Viscerosensory input drives angiotensin II type 1A receptor-expressing neurons in the solitary tract nucleus.

Homeostatic regulation of visceral organ function requires integrated processing of neural and neurohormonal sensory signals. The nucleus of the solitary tract (NTS) is the primary sensory nucleus for cranial visceral sensory afferents. Angiotensin II (ANG II) is known to modulate peripheral visceral reflexes, in part, by activating ANG II type 1A receptors (AT1AR) in the NTS. AT1AR-expressing NTS neurons occur throughout the NTS with a defined subnuclear distribution, and most of these neurons are depolarized by ANG II. In this study we determined whether AT1AR-expressing NTS neurons receive direct visceral sensory input, and whether this input is modulated by ANG II. Using AT1AR-GFP mice to make targeted whole cell recordings from AT1AR-expressing NTS neurons, we demonstrate that two-thirds (37 of 56) of AT1AR-expressing neurons receive direct excitatory, visceral sensory input. In half of the neurons tested (4 of 8) the excitatory visceral sensory input was significantly reduced by application of the transient receptor potential vallinoid type 1 receptor agonist, capsaicin, indicating AT1AR-expressing neurons can receive either C- or A-fiber-mediated input. Application of ANG II to a subset of second-order AT1AR-expressing neurons did not affect spontaneous, evoked, or asynchronous glutamate release from visceral sensory afferents. Thus it is unlikely that AT1AR-expressing viscerosensory neurons terminate on AT1AR-expressing NTS neurons. Our data suggest that ANG II is likely to modulate multiple visceral sensory modalities by altering the excitability of second-order AT1AR-expressing NTS neurons.

Functional and neurochemical characterization of angiotensin type 1A receptor-expressing neurons in the nucleus of the solitary tract of the mouse.

Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (AT1AR) most widely expressed in adult neurons. Activation of the AT1R in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the AT1R occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the AT1AR-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the AT1AR promoter drives expression of green fluorescent protein (GFP). Approximately one-third of AT1AR-expressing neurons express the catecholamine-synthetic enzyme tyrosine hydroxylase (TH), and a subpopulation of these stained for the transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising approximately two-thirds of the AT1AR-expressing NTS neurons, showed Phox2b immunoreactivity alone. A fourth group in the ventral subnucleus expressed neither TH nor Phox2b. In whole cell recordings from slices in vitro, AT1AR-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both AT1AR-GFP neurons and TH-GFP neurons showed similar AT1AR-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of AT1AR-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing.

Dynamic confidence during simulated clinical tasks.

OBJECTIVE: Doctors' confidence in their actions is important for clinical performance. While static confidence has been widely studied, no study has examined how confidence changes dynamically during clinical tasks. METHOD: The confidence of novice (n = 10) and experienced (n = 10) trainee anaesthetists was measured during two simulated anaesthetic crises, bradycardia (easy task) and failure to ventilate (difficult task). RESULTS: As expected, confidence was high in the novice and experienced groups in the easy task. What was surprising, however, was that confidence during the difficult task decreased for both groups, despite appropriate performance. CONCLUSIONS: Given that confidence affects performance, it is alarming that doctors who may be acting unsupervised should lose dynamic confidence so quickly. Training is needed to ensure that confidence does not decrease inappropriately during a correctly performed procedure. Whether time on task interacts with incorrect performance to produce further deficits in confidence should now be investigated.

Restraint stress : differential cardiovascular responses in Wistar-Kyoto and spontaneously hypertensive rats.

With the use of a restraint stress paradigm, both normotensive Wistar-Kyoto (WKY ) rats and spontaneously hypertensive rats (SHR) underwent acute (1-hour restraint in a Perspex tube), chronic (1-hour restraint for 10 consecutive days), or no-restraint (control) stress. Rats experiencing chronic restraint were previously implanted with telemetric probes to measure heart rate and blood pressure. Basal (prestress session) cardiovascular variables did not change during the course of the study (SHR: mean arterial pressure 129+/-1 mm Hg, heart rate 288+/-4 bpm; WKY rats: mean arterial pressure 103+/-1 mm Hg, heart rate 285+/-3 bpm). Restraint caused tachycardia and pressor responses in the WKY rats and SHR, but these effects were greater in the hypertensive strain. The duration of restraint-induced tachycardia did not change in the WKY rats between acute and chronic stress; however, a graded reduction in the duration of restraint-induced tachycardia occurred in the SHR, decreasing to WKY rat levels by day 7 of the 10-day regimen. These data indicate that although the WKY rats can effectively "cope" within a single period of restraint, the coping mechanism is apparently impaired in the SHR compared with the WKY rats. A reduced capacity to cope with processive stressors may thus have an affect on cardiovascular regulation and represent an additional risk factor in hypertension.

Characterisation of vasopressin V(1A), angiotensin AT(1) and AT(2) receptor distribution and density in normotensive and hypertensive rat brain stem and kidney: effects of restraint stress.

In the present study, we have examined neurochemical correlates that may be involved in the differential cardiovascular responses observed in normotensive and hypertensive rats during stress. Using a restraint stress paradigm, both normotensive Wistar Kyoto (WKY) and Spontaneously Hypertensive rats (SHR) underwent acute (1 h restraint in a perspex tube), chronic (1 h restraint for ten consecutive days) or no restraint (control) stress. Following cessation of restraint, rats were processed by incubating sections of brain stem and kidney with [125I]-HO-LVA (0.03 nM) or [125I]Sar(1)Ile(8)-AngiotensinII (0.5 nM), in the presence of PD123319 (10 microM) or losartan (10 microM), to determine the distribution and density of vasopressin V(1A), angiotensin AT(1) and AT(2) receptors, respectively. Analysis of autoradiograms indicated changes in the density of radioligand binding in acutely and chronically-stressed rats, as compared to controls. For example, V(1A) binding in the medial nucleus tractus solitarius (SolM) decreased in the WKY but increased in the SHR. AT(1) binding in SolM did not significantly change in the WKY but decreased in the SHR with repeated restraint. In kidney slices, AT(1) binding decreased with stress in the WKY (-17%) but increased in SHR (+10-15%). AT(2) binding in the kidney showed a pattern similar to that of AT(1) binding in SHR, but not WKY. Graded increases in V(1A) binding were measured in kidney medulla and cortex of both strains (+50-60% with chronic restraint). These results suggest that physiological adaptation to restraint is associated with specific changes in V(1A), AT(1) and AT(2) receptor density within brain nuclei and kidney.

Exploring the effects of icon characteristics on user performance: the role of icon concreteness, complexity, and distinctiveness.

Because icons, signs, and symbols are now widely used to communicate information, it is essential for system designers to know what makes them easy to use and interpret. The authors report a series of studies that examine characteristics considered central to icon usability. After quantifying the properties of icon concreteness, complexity, and discriminability, the authors assessed each property's effects on user performance when user experience, task demands, and presentation context were systematically varied. Findings indicated that the effects of icon concreteness were primarily associated with the initial grasp of meaning, whereas complexity effects were found to persist longer and to be associated with search efficacy. The effects of icon distinctiveness were complex, but distinctiveness was enhanced by using both semantic and visual contrasts. The implications of these findings for interface design are discussed.

Medial prefrontal cortical integration of psychological stress in rats.

The present study aimed to determine whether the medial prefrontal cortex (mPFC) (prelimbic and infralimbic regions) is implicated in the integration of a stress response. Sprague-Dawely rats were implanted with telemetry probes and guide cannulae so that either muscimol or vehicle could be administered locally within the mPFC or dorsomedial hypothalamus (DMH). The heart rate and blood pressure of rats was continuously recorded as either muscimol or vehicle was administered centrally and rats were either exposed to restraint stress or left alone in their home cages. After the stress challenge, or equivalent period, rats that had received intra-mPFC injections were processed for immunohistochemical detection of Fos throughout the neuraxis. Bilateral microinjection of muscimol into the mPFC had no effect upon either baseline cardiovascular parameters or restraint stress-induced tachycardia or pressor responses whereas, in the DMH, pretreatment with muscimol attenuated the cardiovascular stress response. Analysis of Fos expression throughout the CNS of nonstressed rats showed no effect of muscimol injections into the mPFC on baseline expression in the nuclei examined. In contrast, rats that had received muscimol injections into their mPFC and were subsequently restrained exhibited an increase in the number of Fos-positive cells in the DMH, medial amygdala, and medial nucleus tractus solitarius as compared to vehicle-injected rats that experienced restraint stress. These results indicate that, during acute psychological stress, the mPFC does not modulate the cardiovascular system in rats but does inhibit specific subcortical nuclei to exert control over aspects of an integrated response to a stressor.

Measuring symbol and icon characteristics: norms for concreteness, complexity, meaningfulness, familiarity, and semantic distance for 239 symbols.

This paper provides rating norms for a set of symbols and icons selected from a wide variety of sources. These ratings enable the effects of symbol characteristics on user performance to be systematically investigated. The symbol characteristics that have been quantified are considered to be of central relevance to symbol usability research and include concreteness, complexity, meaningfulness, familiarity, and semantic distance. The interrelationships between each of these dimensions is examined and the importance of using normative ratings for experimental research is discussed.

Increased blood pressure responses in neuropeptide Y transgenic rats.

Considering the coexistence of neuropeptide Y (NPY) and norepinephrine in perivascular sympathetic nerves and the known vasoconstrictor cooperation of NPY with norepinephrine, we investigated the involvement of NPY in long-term control of cardiovascular functions using NPY transgenic (NPY-tg) rats. These rats were developed by injection of the rat (Sprague-Dawley) pronuclei with a 14.5-kb clone of the rat structural NPY gene. When compared with nontransgenic littermates, NPY concentrations were significantly increased in a number of cardiovascular tissues of NPY-tg hemizygotes. Direct basal mean arterial pressure and heart rate were not changed, but calculated total vascular resistance was significantly increased in NPY-tg subjects. Arterial pressure increases, in response to norepinephrine injection, were greater in the NPY-tg rats. Also, the hypotension and bradycardia in response to hemorrhage were significantly reduced in NPY-tg subjects. These results indicate that NPY, when expressed in increased amounts, potentiates the pressor effects of norepinephrine and contributes to maintaining blood pressure during hemorrhage, but it does not alter resting blood pressure. These transgenic rats will facilitate studies of the role of NPY signaling in cardiovascular regulation, particularly regarding its functional cooperation with norepinephrine.