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Long-term potentiation of nicotinic transmission by a heterosynaptic mechanism in the stellate ganglion of the cat.

1. In the anesthetized, scopolamine-treated cat, the compound action potential (CAP) evoked by a single supramaximal shock to the third thoracic white ramus (T3WR) was recorded in the inferior cardiac nerve (ICN). The CAP was depressed in a dose-dependent manner by the intravenous administration of the nicotinic antagonist hexamethonium (C6). 2. During steady intravenous infusion of C6, which reduced the amplitude of the CAP by 80-90%, a short train of stimuli (few seconds, 10-40 Hz) to the sympathetic trunk just below T4WR potentiated the CAP for periods of tens of minutes to 1-2 h (heterosynaptic long-term potentiation, LTP). An LTP of similar time course was obtained when both train and single shock were applied to T3WR (homosynaptic LTP). Magnitude and duration of the heterosynaptic LTP were dependent on number, frequency, and intensity of the stimuli. No LTP was produced by a train to the ICN. Heterosynaptic LTP was also observed in the absence of C6. Because of the limited subliminal fringe of the test input under this condition, the LTP was of small magnitude. Heterosynaptic LTP also of the heart rate (HR) response to a test stimulus was observed after a conditioning train. 3. The conditioning train produced a displacement to the right of the dose-response curve for C6. The intravenous dose of C6 required for 50% attenuation of the test CAP increased from 0.84 +/- 0.15 (SE) mg/kg pretrain to 2.56 +/- 0.46 mg/kg posttrain (n = 5, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Cerebral bases of subliminal and supraliminal priming during reading.

Several studies have investigated the neural correlates of conscious perception by contrasting functional magnetic resonance imaging (fMRI) activation to conscious and nonconscious visual stimuli. The results often reveal an amplification of posterior occipito-temporal activation and its extension into a parieto-frontal network. However, some of these effects might be due to a greater deployment of attentional or strategical processes in the conscious condition. Here, we examined the brain activity evoked by visible and invisible stimuli, both of which were irrelevant to the task. We collected fMRI data in a masking paradigm in which subliminal versus supraliminal letter strings were presented as primes while subjects focused attention on another subsequent, highly visible target word. Under those conditions, prime visibility was associated with greater activity confined to bilateral posterior occipito-temporal cortices, without extension into frontal and parietal cortices. However, supraliminal primes, compared with subliminal primes, evoked more extensive repetition suppression in a widely distributed set of parieto-frontal areas. Furthermore, only supraliminal primes caused phonological repetition enhancement in left inferior frontal and anterior insular cortex. Those results suggest a 2-stage view of conscious access: Relative to masked stimuli, unmasked stimuli elicit increased occipito-temporal activity, thus allowing them to compete for global conscious access and to induce priming in multiple distant areas. In the absence of attention, however, their access to a second stage of distributed parieto-frontal processing may remain blocked.

Acoustic Stimulation↗

Enhancement of phrenic nerve activity by digoxin: an effect dependent upon intact ninth and tenth cranial nerves.

Digitalis increases phrenic nerve activity and causes hyperventilation. To determine whether this effect on respiration is caused by central drug actions on brainstem respiratory neurons or by peripheral drug actions which increase excitatory afferent drive to central respiratory neurons, digoxin was administered intravenously to cats with or without intact IXth and Xth cranial nerves. Digoxin caused marked increases in phrenic nerve activity in cats with intact afferent cranial nerves, but it had no effect in cats with severed afferent nerves. This suggested that effects of digoxin on respiration depend upon afferent input to respiratory neurons. However, digoxin may have had subliminal effects on central neurons which increased phrenic activity only in the presence of excitatory input. To test this possibility, effects of intravenously administered digoxin were observed on centrally evoked submaximal responses in the phrenic nerve. Subarrhythmic, arrhythmic or lethal doses of digoxin had no effect on excitatory phrenic responses evoked from the pons. Thus, effects of digoxin on phrenic nerve activity appeared to be due primarily to drug actions on peripheral neural sites which had excitatory influences on respiration.

Animals↗

Monosynaptic reflex depression in cats with organophosphorus neuropathy: effects of tri-o-cresyl phosphate.

The electrophysiology of organophosphorus induced delayed neurotoxicity was studied to determine the extent peripheral nerve changes affect monosynaptic reflex responses of the spinal cord. Cats were given a single dermal dose of 1500 mg/kg or two dermal doses of 500 mg/kg of tri-o-cresyl phosphate. Animals were observed for 60 days after which monosynaptic reflex (MSR) responses were recorded from L7 and S1 ventral roots after stimulation of the tibial or common peroneal nerves. Post-tetanic potentiated responses as well as ventral and dorsal root compound action potentials were also recorded. There was a significant decrease from control in the unconditioned MSR. The post-tetanic potentiated response was significantly decreased in the S1 ventral root, however, when expressed as a factor of potentiation of the unconditioned MSR, it was found to be increased, although not significantly. The dorsal and ventral root compound action potentials were also significantly decreased from control with their conduction velocities being no different from control The decrease in the unconditioned MSR as well as the dorsal and ventral root compound action potentials were attributed to peripheral nerve damage. The absence of any significant change in the post-tetanic potentiated response expressed as a factor of potentiation of the unconditioned MSR was attributed to a decrease in both the discharge zone as well as the subliminal fringe. The absence of any change in the conduction velocity indicates at least some of the large myelinated peripheral fibers were spared from significant damage.

Action Potentials↗

Digoxin toxicity: primary sites of drug action on the sympathetic nervous system.

Increases and decreases in sympathetic nerve activity have been reported to accompany digitalis-induced arrhythmias. These effects may result from drug action on various sites such as the central nervous system, ganglia, chemoreceptor or baroreceptor afferent fibers or peripheral efferent nerve fibers. The relative importance of each possible site of drug action has not been clarified. To define the involvement of some of these sites, digoxin was administered intravenously to cats in order to study its effects on activity of preganglionic splanchnic or postganglionic inferior cardiac nerves in the presence or absence of chemoreceptor and baroreceptor reflexes. In cats with intact reflexes, arrhythmic doses of digoxin had diverse effects on postganglionic activity. In some cats digoxin increased activity and in others it decreased activity. In contrast, digoxin consistently caused large progressive increases in postganglionic activity when baroreceptors and chemoreceptors had been denervated. Digoxin inhibited preganglionic nerve activity only in cats with intact reflexes but had no effect in those without chemoreceptor and baroreceptor reflexes. Thus, the afferent component of the baroreceptor reflex is the apparent site of digoxin-induced inhibition. Digoxin produced increases in activity above control only in postganglionic nerves. This finding suggests that digoxin acts on the ganglion to increase sympathetic activity. Digoxin had no discernible effect on preganglionic activity when baroreceptor and chemoreceptor afferent input had been eliminated. To test further for any subliminal drug effect in the brain, effects of intravenously administered digoxin were observed on centrally evoked submaximal responses in the splanchnic nerve. Lethal doses of digoxin had no effect on responses evoked from the medulla or the hypothalamus. Therefore, these data are not consistent with the hypothesis that a primary site of drug action is in the central nervous system. Instead, the data suggest that neural effects of digoxin result primarily from drug actions within the peripheral autonomic nervous system on sites such as the ganglion and peripheral afferent components of the baroreceptor reflex.

Animals↗

Post-synaptic activity evoked in the nucleus tractus solitarius by carotid sinus and aortic nerve afferents in the cat.

Post-synaptic responses evoked in neurones of the nucleus tractus solitarius by electrical stimulation of the carotid sinus, aortic and vagal nerves, alone or in combination, have been studied in anaesthetized cats using both extracellular and intracellular recording techniques. A total of 292 neurones received an input from at least one of the three nerves tested. The activity of the large majority of these cells (249) could only be shown to be altered by stimulation of one of these nerves and in 222 of these cases this was an excitatory response. These responses showed the expected post-synaptic characteristics including temporal summation and, in intracellular records, a summation of evoked excitatory post-synaptic potentials (e.p.s.p.s). The minimum latency to onset of these responses was variable, both for individual cells and for the population as a whole and varied within the range 2-124 ms. In a small number of cells (twenty-seven), the input was purely inhibitory in nature. In neurones showing a tonic discharge this produced a decrease in the rate of firing. This influence was most marked in intracellular records where membrane hyperpolarizations were noted. Again, the latency to onset was variable, in the range 4-27 ms. Convergent inputs from two or more of the nerves were identified in forty-three neurones. The effects of these were always excitatory. They could be observed both as a facilitation of spike activity recorded extracellularly and as summation of subliminally evoked e.p.s.p.s recorded intracellularly. On the basis of threshold voltages and latency to onset, the afferents to these neurones are indistinguishable from those providing an exclusive input. It can be concluded that at least some of the neurones in the nucleus tractus solitarius and its vicinity receive inputs from more than one source. The implications of these observations on the role of this brain-stem area in cardiorespiratory reflexes is discussed.

Action Potentials↗

Tuning of membrane properties regulates subliminal synapses in dorsal horn neurons of intact rats.

Functional plasticity in receptive field properties underlies the mechanism whereby spinal dorsal horn neurons encode changes in pain sensitivity following peripheral injury. Activation of "silent" or subliminal excitatory synapses was hypothesized to account for this injury-induced neural plasticity. To better characterize the mechanisms governing subliminal inputs, we adapted whole-cell patch clamp to the study of dorsal horn neurons in intact, anesthetized rats. In this report we show that the membrane properties of spinal cells correlate to functional class defined by action potential responses to cutaneous stimuli. In addition, we report the discovery of a novel "silent" population of neurons with solely subliminal excitatory inputs at rest that can be activated by membrane depolarization. Finally, an induced change in baseline membrane potential to a level nearer that of a different functional class results in a corresponding change in the responses to cutaneous stimuli of a given cell to that of the new functional class. In summary our findings suggest that biophysical membrane properties are key factors determining the functional profile of spinal neurons. The rapid change of such properties may regulate the function of silent synapses in spinal neurons and underlie rapid development of neural plasticity.

Action Potentials↗

[The physiological criteria for the ability of stimulus recognition].

Neural mechanisms are considered of such unconscious psychic phenomena as subliminal perception of semantic stimuli, psychological defence, unaccountable emotions. The results are given of many years studies conducted by means of conditioned, electrophysiological and psychophysiological methods. The possibility is proved of semantic analysis of perception on unconscious level and formation of association with the help of unrealized emotionally significant words. At present it is possible to describe only few neural mechanisms of consciousness and unconsciousness; however, the development of contemporary psychophysiology allows to state that the analysis of this problem from scientific positions is the most correct way to learn the nature of the brain processes which are the basis of these complicated psychic phenomena.

Attention↗

Input-output relations in the pathway of recurrent inhibition to motoneurones in the cat.

1. The output from Renshaw cells caused by a phasic motor volley was investigated when these neurones were submitted to a background firing secondary to a tonic motor discharge elicited by a repetitive stimulation of muscle group I afferents. It was invariably found in individual Renshaw cells that tonic excitation produced an increase in the additional ouput caused by the phasic motor volley. The curves displaying this increase exhibited a significant 'jump' when the output resulting from the combined tonic and phasic motor discharges ranged between 2 and 5 spikes during the first 10 msec following the phasic volley. 2. The whole pool of Renshaw cells was also considered by assessing the amount of recurrent inhibition in motoneurones following a phasic motor volley. Similarly it was found that additional recurrent inhibition elicited by a phasic motor volley was enhanced when the Renshaw cells received a tonic excitatory input. 3. The Renshaw cell discharges elicited by stimulation of two different nerves were compared when a conditioning stimulus was previously applied to only one of them. The results strongly suggest that a preceding volley caused a decrease in synaptic efficacy at the terminals of the recurrent collaterals. 4. The firing produced by current injected through the recording micro-electrode was investigated in one intracellularly recorded Renshaw cell. It was found that the current-frequency curve was linear for 'steady-state' firing but displayed a clearcut sigmoid shape for the earliest intervals before the final adaptation. 5. It is demonstrated that this sigmoid input-output relation in individual Renshaw cells is sufficient to explain how the controls acting on these neurones may change the gain in the recurrent pathway when Renshaw cells are fired by a phasic motor discharge. When Renshaw cells are fired by a longlasting tonic motor discharge the linear input-output relation in individual cells should not cause any modifications of the gain in the recurrent pathway. A change in this gain secondary to the effects of segmental and supraspinal control systems is, however, possible if the motor discharge creates a subliminal fringe within the pool of Renshaw cells.

Animals↗

Lateralized readiness potential elicited by undetected visual stimuli.

Visual stimuli undetected by normal subjects as a result of masking procedures can nonetheless activate response preparation in motor areas and yield a motor response. An unanswered question is whether the same holds for undetected subliminal stimuli that are not responded to. To answer this question, in this study normal subjects were tested on a simple visual reaction time task with stimuli above, at, or below the psychophysical threshold while the lateralized readiness potential (LRP), i.e. an electrophysiological correlate of premotor activation in the primary motor cortex, was computed. We found a reliable LRP not only for suprathreshold stimuli but also for subthreshold stimuli to which subjects did not respond. The main thrust of this study is that it provides evidence that activation of the motor cortex occurs even with subthreshold visual stimuli and without an overt response.

Contingent Negative Variation↗

Excitability changes of motor evoked potentials dependent on muscle properties and contraction modes.

Using transcranial magnetic stimulation (TMS), differences in the excitability changes of motor evoked potentials (MEPs) between isometric (force task) and isotonic (movement task) muscle contractions in a distal (first dorsal interosseous; FDI) and a proximal (middle deltoid; MD) muscle were studied. In the FDI muscle, the active threshold of MEP recruitment was significantly lower in the isotonic than that in the isometric muscle contraction in spite of identical background EMG activity levels. Additionally, the dependence of the MEP amplitude on background EMG activity was significantly greater in the isotonic than in the isometric muscle contraction at low EMG activity levels, but the difference disappeared beyond middle EMG activity levels. In the MD muscle, the dependence of the MEP amplitude on background EMG activity was significantly greater in the isotonic than in the isometric muscle contraction, and further this dependence was kept at all muscle contraction levels. These results indicate that the dependence of the MEP amplitude on background EMG activity is modulated not only by the different muscle contraction modes (isotonic and isometric), but also by muscle properties (distal and proximal). Thus, the present findings suggest that the task-specific extra excitation in the proximal muscle is definitely produced corresponding to task differences (task-dependent subliminal fringe), which might be explained by the predominant frequency principle if applied to the proximal muscle. On the other hand, the lack of task-dependent extra excitation in the distal muscle is explained by the predominant recruitment principle for force grading in small hand muscles.

Adult↗

Modulation of regulatory and catalytic subunit levels of cAMP-dependent protein kinase A in anterior pituitary cells in response to direct activation of protein kinases A and C or after GnRH stimulation.

We have previously shown that direct activation of protein kinase A (PKA) and protein kinase C (PKC) induced changes in the expression of genes coding for PKA RII beta and C alpha subunit isoforms in cultured anterior pituitary cells, suggesting the possibility of interconnected regulation at this point. To evaluate whether the cell content of PKA protein subunits could be similarly altered, the catalytic (C) and regulatory type I (RI) and type II (RII) subunits were identified by Western blot analysis using specific immunoaffinity-purified antibodies. Activation of PKA by the permeant cyclic adenosine monophosphate (cAMP) analogue 8-Br-cAMP induced a dramatic time- and concentration-dependent decline of C subunit to a residual level that may represent 10-15% of that in untreated cells. The most profound decrease occurred during the first 5 h following treatment with 0.5-2 mM analogue (by 65 +/- 14 and 79 +/- 5%, respectively). Under identical conditions, RII was increased by about 40% at the higher concentrations, while RI increased slightly, but only at low concentrations (below 1 mM 8-Br-cAMP), and then gradually decreased. Exposure of cells to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) also resulted in decreased levels of the PKA C subunit, however, with a different concentration-dependent profile. In particular, a decline in PKA C was most pronounced (60%) at a low concentration of TPA (10 nM) as compared with the concentrations equal to or above 20 nM (40% decrease). TPA at 10 nM also depressed notably (by 25%) the level of RII subunit, but higher concentrations were essentially ineffective, although a slight and statistically not significant elevation of the cell subunit content was observed as for RI. Simultaneous activation of both PKA and PKC pathways resulted in further depletion of PKA C and an important loss (50%) of RII, a subunit which was enhanced by the activation of either system alone. Finally, gonadotropin-releasing hormone, a neuropeptide that has the potentiality to activate both PKA and PKC signaling in gonadotropes, was able to alter PKA subunit cell content: PKA C was significantly reduced at either a subliminal (0.1 nM) or maximal (10 nM) concentration, whereas RII increased at the low concentration and decreased at the high concentration. In conclusion, these data demonstrate that the pituitary cell contents of RI, RII, and C subunits of PKA are regulated under the activation of PKA itself as well as PKC in a manner that can exhibit further alteration when both systems come simultaneously into play. Changes in the PKA subunit levels in certain cases may correlate with a variation of the mRNAs suggesting multiple control mechanisms, including an alteration of gene expression and changes in subunit degradation, synthesis, and/or turnover. These data, together with those obtained in the presence of gonadotropin-releasing hormone, provide further support for a hormonally induced interplay between PKA and PKC signaling pathways at the crucial level of PKA in the pituitary gland including gonadotropes.

Animals↗

Emotional and semantic networks in visual word processing: insights from ERP studies.

The event-related brain potential (ERP) literature concerning the impact of emotional content on visual word processing is reviewed and related to general knowledge on semantics in word processing: emotional connotation can enhance cortical responses at all stages of visual word processing following the assembly of visual word form (up to 200 ms), such as semantic access (around 200 ms), allocation of attentional resources (around 300 ms), contextual analysis (around 400 ms), and sustained processing and memory encoding (around 500 ms). Even earlier effects have occasionally been reported with subliminal or perceptual threshold presentation, particularly in clinical populations. Here, the underlying mechanisms are likely to diverge from the ones operational in standard natural reading. The variability in timing of the effects can be accounted for by dynamically changing lexical representations that can be activated as required by the subjects' motivational state, the task at hand, and additional contextual factors. Throughout, subcortical structures such as the amygdala are likely to contribute these enhancements. Further research will establish whether or when emotional arousal, valence, or additional emotional properties drive the observed effects and how experimental factors interact with these. Meticulous control of other word properties known to affect ERPs in visual word processing, such as word class, length, frequency, and concreteness and the use of more standardized EEG procedures is vital. Mapping the interplay between cortical and subcortical mechanisms that give rise to amplified cortical responses to emotional words will be of highest priority for future research.

Brain↗

Positive emotional priming of facial affect perception in females is diminished by chemosensory anxiety signals.

Chemosensory communication of anxiety is a common phenomenon in vertebrates and improves perceptual and responsive behaviour in the perceiver in order to optimize ontogenetic survival. A few rating studies reported a similar phenomenon in humans. Here, we investigated whether subliminal face perception changes in the context of chemosensory anxiety signals. Axillary sweat samples were taken from 12 males while they were waiting for an academic examination and while exercising ergometric training some days later. 16 subjects (eight females) participated in an emotional priming study, using happy, fearful and sad facial expressions as primes (11.7 ms) and neutral faces as targets (47 ms). The pooled chemosensory samples were presented before and during picture presentation (920 ms). In the context of chemosensory stimuli derived from sweat samples taken during the sport condition, subjects judged the targets significantly more positive when they were primed by a happy face than when they were primed by the negative facial expressions (P = 0.02). In the context of the chemosensory anxiety signals, the priming effect of the happy faces was diminished in females (P = 0.02), but not in males. It is discussed whether, in socially relevant ambiguous perceptual conditions, chemosensory signals have a processing advantage and dominate visual signals or whether fear signals in general have a stronger behavioural impact than positive signals.

Adult↗

Analysis of the sensitizing effect of veratrum alkaloids to potassium on frog muscle.

1. The sensitizing effect of veratrum alkaloids to potassium is not specific. Reducing the concentration of chloride in Ringer's solution, or treating the muscle with nicotine in a concentration close to threshold after pretreatment with subliminal concentration of cevadine result in a marked mechanical response of the muscle. However, cevadine does not alter the sensitivity of the muscle to caffeine. On the basis of these observations it has been suggested that veratrum alkaloids sensitize the muscle membrane essentially to depolarizing processes. 2. Cevadine, 0.01 mM, fails to depolarize the muscle membrane but increases the depolarizing effect of 10 mM potassium. The depolarizing effect of a reduction of the concentration of chloride from 120 mM to 30 mM is also increased in cevadine pretreated muscle. Cevadine pretreatment increases the depolarizing effect of nicotine, too. 3. The above sensitizing effects are unanimously Na-dependent. Accordingly there is no mechanical response and increased depolarization in muscles equilibrated in sodium-free (choline) Ringer's solution before the cevadine treatment. 4. On the basis of the present data it is suggested that the membrane, when sensitized by veratrum alkaloids, can be triggered by different depolarizing processes and the depolarization increases as the result of increased Na permeability. The increased depolarization at the threshold level becomes sufficient for the automatic regenerative processes of the action potential to develop which activate the contractile elements. However, the mechanical response is a prolonged contraction rather than a contracture, its long period being the result of a very slow repolarization caused by the well-known inhibitory effect of veratrum alkaloids on Na inactivation.

Animals↗

Event-related brain correlates of associative learning without awareness.

Controversy exists about whether associative learning occurs without awareness. In an earlier study using subthreshold (subliminal) stimuli, we reported evidence that such learning could occur as measured by event-related brain potentials [ERP; Cons. Cognit. 6 (1997) 519]. In the present study, we extend these findings by changing several aspects of the methodology in order to provide a more stringent test of this effect and to examine its generality. We used two matched words (murder and cancer) as conditional stimuli (CS); a 100 dB white noise blast as unconditional stimulus (US); a CS-US interval of 3 s; and a full-factorial design with CSs counterbalanced. The conditioning-acquisition phase occurred when the CSs were perceptually unconscious, as confirmed by a subsequent behavioral task. The conditioning-acquisition and postconditioning-extinction phases were examined for ERP evidence of associative learning. The clearest and strongest evidence for associative learning without awareness was observed in the ERP component measures (up to 1 s, poststimulus) in the postconditioning-extinction phase. The CS+ was significantly more positive than the CS- in the P3b-LP component region, which is highly consistent with the results of our earlier study. Differences also were observed in the P1-P2 components. In an unexpected finding, we observed a significant positive slow potential shift for the CS+ in the region between 1 and 3 s poststimulus. We discuss these results and their implications for our understanding of associative learning and awareness.

Adult↗