Burst Activity Research Articles

Spiral attractors in a reduced mean-field model of neuron-glial interaction.

This paper investigates various bifurcation scenarios of the appearance of bursting activity in the phenomenological mean-field model of neuron-glial interactions. In particular, we show that the homoclinic spiral attractors in this system can be the source of several types of bursting activity with different properties.

Barbaloin Protects Pentylenetetrazol-Induced Cognitive Deficits in Rodents via Modulation of Neurotransmitters and Inhibition of Oxidative-Free-Radicals-Led Inflammation.

Epilepsy is defined by an excessive level of activity in the neurons and coordinated bursts of electrical activity, resulting in the occurrence of seizure episodes. The precise cause of epileptogenesis remains uncertain; nevertheless, the etiology of epilepsy may involve neuroinflammation, oxidative stress, and malfunction of the neurotransmitter system. The goal of this investigation was to assess barbaloin's protective properties with respect to pentylenetetrazol (PTZ)-)-induced cognitive deficits in rats via antioxidative, anti-inflammatory, and neurotransmitter-modulating effects. Wistar rats were subjected to PTZ [40 mg/kg (i.p.)], which induced cognitive decline. Behavior assessment using a kindling score, open-field test (OFT), novel object recognition test (NORT), and assays for superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), malondialdehyde (MDA), acetylcholinesterase (AChE), caspase-3, nitric oxide (NO), interleukins-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, nuclear factor kappa-B (NF-κB), Bcl-2 and Bax, and neurotransmitter levels [GABA, DA, NE, and serotonin (5-HT)] were performed. The treatment of rats with barbaloin resulted in behavior improvement and significant changes in the levels of GSH, SOD, CAT, MDA, AChE, NO, IL-6, IL-1β, TNF-α, NF-κB, caspase-3, Bcl-2, and Bax compared to the PTZ control group. Barbaloin treatment resulted in notable changes in neurotransmitter levels (GABA, NE, 5-HT, DA) compared to the PTZ group. The ongoing study has gathered evidence indicating that the injection of barbaloin has resulted in significant improvements in cognitive performance in rats. This is achieved by inhibiting oxidative stress, enhancing the activity of natural antioxidant enzymes, reducing cytokine levels, and increasing the levels of neurotransmitters in the brain. These results were detected in comparison to a PTZ control and can be attributed to the potent anti-inflammatory and antioxidant capabilities of barbaloin, which could be linked to its neuroprotective properties. Barbaloin may potentially increase cognitive decline and boost neuronal survival by altering the expression of Bax, caspase-3, Bcl-2.

Annual rhythm in immune functions of blood leucocytes in an ophidian, Natrix piscator

Annual variations in animal’s physiological functions are an essential strategy to deal with seasonal challenges which also vary according to the time of year. Information regarding annual adaptations in the immune-competence to cope with seasonal stressors in reptiles is scarce. The present research plan was designed to analyze the presence of circannual immune rhythms in defense responses of the leucocytes in an ophidian, Natrix piscator. Peripheral blood leucocytes were obtained, counted, and superoxide anion production, neutrophil phagocytosis, and nitrite release were tested to assess the innate immune functions. Peripheral blood lymphocytes were separated by centrifugation (utilizing density gradient) and the cell proliferation was measured. The Cosinor rhythmometry disclosed the presence of significant annual rhythms in the number of leucocytes, superoxide anion production, nitric oxide production, and proliferation of stimulated lymphocytes. The authors found that respiratory burst activity and proliferative responses of lymphocytes were crucial immune responses that showed the annual rhythm. It was summarized that the immune function of the N. piscator is a labile attribute that makes the animal competent to cope with the seasonal stressor by adjustment in the potency of response.

Emergence and Criticality in Spatiotemporal Synchronization: The Complementarity Model.

This work concerns the long-term collective excitability properties and the statistical analysis of the critical events displayed by a recently introduced spatiotemporal many-body model, proposed as a new paradigm for Artificial Life. Numerical simulations show that excitable collective structures emerge in the form of dynamic networks, created by bursts of spatiotemporal activity (avalanches) at the edge of a synchronization phase transition. The spatiotemporal dynamics is portraited by a movie and quantified by time varying collective parameters, showing that the dynamic networks undergo a "life cycle," made of self-creation, homeostasis, and self-destruction. The power spectra of the collective parameters show 1/f power law tails. The statistical properties of the avalanches, evaluated in terms of size and duration, show power laws with characteristic exponents in agreement with those values experimentally found in the neural networks literature. The mechanism underlying avalanches is argued in terms of local-to-collective excitability. The connections that link the present work to self-organized criticality, neural networks, and Artificial Life are discussed.

Pyrazoles have a multifaceted anti-inflammatory effect targeting prostaglandin E2, cyclooxygenases and leukocytes’ oxidative burst

Elevated levels of prostaglandin E2 have been implicated in the pathophysiology of various diseases. Anti-inflammatory drugs that act through the inhibition of cyclooxygenase enzymatic activity, thereby leading to the suppression of prostaglandin E2, are often associated with several side effects due to their non-specific inhibition of cyclooxygenase enzymes. Consequently, the targeted suppression of prostaglandin E2 production with innovative molecules and/or mechanisms emerges as a compelling therapeutic strategy for the treatment of inflammatory-related diseases. Therefore, in this study, a systematic analysis of 28 pyrazole derivatives was conducted to explore their potential mechanisms for reducing prostaglandin E2 levels. In this context, the evaluation of these derivatives extended to examining their capacity to reduce prostaglandin E2in vitro in human whole blood, inhibit cyclooxygenase-1 and cyclooxygenase-2 enzymes, modulate cyclooxygenase-2 expression, and suppress oxidative burst in human leukocytes. The results enabled the establishment of significant structure-activity relationships, elucidating key determinants for their activities. In particular, the 4-styryl group on the pyrazole moiety and the presence of chloro substitutions were identified as key determinants. Pyrazole 8 demonstrated the capacity to reduce prostaglandin E2 levels by downregulating cyclooxygenase-2 expression, and pyrazole-1,2,3-triazole 18 emerged as a dual-acting agent, inhibiting human leukocytes' oxidative burst and cyclooxygenase-2 activity. Furthermore, pyrazole 26 demonstrated effective reduction of prostaglandin E2 levels through selective cyclooxygenase-1 inhibition. These results underscore the multifaceted anti-inflammatory potential of pyrazoles, providing new insights into the substitutions and structural frameworks that are beneficial for the studied activity.

Study of Macrophage Activity in Cats with FIP and Naturally FCoV-Shedding Healthy Cats.

Coronavirus frequently infects humans and animals, showing the ability to recombine and cross over to different species. Cats can be considered a model for studying coronavirus infection, in which feline coronavirus (FCoV) represents a major enteric pathogen related to gastroenteric disease. In this animal, the virus can acquire tropism for macrophage cells, leading to a deadly disease called feline infectious peritonitis (FIP). In this study, monocyte-derived macrophages were isolated by CD14-positive selection in venous whole blood from 26 cats with FIP and 32 FCoV-positive healthy cats. Phagocytosis and respiratory burst activities were investigated and compared between the groups. This is the first study comparing macrophage activity in cats affected by FIP and healthy cats positive for FCoV infection. Our results showed that in cats with FIP, the phagocytic and respiratory burst activities were significantly lower. Our results support the possible role of host immunity in Coronaviridae pathogenesis in cats, supporting future research on the immune defense against this systemic disease.

Acclimation to higher temperature and antioxidant supplemented diets improved rainbow trout (Oncorhynchus mykiss) resilience to heatwaves

Coldwater species are challenged with increasing water temperatures and fluctuations over their upper thermal limits. This study evaluated the potential of acclimation to higher temperature and dietary antioxidants capacity to mitigate the adverse effects of heat shocks in rainbow trout. To this end, rainbow trout fingerlings were acclimated at optimal (14 °C) and high (20 °C) temperatures and fed on selenium (5 mg/kg) and polyphenol (2 g/kg) supplemented diets for 60 days and then were exposed to heat shocks by increasing water temperature up to 30 °C. Growth performance, survival rate, haemato-immunological parameters, and expression of HSP70α, HSP70β, HSP90β, and IL-1β genes were measured to evaluate the hypothesises. The rainbow trout acclimated to 20 °C and fed on antioxidants supplemented diets showed a significantly higher aftershock survival rate. Moreover, fish acclimated to higher temperature showed higher red blood cell counts as well as serum total protein and albumin during the acclimation trial and heat shocks phase. Acclimation to higher temperature and feeding on antioxidants remarkably enhanced fish immune and antioxidant capacity in comparison to fish adapted to cold water and fed on the basal diet measured by improved respiratory burst and lysozyme activities and upregulation of IL-1β expression during exposure of fish to heat shocks. Furthermore, fish acclimated to higher temperature, especially those fed on antioxidant supplemented diets, showed lower expression levels of HSPs genes during the heat shock phase, indicating that high heat shocks were less stressful for these fish in comparison to cold water acclimated fish. This finding was also supported by lower cortisol levels during heat shocks in fish acclimated to higher temperature. In conclusion, the results of this study indicated that acclimation to higher temperature and/or fed on diets supplemented by selenium and polyphenol, can help to mitigate the adverse effects of the heat shock in rainbow trout.

Sympathetic toggled paroxysmal atrial fibrillation and recurrent premature atrial contractions in ambulatory patients

BackgroundAutonomic nerve activity is important in the mechanisms of paroxysmal atrial fibrillation (PAF). ObjectiveThe purpose of this study was to test the hypothesis that a single burst of skin sympathetic nerve activity (SKNA) can toggle on and off PAF or premature atrial contraction (PAC) clusters. MethodsSimultaneous recording of SKNA and electrocardiogram (neuECG) recording was performed over 7 days in patients with PAF. ResultsIn study 1, 8 patients (7 men and 1 woman; age 62 ± 8 years) had 124 episodes of PAF. An SKNA burst toggled both on and off PAF in 8 episodes (6.5%) (type 1), toggled on but not off in 12 episodes (9.7%) (type 2), and toggled on a PAC cluster followed by PAF in 4 episodes (3.2%) (type 3). The duration of these PAF episodes was <10 minutes. The remaining 100 episodes (80.6%) were associated with active SKNA bursts throughout PAF (type 4) and lasted longer than type 1 (P = .0185) and type 2 (P = .0027) PAF. There were 47 PAC clusters. Among them, 24 (51.1%) were toggled on and off, and 23 (48.9%) were toggled on but not off by an SKNA burst. In study 2, 17 patients (9 men and 8 women; age 58 ± 12 years) had <10 minutes of PAF (4, 8, 0, and 31 of types 1, 2, 3, and 4, respectively). There were significant circadian variations of all types of PAF. ConclusionA single SKNA burst can toggle short-duration PAF and PAC cluster episodes on and off. The absence of continued SKNA after the onset might have affected the maintenance of these arrhythmias.

Immunomodulatory Effects of Mallotus japonicus Extract on Innate Immune Responses in HeteroTilapia buttikoferi Infected with Aeromonas hydrophila

The intensive use of antibiotics in modern aquaculture has been linked to the emergence of multidrug resistance in human health. Despite continuous caution against such use by farmers, antibiotics serve as the primary means of disease control in aquaculture. In this study, we explore the potential of medicinal plant extracts as immunomodulant in enhancing the innate immune defense of a fish host, HeteroTilapia buttikoferi, infected with the prevalent fish pathogenic bacteria Aeromonas hydrophila. Our previous research reveals the bactericidal activity of the medicinal plant, Mallotus japonicus, against the pathogen, but its effectiveness as a prophylactic in enhancing host immune defense has not yet been investigated. Therefore, the objective of this study is to address this knowledge gap.By our findings, it was uncovered that the supplementation of the diethyl ether extract of the plant’s bark as an additive in the fish diet significantly improved the innate immune defense by upregulating the total levels of lysozyme, serum bactericidal activity, globulin and albumin levels, total protein, phagocytosis, respiratory burst activity and overall survival. A dose-dependent increase in immunological parameters was recorded, and this was in sharp contrast to the control group.These findings suggest that M. japonicus has the potential of use to enhance the innate immune defense of H. buttikoferi against the pervasive fish pathogenic bacteria, Aeromonas hydrophila. The improvements in immune parameters indicate the ability of M. japonicus extract to strengthen the hosts to combat bacterial infections.

Contrasting sedimentary and long-lasting geochemical imprints of seismic shaking in a small, groundwater-fed lake basin (Klopeiner See, Eastern European Alps)

In slowly deforming tectonic settings (e.g., European Alps), large earthquakes occur too infrequently to be adequately represented in instrumental and historical records. This leads to uncertainties and inaccuracies of seismic hazard estimations. To extend the seismic record, lacustrine paleoseismologists usually resort to the sedimentary archive of large lakes where earthquakes can be recorded as mass-transport deposits and associated turbidites. The imprint of seismic shaking is generally more subtle and poorly understood in small lakes (&lt;2 km2) with small catchments and therefore such sediment-starved basins are often neglected for paleoseismology. However, these basins might harbour additional information about past earthquakes, thus constituting a valuable supplement to other paleoseismic data. Here, we present the 18 ka-long paleoseismic record of Klopeiner See, a small and rather shallow groundwater-fed lake in the Eastern European Alps. Reflection seismic profiles and sediment cores reveal that several large earthquakes led to extensive mass-wasting in early Late-Glacial times when sedimentation rates were very high (~10 mm/yr). In the Early and Middle Holocene, low sedimentation rates (~0.2-0.5 mm/yr) may have decreased the lake´s sensitivity for recording seismic shaking and no imprints were found for paleo-earthquakes inferred from other records in the region. A short succession of turbidites at ca. 3160 cal BP suggests a burst of strong paleoseismic activity. This may have caused permanent modifications of inflowing ground water systems, archived as a permanent shift in the geochemical signal of the sediment. Such a period of enhanced paleoseismic activity was also inferred from the nearby Lake Wörthersee, but it remains unclear whether these represent the same earthquakes or migrating paleoseismicity. This study highlights the unexpected potential and peculiarities of paleoseismology on small ground-water fed lakes.

10-Day Theta Burst Stimulation Intervention Facilitates the Clinical Rehabilitation of Patients After an Isolated Limb Fracture: A Longitudinal SHAM-Controlled Pilot Study.

We investigated if theta burst stimulation could enhance recovery by reducing key symptoms when implemented acutely postfracture in participants with an isolated upper limb fracture. This was a pilot study with a randomized matched pair, sham-controlled, participant-blind design of a 10-day prolonged continuous theta burst stimulation protocol. Two main groups were included: I) participants with isolated upper limb fracture receiving active theta burst stimulation and II) patients with isolated upper limb fracture receiving SHAM/placebo. Another group (III) of healthy individuals was the reference group. Disability and pain intensity were collected through questionnaires (disabilities of the Arm, Shoulder, and Hand as well as numerical rating scale (NRA)) at three time points (baseline; 72 hrs after intervention, 3 mos after injury). Group III completed the baseline assessment. Seventy-nine participants were enrolled. Individuals in the ACTIVE and SHAM groups had similar baseline measures. For disability, the interaction between intervention and time approached significance (F = 2.33; P = 0.11), whereas it was significant for pain (F = 3.42; P = 0.04). At 3 mos after injury, the ACTIVE group reported reduced disability (F = 4.71; P = 0.04) and pain (F = 5.84; P = 0.02) at 3 mos after injury compared to the SHAM group, with clinical measures from ACTIVE group being like controls. In isolated upper limb fracture patients, a 10-day theta burst stimulation intervention implemented acutely posttrauma had beneficial effects on symptoms of functional recovery and pain at 3 mos after trauma.

A longitudinal study combining the Double Diamond framework and Behavior Change Wheel to co-create a sedentary behavior intervention in police control rooms.

Police work can be sedentary and stressful, negatively impacting health and wellbeing. In a novel co-creation approach, we used the Behavior Change Wheel (BCW) and Double Diamond (DD) design framework to guide the collaborative design and development of a sedentary behavior intervention in the control rooms of two British police forces. Multiple stakeholders participated in four phases of research. In Phase 1, a literature review, focus groups (n=20) and interviews (n=10) were conducted to 'discover' the relationship between physical activity and wellbeing in the police. In Phase 2, a steering group consolidated Phase 1 findings to 'define' a specific behavior for intervention. Phases 3 and 4 'developed' the intervention across six workshops with control room workers and six steering group workshops. The co-creation process identified contextual sedentary behavior as the target behavior, driven by behavioral regulation, social influence and social norms. The sedentary behavior intervention targeted these drivers and aimed to engage control room workers in short bursts of physical activity throughout their shifts. Key intervention features targeted involvement of staff in decision-making and embedding physical activity into work practices. The BCW and DD can be combined to co-create evidence-based and participant-informed interventions and translate science into action.

Spontaneous Bursts of Muscle Sympathetic Nerve Activity Reduce Femoral Arterial Compliance in Humans

Previous studies in rodents have demonstrated tonic sympathetic restraint of arterial compliance. To date, studies in humans have examined sympathetic restraint of compliance via either reflexively or pharmacologically manipulating sympathetic vasoconstriction and measuring resultant changes in compliance. The extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) dynamically regulate arterial compliance in humans on a beat-by-beat basis remains unknown. Herein, we hypothesized that femoral arterial compliance would be transiently reduced following spontaneous bursts of MSNA. Further, we hypothesized that the magnitude of reduction in arterial compliance would be graded to the MSNA burst amplitude (index of net neural outflow). Beat-to-beat blood pressure (BP; Finometer), heart rate (ECG), MSNA (peroneal microneurography), and femoral artery blood flow (duplex Doppler ultrasound) were continuously measured over 10-20 minutes of quiet supine rest in 27 young, healthy men (age: 22 ± 1 years, resting MSNA burst frequency: 11 ± 5 bursts/minute). Customized labview programs were used to time-align neural cardiovascular variables with ultrasound data sampled at 30Hz, enabling the quantification of arterial compliance on a beat-by-beat basis defined as the change in arterial cross-sectional area divided by the change in blood pressure over the cardiac cycle. Bursts of MSNA were tracked for 10 cardiac cycles and changes in arterial compliance were quantified using signal-averaging for all bursts, and subsequently, for bursts of MSNA when sub-classified based on amplitude into quartiles (Q1= smallest 25% of bursts, Q4= largest 25% of bursts). Reductions in arterial compliance were significantly greater following cardiac cycles with bursts of MSNA compared to cardiac cycles without bursts of MSNA (bursts: -5.1 ± 0.6% vs. non-bursts: -0.8 ± 0.2%, p&lt;0.001). Further, reductions in compliance appeared to be graded to MSNA burst amplitude (Q1: -6.5 ± 0.8%; Q4: -9.1 ± 1.3%, P=0.051). The latency (i.e., number of heartbeats) to nadir arterial compliance following bursts of MSNA was 4.2 ± 0.6 cardiac cycles. Collectively, these findings suggest that the sympathetic nervous system dynamically regulates femoral arterial compliance on a beat-to-beat basis. College of Nursing and Health Innovation, University of Texas at Arlington. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Discovery of the First Antiglitch Event in the Rotation-powered Pulsar PSR B0540-69

Using data from the Neutron star Interior Composition ExploreR observatory, we identified a permanent spin frequency decrease of Δν = −(1.04 ± 0.07) × 10−7 Hz around MJD 60132 in the rotation-powered pulsar PSR B0540-69, which exhibits a periodic signal at a frequency of ν ∼ 19.6 Hz. This points to an antiglitch event, a sudden decrease of the pulsar’s rotational frequency without any major alteration in the pulse profile or any significant increase of the pulsed flux. Additionally, no burst activity was observed in association with the antiglitch. To date, observations of the few known antiglitches have been made in magnetars or accreting pulsars. This is the first antiglitch detected in a rotation-powered pulsar. Given its radiatively quiet nature, this antiglitch is possibly of internal origin. Therefore, we tentatively frame this event within a proposed mechanism for antiglitches where the partial “evaporation” of the superfluid component leads to an increase in the normal component’s moment of inertia and a decrease in the superfluid one.

Antioxidant-induced modulation of sympathetic transduction to arterial blood pressure in humans

Purpose: Excess plasma free fatty acids (FAA) promote oxidative stress and an increase in peripheral resistance. Therefore, we tested the hypothesis that excess FAA limits sympathetic control of arterial blood pressure (BP) and that sympathetic control would be restored during co-administration of ascorbic acid, which is an antioxidant with vasodilatory properties. Methods: A 20% IV fat emulsion (Intralipid) was administered for 2 hours to 5 lean, healthy adults with and without co-infusion of ascorbic acid (separate visits) in a double-blinded, crossover study design. Sympathetic control of BP was examined by determining the BP response to individual bursts of muscle sympathetic nerve activity (MSNA) (microneurography). Briefly, beat-to-beat mean arterial pressure (MAP) was measured continuously (finger cuff) and signal-averaged over 15 cardiac cycles following each detected burst of MSNA over a 10-min resting period. Results: In contrast to our hypothesis, no change was observed in sympathetic transduction during lipid infusion (1.5 ± 0.4 vs. 1.4 ± 3 mmHg, P=0.75). However, co-infusion of ascorbic acid significantly increased sympathetic transduction compared with baseline (1.5 ± 0.4 vs. 2.0 ± 3 mmHg, P=0.04), in addition to reducing peripheral resistance (0.73 ± 0.11 vs. 0.53 ± 12 mmHg·min·mL−1, P=0.07). MSNA and MAP were not significantly changed during the 2-hr infusions. Conclusions: These preliminary findings suggest that excess FAA do not modulate sympathetic transduction in lean, healthy adults. However, ascorbic acid infusion reduces peripheral resistance and increases sympathetic transduction, demonstrating an inverse relation between peripheral resistance and sympathetic transduction in healthy adults. Funding and support: R01HL159370-01 (S.W.H.). This work was also supported by a CTSA grant from NCATS awarded to the University of Kansas for Frontiers: University of Kansas Clinical and Translational Science Institute (# UL1TR002366) The contents are solely the responsibility of the authors and do not necessarily represent the offcial views of the NIH or NCATS. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Decreased GABAergic Neurotransmission Promotes Breathing Upon Emergence From Hibernation

The respiratory network must produce reliable output for an animal to survive. Although respiratory motor plasticity is well appreciated, how plasticity mechanisms work to promote robustness following environmental perturbations that disrupt breathing is less clear. During underwater hibernation, respiratory neurons of bullfrogs remain inactive for months, triggering a suite of compensatory mechanisms that aim to maintain respiratory function. We hypothesized that GABAergic inhibition would decrease following hibernation. In control animals, respiratory frequency was under control of GABAAR signaling. Specifically, block of GABAARs dose-dependently decreased respiratory burst frequency in the in vitro brainstem preparation (n=5 preparations). After hibernation, GABAA receptor block had little to no impact on respiratory burst frequency, suggesting the network was no longer reliant on GABAergic inhibition to maintain normal frequency (n=5 preparations). The loss of inhibition was specific to the respiratory network because non-respiratory motor activity and large seizure-like bursts were similarly triggered by GABAA receptor blockade in intact brainstem preparations from controls and hibernators. We next used a semi-intact preparation that maintains functional respiratory-synaptic input onto rhythmic motor neurons to identify compensatory changes in GABAergic tone at the level of the motor neuron. In controls, the firing rate of respiratory motoneurons was constrained by a phasic GABAAR tone because focal application of bicuculline, a GABAAR antagonist, led to an increase in phasic firing frequency (n=12 cells). After hibernation, this bicuculline-mediated increase in phasic firing frequency was attenuated suggesting phasic inhibition onto the motor neuron had decreased (n=9 cells). Brain slice recordings of identified vagal motor neurons revealed that postsynaptic GABAA receptor strength was unchanged following hibernation (n=16 control cells; n=16 hibernation cells). Taken together, our results suggest that GABAergic activity is decreased in premotor networks following hibernation. Despite this dramatic loss of GABAergic function, respiratory output from control preparations was indistinguishable from hibernators. To elucidate the functional impacts of loss of GABAergic activity, we tested the network’s ability to produce output at colder temperatures. In controls, respiratory output slowed as temperature decreased, with most networks nearly silent at 8 degrees Celsius (n=5 preparations). Interestingly, in controls low dose block of GABAA receptors promoted respiratory activity at cold temperatures, with frequency not statistically different than baseline at any temperature tested (n=4 preparations). This suggests that the loss of premotor GABAergic activity we observed could work to promote motor output at colder temperatures, which works adaptively for the animal when emerging from hibernation. NIH R01NS114514 (JS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

On the Regulation of Arterial Blood Pressure by an Intracranial Baroreceptor

Introduction: There is significant evidence for the existence of an intracranial baroreceptor mechanism(s) capable of sensing physiological changes in cerebral blood flow (Marina et al., 2020). However, little is known about the sensitivity of this mechanism to changes in brain perfusion and its interaction with inputs from the peripheral (arterial) baroreceptors. The aim of this study was to characterise the cardiovascular responses to physiological changes in cerebral perfusion induced by experimental manipulations of intracranial pressure (ICP). Methods: The experiments were performed in adult Sprague-Dawley rats (250–300 g), anesthetized with urethane (induction: 1.3 g kg−1, i.p.; maintenance: 10–25 mg kg−1 h−1, i.v.). The femoral artery and vein were cannulated for measurement of arterial blood pressure (ABP) and administration of anaesthetic. The trachea was cannulated, and the animal was mechanically ventilated. The lateral cerebral ventricles were cannulated and connected via saline-filled catheters to a pressure transducer to record ICP and to a “water column” to allow controlled manipulation of ICP. The experiments included the denervation of the arterial baroceptors, stimulation of the aortic depressor nerve and recording of renal sympathetic nerve activity. Results: The resting ICP in rats anesthetized with urethane was 6.2 ± 0.7 mmHg (n=8). Following a small craniotomy that reduced ICP to 0 mmHg, ABP decreased by 11.2 mmHg (n=6) within 30 min. Restoring the integrity of the intracranial space increased ABP to the baseline level. Progressive increases in ABP were observed in response to experimentally-induced increases in ICP by 5, 10, 15 and 20 mmHg, revealing a linear relationship between ICP and systemic arterial pressure within the physiological range of ICP changes. In the absence of inputs from the arterial baroceptors (bilateral sino-aortic denervation and vagotomy) the ABP responses to ICP increases were preserved. Analysis of the ABP and heart rate responses to the electrical stimulation of the aortic depressor nerve suggested baroreflex re-setting at raised ICP. Renal nerve recordings demonstrated increased sympathetic activity at raised ICP (172 ± 34.91 % at 20 mmHg ICP (p=0.003; n=7) with markedly enhanced bursts of activity during the inspiratory phase of the respiratory cycle. Conclusion: These data demonstrate that the intracranial baroceptor mechanism is highly sensitive to changes in cerebral perfusion within the physiological range and suggest that cerebral blood flow is an important determinant of systemic ABP. The data suggest that at raised ICP the baroreflex control of sympathetic vasomotor activity is reset and provides effective control of arterial blood pressure at a higher level required to compensate for reduced brain perfusion. Marina, N., Christie, I.N., Korsak, A., Doronin, M., Brazhe, A., Hosford, P.S., Wells, J.A., Sheikhbahaei, S., Humoud, I., Paton, J.F. and Lythgoe, M.F., 2020. Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow. Nature Communications, 11(1), 131. This PhD Studentship is funded by the British Heart Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Crosstalk Inhibition Between 5-HT2A and Adenosine 2A Receptor-Induced Phrenic Motor Facilitation

Episodic spinal serotonin receptor activation elicits phrenic motor facilitation (pMF), a form of respiratory motor plasticity. Although both intermittent 5-HT2 and 5-HT7 receptor activation elicit pMF, they do so via distinct cellular mechanisms known as the Q (5-HT2A/B) and S (5-HT7) pathways. The Q and S pathways interact via powerful crosstalk inhibition; thus, concurrent activation of both receptor subtypes diminishes/abolishes pMF. At least some of the molecules giving rise to mutually inhibitory interactions between 5-HT2 and 5-HT7 receptors have been identified. Although episodic spinal adenosine 2A (A2A) receptor activation also elicits pMF via the S pathway, we do not know: 1) if 5-HT2 and A2A receptors interact via similar crosstalk inhibition, nor 2) if they do so via the same signaling mechanisms. Thus, we tested the hypothesis that concurrent 5-HT2 and A2A receptor activation diminishes pMF via crosstalk inhibition. Selective 5-HT2A (DOI) and A2A receptor agonists (CGS21680) were delivered to the C4 intrathecal space (3, 6 μl injections, 5-min intervals) in urethane anesthetized, artificially ventilated, vagotomized and paralyzed Sprague Dawley rats. Integrated phrenic nerve burst activity was measured before (baseline), during and 90 minutes post-drug injection. Spinal 5-HT2A and A2A receptor activation both increased phrenic nerve burst amplitude when delivered alone (i.e., pMF); however, pMF was no longer apparent with concurrent receptor activation. The magnitude of pMF, expressed as a % change in phrenic burst amplitude from baseline to 90-min post-injection, was significantly lower with concurrent receptor activation (5-HT2A + A2A= 15 ± 7.7%; n=5) versus 5-HT2A (84 ± 12%; n=5, p=0.0047) and A2A (88 ± 16%; n=5, p=0.0085) alone. Thus, 5-HT2A and A2A receptors interact via crosstalk inhibition similar to 5-HT2 and 5-HT7 receptors. However, the mechanism underlying this crosstalk inhibition remains unknown. NIH HL148030. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Phrenic Long-term Facilitation Following Severe Acute Intermittent Hypoxia Is Preserved in Geriatric Male Rats

Acute intermittent hypoxia (AIH) elicits a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). Both moderate and severe AIH elicit phenotypically similar pLTF but do so via completely distinct cellular mechanisms. With moderate AIH (mAIH), pLTF arises from a serotonin-dominant, adenosine-constrained mechanism. In aged rats, mAIH-induced pLTF is impaired due to increased basal spinal adenosine levels, which constrain serotonin-dependent pLTF. With severe AIH (sAIH), pLTF arises from an adenosine-dominant, serotonin-constrained mechanism. Since spinal adenosine levels are elevated in aged male rats, we hypothesized that age would actually enhance sAIH-induced- pLTF. Young (~3.5 month) and aged (~20 month) male Sprague Dawley rats were urethane anesthetized, artificially ventilated, vagotomized, paralyzed, and exposed to sAIH (3, 5-minute episodes; arterial Po2 = 25-30 mmHg). Integrated phrenic nerve burst activity was measured before (baseline), during hypoxic episodes and 60 minutes after sAIH. Neither baseline phrenic burst amplitude, the short-term hypoxic phrenic response nor pLTF magnitude (assessed as % change in phrenic burst amplitude from baseline to 60 minutes post-sAIH) were different in aged versus young rats (120 ± 22% vs. 98 ± 17%, respectively). Thus, aged male rats preserve the capacity for adenosine driven phrenic motor plasticity. Although we cannot conclude that sAIH-induced pLTF is actually increased, age effects on adenosine versus serotonin-driven plasticity are clearly different. NIH HL148030. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Changes in Tryptophan Hydroxylase 2 and 5HT1A Receptor Density May Contribute to Developmental Variation in Response to Serotonin in the in vitro Bullfrog Brainstem

Bullfrog, Lithobates catesbeiana, is a vertebrate animal model that can be used to study toxicology and developmental physiology. Our research is focused on better understanding vulnerability to brainstem respiratory centers in the pathology of sudden infant death syndrome (SIDS). We propose that a link between nicotine exposure during development leads to changes in the serotonergic signaling cascades of respiratory coordinating neurons. Caudal raphe neurons send serotonergic fibers that arborize and terminate directly on or near respiratory neurons in the brainstem. In bullfrogs, serotonin elicits a developmentally dependent effect on respiratory motor output. Late metamorphic tadpoles demonstrate an increase in lung burst activity with exposure to low concentrations of serotonin (≤ 0.5μM 5-hydroxytryptamine; 5-HT) mediated in part by 5-HT1a receptor (5HT1aR) activation. This developmental change in activity may be due to changes in the number of serotonergic fibers and/or 5-HT1a receptor density. Using the NIH Basic Local Alignment Search Tool (BLAST) we compared human and bullfrog 5HT1aR and tryptophan hydroxylase 2 (TH2) protein sequences and found a 34 and 65 percent identity match respectively. Quantitative western blot analysis of both proteins indicates developmental shifts in the serotonergic network during metamorphosis. These results were supported by immunohistochemical staining of 5HT1aR and TH2 in caudal raphe containing brainstem sections from pre-metamorphic tadpoles and post-metamorphic frogs. Impairments in the maturation of this serotonergic network may underlie the toxidrome associated with developmental nicotine exposure and further support the increased risk of SIDS following that exposure. This research was supported by the University of Wisconsin- La Crosse (UWL) through support from the UWL College of Science and Health, two UWL Undergraduate Research Creative Grants and a UWL FY23/24 Faculty Research Grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.