Reaction-time measurement and real-time data acquisition for neuroscientific experiments in virtual environments.

This paper describes an approach to neuroscientific reaction-time experiments and resulting methods for data processing under real-time constraints in virtual environments (VE). Immersive VEs produce huge amounts of data, which has to be processed in real-time to meet the interactivity requirement of VE. Furthermore, data is needed often with a timing resolution and even more crucial with an accuracy in the range of milliseconds.

NeuroVRAC--a comprehensive approach to virtual reality-based neurological assessment and treatment systems.

We describe a comprehensive software-oriented approach to virtual reality-based neuroscientific systems in order to establish an easy to use framework for neuroscientific assessment and treatment. We have defined a process model and implemented the NeuroVRAC authoring tool for design and execution of experiments in virtual environments. Our system enables the modeling of virtual world objects and the definition of events, which are used to control the experimental process.

Serotoninergic and suprachiasmatic nucleus involvement in the corticotropic response to systemic endotoxin challenge in rats.

We have investigated whether the serotonin system participates in the mechanisms underlying the corticotropic response in experimentally infected rats. Intra-arterial injection of lipopolysaccharide (LPS; 25 microg/kg b.w.

Effects of acute tilt from orthostatic to head-down antiorthostatic restraint and of sustained restraint on the intra-cerebroventricular pressure in rats.

The tail-cast suspension rat model was developed to explore in ground laboratories the physiological effects of some of the stresses prevailing during space flight including and among them those of the headwards body fluid shifts. We recently showed in rats that an acute head-down tilt (45 degrees) from tail-cast orthostatic (OR) to antiorthostatic restraint (AOR) induced within 30 min and for 2 to 4 h an acute stress-like surge in plasma ACTH and corticosterone levels. Considering the proximity of the CRF producing neurons with the 3rd ventricle, we decided to explore the acute and longer-term effects of the OR/AOR tilt on the intra-cerebroventricular pressure (Picv) measured with an indwelling sensor-transmitter catheter stereotaxically implanted in the 3rd ventricle.

Involvement of central histamine in the early phase of ACTH and corticosterone responses to endotoxin in rats.

The involvement of histaminergic transmission in the rapid and sustained plasma ACTH and corticosterone (CORT) responses induced in conscious rats by intra-arterial infusions of 25 micrograms.kg-1 Escherichia coli lipopolysaccharide (LPS) was investigated. LPS challenge produced a rapid and transient increase (+ 62%) in the amount of histamine (HA) in the median eminence 15 min after LPS administration, which contrasted with constant concentrations of plasma HA throughout the entire study (up to 480 min).

Different responses of plasma ACTH and corticosterone and of plasma interleukin-1 beta to single and recurrent endotoxin challenges.

In a parallel study in 10 individual rats, three time series of plasma concentrations of ACTH, corticosterone (CORT), and interleukin-1 beta (IL-1 beta) were measured before (time 0) and at intervals between 15 and 480 min following intra-arterial (i.a.) infusions of 25 microgram/kg lipopolysaccharide (LPS).

Chronic orthostatic and antiorthostatic restraint induce neuroendocrine, immune and neurophysiologial disorders in rats.

The tail-cast suspension rat model has been developed in ground laboratories interested in space physiology for extensive study of mechanisms causing the pathophysiological syndrome associated with space flights. We used individually-caged male rats to explore the effects of acute and chronic (7d) orthostatic restraint (OR) and head-down anti-orthostatic restraint (AOR) on a series of physiological variables. The acute restraint study showed that (1) the installation of the OR device induced an acute reaction for 2 days, with a substantial rise in ACTH (x2) and CORT (x6), and that (2) the head-down tilt from OR to AOR induced (i) within 10 min and lasting 60 min a 2-fold rise in the intra-cerebro-ventricular pressure (Picv) monitored with an icv telemetric recording system, which receded to normal between 60 and 120 min; and (ii) within 30 min a short-lived 4-fold rise in plasma ACTH and CORT levels.

Early hypothalamic activation of combined Fos and CRH41 immunoreactivity and of CRH41 release in push-pull cannulated rats after systemic endotoxin challenge.

We previously showed that intra-arterial endotoxin infusion (lipopolysaccharide [LPS]: 25 micrograms.kg-1) induced an early (15 min) and sustained (480 min) rise in plasma ACTH associated with delayed (60-120 min) increases in plasma concentrations of TNF alpha, IL-6, and IL-1 beta. In the present study, we followed the post-LPS time-course of immunocytochemical expression of Fos-like activity in CRH41 neurons whose immunolabeling was enhanced by icv colchicine pretreatment 48 h before the LPS, and CRH41 release in the push-pull cannulated median eminence of free-moving rats, in parallel with the ACTH response.

Deletion of the ventral noradrenergic bundle obliterates the early ACTH response after systemic LPS, independently from the plasma IL-1β surge.

We have recently shown that total lesion of the ventral noradrenergic bundle (VNAB-X), enhanced the short-lived (<120 min) triggering effect of intra-arterially (i.a.) given IL-1β on plasma ACTH levels.

Removal of adrenal steroids from the medium reverses the stimulating effect of catecholamines on corticotropin-releasing hormone neurons in organotypic cultures.

An organotypic culture system of anterior hypothalamic slices was developed for studying the secretory responses of corticotropin-releasing hormone (CRH) neurons to corticosteroid-catecholamine interactions. The standard culture medium included 5% horse serum containing 50 micrograms/l cortisol. In 1- to 3-day cultures, the tissue viability was demonstrated by the presence of arginine vasopressin immunolabeled perikarya and axons in the paraventricular nucleus and by sustained tissue concentrations of CRH (around 50 pg/mg protein).

[The corticotropic axis response after subcutaneous endotoxin injection is not associated with the increase of plasma interleukin-1 beta].

When injected through an intra-arterial (i. a.) cannula, LPS induced a rapid (15-30 min) and long-lasting (> 300 min) increase in plasma ACTH and corticosterone (CORT) levels.

Short-term but not long-term adrenalectomy modulates amplitude and frequency of the CRH41 episodic release in push-pull cannulated median eminence of free-moving rats.

CRH 41 release in push-pull cannulated median eminence (ME) was measured in unanesthetized male rats, 3 and 7 days after adrenalectomy (ADX) and in sham-lesioned controls. Perfusion started at 13.30 h and perfusate samples were collected at 5 min intervals for 3 h to estimate the mean release rate of CRH41.

Chronic restraint enhances interleukin-1-beta release in the basal state and after an endotoxin challenge, independently of adrenocorticotropin and corticosterone release.

To explore the interactions between the hypothalamic-pituitary-adrenocortical axis and the immune system under stress conditions, we used an experimental rat model for chronic tail-restraint devised earlier for ground studies in space physiology. The system was used in two positions: (1) the orthostatic restraint position (OR) and (2) the antiorthostatic position (AOR) after the rat hind limbs had been raised by a head-down tilt. After 7 days of either restraint, sequential blood samples were taken via an indwelling aortic cannula, before and at various time intervals between 15 and 300 min after an intravascular infusion of 25 micrograms/kg lipopolysaccharide (LPS).

Temporal cascade of plasma level surges in ACTH, corticosterone, and cytokines in endotoxin-challenged rats.

The present study was designed to investigate the coupling mechanisms linking the immune and the neuroendocrine corticotropic systems in an integrated defense response triggered by an infectious aggression. The experimental paradigm used consisted of the exploration in individual conscious rats of the temporal pattern of increased plasma concentrations of the two stress hormones, adrenocorticotropic hormone (ACTH) and corticosterone (Cort), and of three cytokines known as ACTH stimulators, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6, after intra-arterial infusions of lipopolysaccharide (LPS) given at three doses, 5 micrograms/kg (LPS-5), 25 micrograms/kg (LPS-25), and 1 mg/kg (LPS-1,000). Blood samples were taken 30 min and immediately before LPS injection (t0) and at 15, 30, 60, 120, 300, and 480 min post-LPS.

A subpopulation of corticotropin-releasing hormone neurosecretory cells in the paraventricular nucleus of the hypothalamus also contain NADPH-diaphorase.

The coexistence of ND with CRH 41 was explored in the parvicellular neurons of the PVN, using dual histochemical and radioimmunocytochemical labelling with the light microscope, in rats treated with colchicine. Even though the ND staining was scarce, a clear colocalization was evidenced in the parvicellular part of the PVN. Under these conditions, the ratio of neurons expressing both markers, ND and CRH, amounted about 15% of the CRH-containing neuron population.

Evidence for an age-dependent decrease in the immunoreactive prolactin-containing terminals of the median eminence of male rats.

Labelling patterns of immunoreactive prolactin (IR-PRL)-containing and tyrosine hydroxylase (TH)-containing nerve terminals of the median eminence (ME) were compared in young adult (aged 3 months) and old (aged 24 months) male Wistar rats. In the young rats, IR-PRL- and TH-immunostained fibres extended throughout the external most layer of the ME. In the old rats, a significant decrease in the intensity of labelling of IR-PRL terminals was observed in this layer, with a slight reduction in the extent of labelling.

Complex catecholaminergic modulation of the stimulatory effect of interleukin-1 beta on the corticotropic axis.

We recently showed that bilateral neurotoxic microlesions (6-OH-DA) of the ventral noradrenergic ascending bundle (VNAB-X) at stereotaxic coordinates that blocked corticotropic stress responses did not affect the ACTH surge after bilateral intra-paraventricular (i.PVN) injections of interleukin-1 beta (IL-1 beta), and that lesioning at these stereotaxic coordinates obliterated the dorsal axonal populations of the VNAB (dVNAB-X), but spared the bundle's most ventral axons (vVNAB). The present study compares the effects of IL-1 beta given i.

Effects of discrete lesions in the ventral noradrenergic ascending bundle on the corticotropic stress response depend on the site of the lesion and on the plasma levels of adrenal steroids.

Stereotaxic deletion of selected areas of the ventral noradrenergic ascending bundle (VNAB-X) by discrete bilateral injections of 6-hydroxydopamine (6-OHDA; 4 micrograms in 0.2 microliter saline) was used to explore the role of brain catecholamines (CA) and their interaction with corticosteroid feedback in stress responses of the ACTH-corticosterone (CORT) axis. The stereotaxic coordinates used for 6-OHDA lesions and the optimization of postlesion delays were determined by (a) radioautographic labeling of the VNAB axons after tracer injections into the dorsal A2/C2, or the ventral A1/C1 medullary areas, (b) histofluorescence and immunocytochemical location of interrupted CA pathways versus the postlesional scar, and (c) postlesional noradrenaline and adrenaline concentrations in whole hypothalami and paraventricular nuclei (PVN) punch samples.

[Stress. Neurophysiologic studies].

The hypothalamic-pituitary-adrenocortical (HPA) axis knowingly plays a key role in the physiological response to various stressing situations, owing to its gluconeogenetic function, and also, possibly, to its large range of modulating effects on a series of more specific defense mechanisms including the immune system, the latter effect serving to protect the organism against overactive defense reactions. It has long been accepted that under most aggressive conditions the CNS is an essential part of the mechanism controlling the subsequent acute stimulation of the HPA axis. In this line of research, the HPA axis reacts within a few minutes after a standard ether-stress, with a 6 fold increase over the baseline of CRH41 secretion, and at the periphery with 20-fold and 14-fold increases, respectively, in plasma concentrations of ACTH and corticosterone in unanesthetized free-moving rats.

Circadian variations in the amplitude of corticotropin-releasing hormone 41 (CRH41) episodic release measured in vivo in male rats: correlations with diurnal fluctuations in hypothalamic and median eminence CRH41 contents.

The possible correlation between the circadian and episodic release of corticotropin-releasing hormone 41 (CRH41) in male rats was explored in a comparative study, including the measurement at 0700 hr and 1700 hr of (1) the quantitative parameters of the episodic release pattern of CRH41 into the push-pull-cannulated median eminence (ME); (2) CRH41 content measured by radioimmunoassay in the hypothalamus, and immunocytochemically in the ME; and (3) plasma adrenocorticotropic hormone (ACTH). The data showed that in early evening, the 3.4-fold rise in plasma ACTH coincided with a doubling of CRH41 content in the hypothalamus and in the ME, and of the CRH41 release from the perfused ME.

Inhibitory interactions between alpha 2-adrenergic and opoid but not NPY mechanisms controlling the CRF-ACTH axis in the rat.

Following a series of investigations supporting the concept that the brain stem catecholaminergic (CA) system played a major stimulatory role on both basal and stress-triggered states of the hypothalamic-pituitary-adrenocortical (HPA) axis, across alpha 1 and beta receptors and also via alpha 2 receptors, the present study was designed to gain a deeper insight into the fine mechanism of functional interactions between the alpha 2 receptors mediated CA system and two peptidergic mechanisms, both shown to take part in the stimulatory control of the HPA axis: beta-endorphin and NPY. All experiments were conducted on rats whose noradrenergic bundles, which directly innervate the CRF neurons and are strongly implicated in the ether stress-induced corticotropic response, had been bilaterally obliterated by an intracerebral (i.c.

Microinjection of oxytocin into the dorsal vagal complex decreases pancreatic insulin secretion.

Microinjections of oxytocin and of an oxytocin antagonist into the dorsal vagal complex of the medulla oblongata were performed in order to study the possible role of the oxytocin containing axons that innervate this region in the regulation of pancreatic insulin secretion. No significant effect was produced by the intramedullary injection of the oxytocin vehicle alone or of 0.04 pM oxytocin.

In vivo Infusion of Adrenaline Stimulates Corticotropin-Releasing Hormone-Producing Neurons when given Centrally but not Distally.

Abstract There is evidence that adrenaline stimulates the release of corticotropin-releasing hormone (CRH-41) from hypothalamic neurons. This study was carried out to ascertain the effects of adrenaline on the perikarya and/or distal terminals of these cells. All experiments were performed on unrestrained rats having chronic intracerebroventricular cannulas in the lateral ventricle or intracerebral cannulas in the paraventricular nucleus and, additionally, a push-pull median eminence cannula.

A quantitative study of the pulsatile parameters of CRH-41 secretion in unanesthetized free-moving rats.

Having recently improved the sensitivity of the RIA CRH-41 measurements in perfusates from push-pull cannulas implanted in the rat median eminence, we explored quantitatively the pulsatile parameters of the CRH-41 measured with this technique at 2.5 or 5 min intervals in a series of unanesthetized male rats under basal conditions. The data were analysed by computer using 4 algorithms, i.