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1.  Glucocorticoid receptor regulation of action selection and prefrontal cortical dendritic spines 
We recently reported that prolonged exposure to the glucocorticoid receptor (GR) ligand corticosterone impairs decision-making that is dependent on the predictive relationship between an action and its outcome (Gourley et al.; Proceedings of the National Academy of Sciences, 2012). Additionally, acute GR blockade, when paired with action-outcome conditioning, also blocks new learning. We then showed that dendritic spines in the prelimbic prefrontal cortex remodeled under both conditions. Nonetheless, the relationship between deep-layer dendritic spines and outcome-based decision-making remains opaque. We report here that a history of prolonged corticosterone exposure increases dendritic spine density in deep-layer prelimbic cortex. When spines are imaged simultaneously with corticosteroid exposure (i.e., without a washout period), dendritic spine densities are, however, reduced. Thus, the morphological response of deep-layer prelimbic cortical neurons to prolonged corticosteroid exposure may be quite dynamic, with spine elimination during a period of chronic exposure and spine proliferation during a subsequent washout period. We provide evidence, using a Rho-kinase inhibitor, that GR-mediated dendritic spine remodeling is causally related to complex decision-making. Finally, we conclude this report with evidence that a history of early-life (adolescent) GR blockade, unlike acute blockade in adulthood, enhances subsequent outcome-based decision-making. Together, our findings suggest that physiological levels of GR binding enable an organism to learn about the predictive relationship between an action and its outcome, but a history of GR blockade may, under some circumstances, also have beneficial consequences.
PMCID: PMC3917952  PMID: 24563705
RU486; mifepristone; stress; corticosterone; habit; outcome
2.  Corticosteroid-induced neural remodeling predicts behavioral vulnerability and resilience 
Neurons in distinct brain regions remodel in response to postnatal stressor exposure, and structural plasticity may underlie stress-related modifications in behavioral outcomes. Given the persistence of stress-related diseases such as depression, a critical next step in identifying the contributions of neural structure to psychopathology will be to identify brain circuits and cell types that fail to recover from stressor exposure. We enumerated dendritic spines during and after chronic stress hormone exposure in hippocampal CA1, deep-layer prefrontal cortex, and the basal amygdala and also reconstructed dendritic arbors of CA1 pyramidal neurons. Corticosterone modified dendritic spine density in these regions, but with the exception of the orbitofrontal cortex, densities normalized with a recovery period. Dendritic retraction of hippocampal CA1 neurons and anhedonic-like insensitivity to a sucrose solution also persisted despite a recovery period. Using mice with reduced gene dosage of p190rhogap, a cytoskeletal regulatory protein localized to dendritic spines, we next isolated structural correlates of both behavioral vulnerability (spine elimination) and resilience (spine proliferation) to corticosterone within the orbital cortex. Our findings provide novel empirical support for the perspective that stress-related structural reorganization of certain neuron populations can persist despite a “recovery” period from stressor exposure, and that these modifications may lay a structural foundation for stressor vulnerability—or resiliency—across the lifespan.
PMCID: PMC3711631  PMID: 23407965
actin; cytoskeleton; stress; cortisol; orbitofrontal; anhedonia; depression
3.  Regulation of ZBP1 transport dynamics in axons by MyosinVa 
Directed transport of the mRNA binding protein, zipcode binding protein1 (ZBP1), into developing axons is believed to play an important role in mRNA localization and local protein synthesis. The role of molecular motors in this process is unclear. We elucidated a role for Myosin Va (MyoVa) to modulate the axonal localization and transport of ZBP1 in axons. Using cultured rat hippocampal neurons, ZBP1 colocalized with MyoVa in axons and growth cones. Interaction of MyoVa with ZBP1 was evident by co-immunoprecipitation of endogenous and overexpressed proteins. Inhibition of MyoVa function with the globular tail domain (GTD) of MyoVa protein or short hairpin RNA led to an accumulation of ZBP1 in axons. Live cell imaging of mCherryZBP1 in neurons expressing GTD showed an increase in the number of motile particles, run length and stimulated anterograde moving ZBP1 particles, suggesting that MyoVa controls availability of ZBP1 for microtubule-dependent transport. These findings suggest a novel regulatory role for MyoVa in the transport of ZBP1 within axons.
PMCID: PMC3508068  PMID: 23100434
4.  Arc/Arg3.1 mRNA expression reveals a sub-cellular trace of prior sound exposure in adult primary auditory cortex 
Neuroscience  2011;181C:117-126.
Acquiring the behavioral significance of a sound has repeatedly been shown to correlate with long term changes in response properties of neurons in the adult primary auditory cortex. However, the molecular and cellular basis for such changes is still poorly understood. To address this, we have begun examining the auditory cortical expression of an activity-dependent effector immediate early gene (IEG) with documented roles in synaptic plasticity and memory consolidation in the hippocampus: Arc/Arg3.1. For initial characterization, we applied a repeated 10 minute (24 hour separation) sound exposure paradigm to determine the strength and consistency of sound-evoked Arc/Arg3.1 mRNA expression in the absence of explicit behavioral contingencies for the sound. We used 3D surface reconstruction methods in conjunction with fluorescent in-situ hybridization (FISH) to assess the layer-specific sub-cellular compartmental expression of Arc/Arg3.1 mRNA. We unexpectedly found that both the intranuclear and cytoplasmic patterns of expression depended on the prior history of sound stimulation. Specifically, the percentage of neurons with expression only in the cytoplasm increased for repeated versus singular sound exposure, while intranuclear expression decreased. In contrast, the total cellular expression did not differ, consistent with prior IEG studies of primary auditory cortex. Our results were specific for cortical layers 3–6, as there was virtually no sound driven Arc/Arg3.1 mRNA in layers 1–2 immediately after stimulation. Our results are consistent with the kinetics and/or detectability of cortical sub-cellular Arc/Arg3.1 mRNA expression being altered by the initial exposure to the sound, suggesting exposure-induced modifications in the cytoplasmic Arc/Arg3.1 mRNA pool.
PMCID: PMC3074009  PMID: 21334422
immediate early gene; mouse; catFISH; novelty; familiarity; synaptic plasticity
5.  A tool for self-assessment of communication skills and professionalism in residents 
Effective communication skills and professionalism are critical for physicians in order to provide optimum care and achieve better health outcomes. The aims of this study were to evaluate residents' self-assessment of their communication skills and professionalism in dealing with patients, and to evaluate the psychometric properties of a self-assessment questionnaire.
A modified version of the American Board of Internal Medicine's (ABIM) Patient Assessment survey was completed by 130 residents in 23 surgical and non-surgical training programs affiliated with a single medical school. Descriptive, regression and factor analyses were performed. Internal consistency, inter-item gamma scores, and discriminative validity of the questionnaire were determined.
Factor analysis suggested two groups of items: one group relating to developing interpersonal relationships with patients and one group relating to conveying medical information to patients. Cronbach's alpha (0.86) indicated internal consistency. Males rated themselves higher than females in items related to explaining things to patients. When compared to graduates of U.S. medical schools, graduates of medical schools outside the U.S. rated themselves higher in items related to listening to the patient, yet lower in using understandable language. Surgical residents rated themselves higher than non-surgical residents in explaining options to patients.
This appears to be an internally consistent and reliable tool for residents' self-assessment of communication skills and professionalism. Some demographic differences in self-perceived communication skills were noted.
PMCID: PMC2631014  PMID: 19133146
6.  Temporal and Spatial Patterns of Eukaryotic and Bacterial Communities Found in Vernal Pools▿ †  
In this study, we examined the effects of physicochemical variability on the microbial communities of vernal pools. Denaturing gradient gel electrophoresis revealed temporal changes to be more pronounced than spatial changes in eukaryotic and bacterial communities. Sequencing revealed high degrees of richness in decomposers, which supports the notion that vernal pools are heterotrophic habitats.
PMCID: PMC2293170  PMID: 18310431

Results 1-6 (6)