Effects of Sensory Behavioral Tasks on Pain Threshold and Cortical Excitability

Background/Objective

Transcutaneous electrical stimulation has been proven to modulate nervous system activity, leading to changes in pain perception, via the peripheral sensory system, in a bottom up approach. We tested whether different sensory behavioral tasks induce significant effects in pain processing and whether these changes correlate with cortical plasticity.

Methodology/Principal Findings

This randomized parallel designed experiment included forty healthy right-handed males. Three different somatosensory tasks, including learning tasks with and without visual feedback and simple somatosensory input, were tested on pressure pain threshold and motor cortex excitability using transcranial magnetic stimulation (TMS). Sensory tasks induced hand-specific pain modulation effects. They increased pain thresholds of the left hand (which was the target to the sensory tasks) and decreased them in the right hand. TMS showed that somatosensory input decreased cortical excitability, as indexed by reduced MEP amplitudes and increased SICI. Although somatosensory tasks similarly altered pain thresholds and cortical excitability, there was no significant correlation between these variables and only the visual feedback task showed significant somatosensory learning.

Conclusions/Significance

Lack of correlation between cortical excitability and pain thresholds and lack of differential effects across tasks, but significant changes in pain thresholds suggest that analgesic effects of somatosensory tasks are not primarily associated with motor cortical neural mechanisms, thus, suggesting that subcortical neural circuits and/or spinal cord are involved with the observed effects. Identifying the neural mechanisms of somatosensory stimulation on pain may open novel possibilities for combining different targeted therapies for pain control.     

Endogenous neuropeptides and regulation of the brain functional plasticity

This review analysed the data about the neuropeptides secreted from the different brain structures. Involvement of the endogenous neuropeptides in synaptic plasticity was tested at the model of long-term potentiation (LTP) as a form of learning and the memory formation. The most of these neuropeptides or their fragments involves in the induction and maintenance of the LTP and provides the transformation of short-term excitability of the neurones into the long-term one. They may be considered as nootropic compounds. It is proposed that the system of peptidergic regulation of neuronal plasticity functionates in the brain and there are a possibility to correct the activity of this system during the different pathology.     

Pumilio-2 function in the mouse nervous system

Coordinated mRNA translation at the synapse is increasingly recognized as a critical mechanism for neuronal regulation. Pumilio, a translational regulator, is known to be involved in neuronal homeostasis and memory formation in Drosophila. Most recently, the mammalian Pumilio homolog Pumilio-2 (Pum2) has been found to play a role in the mammalian nervous system, in particular in regulating morphology, arborization and excitability of neuronal dendrites, in vitro. However, the role of Pum2 in vivo remains unclear. Here, we report our investigation of the functional and molecular consequences of Pum2 disruption in vivo using an array of neurophysiology, behavioral and gene expression profiling techniques. We used Pum2-deficient mice to monitor in vivo brain activity using EEG and to study behavior traits, including memory, locomotor activity and nesting capacities. Because of the suspected role of Pum2 in neuronal excitability, we also examined the susceptibility to seizure induction. Finally, we used a quantitative gene expression profiling assay to identify key molecular partners of Pum2. We found that Pum2-deficient mice have abnormal behavioral strategies in spatial and object memory test. Additionally, Pum2 deficiency is associated with increased locomotor activity and decreased body weight. We also observed environmentally-induced impairment in nesting behavior. Most importantly, Pum2-deficient mice showed spontaneous EEG abnormalities and had lower seizure thresholds using a convulsing dosage of pentylenetetrazole. Finally, some genes, including neuronal ion channels, were differentially expressed in the hippocampus of Pum2-deficient mice. These findings demonstrate that Pum2 serves key functions in the adult mammalian central nervous system encompassing neuronal excitability and behavioral response to environmental challenges.     

Structural-functional and metabolic changes in the nervous system in low- and high-excitable rats deprived of paradoxical sleep

Studying of the influence of 24-hour deprivation of paradoxical sleep phase (PSPh) on rats with different genetically determined levels of excitability of the nervous system allowed to establish: 1) significant changes in functional state of the central part of the nervous system responsible for elaboration and preservation of defensive conditioned reflexes; 2) considerable lowering of functional state of the peripheral nervous system expressed both in a decrease of tibial nerve excitability thresholds and in changing of morpho-tinctorial characteristics of the studied nerve receptor parameters. The degree of the observed effects of PSPh deprivation is dependent on animal line belonging.     

Characteristics of heterochromatin of heterophase nuclei from interphase neurons of various brain structures selected for the nervous system excitability

Quantitative characteristics (the area and number of chromocenters) of the interphase C-heterochromatin in the nuclei of pyramidal neurons of the midbrain reticular formation, sensorimotor cortex, and hippocampus (CA3) of rat strains with different genetically determined excitability were studied in the normal state of the animals and after exposure to a short-term emotional pain stress. The results indicate a relationship between the excitability of the nervous system and structural-functional state of the neuronal interphase heterochromatin. The role of cytogenetic features of different brain structures in the CNS functioning and behavior and their relation with genetically determined excitability of the nervous system are discussed.     

Systemic control of the molecular,cell, and epigenetic mechanisms of long-lasting consequences of stress

Based on M.E. Lobashev’s views of the systemic control of genetic and cytogeneitc processes and a substantial effect of excitability on plastic changes in the central nervous system (CNS), the effect of prolonged emotional and pain stress (PEPS) on the molecular, cell, and epigenetic mechanisms of injury memory was studied in rat strains bred for a certain excitability of the nervous system. PEPS was for the first time found to cause long-lasting (2 months) morphological alterations of the CA3 region of the hippocampus and to modify the genome activity of its pyramidal neurons. The two phenomena were potentiated by a genetically determined low functional state of the CNS. The post-stress regulation of the genome function in hippocampal neurons was mediated by changes in heterochromatin conformation, activation of methyl-CpG-binding protein (MeCP2) synthesis, and subsequent changes in acetylation of histone H4. Genetically determined high excitability of the nervous system proved to be a risk factor that affects the specifics and time course of the observed molecular, cell, and genetic transformations of neurons. The results provide for a better understanding of the epigenetic mechanisms of injury memory, which forms a pathogenetic basis for posttraumatic stress disorder and other human psychogenic conditions characterized by a prolonged duration.     

Effect of prenatal emotional-pain stress on the status of interphase chromatin in neurons of the rat developing brain with various excitation of the nervous system

A short-term emotional-painful stress, experienced by pregnant rat females differing in threshold of excitability of their nervous system, was used to assess the state of interphase condensed chromatin and C-heterochromatin of neuron nuclei in developing brains of 16-17 day old embryos. To reveal relationships between the genetically determined excitability of rats and the state of interphase chromatin in their neuron nuclei a computer information system has been used that enabled us to classify the neuronal nuclei according to their specific DNA image cytometry features. The results indicate an obvious relationship between excitability of the nervous system and structural-functional state of the neuronal interphase chromatin.     

The origin of spontaneous activity in developing networks of the vertebrate nervous system

Spontaneous neuronal activity has been detected in many parts of the developing vertebrate nervous system. Recent studies suggest that this activity depends on properties that are probably shared by all developing networks. Of particular importance is the high excitability of recurrently connected, developing networks and the presence of activity-induced transient depression of network excitability. In the spinal cord, it has been proposed that the interaction of these properties gives rise to spontaneous, periodic activity.     

The relationship between the formation of trace reactions and the functional state of rats of different genetic lines]

The level of excitability of the nervous system was enhanced in rats of the Krushinsky--Molodkina (K--M) and Wistar (W) lines by means of dynamic and static physical loads and injections of different doses of al-amphetamine. It was shown that a higher level of excitability of the central nervous system produced in both lines of rats improved memory and increased the rate of formation of a conditioned active aboidance reflex (CAAR). A greater physical load or dose of the stimulant drug in the K-M line of rats resulted in a decrease of all parameters characterizing CAAR, while in the other line they rose in progression. The data obtained are believed to be related to a different genetically conditioned initial level of excitability in the indicated lines of rats--a higher one in the K--M line animals as compared with the W line rats, which determines a different norm of the nervous system responsiveness in the indicated groups of animals.     

Progress in neural plasticity

The year 2009 marks the tenth anniversary of the founding of Institute of Neuroscience (ION) in the Shanghai campus of Chinese Academy of Sciences.     

Traces of Drosophila memory

Studies using functional cellular imaging of living flies have identified six memory traces that form in the olfactory nervous system after conditioning with odors. These traces occur in distinct nodes of the olfactory nervous system, form and disappear across different windows of time, and are detected in the imaged neurons as increased calcium influx or synaptic release in response to the conditioned odor. Three traces form at or near acquisition and coexist with short-term behavioral memory. One trace forms with a delay after learning and coexists with intermediate-term behavioral memory. Two traces form many hours after acquisition and coexist with long-term behavioral memory. The transient memory traces may support behavior across the time windows of their existence. The experimental approaches for dissecting memory formation in the fly, ranging from the molecular to the systems, make it an ideal system for elucidating the logic by which the nervous system organizes and stores different temporal forms of memory.     

Aging in Sensory and Motor Neurons Results in Learning Failure in Aplysia californica

The physiological and molecular mechanisms of age-related memory loss are complicated by the complexity of vertebrate nervous systems. This study takes advantage of a simple neural model to investigate nervous system aging, focusing on changes in learning and memory in the form of behavioral sensitization in vivo and synaptic facilitation in vitro. The effect of aging on the tail withdrawal reflex (TWR) was studied in Aplysia californica at maturity and late in the annual lifecycle. We found that short-term sensitization in TWR was absent in aged Aplysia. This implied that the neuronal machinery governing nonassociative learning was compromised during aging. Synaptic plasticity in the form of short-term facilitation between tail sensory and motor neurons decreased during aging whether the sensitizing stimulus was tail shock or the heterosynaptic modulator serotonin (5-HT). Together, these results suggest that the cellular mechanisms governing behavioral sensitization are compromised during aging, thereby nearly eliminating sensitization in aged Aplysia.     

Patterns in the ontogenetic development of certain forms of higher nervous activity in rhesus macaques

Studies have been made on ontogenetic development of simple and complex behavioural forms, realization of certain sequence of motor feeding conditioned reflexes, visual differentiation of signals, short-term memory and probability prediction in rhesus monkeys. Evolutionary features of ontogenetic development of some of the forms of the higher nervous activity were revealed. Both similarities and differences were noted in animals from three age groups. In ontogenesis of lower monkeys, the development of the main nervous processes of the higher nervous activity (learning, memory, etc.) takes place gradually depending on the age of a baby and the level of integrative activity of the brain.     

The regulatory effect of dipeptides on cell proliferation in mammalian nerve tissue culture and olfactory associative learning in insects

The study addresses the effects of dipeptides AspPro and AspSer and their constituent amino acids (aspartic acid—Asp, proline—Pro, and serine—Ser) on proliferative activity of rat brain cortical and subcortical tissue explants and functional activity of the honeybee central nervous system. The area index was calculated as a ratio of the total explant area to the area of its central zone. The number of bees which exhibited a conditioned response, namely proboscis extension towards the odorized solution, 1 min (short-term memory) and 180 min (long-term memory) after single trial learning was also measured. Both dipeptides, as well as aspartate itself, stimulated the expansion of the growth zone of rat subcortical tissue explants and increased the number of bees that retained in their short-term/long-term memory the acquired conditioned response, regardless of the effect of the second component of the dipeptide. The similarity of these effects suggests that common mechanisms of reception and signal transduction have evolved in insects and mammals, and this requires further study.     

Modeling neural mechanisms of vertebrate habituation: Locus specificity and pattern discrimination

A critical problem in neurobiology is to explain how the central nervous system coordinates pattern discrimination and locus specificity in learning. This problem is investigated in anuran amphibians who demonstrate both locus specificity and pattern discrimination in visual habituation. A neural mechanism is proposed whereby neural circuitry for pattern discrimination is shared by a spatial memory system. Such learning processes are argued to occur in the medial pallium (MP), the anuran's homolog of mammalian hippocampus. Necessary mapping from the shared network to spatial memory is set up by a mechanism that forms topographical connections, with desired orientation determined by activity gradient in presynaptic and postsynaptic layers. The model of MP is tested on both locus and stimulus specific habituation, which involve short-term as well as long-term synaptic plasticity. Successful modeling yields a set of predictions concerning MP organization and learning properties.     

Network, cellular and molecular mechanisms of plasticity in simple nervous systems

In the present study we will try to single out several principles of the nervous system functioning essential for describing mechanisms of learning and memory basing on our own experimental investigation of cellular mechanisms of memory in the nervous system of gastropod molluscs and literature data: main changes in functioning due to learning occur in effectivity of synaptic inputs and in the intrinsic properties of postsynaptic neurons; due to learning some synaptic inputs of neurons selectively change its effectivity due to pre- and postsynaptic changes, but the induction of plasticity always starts in postsynapse, maintaining of long-term memory in postsynapse is also shown; reinforcement is not related to activity of the neural chain receptor-sensory neuron-interneuron-motoneuron-effector; reinforcement is mediated via activity of modulatory neurons, and in some cases can be exerted by a single neuron; activity of modulatory neurons is necessary for development of plastic modifications of behavior (including associative), but is not needed for recall of conditioned responses. At the same time, the modulatory neurons (in fact they constitute a neural reinforcement system) are necessary for recall of context associative memory; changes due to learning occur at least in two independent loci in the nervous system. A possibility for erasure of memory with participation of nitroxide is experimentally and theoretically based.     

Effect of long-term thermal acclimation on the electrical avoidance conditioning of fish

The learning behaviour and memory formation of ectotherms, especially of fish, depend significantly on the acclimation temperature. Although temperature is known to affect different physiological factors in the nervous system, the exact manner in which memory and learning are affected by these alterations is not clear. Large variations in the acclimation time before learning takes place, are striking. With regard to long-lasting compensatory changes in the polarity of membrane-bound neuronal gangliosides (1) and in the bio-electrical activity of the CNS (post-synaptic potential amplitudes (2)) following thermal acclimation it was of interest to investigate the time course of acclimation on the learning ability of fish subjected to a new environmental temperature.     

Glial calcium signaling and neuron-glia communication

The existence of bidirectional signaling between astrocytes and neurons has revealed an important active role of astrocytes in the physiology of the nervous system. As a consequence, there is a new concept of the synaptic physiology-"the tripartite synapse", where astrocytes exchange information with the pre- and postsynaptic elements and participate as dynamic regulatory elements in neurotransmission. The control of the Ca2+ excitability in astrocytes is a key element in this loop of information exchange. The ability of astrocytes to respond to neuronal activity and discriminate between the activity of different synapses, the modulation of the astrocytic cellular excitability by the synaptic activity, and the expression of cellular intrinsic properties indicate that astrocytes are endowed with cellular computational characteristics that process synaptic information. Therefore, we propose that astrocytes can be considered as cellular elements involved in the information processing by the nervous system.     

Dopamine Modulates the Excitability of Projection Neurons in the Robust Nucleus of the Arcopallium in Adult Zebra Finches

Background

The nervous system in songbirds is an accessible system for studying vocal learning and memory in vertebrates. In the song system, the anterior forebrain pathway (AFP) is essential for song learning and the vocal motor pathway (VMP) is necessary for song production. The premotor robust nucleus of the arcopallium (RA) located in the VMP receives input from the AFP. The RA receives dopaminergic innervations from the periaqueductal gray and ventral tegmental area–substantia nigra pars compacta, but the physiological functions of this projection remain unclear. In this study, we investigated the effects of dopamine (DA) on the excitability of projection neurons (PNs) in the RA.

Methodology

We recorded the electrophysiological changes from neurons in brain slices of male adult zebra finches using a whole-cell recording technique.

Conclusions/Significance

We found that DA significantly increased the excitability of RA PNs. Furthermore, a D1-like receptor agonist increased the excitability of RA PNs, and a D1-like receptor antagonist suppressed the excitability induced by DA. However, a D2-like receptor agonist had no effect on the excitability of RA PNs. Moreover, the D2-like receptor agonist did not change the excitability induced by the D1 receptor agonist. These findings suggest that DA can significantly increase the excitability of RA PNs and that D1 receptors play the main role in regulating the excitability of RA PNs in response to DA, thereby providing direct evidence toward understanding the mechanism of DA signal mediation by its receptors to modulate the excitability of RA PNs.     

Interrelations between the contents of transmitter amino acids in the brain structures and the level of convulsion readiness in rats

In rats with high and low levels of the audiogenic excitability (68 and 62 animals, respectivels, we measured the thresholds of convulsive reactions elicited by electrical stimulation of a few limbic and brainstem structures. The obtained figures were compared with the those of the levels of transmitter amino acids (glutamate, aspartate, glycine, and taurine) measured in the same brain structures in corresponding groups of the animals (80 rats in each group. It was found that the thresholds of convulsive reactions evoked by electrical stimulation of most tested brain structures are lower in the audiogenically excitable animals than those in the animals with high thresholds of the audiogenic excitability. These dissimilarities demonstrated certain correlation with increased glutamate concentrations in some structures under study and, probably, to a considerable extent depended on a deficiency of inhibitory amino acids, glycine and taurine, in most tested brain structures.