5,7-DHT injection. Our results suggest that serotonin release due to aversive conditionining or elicited by the neurotoxin administration triggers similar changes in resting membrane potential and AP threshold in response to bath applications of 5-HT or its precursor 5-HTP

MODULATION OF DEFENSIVE REFLEX CONDITIONING IN SNAILS BY SEROTONIN

We studied the role of serotonin in the mechanisms of learning in terrestrial snails. To produce a serotonin deficit, the neurotoxic analogues of serotonin, 5,6- or 5,7-dihydroxytryptamine (5,6/5,7-DHT) were used. Injection of 5,6/5,7-DHT was found to disrupt defensive reflex conditioning. Within two weeks of neurotoxin application, the ability to learn had recovered. Daily injection of serotonin before a training session accelerated defensive reflex conditioning and daily injections of 5-HTP in snails with a deficiency of serotonin induced by 5,7-DHT restored the snail’s ability to learn. We discovered that injections of the neurotoxins 5,6/5,7-DHT as well as serotonin, caused a decrease in the resting and threshold potentials of the premotor interneurons LPa3 and RPa3

Investigation of NO Role in Neural Tissue in Brain and Spinal Cord Injury

Nitric oxide (NO) production in injured and intact brain regions was compared by EPR spectroscopy in a model of brain and spinal cord injury in Wistar rats. The precentral gyrus of the brain was injured, followed by the spinal cord at the level of the first lumbar vertebra. Seven days after brain injury, a reduction in NO content of 84% in injured brain regions and 66% in intact brain regions was found. The difference in NO production in injured and uninjured brain regions persisted 7 days after injury. The copper content in the brain remained unchanged one week after modeling of brain and spinal cord injury. The data obtained in the experiments help to explain the problems in the therapy of patients with combined brain injury