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By: David Bruce Bartlett, PhD

  • Assistant Professor in Medicine
  • Member of the Duke Cancer Institute
  • Member of Duke Molecular Physiology Institute

https://medicine.duke.edu/faculty/david-bruce-bartlett-phd

Following the washout period symptoms rotator cuff injury 50 mg cytoxan sale, the animal completed a Pavlovian conditioned approach task (sign/goal tracking) with a palatable food reward treatment hyperkalemia best cytoxan 50 mg. This task examines individual differences of targeting motivation and rats are identified as sign trackers (preference for predictive lever) or goal trackers (food cup preference) treatment 001 cytoxan 50mg on-line. Rats were tested for free intake of familiar and novel palatable foods medicine park ok buy 50 mg cytoxan visa, homeostatic regulation of intake by acute hunger or satiety, locomotor response to novelty, and novel context preference. We observed increased binge-like intake, altered modulation of intake after hunger, and altered responses to novelty. Several longitudinal studies of children and adolescents prenatally exposed to marijuana reported a significant impairment of higher cognitive functions (Smith et al. Preclinical studies indicate that prenatal exposure to cannabinoids induces cognitive deficits in rat offspring (Ferraro et al. Furthermore, how this experience impacts behavior later in life has not been well documented. We observed delays in reaching important developmental milestones, such as eye opening, forelimb grasping and ambulations in an open field, with morphine-exposed mice taking longer to reach criteria and trends toward a genotype x morphine interaction. Morphine treated animals showed increased anxiety-like behavior, as measured by reduced time spent in the open arms of the elevated zero maze. Sensitivity to repeated morphine administration assayed through locomotor response showed that morphine exposed animals exhibit significantly blunted locomotor sensitization to repeated morphine. The present set of studies utilizes a model of both short and long access oxycodone self-administration in rats which begins prior to conception and continues throughout pregnancy. This leads to increased activation of intracellular signaling, ionic imbalances and increased neurotransmitter activity. Data from adult animal models have greatly contributed to our understanding and treatment of opioid tolerance, addiction and withdrawal, however, only a limited number of studies have been conducted to understand the same in neonates. However, challenges exist with all animal models and in small mammal models brain development at birth differs from that in human neonates. Drugs of Abuse and Addiction Title: Social-based voluntary abstinence prevents the emergence of incubation of drug craving Authors: *M. Here we determined whether this incubation phenomenon would occur after a period of voluntary abstinence where the alternative reward is access to a social peer. Methods: We first trained rats to lever-press for either access to a social peer (60-s, 2-h/day, 6 days) or palatable food (5 pellets) and then methamphetamine (0. Between tests, different groups of rats underwent either social-based voluntary abstinence (15 trials/day), food-based voluntary abstinence (15 trials/day), or homecage forced abstinence. Results: As in our previous studies, non-reinforced responding on the methamphetamine-associated lever in the relapse tests was higher after 15 days of food-choice voluntary abstinence or forced abstinence (incubation of methamphetamine craving). More importantly, rats demonstrated a strong preference for the social peer over methamphetamine (social-based voluntary abstinence). Additionally, prior exposure to social-based voluntary abstinence prevented the emergence of incubation of methamphetamine craving (lever-presses during the relapse test were similar on test days 1 and 15). Conclusions: Results show that exposure to social -based voluntary abstinence prevented the emergence of incubation of drug craving and demonstrate the critical role of social factors in drug relapse, as assessed in animal models. We are currently exploring brain mechanisms underlying the inhibitory effect of socialbased voluntary abstinence on incubation of drug craving. Stakes corresponded to the amount of real-world money that can be earned per trial. Physiological (heart rate, blood pressure) and subjective effects of the capsule were collected over the course of each session. These findings provide insight about the causes of heterogeneous response to stimulants in humans, and suggest a gene/behavior/brain network that underlies susceptibility to drug effects and use. The highly addictive psychostimulants cocaine and methamphetamine, alter the mesolimbic dopamine pathway and somatodendritic dopamine neurotransmission. Cross-sensitization between cocaine and methamphetamine has been shown in selfadministration behavioral paradigms, however few studies have examined the cellular mechanisms underlying cross-sensitization. In this study we examined the effects of methamphetamine self-administration in mice and alterations in dopamine neurotransmission. Adult mice were trained to nose-poke under a fixed ratio 3 schedule for intravenous infusions of methamphetamine (0. Whole-cell patch clamp electrophysiology was performed 24 hours following methamphetamine intake. A calcium-dependent decrease in dopamine inhibitory neurotransmission in response to methamphetamine but not to cocaine indicates that there is little adaptation in dopamine transporter function following methamphetamine self-administration.

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However medicine pill identification purchase cytoxan 50 mg amex, this approach requires the identification of patients at the very onset of disease or those who are at extremely high risk of developing disease and adds impetus to medicine 5325 buy 50mg cytoxan free shipping studies to symptoms 0f high blood pressure buy cytoxan 50 mg line identify the disease susceptibility genes for the development of autoimmune diseases medications safe in pregnancy buy cytoxan 50mg without prescription. Unlike human diabetes, which follows a chronic progressive course in humans, multiple sclerosis is a chronic relapsing disease with acute episodes followed by periods of quiescence. This suggests a balance between autoimmune and protective T cells that can alter at different stages of the disease. However, it remains to be proven whether the specific suppressive cells discussed in this section exist naturally and contribute to selftolerance, or whether they arise only upon artificial stimulation or in response to autoimmune attack. Nevertheless, because they can play an active, dominant part in self-tolerance, they are particularly attractive potential mediators for immunotherapy of autoimmune disease. Antigens in immunologically privileged sites do not induce immune attack but can serve as targets. For instance, the brain and the anterior chamber of the eye are sites in which tissues can be grafted without inducing rejection. It was originally believed that immunological privilege arose from the failure of antigens to leave privileged sites and induce immune responses. Subsequent studies have shown, however, that antigens do leave immunologically privileged sites, and that these antigens do interact with T cells; but instead of eliciting a destructive immune response, they induce tolerance or a response that is not destructive to the tissue. First, the communication between the privileged site and the body is atypical in that extracellular fluid in these sites does not pass through conventional lymphatics, although proteins placed in these sites do leave them and can have immunological effects. Naive lymphocytes, similarly, may be excluded by the tissue barriers of privileged sites, such as the blood-brain barrier. Second, humoral factors, presumably cytokines, that affect the course of an immune response are produced in privileged sites and leave them together with antigens. Third, the expression of Fas ligand by the tissues of immunologically privileged sites may provide a further level of protection by inducing apoptosis of Fas-bearing lymphocytes that enter these sites. This mechanism of protection is not fully understood, as it appears that under some circumstances the expression of Fas ligand by tissues may trigger an inflammatory response by neutrophils. Tissue grafts placed in these sites often last indefinitely, and antigens placed in these sites do not elicit destructive immune responses. Paradoxically, the antigens sequestered in immunologically privileged sites are often the targets of autoimmune attack; for example, brain autoantigens such as myelin basic protein are targeted in multiple sclerosis. It is therefore clear that this antigen does not induce tolerance due to clonal deletion of the self-reactive T cells. Thus, at least some antigens expressed in immunologically privileged sites induce neither tolerance nor activation, but if activation is induced elsewhere they can become targets for autoimmune attack (see Section 13-25). It seems plausible that T cells specific for antigens sequestered in immunologically privileged sites are more likely to remain in a state of immunological ignorance. If one eye is ruptured by a blow or other trauma, an autoimmune response to eye proteins can occur, although this happens only rarely. Immuno-suppression and removal of the damaged eye, the source of antigen, is frequently required to preserve vision in the undamaged eye. In the disease sympathetic ophthalmia, trauma to one eye releases the sequestered eye antigens into the surrounding tissues, making them accessible to T cells. The effector cells that are elicited attack the traumatized eye, and also infiltrate and attack the healthy eye. Thus, although the sequestered antigens do not induce a response by themselves, if a response is induced elsewhere they can serve as targets for attack. It is not surprising that effector T cells can enter immunologically privileged sites: such sites can become infected, and effector cells must be able to enter these sites during infection. As we learned in Chapter 10, effector T cells enter most or all tissues after activation, but accumulations of cells are seen only when antigen is recognized in the site, triggering the production of cytokines that alter tissue barriers. B cells with receptors specific for peripheral autoantigens are held in check by a variety of mechanisms. During B-cell development in the bone marrow, B-cell antigen receptors specific for self molecules are produced as a consequence of the random generation of the repertoire. If a self molecule is expressed in the bone marrow in an appropriate form, clonal deletion and receptor editing can remove all of these self-reactive B cells while they are still immature (see Sections 7-9 and 7-10). There are, however, many self molecules available only in the periphery whose expression is restricted to particular organs.

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Since alterations in beta oscillations have been seen with ageing (Rossiter et al symptoms toxic shock syndrome cytoxan 50 mg. Twenty young (18-30 years) and twenty elderly (62-77 years) healthy adults were trained on a motor sequence tracking task and subsequently tested for early (45-60 min) and late (24 hours) retention shinee symptoms mp3 buy discount cytoxan 50 mg on-line. Crucially medications gerd buy discount cytoxan 50 mg online, we found that pre-training levels of resting beta power from contralateral sensorimotor cortex were correlated with early motor sequence retention (r = -0 treatment episode data set purchase cytoxan 50mg with visa. These findings contribute to our understanding of the neurophysiological mechanisms underlying motor learning, and suggest that beta oscillations as potential markers of the net inhibitory and excitatory mechanisms in human sensorimotor cortex are linked to individual differences in the capacity to retain learned motor skills. In the context of disease, beta oscillations may offer novel targets for therapeutic interventions designed to promote rehabilitative outcomes after brain injury. An issue of increasing concern is the effects of concussion history on skilled performance and motor learning, particularly in asymptomatic young athletes competing at or hoping to compete at elite levels. As expected there was a main effect of group on improvement in slalom course movement time (p<0. These data show that there are subtle differences in the ability to learn complex skills in young elite athletes with a concussion history, despite being deemed recovered by current standards. Most stroke survivors access neurorehabilitation to improve sensory and motor function. However, little is known about how stroke influences basic mechanisms of sensorimotor learning, and understanding these mechanisms may help improve rehabilitation outcomes. Here we examine motor learning patterns in a task that required stroke survivors and healthy adults to adapt their reaching movements to a novel visuomotor rotation. Subjects (5 stroke survivors; 21 healthy adults) interacted with a virtual reality system through the movement of their arms. The position of their fingertip was displayed in real time using a white cursor (0. We asked subjects to reach back-and-forth between two circular targets (2cm diameter) positioned 10-cm apart. We then introduced a 30counter-clockwise rotation onto the hand feedback cursor to examine how subjects adapted their movements. Subjects then performed another 25 movements with true hand feedback to examine how they de-adapted their movements. Preliminary analysis revealed marked differences in the learning patterns of stroke subjects and healthy adults. Although the overall extent of learning was similar across groups, stroke subjects required more trials to adapt (>90 trials) their movements to the same visuomotor rotation as healthy adults (<40 trials). Our analysis suggests a reduction in trial-bytrial retention of learning may contribute to the slower learning rates displayed by stroke survivors (U(25) = 2. Collectively, our results suggest stroke survivors can indeed adapt their movements to the same overall extent as healthy, age-matched adults. However, this learning is achieved at a slower rate due to a reduction in the amount of learning that is retained from movement to movement. Thus, stroke subjects need to perform many more movement repetitions than healthy adults to adapt to the same visuomotor rotation. The visuomotor rotation was added by the cursor being rotated with respect to the direction of actual tilt of the device. In our experiment, the visuomotor rotation was gradually increased to 15 degrees, and it gradually decreased to zero so that the participants could not be aware of the perturbation. The adaptation to the perturbation was quantified by calculating a slope of the learning curve. Evidence for this is based on a paradigm that evokes spontaneous recovery after learning a visuomotor rotation. The recovery allows inferring a fast process that learns and decays quickly, and a slow process that responds weakly to error but decays slowly. Recently, it has been suggested that the fast motor learning process shares resources with declarative memory processes. Hence, a deficiency in declarative memory should affect the fast, but not the slow process in motor learning. Participants performed reaching movements to a target while holding the handle of a robotic manipulandum. Visual feedback of hand position (cursor) and target position was provided in the plane of movement.

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American bullfrogs medicine man purchase cytoxan 50mg free shipping, Lithobates catesbeianus treatment 2014 trusted cytoxan 50mg, undergo respiratory motor inactivity during the cold winter months (Santin & Hartzler medications known to cause weight gain generic cytoxan 50 mg visa, 2017 medicine used to induce labor buy cytoxan 50mg online, J. After winter, however, they produce normal respiratory motor output (Santin & Hartzler, 2016, J. We hypothesized that respiratory motoneurons undergo increases in excitatory synaptic strength and/or intrinsic excitability to preserve respiratory network output following 2-3 months of respiratory inactivity. To determine if increases in excitatory synaptic strength on motoneurons preserve output from the respiratory network after months of inactivity, we recorded vagal nerve discharge from an in vitro brainstem preparation that produces respiratory burst activity resembling breathing in vivo. This indicates that increased excitatory synaptic strength on respiratory motoneurons preserves motor output after months of natural inactivity linking mechanisms of compensatory neural plasticity to a critical adaptation for survival in an animal. Presumably, cortical disinhibition helps to compensate for the drop in afferent drive and restores the net output from the cortical column to its homeostatic set point. To test this directly, we tracked daily changes in layer 5 (L5) projection neurons in the auditory cortex before and after a selective loss of auditory nerve afferent synapses. These findings reveal short-term dynamics in the auditory corticofugal pathway following cochlear synaptopathy and suggest that local circuit changes in the auditory cortex might allow corticofugal projection neurons to stabilize their output in the face of large swings in afferent drive. Our ongoing work examines the local circuit mechanisms that support this homeostatic plasticity. Increased "central gain" is associated with variable levels of recovered cortical processing; some mice regain normal auditory thresholds while other mice show no recovery of auditory processing, despite an equivalent loss of cochlear afferent synapses and auditory brainstem responses. How do auditory cortical neurons recover responses to sound following peripheral denervation? Further, homeostatic regulation of postsynaptic receptors could differ between excitatory and inhibitory cortical neurons, and the opposing directions of receptor shifts between these two populations could work synergistically to maximally increase central gain. We tracked daily changes in sound-evoked responses for five days following near-complete denervation of cochlear afferent nerve fibers and documented variable levels of damage and functional recovery between mice. Extensively investigated in the developing Xenopus nervous system (Spitzer, 2017), it has recently been discovered in adult rodents (Dulcis et al. No cell death or neurogenesis was associated with these changes in the hilus although increased neurogenesis was observed in the subgranular zone. Three weeks of running increase episodic memory evaluated with the object recognition test (Bolz et al. We found that mice spend more time interacting with the novel object than the familiar one after one week of running, compared to controls. Keck Foundation Title: Regulation of motor coordination by neurotransmitter switching in the brainstem Authors: *H. Exercise is a therapy that improves motor coordination but the mechanism is obscure. Adult mice given free access to running wheels for 1 week had enhanced motor coordination compared to non-runner controls, exemplified by a higher speed at fall from an accelerating rotarod and a shorter time to cross a balance beam. We are currently investigating how long the enhancement of coordination is sustained. Cell-wide homeostatic plasticity was initially reported as a global mechanism for stabilizing the output firing rate of a cell by uniformly scaling up or down the effective strength of all its synapses. More recent experimental evidence in vitro has suggested the existence of local homeostatic mechanisms acting at the level of dendritic stretches or even at single synapses that would potentially confer rich functional compartmentalization within the dendritic tree. However, the existence and nature of local homeostatic plasticity in vivo and its implications for the coherent reorganization of single cell responses remains unexplored. Here we have used visualoptogenetic pairing to demonstrate that induction of receptive field plasticity in single visual cortex neurons of awake mice alters identified synapses on neuronal dendrites. Such plasticity potentiates specific synapses and depresses others within short stretches of the same dendrite, consistent with functionally heterogeneous local sets of synapses that convey diverse receptive field inputs to a neuron. Crucially, depressed spines lie in close proximity to potentiated spines, indicating coordinated Hebbian and homeostatic plasticity in vivo that involves neighboring synapses. The spatially local distribution of depressed spines around potentiated spines, in conjunction with functionally intermixed synaptic inputs to dendrites, highlight a possible mechanism that organizes cell-wide plasticity with local dendritic interactions. Furthermore, because conventional transfection methods such as viral vectors require weeks to express, they are less suitable for the expression of molecular probes to study synaptic dynamics during development. To overcome these issues, we delivered plasmids into individual neurons of mouse primary visual cortex (V1) by two-photon guided electroporation.

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References:

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  • http://downloads.lww.com/wolterskluwer_vitalstream_com/sample-content/9780781761451_Bruyere/samples/Bruyere_Case52_001-006_DS.pdf
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