scholarly journals A novel weight lifting task for investigating effort and persistence in rats

2019 ◽  
Author(s):  
Blake Porter ◽  
Kristin L. Hillman

AbstractHere we present a novel effort-based task for laboratory rats: the weight lifting task (WLT). Studies of effort expenditure in rodents have typically involved climbing barriers within T-mazes or operant lever pressing paradigms. These task designs have been successful for neuropharmacological and neurophysiological investigations, but both tasks involve simple action patterns prone to automatization. Furthermore, high climbing barriers present risk of injury to animals and/or tethered recording equipment. In the WLT, a rat is placed in a large rectangular arena and tasked with pulling a rope 30 cm to trigger food delivery at a nearby spout; weights can be added to the rope in 45 g increments to increase the intensity of effort. As compared to lever pressing and barrier jumping, 30 cm of rope pulling is a multi-step action sequence requiring sustained effort. The actions are carried out on the single plane of the arena floor, making it safer for the animal and more suitable for tethered equipment and video tracking. A microcontroller and associated sensors enable precise timestamping of specific behaviors to synchronize with electrophysiological recordings. The rope and reward spout are spatially segregated to allow for spatial discrimination of the effort zone and the reward zone. We validated the task across five cohorts of rats (total n=35) and report consistent behavioral metrics. The WLT is well-suited for neuropharmacological and/or in vivo neurophysiological investigations surrounding effortful behaviors, particularly when wanting to probe different aspects of effort expenditure (intensity vs. duration).

2013 ◽  
Vol 136 (1) ◽  
Author(s):  
Ameet K. Aiyangar ◽  
Liying Zheng ◽  
Scott Tashman ◽  
William J. Anderst ◽  
Xudong Zhang

Availability of accurate three-dimensional (3D) kinematics of lumbar vertebrae is necessary to understand normal and pathological biomechanics of the lumbar spine. Due to the technical challenges of imaging the lumbar spine motion in vivo, it has been difficult to obtain comprehensive, 3D lumbar kinematics during dynamic functional tasks. The present study demonstrates a recently developed technique to acquire true 3D lumbar vertebral kinematics, in vivo, during a functional load-lifting task. The technique uses a high-speed dynamic stereo-radiography (DSX) system coupled with a volumetric model-based bone tracking procedure. Eight asymptomatic male participants performed weight-lifting tasks, while dynamic X-ray images of their lumbar spines were acquired at 30 fps. A custom-designed radiation attenuator reduced the radiation white-out effect and enhanced the image quality. High resolution CT scans of participants' lumbar spines were obtained to create 3D bone models, which were used to track the X-ray images via a volumetric bone tracking procedure. Continuous 3D intervertebral kinematics from the second lumbar vertebra (L2) to the sacrum (S1) were derived. Results revealed motions occurring simultaneously in all the segments. Differences in contributions to overall lumbar motion from individual segments, particularly L2–L3, L3–L4, and L4–L5, were not statistically significant. However, a reduced contribution from the L5–S1 segment was observed. Segmental extension was nominally linear in the middle range (20%–80%) of motion during the lifting task, but exhibited nonlinear behavior at the beginning and end of the motion. L5–S1 extension exhibited the greatest nonlinearity and variability across participants. Substantial AP translations occurred in all segments (5.0 ± 0.3 mm) and exhibited more scatter and deviation from a nominally linear path compared to segmental extension. Maximum out-of-plane rotations (<1.91 deg) and translations (<0.94 mm) were small compared to the dominant motion in the sagittal plane. The demonstrated success in capturing continuous 3D in vivo lumbar intervertebral kinematics during functional tasks affords the possibility to create a baseline data set for evaluating the lumbar spinal function. The technique can be used to address the gaps in knowledge of lumbar kinematics, to improve the accuracy of the kinematic input into biomechanical models, and to support development of new disk replacement designs more closely replicating the natural lumbar biomechanics.


2020 ◽  
Author(s):  
Blake S. Porter ◽  
Kristin L. Hillman

AbstractWhen performing a physically demanding behavior, sometimes the optimal choice is to quit the behavior rather than persist and waste time and energy. The dorsomedial prefrontal cortex (dmPFC), consisting of the anterior cingulate cortex and secondary motor area, likely contributes towards such utility assessments. Here, we examined how rodent dmPFC single unit and ensemble level activity corresponded to changes in motivation and quitting in an effortful weight lifting task. Rats carried out two task paradigms: one that became progressively more physically demanding over time and a second fixed effort version. Rats could quit the task at any time. Dorsomedial PFC neurons were highly responsive to each behavioral stage of the task, consisting of rope pulling, reward retrieval, and reward area leaving. Activity was highest early in sessions, commensurate with the highest relative task utility, then decreased until the point of quitting. Neural ensembles showed stable task representations across the entirety of sessions. However, these representations drifted and became more distinct over the course of the session. These results suggest that dmPFC neurons represent behavioral states that are dynamically modified as behaviors lose their utility, culminating in task quitting.


1986 ◽  
Vol 60 (3) ◽  
pp. 868-875 ◽  
Author(s):  
J. S. Tepper ◽  
B. Weiss

Three separate experiments were performed to evaluate how the topography of a behavioral response and its consequences influence the behavioral effects produced by ozone (O3) exposure. The first experiment measured the responding of food-deprived rats working to obtain intermittent delivery of small pellets of food by completing an active response, wheel running. Low O3 concentrations (0.12 ppm) reduced the frequency of running responses maintained by this fixed-interval 10-min schedule of food delivery. The second experiment examined the effects of O2 on food-deprived rats performing a response (nose poking) that required minimal physical effort to produce deliveries of food pellets. Rats in this situation began to show reductions in responding at 0.5 ppm O3. A third experiment showed that responses requiring minimal physical effort, such as lever pressing, can be a sensitive index of O3 exposure if the response provides access to wheel running. We concluded that increased physical activity during exposure appeared to be an important variable in determining sensitivity to O3 exposure.


2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S32-S33
Author(s):  
Kaitlin Mitchell ◽  
Erin McElvania ◽  
Meghan Wallace ◽  
Amy Robertson ◽  
Lars Westblade ◽  
...  

Abstract Members of the genus Corynebacterium are increasingly recognized as causes of opportunistic infection; some species can be multidrug resistant, posing a treatment challenge. Daptomycin is frequently used as therapy of last resort in this setting, but previous work from our group demonstrated the ability of C striatum clinical isolates to rapidly develop high-level resistance to daptomycin, both in vivo and in vitro. Here, our objective was to expand this investigation into a multicenter study evaluating multiple Corynebacterium species. Corynebacterium strains from three tertiary-care academic medical centers (total, n = 76; site 1, n = 44; site 2, n = 15; site 3, n = 17) were evaluated, representing 16 species. Isolates were identified during routine clinical testing and reported to species level in accordance with each laboratory’s standard operating procedures. Identification of each species was confirmed using both VITEK MS and Bruker BioTyper MALDI-TOF MS. MICs to daptomycin (Etest), vancomycin (Etest), and telavancin (Liofilchem) at baseline were determined using gradient diffusion methods on Mueller-Hinton agar with blood (Hardy Diagnostics). Each isolate was then inoculated in duplicate to 5 mL Tryptic Soy Broth. A daptomycin Etest was submerged in one tube from each pair, and growth was observed after 24-hour incubation. If turbidity was observed in the tube with daptomycin, MICs for each of the 3 antimicrobials were reassessed. High-level daptomycin resistance emerged in 24 strains: C aurimucosum (1/1 isolate tested), C bovis (1/2), C jeikeium (2/11), C macginleyi (3/3), C resistens (1/1), C simulans (1/1), C striatum (14/14 isolates), and C ulcerans (1/1). The majority of these isolates had MIC values >256 µg/mL following exposure to daptomycin. Forty-eight other isolates remained susceptible to daptomycin: C afermentans (1/1), C amycolatum (19/20), C diphtheriae (1/1), C jeikeium (7/11), C kroppenstedtii (2/2), C propinquum (3/3), C pseudodiphtheriticum (6/6), C tuberculostearicum (0/6), and C urealyticum (0/3). Many of these isolates did not undergo MIC testing postdaptomycin exposure in broth due to complete lack of growth. Among those that did (n = 19), the median daptomycin MIC was 0.38 µg/mL (mean 0.42 µg/mL; range 0.023-1.0 µg/mL). One isolate of C bovis and two isolates of C jeikeium yielded variable susceptibility to daptomycin; a subset of resistant colonies grew adjacent to the gradient diffusion strip. Upon isolation and further MIC testing, these colonies maintained high-level resistance. In addition, one isolate of C amycolatum exhibited high-level daptomycin resistance (MIC >256 µg/mL) prior to in vitro exposure. All isolates in the cohort were susceptible to vancomycin and telavancin, both before and after daptomycin exposure. Our findings suggest that multiple Corynebacterium species can rapidly develop high-level daptomycin resistance after a short period of exposure to this antimicrobial. This finding has important clinical implications, especially in the treatment of invasive infections or infections of indwelling medical devices.


1997 ◽  
Vol 273 (1) ◽  
pp. R331-R336 ◽  
Author(s):  
J. N. Benoit

The present study examined the effects of alpha 1- and alpha 2-adrenergic stimuli on rat mesenteric collecting lymphatics in vivo. Sprague-Dawley rats were anesthetized, and the mesentery was prepared for intravital microscopic study. Mesenteric collecting lymphatic diameter was continuously monitored by using a computerized video tracking system, and indexes of lymphatic pumping (e.g., contraction frequency, stroke volume, ejection fraction, and muscle shortening velocity) were determined from the diameter record. Contractile activity was monitored before and during the administration of various adrenergic agonists and antagonists. The receptor antagonists prazosin (alpha 1) and yohimbine (alpha 2) did not significantly alter baseline diameter or contractile activity, which suggests that lymphatics possess no basal adrenergic tone. Norepinephrine and phenylephrine (01-1.0 microM) produced dose-dependent increases in frequency and decreases in diameter. Lymphatic pump flow increased in direct proportion to frequency, because stroke volume did not change. The changes in lymphatic pumping produced by 1 microM norepinephrine were completely blocked by prazosin or phentolamine and only partially blocked by yohimbine. The alpha 2-adrenoceptor agonist (alpha-methyl-norepinephrine) produced no changes in lymphatic activity. This latter observation suggests that a role for postjunctional alpha 2-adrenoceptors in modulating mesenteric lymphatic smooth muscle is unlikely. The results of these studies support the existence of alpha-adrenoceptors on lymphatic smooth muscle. It is concluded that conditions characterized by increased sympathetic outflow may augment lymphatic function through alpha 1- but not alpha 2-adrenoceptors.


Author(s):  
K. Aston ◽  
W.J. Fisher ◽  
A.B. McAllan

Recent trials with cows fed grass silage have shown significant increases in intake and in yields of milk and milk solids when the crude protein (CP) concentration in a supplementary concentrate was raised. Giving additional CP in the concentrate was a more effective strategy for improving yields of milk and milk protein than giving extra energy (Aston et al 1992). The objective of this trial was to examine the influence of changes to the amount and pattern of distribution of CP supplied in a fixed concentrate ration given with grass silage ad libitum.Fifty-five Holstein-Friesian cows in their second and subsequent lactations were given a standard diet for two weeks from calving and then were used in a continuous feeding trial from weeks 4 to 21. The cows received 5 kg of fresh concentrate daily containing 156 (LP), 245 (MP) or 338 (HP) g CP per kg dry matter (DM), MP comprised equal amounts of LP and HP. Concentrate carbohydrate sources were cereals and digestible fibre and CP was increased by a mixture of 3:1 soya:fish meals. Grass silage contained 253 g toluene DM/kg, 162 g CP/kg DM, D value in vivo 0.723, pH 3.7, fermentation acids 135 g/kg DM of which 0.85 was lactic acid and NH3-N 91 g/kg total N.


Author(s):  
William L. Coleman ◽  
R. Michael Burger

Small biogenic changes in voltage such as action potentials in neurons can be monitored using extracellular single unit recording techniques. This technique allows for investigation of neuronal electrical activity in a manner that is not disruptive to the cell membrane, and individual neurons can be recorded from for extended periods of time. This chapter discusses the basic requirements for an extracellular recording setup, including different types of electrodes, apparatus for controlling electrode position and placement, recording equipment, signal output, data analysis, and the histological confirmation of recording sites usually required for in vivo recordings. A more advanced extracellular recording technique using piggy-back style multibarrel electrodes that allows for localized pharmacological manipulation of neuronal properties is described in detail. Strategies for successful signal isolation, troubleshooting advice such as noise reduction, and suggestions for general laboratory equipment are also discussed.


Blood ◽  
2010 ◽  
Vol 116 (16) ◽  
pp. 3080-3088 ◽  
Author(s):  
Ronjon Chakraverty ◽  
Guillermo Orti ◽  
Michael Roughton ◽  
Jun Shen ◽  
Adele Fielding ◽  
...  

Abstract In vivo alemtuzumab reduces the risk of graft-versus-host disease (GVHD) and nonrelapse mortality after reduced intensity allogeneic transplantation. However, it also delays immune reconstitution, leading to frequent infections and potential loss of graft-versus-tumor responses. Here, we tested the feasibility of alemtuzumab dose deescalation in the context of fludarabine-melphalan conditioning and human leukocyte antigen (HLA)–identical sibling transplantation. Alemtuzumab was given 1-2 days before graft infusion, and dose reduced from 60 mg to 20 mg in 4 sequential cohorts (total n = 106). Pharmacokinetic studies were fitted to a linear, 2-compartment model in which dose reduction led to incomplete saturation of CD52 binding sites and greater antibody clearance. Increased elimination was particularly evident in the 20-mg group in patients who had CD52-expressing tumors at time of transplantation. The 20-mg dose was also associated with greater risk of severe GVHD (acute grade III-IV or chronic extensive) compared with > 20 mg (hazard ratio, 6.7; 95% CI, 2.5-18.3). In contrast, dose reduction to 30 mg on day −1 was associated with equivalent clinical outcomes to higher doses but better lymphocyte recovery at 12 months. In conclusion, alemtuzumab dose reduction to 30 mg is safe in the context of reduced intensity conditioning and HLA-identical sibling transplantation. This trial was registered at http://www.ncrn.org.uk as UKCRN study 1415.


2005 ◽  
Vol 05 (02) ◽  
pp. 391-395
Author(s):  
SILVIA FANTOZZI ◽  
ALBERTO LEARDINI ◽  
ANDREA ENSINI ◽  
ANGELO CAPPELLO ◽  
FABIO CATANI

Accurate measurement of in vivo kinematics of total joint replacement is fundamental to improve prosthesis design and clinical outcome. In fluoroscopic analysis, the 3D relative pose of joint prosthesis components is reconstructed from the knowledge of the 3D geometry of each component and from a single plane projection. This is achieved with an accuracy of a few millimetres and a few degrees. Twenty-three patients with cruciate retaining and posterior stabilized prostheses were analyzed in order to assess the in vivo performance of the spine-cam mechanism. The posterior stabilized design exhibits a more physiological pattern of the anteroposterior motion of the condyles during flexion. This result is well-suited with the larger active knee flexion exhibited by the posterior stabilized knees.


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