Effects of antisense oligonucleotides to mRNA for the early gene zif268 on the mechanisms of synapse-specific plasticity

Acquisition of nociceptive sensitization in common snails was accompanied by long-term facilitation of the responses of defensive behavior command neuron LPl1 to sensory stimulation of chemoreceptors on the head and mechanoreceptors on the head and foot. Acquisition of sensitization during intracellular administration of antisense oligonucleotides to mRNA encoding the early gene zif268 showed suppression of synaptic facilitation in the responses of neuron LPl1 to tactile and chemical stimulation of the snail’s head. Synaptic facilitation in the responses to tactile stimulation of the foot developed as in neurons of control sensitized animals. These results suggest that the early gene zif268 is selectively involved in the mechanisms of the specific regulation of the synaptic inputs of neuron LPl1 from sensory receptors on the snail’s head. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 56, No. 4, pp. 499–505, July–August, 2006.     

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 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.     

The Critical Role of Intracellular Calcium in the Mechanisms of Plasticity of Common Snail Defensive Behavior Command Neurons LPl1 and RPl1 in Nociceptive Sensitization

Studies on semi-intact common snail preparations addressed the involvement of intracellular calcium in changes in the excitability and responses to sensory stimuli of defensive behavior command neurons LPl1 and RPl1 during the acquisition of nociceptive sensitization. Application of sensitizing stimuli to the heads of control snails led to depolarization of neuron membranes, increases in neuron excitability, and depression of the responses of neurons to sensory stimuli during the short-term stage, and marked facilitation of responses in the long-term stage of sensitization. Acquisition of sensitization during profound hyperpolarization of neurons led to suppression of the increase in excitability, along with depression of responses to chemical stimulation of the head in the short- and long-term stages of sensitization. Neuron responses to tactile stimulation of the head and foot showed synaptic facilitation, similar to that seen in neurons of control animals. Acquisition of sensitization during intracellular injection of the calcium chelators EGTA and BAPTA led to suppression of synaptic facilitation in the responses of neurons to both chemical and tactile stimulation. In these conditions, membrane excitability increased to a greater extent than in neurons of control animals. The results of these experiments suggest that changes in responses to sensory stimulation in sensitized snails are associated with postsynaptic calcium-dependent mechanisms of plasticity in neurons LPl1 and RPl1.     

Visual and somatosensory processing in the macaque temporal cortex: the role of ‘expectation’

Summary The somatosensory and visual properties of cells in a polymodal region of temporal cortex were studied in 4 awake behaving macaque monkeys. When stimulated passively and out of sight, cells with tactile responses were found to have very large receptive fields covering most of the body surface and an apparent lack of selectivity for size, shape or texture of the tactile stimulus. These properties are equivalent to those described for the anaesthetized preparation (Bruce et al. 1981). Our study revealed that tactile responses were influenced by the degree to which stimuli could be expected. Tactile stimulation arising from active exploration of novel surfaces produced vigourous neuronal responses but equivalent stimulation of the skin arising when the monkey contacted expected surfaces such as itself or items with which it had become familiar produced no responses. The responses of cells to active or passive tactile stimulation were attenuated when the monkey could see the objects causing the stimulation. For cells responsive to more than one sensory modality, visual and somatosensory responses were associated in a compatible manner. Cells responsive to the onset of touch were selective for the sight of objects moving towards the monkey, whereas cells selective for the offset of touch were responsive to the sight of movements away from the monkey.     

Neuronal mechanisms of site-specific nociceptive sensitization in the common snail

Comparative studies of the electrophysiological effects of site-specific nociceptive sensitization were performed on LPl1 and RPl1 command neurons in the common snail, after placing concentrated quinine solution (10%), on the animal's head or mantle ridge. Greater synaptic facilitation was observed in command neuron responses to tactile test stimuli applied to the same part of the body as the sensitizing stimulus, as compared with the level of synaptic facilitation in responses to tactile stimulation of other parts of the body. Synaptic facilitation of responses of neurons LPl1 and RPl1 to tactile stimulation of the head appeared 1 h after sensitizing stimulation and consisted of two phases: the first phase was characterized by a peak-like increase in the area of slow EPSP (sEPSP) and lasted 1 h; the second phase was characterized by maintenance of a relatively stable level of facilitation of sEPSP, which lasted to the end of the observation period (2–3 h). Synaptic facilitation of neuron responses to tactile stimulation of the mantle ridge appeared 40–60 min, after facilitation of responses to test stimulation of the snail's head, and was characterized by maintenance of a relatively stable level of sEPSP facilitation. It is suggested that the specificity of synaptic facilitation occurring in snail defensive behavior command neurons during the period of long-term nociceptive sensitization is associated with the genetic regulation of the various synaptic “inputs” to neurons. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti, Vol. 47, No. 6, pp. 994–1003, November–December, 1997.     

NMDA Glutamate Receptor Antagonists Selectively Affect the Synaptic Mechanisms of Nociceptive Sensitization in Snails

Defensive behavior command neurons LPl1 and RPl1 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.     

The effect of central retinal lesions on optokinetic nystagmus in the monkey

Summary In alert monkeys (Macaca mulatta and fascicularis) the effect of central retinal lesions on fast optokinetic responses was investigated during high velocity optokinetic and visual-vestibular conflict stimulation. The fast component of the optokinetic response manifests itself as a rapid rise in the slow-phase eye velocity after light-on, during high velocity optokinetic stimulation; and a sudden drop in eye velocity after light-off. In contrast, the velocity storage component leads only to gradual changes in eye velocity during continuous optokinetic stimulation and after light-off (optokinetic after-nystagmus).Retinal lesions were placed by laser coagulation in and around the fovea. Responses of the normal and lesioned eye were compared. It was found that central lesions up to 12 deg (fovea diameter 6 deg) had only a negligible effect on fast optokinetic responses. With lesions of more than 25–30 deg diameter centered on the fovea definite fast responses could still be obtained, on average reduced to about 50% of the responses of the normal eye. Some monkeys showed initially no fast optokinetic responses and had, therefore, to be excluded from lesion experiments.The results demonstrate that fast optokinetic responses also can be obtained from extrafoveal areas, i.e. areas which are not generally involved in smooth pursuit eye movements. These results are discussed in relation to reports that the smooth pursuit eye movement system is also used to generate fast optokinetic responses.Supported by Swiss National Foundation for Scientific Research 3.343-2.78 and Deutsche Forschungsgemeinschaft, SFB 200 A2These experiments were performed at the Dept. of Neurology, University of Zürich. A preliminary report of this work was presented at the workshop on Physiological and pathological aspects of eye movements in Habay-la-Neuve (Belgium) and at the 8th Extraordinary Meeting of the Barany Society in Basel (Switzerland)     

Serotonin imatates 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 μM) 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 μM) 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 (Ca_b) levels in command neurons. This set of serotonin-induced neurophysiological effects is simular 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. P. K. Anokhin Institute of Normal Physiology, Russian Academy of Medical Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 47, No. 3, pp. 532–542, May–June, 1997.     

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 M) 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 M) produced only depression of responses to tactile stimulation of the head. Application of leu-enkephalin (10 M) 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 M). 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.     

Domain structure of the myosin head in correlation-averaged images of shadowed molecules

Summary Electron microscope images of rotary shadowed myosin heads and subfragment-1 (S1) have been computationally aligned and averaged using correlation methods. Average images show reproducible detail within the pear-shaped envelope of the head; the major features are invariant in S1 and in intact heads, in two mirror-related views of the head, and in the presence and absence of ATP. The averages support the view that the head contains two main structural domains separated by a cleft, and that the region of the neck close to the head-rod junction is flexible. They also reveal the inadequacy of the conventional method of correcting the measured dimensions of shadowed particles for the supposed thickness of the metal coat.     

The effects of cAMP on the excitability and responses of defensive behavior command neurons in the common snail evoked by sensory stimuli

Experiments on snails showed that extracellular application of dibutyryl-cAMP (db-cAMP) or intracellular application of cAMP for 30 min evoked increases in excitability and synaptic facilitation in responses to sensory stimulation of defensive behavior command neurons LP11 and RP11. Extitability increased 45–60 min after the start of addition of db-cAMP or cAMP and remained elevated until the end of the experiment (3–4h). Synaptic facilitation started 50–60 min after the onset of extracellular application of db-cAMP and remained detectable in the responses of neurons to tactile stimulation of the head for 1 h and to application of dilute quinine solution for 2–4 h. Application of db-cAMP produced no changes in responses to tactile stimulation of the foot or mantle ridge. Intracellular injection of cAMP induced facilitation of neuron responses only to weak quinine solutions. The responses of neurons to tactile stimulation of the head, foot, and mantle ridge did not change after injections of cAMP. It is suggested that cAMP is involved in the mechanisms controlling the excitability of neurons LP11 and RP11. In addition, cAMP is selectively involved in the postsynaptic mechanism inducing the transient stage of long-term facilitation of synaptic “inputs”, which mediates excitation evoked by chemical stimuli. This set of effects of cAMP is similar to effects arising during the development of nociceptive sensitization and in response to serotonin. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 85, No. 2, pp. 237–245, February, 1999.     

The contractile behaviour of EGTA- and detergent-treated heart muscle

Summary Tension responses of rat ventricular trabeculae subjected to successive treatment with EGTA and Triton X-100 are described in order to investigate the effects of chemical skinning techniques. In some preparations the alkaloid saponin was also used before Triton. Ultrastructural evidence is cited that the EGTA-treatment fails to render cells hyperpermeable, i.e. freely permeable to small ions, whereas both saponin and Triton do so. In this paper we show that contractile responses like those described previously for the EGTA-treated tissue can be obtained. However, more detailed examination shows that such behaviour is quantitatively distinct from that of conventionally skinned fibres in a way that is incompatible with the notion of hyperpermeability. The Ca-sensitivity after treatment with either EGTA, saponin or Triton is identical in our hands. However, this is not explained by free access of Ca (and EGTA) to the intracellular space in the EGTA-treated preparation: contractures develop with very different time courses, being fastest after Triton and only marginally slower when first exposed to saponin but a factor of five times slower after EGTA-treatment alone. This applies to contractures evoked direct from Ca²⁺ concentration 10^–9 m to the test Ca²⁺ concentration at constant total buffer concentration.EGTA-treated fibres develop tension when ATP or creatine phosphate (CrP) are removed from the bath. However, responses to ADP and to CrP changes persist with millimolar levels of ATP present, quite unlike the Triton-skinned muscle. Exposure to each of a variety of solutions for 24h produce preparations showing similar behaviour: whatever the explanation for the EGTA-skinning phenomenon it is not dependent upon low bathing Ca²⁺ concentration. On the basis of the functional characteristics described here, and the structural results cited, we conclude that the cell membrane continues to function as a selective permeability barrier after EGTA-treatment: this treatment does not produce a model of a selectively skinned cardiac cell.     

Diversity in receptive field properties of vertical neuronal arrays in the crown of the postcentral gyrus of the conscious monkey

Summary Single neuronal activity was recorded in the crown of the postcentral gyrus (areas 1 and 2) in 5 conscious monkeys. A total of 93 penetrations were made in the hand and finger region of 9 hemispheres and 827 neurons were isolated. The receptive field characteristics of neurons recorded along each of 88 penetrations which entered perpendicularly to the cortical surface were compared. The majority of neurons in this region were responsive to skin stimulation. In 54 penetrations, neurons related to different sensory submodalities were mixed. In 30, skin neurons predominated, and in 8, deep neurons, while in the remaining 16 penetrations neurons related to different submodalities were equally mixed. In 16 penetrations, neurons responded exclusively to stimulation of skin, hair or nails. In 9 penetrations, neurons were exclusively related to joint manipulation or other types of deep submodality. In 9 penetrations, unidentified neurons were in the majority. In each penetration, the receptive field positions varied considerably on the same finger or encompassed more than one finger. Although neurons of the same submodality, either skin or deep tended to be set in an array, the most adequate stimulus could vary among neurons of a given array. The variability in the receptive field positions or the most adequate stimuli remained constant irrespective of the angle of the electrode penetration in the cortex. The results are compatible with the idea that vertically arranged neuronal array receive inputs of multiple sources, both thalamacortical and corticocortical, so that interactions between different inputs can readilly occur.Supported by grants from the Japanese Ministry of Education     

TRP channels: a TR(I)P through a world of multifunctional cation channels

The transient receptor potential (TRP) family of ion channels comprises more than 50 cation-permeable channels expressed from yeast to man. On the basis of structural homology, the TRP family can be subdivided in to seven main subfamilies: the TRPC (Canonical) group, the TRPV (Vanilloid) group, the TRPM (Melastatin) group, the TRPP (Polycystin), the TRPML (Mucolipin), the TRPA (Ankyrin) and the TRPN (NOMP) family. The cloning and characterization of members of this cation channel family has exploded during recent years, leading to a plethora of data concerning TRPs in a variety of cell types, tissues and species. This paper briefly reviews the TRP superfamily and the basic properties of its many members as a readers guide in this Special Issue. Hopefully, a better understanding of TRP channel physiology will provide important insight into the relationship between TRP channel dysfunction and human diseases.