Synapse-specific plasticity in command neurons during learning of edible snails under the action of caspase inhibitors

The effect of caspase inhibitors on long-term synaptic facilitation induced by nociceptive sensitization (a simple form of learning) was studied on the defensive behavior command neurons (left pleural neuron-1) in edible snail. Acquisition of sensitization under conditions of threatment with caspase-3 or caspase-8 inhibitors selectively inhibits synaptic transmission in the responses of the left pleural neuron-1 to tactile stimulation of the snail head, but not in responses to chemical stimulation of the head or tactile stimulation of the foot. Application of a wide-spectrum caspase inhibitor z-VAD-fmk to neurons of sensitized snails suppressed facilitation of responses evoked by chemical stimulation of the head. Probably, various caspases could be selectively involved into induction of long-term synapse-specific plasticity during learning. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 12, pp. 604–608, December, 2007     

The effects of nitrite on the excitability of brain neurons in the common snail

Electrophysiological studies were performed on the effects of sodium nitrite (0.01–1 mM) on identified command neurons in the brain of the common snail. These studies showed that short periods of exposure to nitrite (from a few minutes up to 30 min) had little effect, producing a low level of depolarization and increases in neuron spike activity in only a few cases. Incubation of isolated brains with nitrite (1 mM) for periods ranging from 2 h to several days reduced excitation thresholds, significantly increased spike activity, increases responses to stimulation, and increases the levels of synaptic activity of the neurons studied. These effects increased with time and were stable, but were reversible on washing and were accompanied by depolarization and increased input resistance. The action of nitrite was imitated by known NO donors, and blockers of NO synthesis had the opposite effect. The possible mediation of the effects of nitrite by NO synthesis and the development of hypoxia is discussed. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 84, No. 11, pp. 1264–1272, November, 1999.     

Comparative studies of the effects of chlorpromazine and 5,6-dihydroxytryptamine on locomotion, defensive reactions in the snail Helix Lucorum, and command neuron excitability in long-term sensitization

The actions of the neuroleptic chlorpromazine (CPZ) and the neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) on defensive reactions, locomotion, formation of long-term sensitization, and the electrical characteristics of command neurons in the common snail were compared. Prolonged (chronic) treatment with CPZ led to a significant increase in the pneumostoma closure time, as well as changes in motor behavior, with a decrease in the rate of locomotion. Administration of 5,6-DHT in small daily doses for one week was accompanied by gradual decreases in the rate of locomotion of the snails, which persisted for one week. A similar effect was seen after administration of the same total dose of neurotoxin, 30 mg/kg, as a single injection. Administration of CPZ prevented the formation of long-term sensitization, as did treatment with 5,6-DHT. The procedures of treatment with CPZ, long-term sensitization, long-term sensitization followed by CPZ, and acquisition of long-term sensitization on the background of treatment with CPZ gave a locomotion speed which was directly proportional to the length of the sole. No such relationship was seen during the acquisition of long-term sensitization on the background of treatment with 5,6-DHT. Electrophysiological studies showed that chronic CPZ led to a depolarization shift in the membrane potential and a decreased action potential generation threshold in command neurons, which also occurred on treatment with 5,6-DHT. It is concluded that the actions of the neuroleptic CPZ on defensive behavior and locomotion in the common snail, as well as on the electrical characteristics of identified neurons, were similar to the toxic actions of serotonin. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 91, No. 7, pp. 791–801, July, 2005.     

The effects of 6-Hydroxydopamine on the electrical characteristics of snail neurons in long-term sensitization

The effects of the neurotoxin 6-hydroxydopamine on the formation of long-term sensitization and changes in the membrane characteristics of identified neurons were studied. Injections of the neurotoxin 6-hydroxydopamine blocked the acquisition of long-term sensitization; when neurotoxin injections were given after the formation of long-term sensitization, they had no subsequent effect on conduction parameters. At the cellular level, recording of the electrical characteristics of common snail defensive behavior command neurons (LPa3, RPa3, LPa2, and RPa2) showed that the effects of 6-hydroxydopamine consisted of a small depolarization shift in the membrane potential and a change in the action potential generation threshold. Formation of long-term sensitization after injections of 6-hydroxydopamine did not lead to further decreases in the membrane and threshold potentials of command neurons as compared with snails only given injections of 6-hydroxydopamine. The changes in electrical measures of command neurons induced by administration of the neurotoxin 6-hydroxydopamine lasted at least two weeks.Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 89, No. 9, pp. 1067–1077, September, 2003.     

Heterosynaptic potentiation of cholinergic excitatory postsynaptic responses of command neurons in the common snail

Short-term heterosynaptic potentiation of cholinergic excitatory postsynaptic currents and potentials in defensive behavior command neurons was found to be evoked by stimulation of the visceral sac in the common snail. It is suggested that a mechanism increasing the choline resistance of the postsynaptic zones of command neuron membranes is involved in potentiating the excitatory postsynaptic responses to sensory stimulation. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 57, No. 6, pp. 612–720, November–December, 2007.     

Influence of small cardioactive peptide (b) on the efficiency of synaptic transmission and the excitability of command neurons of the defensive behavior of the edible snail

The application of a small cardioactive peptide (SCPb) (mCPb) in a concentration of 5 ·10^–8 mole/l to a physiological solution washing the isolated central nervous system of the edible snail leads to an increase in the amplitude of the summated EPSP evoked by rhythmic stimulation of the intestinal nerve in the command neurons of defensive behavior by 55±20%. In addition to the change in the magnitude of the synoptic input, SCPb induces an increase in the excitability of the same neurons by 92±57%, tested intracellularly. These influences may lead to a total decrease in the threshold of the reaction of the neuronal network of the defensive behavior in response to stimulation. The possibility of the integration of integral behavior with the aid of peptides which are effective in very small concentrations is discussed.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 41, No. 1, pp. 107–112, January–February, 1991.     

Effects of protein synthesis inhibitors on the sensitization of a defensive response in common snails and potentiation of the cholinosensitivity of command neurons

The effects of protein synthesis inhibitors on short-term sensitization of a defensive reaction in common snails and the potentiation of the cholinosensitivity of command neurons were studied. The protein synthesis inhibitor anisomycin did not prevent behavioral sensitization. Anisomycin and the irreversible protein synthesis inhibitor saporin changed the dynamics of potentiation of command neuron cholinosensitivity. We suggest that the sensitization of the defensive response of the common snail studied here does not require the synthesis of new proteins. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 56, No. 3, pp. 355–362, May–June, 2006.     

Sex differences in the responses of orexin neurons in the lateral hypothalamic area and feeding behavior to fasting

Because there are sex differences in feeding-related behavior and orexin neurons are involved in feeding, we looked for a possible sex difference in the response of orexin neurons in the lateral hypothalamic area to fasting, using the phosphorylated cyclic AMP response element-binding protein (pCREB) as a marker of neural activity. Intact male and female rats at proestrus, estrus, or diestrus, were fed normally or fasted for 48 h. After fasting, they were intravenously injected with saline or glucose and subjected to immunohistochemical processing for the detection of orexin and pCREB. In the rats fed normally and injected with saline, only a small population of orexin neurons expressed pCREB in both male and female rats. However, fasting increased the number of orexin neurons with pCREB (double-stained cells) in female rats regardless of the estrous day but not in male rats, revealing a significant sex difference in the response of orexin neurons to fasting. Glucose injection in fasted rats decreased the number of double-stained cells in female rats, and the magnitude of glucose-dependent decrease was greater at proestrus and estrus than at diestrus 2. We also found that female rats, but not male rats, showed an increase in total food intake after fasting (rebound feeding). We speculate that the demonstrated sex differences in the response of orexin neurons to fasting reflect the vulnerability of feeding mechanisms in females.     

The effect of cAMP signaling on the longitudinal extension of spinal sensory neurons in the chicken embryo

Developing sensory axons grow into the spinal cord in a three‐step process: the axons extend toward and into the cord, then branch rostrally and caudally to establish a longitudinal pathway, and finally grow into the grey matter. This study investigated regulation by cAMP of the longitudinal extension of this pathway within the spinal cord. The cAMP pathway was pharmacologically altered in chicken embryos to determine its effects on the establishment of the longitudinal extension of the dorsal funiculus. A forskolin‐induced increase in cAMP in ovo inhibited longitudinal growth by sensory afferents. Furthermore, blocking cAMP activation of protein kinase A (PKA) in ovo with H‐89 substantially increased longitudinal extension. These results demonstrate a specific role for the cAMP/PKA pathway in the initial longitudinal spinal afferent growth in the chicken embryo.     

Membrane responses and changes in cAMP levels in Aplysia sensory neurons produced by serotonin, tryptamine, FMRFamide and small cardioactive peptideB (SCPB)

While recent evidence indicates a role for serotonin (5-HT) in modulating the defensive tail-withdrawal reflex in Aplysia, little information exists concerning the specificity of these 5-HT effects. As a first-step in addressing this issue we have examined the dose-response relationship for one aspect of the 5-HT modulation (enhancement of cAMP levels in isolated clusters of sensory neurons) and compared the effects of 5-HT with three potential neurotransmitters: tryptamine, FMRFamide (Phe-Met-Arg-Phe-NH2) and small cardioactive peptideB (SCPB). Cyclic adenosine monophosphate (cAMP) levels were enhanced as a graded function of the concentration of 5-HT with an EC50 of 14 microM. At a concentration of 5 microM, both 5-HT and SCPB produced nearly identical increases in the cAMP content of sensory neurons. In contrast, 5 microM tryptamine or 5 microM FMRFamide had little or no effect on cAMP levels. We also examined the effects of these agents on membrane currents and membrane conductance. Both 5-HT and SCPB produced an inward current associated with a decrease in input conductance. Tryptamine had little or no effect, while FMRFamide produced a response opposite to that of 5-HT and SCPB; an outward current associated with an increase in membrane conductance.     

The appearance of long-latency responses to a conditioned signal in the cortex is explained by strengthening of collateral connections between pyramidal neurons

Experimental analysis and computer simulation of the neurophysiological processes underlying the stable and local electrophysiological expression of conditioned reflexes in the cerebral cortex, a phenomenon discovered in Asratyans laboratory in the 1960s, showed that the long-latency components of cortical evoked potentials to a conditioned signal correspond to the late phases of the responses of motor cortex neurons, which are analogous to and probably generated by the same mechanism as long-latency epileptiform reactions of neurons in the epileptogenic cortex. Late long-latency components are generated via activation of NMDA receptors in the collateral connections between pyramidal neurons. The delay in the generation of responses depends on the initial activation of GABA_A receptors and the slow kinetics of the current through NMDA channels. The appearance of late components as a result of training is explained by increases in the efficiency of collateral excitatory connections between pyramidal neurons.Translated from Zhurnal Vysshei Nervnoi Deyatelnosti, Vol. 54, No. 3, pp. 403–408, May–June, 2004.     

Suppression of synaptic input of defense behavior command neurons by stimulation of neurons of the mesocerebrum in a preparation of the isolated CNS of the common snail

The intestinal nerve was stimulated in combination and uncombined with extracellular stimulation of the mesocerebral region of the brain, as well as with stimulation of serotoninergic neurons, in experiments on a preparation of the isolated CNS of the common snail, with preservation of the nerve connections with the sexual system. Reponses were recorded in command neurons of defense behavior. The data were obtained indicating that, in the case of combinations with extracellular stimulation of the mesocerebrum, an analog of a conditioned reaction of diminution of EPSP in the command neurons of the serotoninergic neurons, sensitization appears, both in the case of combined and uncombined presentation of the stimuli. This study was supported by the Russian Basic Research Fund (project No. 94-04-122090). Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 45, No. 1, pp. 163–170, January–February, 1995.     

Differential effects of cAMP and serotonin on membrane current, action-potential duration, and excitability in somata of pleural sensory neurons of Aplysia

1. In somata of sensory neurons in the pleural ganglia of Aplysia californica, serotonin (5-HT) modulates at least three K+ currents: the S K+ current (IK,S), a slow component of the Ca2(+)-activated K+ current (IK,Ca), and the delayed or voltage-dependent K+ current (IK,V). The modulation of IK,S and the slow component of IK,Ca by 5-HT has been shown previously to be mediated via adenosine 3',5'-cyclic monophosphate (cAMP). To determine whether the modulation of IK,V by 5-HT also is mediated via cAMP, we used two-electrode voltage-clamp techniques to compare the modulation of membrane current by cAMP and 5-HT. 2. Current responses were elicited by brief (200 ms) voltage-clamp pulses before and after the bath application of analogues of cAMP. At all voltage-clamp potentials examined (-40-30 mV), analogues of cAMP reduced the amplitude of the current response. The properties of the cAMP-sensitive component of membrane current were revealed by computer subtraction of current responses elicited in the presence of the analogue of cAMP from current responses elicited before application of the analogue. The characteristics of the resulting cAMP difference current (IcAMP) suggested that cAMP modulated a component of membrane current that was relatively voltage independent, did not inactivate, and was active over a wide range of membrane potentials. In addition, the current-voltage (I-V) relationship of the cAMP difference current had a positive slope. These properties of the cAMP difference current were consistent with those of IK,S but did not indicate that IK,V was modulated by cAMP. 3. The cAMP-independent modulation of membrane current by 5-HT was examined by eliciting current responses first in the presence of an analogue of cAMP and again after the addition of 5-HT to the bath, which still contained the analogue. The presence of the analogue of cAMP occluded further modulation of IK,S by 5-HT. However, the analogue of cAMP did not occlude the modulation of IK,V by 5-HT. This cAMP-independent effect of 5-HT on membrane current was revealed by computer subtraction of current responses elicited in the presence of 5-HT from current responses elicited before the application of 5-HT (the analogue of cAMP was present throughout). The resulting cAMP-independent 5-HT difference current (I5-HT) was highly voltage dependent, had complex kinetics, and its I-V relationship had a negative slope at membrane potentials above 0 mV.(ABSTRACT TRUNCATED AT 400 WORDS)     

The Selective Effect of a Protein Kinase C Inhibitor on Synaptic Plasticity in Defensive Behavior Command Neurons During Development of Sensitization in the Snail

Studies of defensive behavior command neurons LP11 and RP11 in semi-intact common snail preparations addressed the effects of the protein kinase C antagonist polymyxin B on the effect of nociceptive sensitization. Neurons in control snails responded to application of nociceptive stimuli to the head with membrane depolarization, increases in excitability, and depression of neuron responses to sensory stimulation during the short-term stage, with marked facilitation of responses during the long-term stage of sensitization. Acquisition of sensitization in the presence of polymyxin B resulted in partial suppression of responses to nociceptive stimuli. Changes in command neuron membrane excitability in these conditions, as well as changes in responses to tactile stimulation of the foot and chemical stimulation of the head, were similar to those seen in neurons of sensitized control animals. The inhibitor also had no effect on short-term depression of neuron responses induced by tactile stimulation of the head. In addition, acquisition of sensitization during administration of polymyxin B led to complete suppression of the facilitation of responses to tactile stimulation of the snail's head during the long-term stage of sensitization. It is suggested that in sensitized common snails, protein kinase C is involved in controlling the mechanisms of nociception and is also involved in the mechanisms of selective induction of plasticity in the synaptic inputs of command neurons, which are activated by tactile stimulation of the animal's head.