Modulation of corticospinal excitability during acquisition of action sequences by observation

Excitability of the corticospinal pathway increases during observation of an action. However, how corticospinal excitability changes during observation of sequential actions in the course of acquiring novel skills (observational learning) remains unexplored. To investigate this, we used a previously unpracticed sequence of ten hand postures. Participants were asked to repeat observation and replication of the sequence. This block of observation and replication was repeated 5 times. During observation of a given hand posture (OK sign), motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation were recorded from hand muscles. In experiment 1, the OK sign appeared in the 9th position of the sequence. Almost all participants could replicate the OK sign only at the 5th block of the experiment. MEP amplitude was greater than that in the control, and decreased with the stages. This suggested that during observational learning of sequential hand postures MEP changed with the progress of the learning. To evaluate this idea, we performed two additional experiments. In experiment 2, the OK sign appeared in the 2nd position. Almost all participants replicated the OK sign even in the 1st block. The MEP amplitude did not change across stages. In experiment 3, the OK sign appeared in the 9th position, but the order of other signs was randomized in every stage. Many participants were not able to replicate the OK sign even during the 5th block of the experiment. The MEP amplitude did not change across stages. These results suggest that: (1) During observational learning modulation of corticospinal excitability is associated with the learning process. (2) Corticospinal excitability decreases as learning progresses.     

Modulation of caudate activity by action contingency

Research has increasingly implicated the striatum in the processing of reward-related information in both animals and humans. However, it is unclear whether human striatal activation is driven solely by the hedonic properties of rewards or whether such activation is reliant on other factors, such as anticipation of upcoming reward or performance of an action to earn a reward. We used event-related functional magnetic resonance imaging to investigate hemodynamic responses to monetary rewards and punishments in three experiments that made use of an oddball paradigm. We presented reward and punishment displays randomly in time, following an anticipatory cue, or following a button press response. Robust and differential activation of the caudate nucleus occurred only when a perception of contingency existed between the button press response and the outcome. This finding suggests that the caudate is involved in reinforcement of action potentially leading to reward, rather than in processing reward per se.     

Modulation of respiration during brain hypoxia

This review is a summary of the effects of brain hypoxia on respiration with a particular emphasis on those studies relevant to understanding the cellular basis of these effects. Special attention is given to mechanisms that may be responsible for the respiratory depression that appears to be the primary sequela of brain hypoxia in animal models. Although a variety of potential mechanisms for hypoxic respiratory depression are considered, emphasis is placed on changes in the neuromodulator constituency of the respiratory neuron microenvironment during hypoxia as the primary cause of this phenomenon. Hypoxia is accompanied by a net increase in neuronal inhibition due to both decreased excitatory and increased inhibitory neuromodulator levels. A survey of hypoxia-tolerant cellular systems and organisms suggests that hypoxic respiratory depression may be a manifestation of the depression of cellular metabolism, which appears to be a major adaptation to limited oxygen availability in these systems.     

Modulation of solubilized brain fucosyltransferase activity by phospholipids

Phospholipids interact on Triton X-100 solubilized GDP-fucose: asialofetuin fucosyltransferase (EC 2.4.1.68) isolated from sheep brain. This enzymatic activity is modulated by charged phospholipids. In particular, phosphatidic acid and analogues markedly inhibit the transfer of fucose from GDP-[14C]fucose. Kinetic studies show that phosphatidic acid interacts as a mixed inhibitor: the velocity and affinity of fucosyltransferase for the GDP-fucose and asialofetuin substrates are strongly decreased. However, this inhibitory effect is not related to stereospecificity, and the different parameters involved in the enzymatic reaction of glycosylation are not modified. The nature of fatty acids and chemical bond (ester or ether) occurring in the carbohydrate chain does not modify the behaviour of phosphatidic acid with respect to fucosyltransferase activity. Further, the physical state of phosphatidic acid (gel phase or liquid crystalline phase) has no influence. However, as the inhibition is closely pH-dependent, these data suggest that phosphatidic acid might directly interact with the active site of the enzyme and induce a conformational change.     

Substantia nigra neurons activity in cat brain during realization of self-initiation of behavioural action

Activity of 50 dopamine and 67 non-dopamine neurons was studied during motivated behavioural actions in the cat brain black substance. 66% of former and 88% of latter neurons modified their activity before and during autoinitiated voluntary movements. The data obtained suggest that dopamine neurons are involved in organisation of movements in behavioural actions with cognitive components.     

Cystatins from bovine brain: Purification,some properties,and action on substance P degrading activity

Two cystatins were purified from tissue extract of bovine brain by alkaline treatment, acetone fractionation, gel chromatography on Sephadex G-75, and affinity chromatography on S-carboxymethyl-papain-Sepharose. One of the inhibitors had a relatively high molecular mass, 25 kDa (HMM-cystatin) with pI 4.7, and the other, 11 kDa (LMM-cystatin) with pI 5.23. Both inhibitors showed considerable stability at pH 2 and 80°C. The cystatins inhibited papain, ficin, and cathepsins B and H, but not trypsin, chymotrypsin, thermolysin, nagarse, and cathepsin D. K_i values for the complexes of papain and the inhibitors were estimated to be 2.8×10^–10 M for HMM-cystatin and 1.3×10^–9 M for LMM-cystatin. Both purified cystatins prevented degradation of substance P by soluble fraction and lysosomal extract obtained from synaptosomes, but did not suppress the cleavage of the peptide by synaptosomal plasma membranes.Abbreviations HMM-cystatin high molecular mass inhibitor - LMM-cystatin low molecular mass inhibitor - SP substance P - SPM synaptosomal plasma membranes - p-CMB 4-chloromercuribenzoic acid - BK bradykinin - Bz-Arg-Nap N-benzoyl-dl-arginine--naphthylamide - Arg-Nap dl-arginine--naphthylamide - P-Pxy-Hb hemoglobin initially coupled with pyridoxal-5-phosphate     

Modulation of rat brain insulin receptor kinase activity in diabetes

Insulin receptors from rat brain regions were studied for insulin binding and receptor associated kinase activity, in alloxan induced short-term and long-term diabetes, and insulin induced hypoglycemia. Insulin receptor activity was assessed by [¹²³I]insulin binding, and basal as well as insulin stimulated kinase activity of the receptor, expressed as phosphorylation of the synthetic peptide poly (Glu-Tyr (4:1)). Regional distribution pattern elicited the highest binding and kinase activity in the olfactory bulb. Diabetes caused a significant increase in the kinase activity. The data suggests that brain insulin receptor kinase is regulated differently compared to peripheral tissues and supports the concept of an active brain insulin receptor in vivo.     

Modulation of upper airway collapsibility during sleep: influence of respiratory phase and flow regimen.

We hypothesized that upper airway collapsibility is modulated dynamically throughout the respiratory cycle in sleeping humans by alterations in respiratory phase and/or airflow regimen. To test this hypothesis, critical pressures were derived from upper airway pressure-flow relationships in six tracheostomized patients with obstructive sleep apnea. Pressure-flow relationships were generated by varying the pressure at the trachea and nose during tracheostomy (inspiration and expiration) (comparison A) and nasal (inspiration only) breathing (comparison B), respectively. When a constant airflow regimen was maintained throughout the respiratory cycle (tracheostomy breathing), a small yet significant decrease in critical pressure was found at the inspiratory vs. end- and peak-expiratory time point [7.1 +/- 1.6 (SE) to 6.6 +/- 1.9 to 6.1 +/- 1.9 cmH(2)O, respectively; P < 0.05], indicating that phasic factors exerted only a modest influence on upper airway collapsibility. In contrast, we found that the inspiratory critical pressure fell markedly during nasal vs. tracheostomy breathing [1.1 +/- 1.5 (SE) vs. 6.1 +/- 1.9 cmH(2)O; P < 0.01], indicating that upper airway collapsibility is markedly influenced by differences in airflow regimen. Tracheostomy breathing was also associated with a reduction in both phasic and tonic genioglossal muscle activity during sleep. Our findings indicate that both phasic factors and airflow regimen modulate upper airway collapsibility dynamically and suggest that neuromuscular responses to alterations in airflow regimen can markedly lower upper airway collapsibility during inspiration.     

Modulation of BK(Ca) channel activity by fatty acids: structural requirements and mechanism of action

To determinethe mechanism of fatty acid modulation of rabbit pulmonary arterylarge-conductance Ca²⁺-activated K⁺(BK_Ca) channel activity, we studied effects of fatty acidsand other lipids on channel activity in excised patches withpatch-clamp techniques. The structural features of the fatty acidrequired to increase BK_Ca channel activity (or averagenumber of open channels, NP_o) were identified tobe the negatively charged head group and a sufficiently long (C > 8) carbon chain. Positively charged lipids like sphingosine, which havea sufficiently long alkyl chain (C  8), produced a decrease inNP_o. Neutral and short-chain lipids did notalter NP_o. Screening of membrane surface chargewith high-ionic-strength bathing solutions (330 mM K⁺ or130 mM K⁺, 300 mM Na⁺) did not alter themodulation of the BK_Ca channel NP_oby fatty acids and other charged lipids, indicating that channelmodulation is unlikely to be due to an alteration of the membraneelectric field or the attraction of local counterions to the channel.Fatty acids and other negatively charged lipids were able to modulate BK_Ca channel activity in bathing solutions containing 0 mMCa²⁺, 20 mM EGTA, suggesting that calcium is not requiredfor this modulation. Together, these results indicate that modulationof BK_Ca channels by fatty acids and other charged lipidsmost likely occurs by their direct interaction with the channel proteinitself or with some other channel-associated component.

     

Modulation of the activity of monoaminergic brain systems and emotional condition by dalargin in rats during development of emotional resonance response

Rats were divided in two groups by the reaction of emotional resonance (RER): with emotionally positive reactions (I, with fast RER acquisition, up to 100 s) and with emotionally negative reactions (II, with slow RER acquisition, more than 200 s). After the RER acquisition, the activity of 5-hydroxitryptophan (5-HT) system of the I group of animals was lower than in the II group. The activity of noradrenaline (NA) and dopamine (DA) systems of the I group of animals was higher than in the II group. The between-group differences were enhanced by subcutaneous injection of dalargin. In some brain structures dalargin reversed these relations. These findings point to a complicated interpenetrating character of emotionally positive and emotionally negative states. Emotionally positive states include components of emotionally positive states, and emotionally negative states include components of emotionally positive states. Increase in 5-HT activity and decrease in activity of NA, DA, and opioid (OP) systems induce formation of emotionally negative states. Decrease in 5-HT activity and increase in activity of NA, DA, and OP systems induce formation of the emotionally positive state. It is suggested that 5-HT, NA, and DA systems play the central role in the processes of reinforcement, acquire the evaluative function, and are included in realization of all types of behaviors. OP is a primary modulator system which accompanies the unconditioned pain stimulus and connects it with systems of evaluative function.     

Modulation of brain Ca2+-calmodulin-dependent phosphodiesterase activity by naphthalene sulfamides

Several W-7 analogs were synthesized. These compounds were shown to inhibit the calmodulin-activated phosphodiesterase. A comparative analysis of kinetic parameters of W-7 and its analogs was carried out. A hypothetical model of the effects of calmodulin inhibitors is proposed.     

Reutericyclin: biological activity,mode of action,and potential applications

Reutericyclin is an inhibitory compound produced by sourdough isolates of Lactobacillus reuteri that is structurally but not functionally related to naturally occurring tetramic acids. It is bacteriostatic or bactericidal to gram-positive bacteria based on its activity as a proton-ionophore, and a broad range of food-related spoilage organisms and pathogens is inhibited by reutericyclin. Gram-negative bacteria are resistant to reutericyclin because of the barrier properties of their outer membrane, and resistance of beer-spoiling lactobacilli towards hop bitter acids provides cross-protection to reutericyclin. Remarkably, reutericyclin-producing strains were shown to persist for a period of 10 years in an industrial sourdough fermentation, and reutericyclin was shown to be produced in concentrations active against competitors during growth of L. reuteri in sourdough. Based on the known properties of reutericyclin and L. reuteri, reutericyclin-producing strains may have applications in the biopreservation of foods. Furthermore, these strains were shown to colonize reconstituted lactobacilli-free mice at high levels. Therefore, they could serve as a suitable model system to evaluate a possible impact of antimicrobial compounds on the intestinal microflora of humans and animals.     

Neural network development in late adolescents during observation of risk-taking action

Emotional maturity and social awareness are important for adolescents, particularly college students beginning to face the challenges and risks of the adult world. However, there has been relatively little research into personality maturation and psychological development during late adolescence and the neural changes underlying this development. We investigated the correlation between psychological properties (neuroticism, extraversion, anxiety, and depression) and age among late adolescents (n?=?25, from 18 years and 1 month to 22 years and 8 months). The results revealed that late adolescents became less neurotic, less anxious, less depressive and more extraverted as they aged. Participants then observed video clips depicting hand movements with and without a risk of harm (risk-taking or safe actions) during functional magnetic resonance imaging (fMRI). The results revealed that risk-taking actions elicited significantly stronger activation in the bilateral inferior parietal lobule, temporal visual regions (superior/middle temporal areas), and parieto-occipital visual areas (cuneus, middle occipital gyri, precuneus). We found positive correlations of age and extraversion with neural activation in the insula, middle temporal gyrus, lingual gyrus, and precuneus. We also found a negative correlation of age and anxiety with activation in the angular gyrus, precentral gyrus, and red nucleus/substantia nigra. Moreover, we found that insula activation mediated the relationship between age and extraversion. Overall, our results indicate that late adolescents become less anxious and more extraverted with age, a process involving functional neural changes in brain networks related to social cognition and emotional processing. The possible neural mechanisms of psychological and social maturation during late adolescence are discussed.     

Haemolymph ecdysteroid titres during larval-adult development in Rhodnius prolixus: Correlations with moulting hormone action and brain neurosecretory cell activity

A haemolymph ecdysteroid titre of the fifth (last)-larval instar of the hemipteran, Rhodnius prolixus has been determined by radioimmunoassay. During the last-larval stadium the ecdysteroid titre increases from a negligible level in the unfed insect to a detectable level within minutes following a blood meal. The titre reaches a plateau of ～50–70 ng/ml at 3–4 hr and this level is maintained until day 5–6, the time of the head-critical period in Rhodnius. At the head-critical period the titre begins to increase again, this time dramatically, reaching a peak of ～ 3500 ng/ml at day 13. From day 14 to ecdysis (day 21) the titre declines to a low level, ～ 30 ng/ml. Basal levels of ecdysteroids, ～ 15 ng/ml, were detectable in young adult males and females. A survey of haemolymph volumes during the last-larval instar indicates that the changes in the ecdysteroid titre reflect changes in the rates of ecdysteroid synthesis, and not changes in haemolymph volume. Excretion of ecdysteroids varies systematically during the instar, suggesting that control of ecdysteroid excretion may be important in regulation of the haemolymph titre. Qualitative analysis of the haemolymph ecdysteroid RIA activity revealed the presence of only ecdysone and 20-hydroxy-ecdysone. For the large peak preceding larval-adult ecdysis, 20-hydroxy-ecdysone was the predominant hormone. These results indicate that there may be two periods of release of prothoracicotropic hormone (PTTH) from the brain in Rhodnius, one immediately following the blood meal and the second on day 5 or 6. The significance of these times of PTTH release is discussed in relation to classical evidence of the timing of moulting hormone action, the response of target tissues, and with more recent findings on the timing of release of neurosecretory material from the brain of Rhodnius during moulting.