Biomedical subjects

Trevor A Day

Publications and source records attributed to Trevor A Day.

12 recordsLinked to original sources

PubMed2026

High-altitude hypoxia alters the visual control of standing balance in lowlanders and Tibetan highlanders.

High-altitude hypoxia affects both visual function and postural control, yet the influence of optic-flow perturbations on standing balance under hypoxic stress remains unclear. Tibetan highlanders (TH) exhibit adaptations to chronic hypoxia, but whether their visually driven postural responses differ from those of lowlanders (LL) has not been investigated. We examined how high-altitude exposure and acclimatization influence static and dynamic visual contributions to balance by delivering sinusoidal optic-flow perturbations in virtual reality at low altitude (1,400 m) and after incremental ascent to high altitude (4,300 m) in acclimatizing LL (n = 15) and TH (n = 14). Anteroposterior center of pressure (AP CoP) velocity and mean power frequency (MPF) were measured during three visual-field conditions (full-, central-, and peripheral-vision) and two optic-flow velocities (peak 1 m/s and 8 m/s at 0.25 Hz). At high altitude, both groups showed attenuated responses to optic flow compared with 1,400 m, reflected by reduced AP CoP velocity and lower MPF across visual-field conditions, consistent with reduced responsiveness to dynamic visual-motion cues under high altitude hypoxia. In contrast, during eyes-open quiet stance [no virtual reality (VR)], TH but not LL exhibited increased AP CoP velocity and MPF at 4,300 m, and no altitude effect was observed with eyes-closed in either group. This finding indicates that TH adopt a visually dependent postural strategy at altitude, whereas LL show minimal changes in static visual balance control but reduced responsiveness to fast dynamic motion. Together, these findings demonstrate that high-altitude hypoxia disrupts dynamic visual processing for balance control in both groups, while revealing group differences in the use of static visual cues during quiet stance.NEW & NOTEWORTHY This is the first study to investigate how high-altitude hypoxia alters visually driven postural control using virtual reality (VR) optic-flow perturbations. We show that hypoxia attenuates sway responses to optic-flow in both lowlanders and Tibetan highlanders, and that visual weighting differs between these groups. These findings reveal altitude- and population-related changes in sensory weighting during standing balance, advancing sensorimotor understanding of postural control in hypoxia.

Humans↗

PubMed2006

Brainstem PCO2 modulates phrenic responses to specific carotid body hypoxia in an in situ dual perfused rat preparation.

Inputs from central (brainstem) and peripheral (carotid body) respiratory chemoreceptors are coordinated to protect blood gases against potentially deleterious fluctuations. However, the mathematics of the steady-state interaction between chemoreceptors has been difficult to ascertain. Further, how this interaction affects time-dependent phenomena (in which chemoresponses depend upon previous experience) is largely unknown. To determine how central P(CO2) modulates the response to peripheral chemostimulation in the rat, we utilized an in situ arterially perfused, vagotomized, decerebrate preparation, in which central and peripheral chemoreceptors were perfused separately (i.e. dual perfused preparation (DPP)). We carried out two sets of experiments: in Experiment 1, we alternated steady-state brainstem P(CO2) between 25 and 50 Torr in each preparation, and applied specific carotid body hypoxia (60 Torr P(O2) and 40 Torr P(CO2)) under both conditions; in Experiment 2, we applied four 5 min bouts (separated by 5 min) of specific carotid body hypoxia (60 Torr P(O2) and 40 Torr P(CO2)) while holding the brainstem at either 30 Torr or 50 Torr P(CO2). We demonstrate that the level of brainstem P(CO2) modulates (a) the magnitude of the phrenic responses to a single step of specific carotid body hypoxia and (b) the magnitude of time-dependent phenomena. We report that the interaction between chemoreceptors is negative (i.e. hypo-additive), whereby a lower brainstem P(CO2) augments phrenic responses resulting from specific carotid body hypoxia. A negative interaction may underlie the pathophysiology of central sleep apnoea in populations that are chronically hypocapnic.

Animals↗

PubMed2006

A method for tracking rats in a complex and completely dark environment using computerized video analysis.

The automated tracking of rodents in open field environments has become a standard laboratory technique for the investigation of the effects of drugs, novel therapeutic interventions and genetic mutations on behavior. Here, we develop an extension of this technique that permits tracking in full darkness through a complex ('enriched') environment comprising naturalistic structures such as tunnels and hides. To eliminate unwanted light reflections and tape noise, we developed a unique video filter that combines the advantages of differential and non-differential filtering. This filter enabled the tracking of albino rats against a relatively dark background to an accuracy of approximately 97% compared to hand tracking of the same animal, irrespective of whether the rat was inside a hide box or tunnel or out in the open field. The system as a whole can be easily deployed using standard PCs and inexpensive infrared cameras and lights.

Algorithms↗

PubMed2005

Defining stress as a prelude to mapping its neurocircuitry: no help from allostasis.

The way in which researchers conceptualise and thus define stress shapes the way in which they approach the task of mapping the brain's stress control pathways. Unfortunately, much of the research currently being done on stress neurocircuitry is occurring within a poorly developed conceptual framework, a framework that limits the depth of the questions that our studies ask, and even our ability to fully appreciate and make use of the data that they yield. Consequently, any attempt to improve our conceptual framework merits close attention. In that regard it is notable that in recent years it has been argued that the concept of homeostasis should be supplemented by the concepts of allostasis (literally 'stability through change') and allostatic load (in effect, the cost of allostasis). One of the purported benefits of this change has been that it will clarify the concept of stress. A close review of the arguments leads us to conclude that the introduction of the concept of allostasis has largely occurred as a result of misunderstandings and misapprehensions concerning the concept of homeostasis. In terms of understanding how the organism operates, it is not clear that the concepts of 'allostasis' or 'allostatic load' offer us anything that was not already apparent, or at least readily derivable, from an accurate reading of the original concept of homeostasis. Not surprisingly then, these more recently proposed concepts also offer little help in clarifying our understanding of stress. Indeed, rather than clarifying the concept of stress, the primary effort appears to be directed at subsuming the concept of stress within the concept of allostasis, which has the inadvertent effect of collapsing the study of homeostatic responses and stress responses together. This seems to be out of step with the fact that there is now considerable evidence that the brain does indeed possess certain pathways that merit the title of 'stress neurocircuitry'. The attempt to subsume the concept of stress within the concept of allostasis is also counter-productive in that it distracts stress researchers from the important task of developing conceptual frameworks that allow us to tackle fundamental issues such as how the organism differentiates stressful from non-stressful challenges.

Animals↗

PubMed2005

Specific carotid body chemostimulation is sufficient to elicit phrenic poststimulus frequency decline in a novel in situ dual-perfused rat preparation.

Time-dependent ventilatory responses to hypoxic and hypercapnic challenges, such as posthypoxic frequency decline (PHxFD) and posthypercapnic frequency decline (PHcFD), could profoundly affect breathing stability. However, little is known about the mechanisms that mediate these phenomena. To determine the contribution of specific carotid body chemostimuli to PHxFD and PHcFD, we developed a novel in situ arterially perfused, vagotomized, decerebrate rat preparation in which central and peripheral chemoreceptors are perfused separately (i.e., a nonanesthetized in situ dual perfused preparation). We confirmed that 1) the perfusion of central and peripheral chemoreceptor compartments was independent by applying specific carotid body hypoxia and hypercapnia before and after carotid sinus nerve transection, 2) the PCO(2) chemoresponse of the dual perfused preparation was similar to other decerebrate preparations, and 3) the phrenic output was stable enough to allow investigation of time-dependent phenomena. We then applied four 5-min bouts (separated by 5 min) of specific carotid body hypoxia (40 Torr PO(2) and 40 Torr PCO(2)) or hypercapnia (100 Torr PO(2) and 60 Torr PCO(2)) while holding the brain stem PO(2) and PCO(2) constant. We report the novel finding that specific carotid body chemostimuli were sufficient to elicit several phrenic time-dependent phenomena in the rat. Hypoxic challenges elicited PHxFD that increased with bout, leading to progressive augmentation of the phrenic response. Conversely, hypercapnia elicited short-term depression and PHcFD, neither of which was bout dependent. These results, placed in the context of previous findings, suggest multiple physiological mechanisms are responsible for PHxFD and PHcFD, a redundancy that may illustrate that these phenomena have significant adaptive advantages.

Animals↗

PubMed2005

Medial prefrontal cortex control of the paraventricular hypothalamic nucleus response to psychological stress: possible role of the bed nucleus of the stria terminalis.

The medial prefrontal cortex (mPFC) has been strongly implicated in control of the paraventricular nucleus of the hypothalamus (PVN) response to stress. Because of the paucity of direct projections from the mPFC to the PVN, we sought to investigate possible brain regions that might act as a relay between the two during psychological stress. Bilateral ibotenic acid lesions of the rat mPFC enhanced the number of Fos-immunoreactive cells seen in the PVN after exposure to the psychological stressor, air puff. Altered neuronal recruitment was seen in only one of the candidate relay populations examined, the ventral bed nucleus of the stria terminalis (vBNST). Furthermore, bilateral ibotenic acid lesions of the BNST caused a significant attenuation of the PVN response to air puff. To better characterize the structural relationships between the mPFC and PVN, retrograde tracing studies were conducted examining Fos expression in cells retrogradely labeled with cholera toxin b subunit (CTb) from the PVN and the BNST. Results obtained were consistent with an important role for both the mPFC and BNST in the mpPVN CRF cell response to air puff. We suggest a set of connections whereby a direct PVN projection from the ipsilateral vBNST is involved in the mpPVN response to air puff and this may, in turn, be modulated by an indirect projection from the mPFC to the BNST.

Animals↗

PubMed2004

Role of catecholaminergic inputs to the medial prefrontal cortex in local and subcortical expression of Fos after psychological stress.

A wide variety of stressors elicit Fos expression in the medial prefrontal cortex (mPFC). No direct attempts, however, have been made to determine the role of the inputs that drive this response. We examined the effects of lesions of mPFC catecholamine terminals on local expression of Fos after exposure to air puff, a stimulus that in the rat acts as an acute psychological stressor. We also examined the effects of these lesions on Fos expression in a variety of subcortical neuronal populations implicated in the control of adrenocortical activation, one classic hallmark of the stress response. Lesions of the mPFC that were restricted to dopaminergic terminals significantly reduced numbers of Fos-immunoreactive (Fos-IR) cells seen in the mPFC after air puff, but had no significant effect on stress-induced Fos expression in the subcortical structures examined. Lesions of the mPFC that affected both dopaminergic and noradrenergic terminals also reduced numbers of Fos-IR cells observed in the mPFC after air puff. Additionally, these lesions resulted in a significant reduction in stress-induced Fos-IR in the ventral bed nucleus of the stria terminalis. These results demonstrate a role for catecholaminergic inputs to the mPFC, in the generation of both local and subcortical responses to psychological stress.

Animals↗

PubMed2004

Hypothalamic paraventricular nucleus neurons regulate medullary catecholamine cell responses to restraint stress.

Both physical and psychological stressors recruit catecholamine cells (CA) located in the ventrolateral medulla (VLM) and the nucleus of the solitary tract (NTS). In the case of physical stressors, this effect is initiated by signals that first access the central nervous system at or below the level of the medulla. For psychological stressors, however, CA cell recruitment depends on higher structures within the neuraxis. Indeed, we have recently provided evidence of a pivotal role for the medial amygdala (MeA) in this regard, although such a role must involve a relay, as MeA neurons do not project directly to the medulla. However, some of the MeA neurons that respond to psychological stress have been found to project to the hypothalamic paraventricular nucleus (PVN), a structure that provides significant input to the medulla. To determine whether the PVN might regulate medullary CA cell responses to psychological stress, animals were prepared with unilateral injections of the neurotoxin ibotenic acid into the PVN (Experiment 1), or with unilateral injections of the retrograde tracer wheat germ agglutinin-gold (WGA-Au) into the CA cell columns of the VLM or NTS (Experiment 2). Seven days later, animals were subjected to a psychological stressor (restraint; 15 minutes), and their brains were subsequently processed for Fos plus appropriate cytoplasmic markers (Experiment 1), or Fos plus WGA-Au (Experiment 2). PVN lesions significantly suppressed the stress-related induction of Fos in both VLM and NTS CA cells, whereas tracer deposits in the VLM or NTS retrogradely labeled substantial numbers of PVN cells that were also Fos-positive after stress. Considered in concert with previous results, these data suggest that the activation of medullary CA cells in response to psychological stress may involve a critical input from the PVN.

Animals↗

PubMed2004

Thalamic paraventricular nucleus lesions facilitate central amygdala neuronal responses to acute psychological stress.

The thalamic paraventricular nucleus (PVT) is activated by stress and projects to forebrain structures directly implicated in processing stress-related information. Accordingly, it seems likely the PVT plays an important role in modulating stress responses. We examined effects of excitotoxic PVT lesions on forebrain Fos expression patterns normally elicited by an acute psychological stressor. PVT lesions significantly increased stress-induced Fos in a key stress-processing region, the central amygdala.

Air↗

PubMed2003

Evidence that the bed nucleus of the stria terminalis contributes to the modulation of hypophysiotropic corticotropin-releasing factor cell responses to systemic interleukin-1beta.

Systemic infection activates the hypothalamic-pituitary-adrenal (HPA) axis, and brainstem catecholamine cells have been shown to contribute to this response. However, recent work also suggests an important role for the central amygdala (CeA). Because direct connections between the CeA and the hypothalamic apex of the HPA axis are minimal, the present study investigated whether the bed nucleus of the stria terminalis (BNST) might act as a relay between them. This was done by using an animal model of acute systemic infection involving intravascular delivery of the proinflammatory cytokine interleukin-1beta (IL-1beta, 1 microg/kg). Unilateral ibotenic acid lesions encompassing the ventral BNST significantly reduced both IL-1beta-induced increases in Fos immunoreactivity in corticotropin-releasing factor (CRF) cells of the hypothalamic paraventricular nucleus (PVN) and corresponding increases in adrenocorticotropic hormone (ACTH) secretion. Similar lesions had no effect on CRF cell responses to physical restraint, suggesting that the effects of BNST lesions were not due to a nonspecific effect on stress responses. In further studies, we examined the functional connections between PVN, BNST, and CeA by combining retrograde tracing with mapping of IL-1beta-induced increases in Fos in BNST and CeA cells. In the case of the BNST, these studies showed that systemic IL-1beta administration recruits ventral BNST cells that project directly to the PVN. In the case of the CeA, the results obtained were consistent with an arrangement whereby lateral CeA cells recruited by systemic IL-1beta could regulate the activity of medial CeA cells projecting directly to the BNST. In conclusion, the present findings are consistent with the hypothesis that the BNST acts as a relay between the CeA and PVN, thereby contributing to CeA modulation of hypophysiotropic CRF cell responses to systemic administration of IL-1beta.

Adrenocorticotropic Hormone↗

PubMed2003

Catecholamine and oxytocin cells respond to hypovolaemia as well as hypotension.

Medullary catecholamine and hypothalamic neurosecretory oxytocin cells are activated by hypotension, but previous studies have provided uncertain outcomes concerning their ability to respond to a purely hypovolaemic stimulus. In the present study, injections of PEG/water and pentolinium were used to elicit non-hypotensive, isosmotic hypovolaemia and isovolaemic, isosmotic hypotension, respectively, in conscious rats. Animals were sacrificed 2 h after treatment. Immunolabelling for Fos, tyrosine hydroxylase and oxytocin established that these two stimuli activate almost identical populations of catecholamine neurons in the ventrolateral and dorsomedial medulla, and very similar populations of oxytocin cells in the supraoptic and paraventricular nuclei of the hypothalamus.

Animals↗

PubMed2002

Systemic administration of interleukin-1beta activates select populations of central amygdala afferents.

The central nucleus of the amygdala (CeA) is activated robustly by an immune challenge such as the systemic administration of the proinflammatory cytokine interleukin-1beta (IL-1beta). Because IL-1beta is not believed to cross the blood-brain barrier in any significant amount, it is likely that IL-1beta elicits CeA cell recruitment by means of activation of afferents to the CeA. However, although many studies have investigated the origins of afferent inputs to the CeA, we do not know which of these also respond to IL-1beta. Therefore, to identify candidate neurons responsible for the recruitment of CeA cells by an immune challenge, we iontophoretically deposited a retrograde tracer, cholera toxin b-subunit (CTb), into the CeA of rats 7 days before systemic delivery of IL-1beta (1 microg/kg, i.a.). By using combined immunohistochemistry, we then quantified the number of Fos-positive CTb cells in six major regions known to innervate the CeA. These included the medial prefrontal cortex, paraventricular thalamus (PVT), ventral tegmental area, parabrachial nucleus (PB), nucleus tractus solitarius, and ventrolateral medulla. Our results show that after deposit of CTb into the CeA, the majority of double-labeled cells were located in the PB and the PVT, suggesting that CeA cell activation by systemic IL-1beta is likely to arise predominantly from cell bodies located in these regions. These findings may have significant implications in determining the central pathways involved in generating acute central responses to a systemic immune challenge.

Afferent Pathways↗