Demonstrating Cerebral Vascular Networks: A Comparison of Methods for the Teaching Laboratory

One challenge of neuroscience educators is to make accessible to students as many aspects of brain structure and function as possible. The anatomy and function of the cerebrovasculature is among many topics of neuroscience that are underrepresented in undergraduate neuroscience education. Recognizing this deficit, we evaluated methods to produce archival tissue specimens of the cerebrovasculature and the “neurovascular unit” for instruction and demonstration in the teaching lab. An additional goal of this project was to identify the costs of each method as well as to determine which method(s) could be adapted into lab exercises, where students participate in the tissue preparation, staining, etc. In the present report, we detail several methods for demonstrating the cerebrovasculature and suggest that including this material can be a valuable addition to more traditional anatomy/physiology demonstrations and exercises

Behavioral and Neuroanatomical Abnormalities in Pleiotrophin Knockout Mice

Pleiotrophin (PTN) is an extracellular matrix-associated protein with neurotrophic and neuroprotective effects that is involved in a variety of neurodevelopmental processes. Data regarding the cognitive-behavioral and neuroanatomical phenotype of pleiotrophin knockout (KO) mice is limited. The purpose of this study was to more fully characterize this phenotype, with emphasis on the domains of learning and memory, cognitive-behavioral flexibility, exploratory behavior and anxiety, social behavior, and the neuronal and vascular microstructure of the lateral entorhinal cortex (EC). PTN KOs exhibited cognitive rigidity, heightened anxiety, behavioral reticence in novel contexts and novel social interactions suggestive of neophobia, and lamina-specific decreases in neuronal area and increases in neuronal density in the lateral EC. Initial learning of spatial and other associative tasks, as well as vascular density in the lateral EC, was normal in the KOs. These data suggest that the absence of PTN in vivo is associated with disruption of specific cognitive and affective processes, raising the possibility that further study of PTN KOs might have implications for the study of human disorders with similar features

High source levels and small active space of high-pitched song in bowhead whales (Balaena mysticetus)

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Public Library of Science, doi:10.1371/journal.pone.0052072.The low-frequency, powerful vocalizations of blue and fin whales may potentially be detected by conspecifics across entire ocean basins. In contrast, humpback and bowhead whales produce equally powerful, but more complex broadband vocalizations composed of higher frequencies that suffer from higher attenuation. Here we evaluate the active space of high frequency song notes of bowhead whales (Balaena mysticetus) in Western Greenland using measurements of song source levels and ambient noise. Four independent, GPS-synchronized hydrophones were deployed through holes in the ice to localize vocalizing bowhead whales, estimate source levels and measure ambient noise. The song had a mean apparent source level of 185±2 dB rms re 1 µPa @ 1 m and a high mean centroid frequency of 444±48 Hz. Using measured ambient noise levels in the area and Arctic sound spreading models, the estimated active space of these song notes is between 40 and 130 km, an order of magnitude smaller than the estimated active space of low frequency blue and fin whale songs produced at similar source levels and for similar noise conditions. We propose that bowhead whales spatially compensate for their smaller communication range through mating aggregations that co-evolved with broadband song to form a complex and dynamic acoustically mediated sexual display.This work was funded by the Oticon Foundation (grant # 08-3469 to Arctic Station, OT). OT and MC were additionally funded by AP Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal, MS by a PhD scholarship from the Oticon Foundation, FHJ by a Danish Council for Independent Research, Natural Sciences post-doctoral grant, SEP by a grant from the U.S. Office of Naval Research, and PTM by frame grants from the Danish Natural Science Research Council

Behavioral and neuroanatomical abnormalities in pleiotrophin knockout mice.

Pleiotrophin (PTN) is an extracellular matrix-associated protein with neurotrophic and neuroprotective effects that is involved in a variety of neurodevelopmental processes. Data regarding the cognitive-behavioral and neuroanatomical phenotype of pleiotrophin knockout (KO) mice is limited. The purpose of this study was to more fully characterize this phenotype, with emphasis on the domains of learning and memory, cognitive-behavioral flexibility, exploratory behavior and anxiety, social behavior, and the neuronal and vascular microstructure of the lateral entorhinal cortex (EC). PTN KOs exhibited cognitive rigidity, heightened anxiety, behavioral reticence in novel contexts and novel social interactions suggestive of neophobia, and lamina-specific decreases in neuronal area and increases in neuronal density in the lateral EC. Initial learning of spatial and other associative tasks, as well as vascular density in the lateral EC, was normal in the KOs. These data suggest that the absence of PTN in vivo is associated with disruption of specific cognitive and affective processes, raising the possibility that further study of PTN KOs might have implications for the study of human disorders with similar features

Pharmacological inhibition of NPY receptors illustrates dissociable features of experimental colitis in the mouse DSS model: Implications for preclinical evaluation of efficacy in an inflammatory bowel disease model.

Administration of dextran sodium sulfate (DSS) to rodents at varying concentrations and exposure times is commonly used to model human inflammatory bowel disease (IBD). Currently, the criteria used to assess IBD-like pathology seldom include surrogate measures of visceral pain. Thus, we sought to standardize the model and then identify surrogate measures to assess effects on visceral pain. We used various 4% DSS protocols and evaluated effects on weight loss, colon pathology, biochemistry, RNA signature, and open field behavior. We then tested the therapeutic potential of NPY Y1 and/or Y2 receptor inhibition for the treatment of IBD pathology using this expanded panel of outcome measures. DSS caused weight loss and colon shrinkage, increased colon NPY and inflammatory cytokine expression, altered behaviors in the open field and induced a distinct gene metasignature that significantly overlapped with that of human IBD patients. Inhibition of Y1 and/or Y2 receptors failed to improve gross colon pathology. Y1 antagonism significantly attenuated colon inflammatory cytokine expression without altering pain-associated behaviors while Y2 antagonism significantly inhibited pain-associated behaviors in spite of a limited effect on inflammatory markers. A protocol using 7 days of 4% DSS most closely modeled human IBD pathology. In this model, rearing behavior potentially represents a tool for evaluating visceral pain/discomfort that may be pharmacologically dissociable from other features of pathology. The finding that two different NPY receptor antagonists exhibited different efficacy profiles highlights the benefit of including a variety of outcome measures in IBD efficacy studies to most fully evaluate the therapeutic potential of experimental treatments

Latencies to escape the Morris water maze for PTN KOs (n = 13) and WTs (n = 13).

<p>(a) Spatial version, first maze; (b) cued version, first maze; (c) cued version, second maze; (d) spatial version, second maze. *p = <0.05.</p

Social approach behavior in PTN KOs and WTs.

<p>(a) Time spent in the stranger 1 chamber, empty chamber, and center chamber during the sociability test; (b) time spent in the stranger 1 chamber, stranger 2 chamber, and center chamber during social novelty test; (c) total number of chamber entries made during the sociability and social novelty tests for KOs (n = 11) and WTs (n = 9). *p = <0.05.</p

Entorhinal cortical cellular characteristics in PTN KOs and WTs.

<p>(a) Neuronal area and (b) interneuronal distance in layer IV and layer V of the entorhinal cortex in KOs (n = 9) and WTs (n = 10). Nissl-stained sections of layer IV of entorhinal cortical tissue in a (c) WT and (d) KO; and whole sections of entorhinal cortex in a (e) WT and (f) KO. Scale bar = 250 mm. *p = <0.05.</p

Elevated plus maze behavior in PTN KOs and WTs.

<p>(a) Percentage of time spent in, and entries into, open arms, (b) total number of arm entries, and (c) latency to first arm entry for KOs (n = 8) and WTs (n = 6). *p = <0.05.</p