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The role of claustrum in Pavlovian heart rate conditioning in the rabbit (Oryctolagus cuniculus): anatomical, electrophysiological, and lesion studies.

The role of the claustrum in Pavlovian heart rate (HR) conditioning was studied in the rabbit (Oryctolagus cuniculus) by (a) mapping claustral projections to the prefrontal cortex (PFC), (b) recording claustral single-unit discharge to sensory stimulation and conditioning stimuli during HR conditioning, and (c) assessing the effects of claustral damage on HR conditioning. Contralateral and ipsilateral claustral projections to the PFC were found. Claustral cells responded to nonsignal stimulation with increased discharge and also showed conditioned stimulus-evoked increases in discharge during Pavlovian HR conditioning. Moreover, claustral lesions diminished the magnitude of the HR-conditioned response without affecting the cardiac-orienting response to the conditioned stimulus or the cardiac-unconditioning response to the unconditioned stimulus, suggesting a role for the claustrum in associative learning.

Action Potentials↗

Contribution of CD54 to human eosinophil and neutrophil superoxide production.

We have reported that CD54 on eosinophils is involved in eosinophil degranulation. However, the role of CD54 in eosinophil and neutrophil superoxide production is still uncertain. We assessed the effect of CD54 on eosinophils and neutrophils in recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF)- or phorbol myristate acetate (PMA)-induced superoxide production through CD18. Anti-CD54 monoclonal antibody attenuated leukocyte aggregation and superoxide production of rGM-CSF- or PMA-stimulated neutrophils and PMA-stimulated eosinophils. Anti-CD18 monoclonal antibody or theophylline attenuated superoxide production of eosinophils and neutrophils stimulated by either stimuli. Flow cytometric analysis demonstrated CD54 expression on freshly isolated neutrophils but not on freshly isolated eosinophils. CD54 newly expressed on eosinophils reached its peak expression 30 min after PMA stimulation. The increase in CD18 and CD54 expression on neutrophils caused by rGM-CSF stimulation was partially inhibited by theophylline. These data demonstrated that CD54 and CD18 interaction of eosinophils or neutrophils is involved in superoxide production and that the inhibition of superoxide production by theophylline may be at least partly due to the inhibition of CD54 and CD18.

Analysis of Variance↗

Behavioral functions of nucleus accumbens dopamine: empirical and conceptual problems with the anhedonia hypothesis.

Nucleus accumbens (DA) has been implicated in a number of different behavioral functions, but most commonly it is said to be involved in "reward" or "reinforcement". In the present article, the putative reinforcement functions of accumbens DA are summarized in a manner described as the "General Anhedonia Model". According to this model, the DA innervation of the nucleus accumbens is conceived of as a crucial link in the "reward system", which evolved to mediate the reinforcing effects of natural stimuli such as food. The reward system is said to be activated by natural reinforcing stimuli, and this activation mediates the reinforcing effects of these natural stimuli. According to this view, other stimuli such as brain stimulation and drugs can activate this system, which leads to these stimuli being reinforcing as well. Interference with DA systems is said to blunt the reinforcing effects of these rewarding stimuli, leading to "extinction". This general model of the behavioral functions of accumbens DA is utilized widely as a theoretical framework for integrating research findings. Nevertheless, there are several difficulties with the General Anhedonia Model. Several studies have observed substantial differences between the effects of extinction and the effects of DA antagonism or accumbens DA depletions. Studies involving aversive conditions indicate that DA antagonists and accumbens DA depletions can interfere with avoidance behavior, and also have demonstrated that accumbens DA release is increased by stressful or aversive stimuli. Although accumbens DA is important for drug abuse phenomena, particularly stimulant self-administration, studies that involve other reinforcers are more problematic. A large body of evidence indicates that low doses of dopamine antagonists, or depletions of accumbens DA, do not impair fundamental aspects of food motivation such as chow consumption and simple instrumental responses for food. This is particularly important, in view of the fact that many behavioral researchers consider the regulation of food motivation to be a fundamental aspect of food reinforcement. Finally, studies employing cost/benefit analyses are reviewed, and in these studies considerable evidence indicates that accumbens DA is involved in the allocation of responses in relation to various reinforcers. Nucleus accumbens DA participates in the function of enabling organisms to overcome response costs, or obstacles, in order to obtain access to stimuli such as food. In summary, nucleus accumbens DA is not seen as directly mediating food reinforcement, but instead is seen as a higher order sensorimotor integrator that is involved in modulating response output in relation to motivational factors and response constraints. Interfering with accumbens DA appears to partially dissociate the process of primary reinforcement from processes regulating instrumental response initiation, maintenance and selection.

Animals↗

Methylphenidate speeds evaluation processes of attention deficit disorder adolescents during a continuous performance test.

Forty-six Attention Deficit Disorder (ADD) adolescents took a Continuous Performance Test (CPT) under placebo and methylphenidate (35.33 mg/day). The task required pressing one button for targets (p = .133), and another button for nontargets. Subjects displayed a strong bias to make the more frequent negative response before completely evaluating stimuli. Consistent with this assumption, subjects responded faster (by an average of 87 ms) to nontargets than to targets. Methylphenidate increased accuracy and speeded reaction times (RTs) to targets. The drug also increased the amplitude of the P3b component of the event-related potential for nontargets and shortened the latency of P3b for both targets and nontargets. These results suggest increased capacity allocation to and faster evaluation of task stimuli. Finally, the stimulant lengthened relative motor processing time (RT-P3b latency) for nontargets, a finding implying that response processing was accomplished with the benefit of earlier completion of evaluation processes for these stimuli.

Adolescent↗

Capsaicin-induced bladder hyperactivity in normal conscious rats.

Capsaicin, instilled intravesically in normal, unanesthetized rats induced a concentration-dependent bladder hyperactivity, which could be abolished by hexamethonium, given intra-arterially near the bladder, or by morphine administered intrathecally. The effect was reversible and could be repeated. The NK-2 receptor selective antagonist SR 48,968 and the nonselective NK receptor antagonist spantide, given intra-arterially near the bladder, which by themselves, in the concentrations used, did not affect cystometric parameters, both counteracted the capsaicin-induced hyperactivity, whereas the NK-1 receptor selective antagonist RP 67,580 failed to do so. Blockade of tachykinin receptors in the urinary bladder does not seem to produce changes of the micturition reflex associated with bladder filling in the conscious rat. However, tachykinins released from capsaicin-sensitive nerves by various stimuli may, through stimulation of NK-2 receptors, lower the threshold for initiation of the micturition reflex. In the rat, intravesical capsaicin may be a suitable model for studies of afferent activity caused by stimuli releasing peptides from sensory nerves in the bladder, thereby provoking bladder hyperactivity.

Administration, Intravesical↗

Automatic implantable cardioverter/defibrillator (AICD) and antitachycardia pacemaker (Tachylog): combined use in ventricular tachyarrhythmias.

UNLABELLED: Antitachycardia pacing in ventricular tachyarrhythmias (VT) is associated with potential acceleration of VT; frequency of VT and discomfort of the patient (pt) can limit treatment with the AICD. We therefore evaluated the combined use of antitachycardia pacing and AICD in 6 of 14 patients (age 50-70, mean 60 years) with AICD implantation because of VT, which could be terminated by temporary overdrive pacing. With the interactive mode of the Tachylog, termination of VT by the pacemaker as well as by the AICD was assessed after implantation. In the automatic mode, the Tachylog functioned as a bipolar VVI device with antitachycardia burst stimulation: 2-5 stimuli, interval 260-300 ms, 1-2 interventions. During follow-up of 12 +/- 5 months, the Tachylog terminated VT reliably 20 to 327 times per patient. In three patients, burst stimulation accelerated VT, which was terminated then by the AICD discharge. CONCLUSION: Drug resistant ventricular tachyarrhythmias can be terminated by the Tachylog pacemaker avoiding patients' discomfort. In case of acceleration, ventricular tachyarrhythmias can be controlled by the automatic implantable cardioverter/defibrillator. A universal pacemaker should combine antitachycardia pacing with back-up defibrillation mode.

Aged↗

Response of human jaw muscles to axial stimulation of the incisor.

The role of periodontal mechanoreceptors (PMRs) in the reflex control of the jaw muscles has thus far been mainly derived from animal studies. To date, the work that has been done on humans has been limited and confined to orthogonal stimulation of the labial surface of the tooth. The purpose of this study was to investigate the response of the masseter and digastric muscles in humans to controlled axial stimulation of the upper left central incisor, both before and during a local anaesthetic block of the PMRs. Ten neurologically normal young adult females were tested, each on two separate occasions to confirm the reproducibility of the results. It was found that the reflex response in the masseter was modulated by the rate of rise of the stimulus used and, to a lesser degree, the level of background muscle activity. There was little detectable change in the activity of the digastric muscle under the tested conditions and what was found could be attributed to cross-talk with the masseter. The reflex responses obtained were significantly different between subjects; however retesting the same subject on a different occasion yielded similar results. The results indicate that the most common response of the masseter muscle to brisk axial stimulation of the incisor is a reflex inhibition at 20 ms, followed by a late excitation at 44 ms. However, it is possible that this late excitation could be due to delayed action potentials and hence be artefactual. As the application of a local anaesthetic block removed or significantly reduced both of these responses, it was concluded that they originated from the PMRs. Unlike during orthogonal stimulation, slowly rising stimuli did not produce any excitatory reflex activity. This indicated a difference in jaw reflexes to forces applied in different directions, possibly due to the activation of different receptor types when stimulating the tooth in either the orthogonal or axial directions.

Adolescent↗

Maximum likelihood estimation of ion channel kinetics from macroscopic currents.

We describe a maximum likelihood method for direct estimation of rate constants from macroscopic ion channel data for kinetic models of arbitrary size and topology. The number of channels in the preparation, and the mean and standard deviation of the unitary current can be estimated, and a priori constraints can be imposed on rate constants. The method allows for arbitrary stimulation protocols, including stimuli with finite rise time, trains of ligand or voltage steps, and global fitting across different experimental conditions. The initial state occupancies can be optimized from the fit kinetics. Utilizing arbitrary stimulation protocols and using the mean and the variance of the current reduce or eliminate problems of model identifiability (Kienker, 1989). The algorithm is faster than a recent method that uses the full autocovariance matrix (Celentano and Hawkes, 2004), in part due to the analytical calculation of the likelihood gradients. We tested the method with simulated data and with real macroscopic currents from acetylcholine receptors, elicited in response to brief pulses of carbachol. Given appropriate stimulation protocols, our method chose a reasonable model size and topology.

Algorithms↗

Luminol-enhanced chemiluminescence induced in peripheral blood-derived human phagocytes: obligatory requirement of myeloperoxidase exocytosis by monocytes.

Luminol-enhanced chemiluminescence (LCL) of phagocytes is often used to monitor for the generation of reactive oxygen mediators. A strong LCL reaction, as observed in triggered peripheral blood monocytes and neutrophils, depends on both the activation of an NAD(P)H-dependent oxidase and a functional myeloperoxidase (MPO). The aim of this work was to compare the LCL response induced by soluble and particulate stimuli in monocytes with that of polymorphonuclear leukocytes (PMNs). In agreement with earlier results, neutrophils showed a first peak of LCL activity within 1 min and a second peak around 3 min when stimulated with soluble stimuli. The first peak is sensitive to oxygen scavengers and requires the presence of extracellular luminol, whereas the second peak is much less sensitive to oxygen scavengers and does not require the presence of extracellular luminol. The first peak of LCL is therefore thought to represent extracellular and the second peak intracellular LCL. Monocytes, in contrast, showed only the first peak of LCL activity. This peak was sensitive to oxygen scavengers, required the extracellular presence of luminol, and could be suppressed by a rapid pH shift to a pH not allowing LCL (i.e., to pH 5). These results suggest that the stimulus-dependent extracellular release of oxygen metabolites and of MPO is an obligatory requirement for LCL induced in monocytes. An exclusively extracellular LCL was noted upon stimulation with aggregated immunoglobulin G, f-Met-Leu-Phe, phorbol myristate acetate, A23187, anti-CD36 antibodies, opsonized zymosan, and opsonized E. coli. With the addition of H2O2 in excess (1 microM), the LCL response of monocytes therefore reflected the stimulus-dependent degranulation of MPO, and LCL-based determination of MPO release closely correlated with enzymatic MPO determination. The question of why LCL induced in monocytes, but not in PMNs, is restricted to the extracellular compartment was addressed. Although flow cytometric experiments were consistent with the hypothesis that extracellular H2O2 entered the cytoplasm of monocytes less efficiently than that of PMNs, other more important factors are assumed to contribute. Collectively, these results point to previously unrecognized differences in monocyte and PMN LCL which may reflect cellular differences of potential pathophysiological significance.

Azides↗

Motion perception of saccade-induced retinal translation.

Active visual perception relies on the ability to interpret correctly retinal motion signals induced either by moving objects viewed with static eyes or by stationary objects viewed with moving eyes. A motionless environment is not normally perceived as moving during saccadic eye movements. It is commonly believed that this phenomenon involves central oculomotor signals that inhibit intrasaccadic visual motion processing. The keystone of this extraretinal theory relies on experimental reports showing that physically stationary scenes displayed only during saccades, thus producing high retinal velocities, are never perceived as moving but appear as static blurred images. We, however, provide evidence that stimuli optimized for high-speed motion detection elicit clear motion perception against saccade direction, thus making the search for extraretinal suppression superfluous. The data indicate that visual motion is the main cue used by observers to perform the task independently of other perceptual factors covarying with intrasaccadic stimulation. By using stimuli of different durations, we show that the probability of perceiving the stimulus as static, rather than moving, increases when the intrasaccadic stimulation is preceded or followed by a significant extrasaccadic stimulation. We suggest that intrasaccadic motion perception is accomplished by motion-selective magnocellular neurons through temporal integration of rapidly increasing retinal velocities. The functional mechanism that usually prevents this intrasaccadic activity from being perceived seems to rely on temporal masking effects induced by the static retinal images present before and/or after the saccade.

Humans↗

Involvement of spinal glia in tetanically sciatic stimulation-induced bilateral mechanical allodynia in rats.

The previous study showed involvement of spinal glia in tetanically sciatic stimulation-induced long-term potentiation (LTP) of C-fiber-evoked field potentials in the spinal dorsal horn. In the present study, the electrophysiological recording and paw withdrawal threshold (PWT) to von Frey stimulation were assessed following unilaterally tetanically sciatic stimulation in rats. Tetanic stimuli elicited LTP of both A- and C-fiber-evoked field potentials. After stimulation with the same parameter, bilateral PWTs to mechanical stimuli decreased. Intrathecal administration of fluorocitrate (1 nmol/10 microl), an astrocyte inhibitor, partially inhibited tetanic stimulation-induced reduction of bilateral PWTs. A similar effect also occurred at the contralateral side. And this bilateral inhibition of mechanical threshold lasted 8 days. Similarly, intrathecal administration of d-amino acid oxygenase (50 microg/mul, 10 microl), D-serine inhibitor, partially inhibited tetanic sciatic stimulation-induced reduction of bilateral PWTs for 24 h. The results showed that spinal glia plays an important role in bilaterally mechanical allodynia by tetanic sciatic stimulation of the sciatic nerve.

Animals↗

A possible role of evoked alpha in primary sensory processing: common properties of cat intracranial recordings and human EEG and MEG.

Regarding the evoked potential (EP) as a superposition of evoked EEG rhythms in several frequency ranges, we investigated the following issue: Are distinct evoked rhythms, in particular the alpha (8-15 Hz) response, related to separable physiological processes? Frequency domain analysis of EPs was used to evaluate results of cross-modality experiments, i.e.: responses to auditory stimuli were simultaneously recorded from the auditory cortex (adequate stimulation) and from the visual cortex (inadequate stimulation). Responses to visual stimuli were recorded from the same sites. The results of these experiments and further measurements (EEG and MEG responses in humans, among them multiple sclerosis patients) are consistent in the following respect: The amplitudes of alpha responses are dependent on whether or not a stimulus applied is adequate. Alpha responses may thus be related mostly to primary sensory processing. In contrast, theta responses (4-7 Hz) were observed for adequate as well as inadequate stimuli. They may be related rather to associative and cognitive processing than to primary sensory processing. Thus frequency responses, in particular the alpha response, are not artificial results of digital filtering, but functionally significant brain responses.

Acoustic Stimulation↗

[Repetitive ventricular response by programmed electrostimulation of the heart: frequency and clinical significance].

The induction of a repetitive ventricular response (RVR) by programmed electrical stimulation (PES) in patients with malignant ventricular arrhythmias such as ventricular tachycardia or ventricular fibrillation is associated with poor prognosis. However, the incidence and clinical significance of RVR in patients with normal hearts and in those with coronary artery disease (CAD) who do not have a history of malignant ventricular arrhythmias are unknown. In this paper, we present our views on the clinical value of PES in those patients. The incidence of RVR in patients without evidence of heart disease remains controversial. The possible reasons for the disparities between studies are due to differences in the study populations and stimulation protocols used. In 38 patients with normal hearts proven by left ventricular and coronary angiography no patient had three or more ventricular depolarizations in response to PES with single and double premature stimuli. The same stimulation protocol was used in 136 patients with coronary artery disease. The incidence of RVR greater than or equal to 3 (three or more ventricular depolarizations in response to PES) was related to the time interval to prior acute myocardial infarction and to the degree but not to the extent of left ventricular wall motion abnormalities. The relationship between spontaneous ventricular arrhythmias and those induced by PES was compared in 267 patients. Although there was some correlation between absence or presence of both types of arrhythmias, the presence of RVR greater than or equal to 3 did not predict precisely the presence of high grade ventricular arrhythmias during Holter-monitoring. The prognostic significance of RVR greater than or equal to 3 in patients with chronic stable coronary artery disease remains to be determined. However in patients with recent acute myocardial infarction it has been found that subjects at risk of sudden death (SD) can be identified by PES. We feel that until the prognostic significance of RVR is better defined its use as a basis for guiding antiarrhythmic therapy is not warranted.

Arrhythmias, Cardiac↗

Modulation of spinal reflexes by pyramidal tract stimulation in an in vitro brainstem-spinal cord preparation from the hamster.

Electrophysiological evidence is presented showing that the pyramidal tract (PT) of the hamster modulates spinal reflexes in an in vitro brainstem-spinal cord preparation. Three spinal reflexes were studied. Stimulation of a dorsal root (DR) while recording from a ventral root (VR) of the same spinal segment evoked two reflexes: the monosynaptic reflex, and a long latency polysynaptic reflex. Stimulation of a DR while recording from a DR immediately rostral to it elicited a volley of antidromic discharges characteristic of the dorsal root reflex (DRR). The effect of PT stimulation on reflex transmission was tested by stimulating the PT at varying intervals prior to evoking a reflex. The results show that the amplitude of the monosynaptic reflex is progressively inhibited when preceded at shorter delays by a train of PT stimuli. Similarly, PT stimulation also suppresses the long latency reflex. In contrast, the PT facilities the DRR and repeated stimulation of the PT may evoke antidromic discharges recorded from the DRs. These data from the in vitro brainstem-spinal cord preparation indicate that the PT of the hamster exerts both inhibitory and facilitatory effects on reflex transmission in the spinal cord. The present study shows that it is possible to examine the descending control of spinal circuitry using an in vitro brainstem-spinal cord preparation.

Action Potentials↗

Relationships between characteristics of electrical stimulation, muscle pain and blink responses in man.

The present research was undertaken in 11 healthy volunteers with the aim of investigating the relationship between blink response, a feature of the startle reaction, and muscular pain evoked by muscle electrical stimulation (train of stimuli). At a repetition rate of 0.1 Hz, a close relationship was found between the threshold for muscle pain and that for the blink response, without apparent habituation. At the same rate and with stimulation intensity maintained at pain threshold, the subject could voluntarily inhibit the blink response, but not pain. Under the same conditions both pain and blink response were inhibited during a mental task. By increasing the current intensity pain became more intense and the blink response tended to increase in amplitude and to decrease in latency. Similar effects were achieved by increasing the repetition rate with the current intensity maintained at pain threshold. Habituation of the blink response, but not of pain, was found at repetition rates of 1 Hz or more. Present results indicate that nociceptive inputs from muscle have a facilitatory effect on central mechanisms subserving the blink response. It is suggested that the comparative analysis of pain sensation and the blink response may be a useful tool for pain research in man.

Adult↗

Chromatographic and immunochemical characterization of neurotensin in cat adrenal gland and its release during splanchnic nerve stimulation.

A subpopulation of norepinephrine-containing cells in the cat adrenal medulla contain neurotensin (NT) immunoreactive material. Using high performance liquid chromatography (HPLC) and radioimmunoassay with region-specific antisera we have demonstrated that electrical stimulation of the splanchnic nerve releases NT and its metabolites NT(1-8) and NT(1-12) from cat adrenal gland into the circulation. Blood samples from anesthetized cats were simultaneously collected from the adrenolumbar vein and femoral artery over a 10-min period prior to and during splanchnic nerve stimulation. Trains of stimuli (15 Hz/10V) were applied at 30-s intervals over 10 min. Plasma samples were extracted, run on HPLC and column fractions assayed with C- und N-terminal directed antisera. During splanchnic nerve stimulation unchanged. Concomitant with the increase in NT was a two- to threefold increase in the levels of NT(1-8) and NT(1-12). The chromatographic profiles of extracted adrenal glands showed a major peak of immunoreactive material with the same retention time as NT (18.6 +/- 3.0 pmol/g weight wet of tissue) as well as a small peaks on NT(1-8) (0.96 +/- 0.18 pmol/g) and NT(1-12) (2.05 +/- 0.1 pmol/g). HPLC analysis of a tryptic digest of the NT-like material gave 1.0 equivalent of NT(1-8) and NT(9-13). These results are consistent with the presence of NT in adrenal tissue and its release and metabolism during stimulation of the splanchnic nerve.

Adrenal Glands↗

Enhanced performance with brain stimulation: attentional shift or visual cue?

The premotor theory of visual spatial attention proposes that the same brain activity that prepares for saccades to one part of the visual field also facilitates visual processing at that same region of the visual field. Strong support comes from improvements in performance by electrical stimulation of presaccadic areas, including the frontal eye field and superior colliculus (SC). Interpretations of these stimulation experiments are hampered by the possibility that stimulation might be producing an internal visual flash or phosphene that attracts attention as a real flash would. We tested this phosphene hypothesis in the SC by comparing the effect of interchanging real visual stimuli and electrical stimulation. We first presented a veridical visual cue at the time SC stimulation improved performance; if a phosphene improved performance at this time, a real cue should do so in the same manner, but it did not. We then changed the time of SC visual-motor stimulation to when we ordinarily presented the veridical visual cue, and failed to improve performance. Last, we shifted the site of SC stimulation from the visual-motor neurons of the SC intermediate layers to the visual neurons of the superficial layers to determine whether stimulating visual neurons produced a larger improvement in performance, but it did not. Our experiments provide evidence that a phosphene is not responsible for the shift of attention that follows SC stimulation. This added evidence of a direct shift of attention is consistent with a key role of the SC in the premotor theory of attention.

Animals↗

Functional properties of postganglionic sympathetic neurones supplying the submandibular gland in the anaesthetized rat.

Sympathetic neurones supplying the submandibular salivary gland innervate blood vessels, secretory and myoepithelial cells. Here we examined whether these functionally different sympathetic neurones show distinct reflex response patterns. In anaesthetized rats, single unit activity was recorded from postganglionic axons projecting to the gland. Neurones were tested for their responses to stimulation of baroreceptors, cutaneous nociceptors and cold receptors and to gustatory stimuli applied to the tongue. Respiratory modulation was also analysed. Only a few postganglionic neurones identified electrically (5-10%) were spontaneously active. They were excited by noxious and cold stimuli, inhibited by baroreceptor stimulation and exhibited respiratory modulation. None of the units responded to gustatory stimuli. Thus, in anaesthetized rats spontaneously active sympathetic neurones supplying the submandibular gland behave like vasoconstrictor neurones. Sympathetic neurones with other functions are probably silent.

Anesthesia, General↗