Evaluating the Effects of Ketamine on Cognitive Flexibility in Rats Using a Probabilistic Reversal Learning Task

Depression is one of the most debilitating and widespread mental health conditions in the world today. Drugs that are traditionally prescribed to combat depression are flawed in several ways, and because of this, new treatments are needed. One drug that seems capable of overcoming the limitations of traditional antidepressants is ketamine. In clinical research, a single dose of ketamine can significantly reduce symptoms of depression quickly, its effects may last for weeks to months, and its side effects appear to be limited and relatively harmless. However, clinical research is ongoing, and more research is needed to fully understand ketamine\u27s beneficial effects. One way that research can help understand how ketamine works is by using animal models of behavior. These models are beneficial because they allow researchers to isolate very specific variables that sometimes are not possible with human research. The specific approach used here is called reinforcement learning, which is well-suited to studying basic decision-making processes and how behavior changes based on receiving rewards and punishments. The experiment in Chapter 2 was designed to test the effects of different ketamine doses on behavioral adaptation, something that depressed individuals struggle with. Regardless of dose, ketamine did not enhance this ability, and instead appeared to cause short-lived impairments in healthy rats. The experiment in Chapter 3 was designed to assess the effects of ketamine on behavior when two different forms of negative outcomes were either combined or not. Ketamine again did not have any long-lasting effects, but rats showed enhanced behavioral adaptation and persistence when they experienced a combination of two negative outcomes. Together, these studies aimed to improve our understanding of what aspects of depression ketamine might be useful for, and how to improve upon future research using reinforcement learning procedures with non-human animals

Pressure Points at the Intersection of the Education and Justice Systems: Strategies to Improve Student Success and Reduce Juvenile Court Contacts

This article explores an under examined facet of the school to prison pipeline by focusing a magnifying glass on the real life stories of youth in Washington State who have become stuck in a cycle of school failure and escalating involvement in the juvenile and criminal justice systems. These concrete case studies allow us to explore the ways that the public education and juvenile justice systems have become entangled and how this entanglement creates significant barriers for youth in their attempts to successfully pursue meaningful educational goals, including high school graduation. The article also explores how this entanglement makes it difficult for youth to extricate themselves from the juvenile and criminal justice systems. The article will examine the impact of indefinite exclusion from school for a wide array of school based behaviors and the lack of a clear path back to school enrollment and will look more closely at school discipline practices and their impact on probation violations in juvenile court. The article will also explore the criminalization of disability-related behaviors in school. Finally, the article will look at re-entry to public schools after time spent in detention and prison. Through analysis of the stories of youth and the systems they interact with, successful strategies for creating better outcomes for individual youth will be identified and changes proposed that would disentangle the public education and the juvenile justice systems, thus making room for better educational and community-based outcomes for all youth

The high partial wave phenomenon of spin changing atomic transitions

The collisional transition between two highly excited atomic states with different spin is investigated theoretically. Taking helium-like n1S − n3P as an example, it is found that the transition is driven in the highly ion-ized Fe ion purely by exchange, and the cross section becomes increasingly dominated by partial waves of high orbital angular momentum as the scattering energy increases. Whereas for the near-neutral Li ion the transition is dominated by channel coupling in low partial waves. Analytical bench-marks and numerical methods are developed for the accurate calculation of the exchange integral at high angular momentum. It is shown how the partial wave and energy dependence of the collision strength for high n spin changing transitions in the highly ionized ion is related to the overlap of the extended atomic orbitals.</p

Blood brain barrier dysfunction and a role for inflammation in age-dependent salt-sensitive hypertension

Hypertension is the principal risk factor for chronic kidney disease, myocardial infarction, and stroke, and is responsible for 10% of deaths globally. Normal aging and elevated dietary sodium intake have both been identified as contributors to hypertension, the salt sensitivity of blood pressure, and elevations in sympathetic tone. Normal aging has also been identified as a contributor to vascular dysfunction and inflammation. We hypothesize that normal aging and increased dietary sodium intake contribute to the development and maintenance of age-related salt-sensitive hypertension. We anticipate with age that there are elevations in sympathetic tone, decreases in the vascular integrity of the blood brain barrier, and an increase in the inflammatory response of the innate immune system of the brain by astrocytes and microglia. Using male Sprague-Dawley (SD) rats aged 3-, 8- and 16-months-old as a model of normal aging, rodents were randomly assigned to a normal salt (NS; 0.6% NaCl) or high salt (HS; 4% NaCl) diet. We then assessed the development of hypertension, the salt sensitivity of blood pressure, changes in central vascular integrity, and a role for central inflammation in age-dependent hypertension. We observed a robust age-dependent increase in blood pressure in rodents on a NS diet suggesting male SD rats develop age-dependent hypertension. We also observed that aged rats develop the salt sensitivity of blood pressure. We saw significant elevations in global sympathetic tone, sympathetic tone to the vasculature, and sympathetic tone to the kidney in response to normal aging. Further, there was a dramatic extravasation of intravascularly infused dextrans in the paraventricular nucleus of the hypothalamus (PVN) with age, suggesting a loss in vascular integrity of the blood brain barrier, regardless of dietary sodium intake. Astrocytic density in the PVN was maintained in animals on a NS diet. In rodents on a HS diet, both young and middle aged rats, but not in aged rats showed increased levels of astrocytic density. There was no difference in interstitial astrocyte densities, which excluded perivascular astrocytes, compared to total astrocyte density, suggesting that perivascular astrocytes did not play a significant role in astrocyte activation. Microglial branching complexity was maintained in all groups regardless of salt intake, suggesting that microglial activation was the same through all groups. However, microglial morphology showed a trending increase in activation level on a NS with age. On a HS diet, there is an increase in activation state at 8-months-old. Overall, normal aging and increases in dietary sodium intake contribute to increases in blood pressure, elevations in sympathetic tone, and ultimately a loss in vascular integrity of the blood brain barrier. Importantly, the following studies reveal a novel breakdown in the blood brain barrier in a normal aging model of hypertension by which increased blood pressure and aging evokes an increase in blood brain barrier permeability

Galectin-3 interacts with components of the nuclear ribonucleoprotein complex

Differentially spliced mRNAs following galectin‐3 depletion. (PDF 122 kb

Atomically resolved structural determination of graphene and its point defects via extrapolation assisted phase retrieval

Previously reported crystalline structures obtained by an iterative phase retrieval reconstruction of their diffraction patterns seem to be free from displaying any irregularities or defects in the lattice, which appears to be unrealistic. We demonstrate here that the structure of a nanocrystal including its atomic defects can unambiguously be recovered from its diffraction pattern alone by applying a direct phase retrieval procedure not relying on prior information of the object shape. Individual point defects in the atomic lattice are clearly apparent. Conventional phase retrieval routines assume isotropic scattering. We show that when dealing with electrons, the quantitatively correct transmission function of the sample cannot be retrieved due to anisotropic, strong forward scattering specific to electrons. We summarize the conditions for this phase retrieval method and show that the diffraction pattern can be extrapolated beyond the original record to even reveal formerly not visible Bragg peaks. Such extrapolated wave field pattern leads to enhanced spatial resolution in the reconstruction.Comment: 10 pages, 4 figure

How Well Do We Know the Orbits of the Outer Planets?

This paper deals with the problem of astrometric determination of the orbital elements of the outer planets, in particular by assessing the ability of astrometric observations to detect perturbations of the sort expected from the Pioneer effect or other small perturbations to gravity. We also show that while using simplified models of the dynamics can lead to some insights, one must be careful to not over-simplify the issues involved lest one be misled by the analysis onto false paths. Specifically, we show that the current ephemeris of Pluto does not preclude the existence of the Pioneer effect. We show that the orbit of Pluto is simply not well enough characterized at present to make such an assertion. A number of misunderstandings related to these topics have now propagated through the literature and have been used as a basis for drawing conclusions about the dynamics of the solar system. Thus, the objective of this paper is to address these issues. Finally, we offer some comments dealing with the complex topic of model selection and comparison.Comment: Accepted for publication in the Ap