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Reports suggest that after bariatric surgery, the rate of drug and alcohol use increases. Because dopamine mediates the effects of both food and drugs, the question of whether or not altering diet would have an effect on drug reward was posed. In these experiments, animals received high fat (HF), control (CF), or high fat followed by control (HF/ CF) food. We predicted that rats in HF food would develop less sensitivity to cocaine whereas HF/CF and CF rats would a have higher sensitivity. Condition place preference (CPP) was performed starting on day 32. The apparatus had 2 sides. During the pretest (day 1), rats were placed in the box with no divider and allowed to roam freely on both sides for 30 minutes. On days 2 to 4, rats were injected in the morning with saline and placed on the side they preferred during the pretest. In the afternoon, they were injected with cocaine (1 to 10 mg/kg) and placed on the side they least preferred. After 3 days of training, rats were placed in the boxes without dividers to determine preference.
Cocaine was more potent as a reward in the HF/CF rats with significant reward observed at 3 mg/kg. In contrast, the lowest dose at which reward was seen in the CF and HF groups was 5 mg/kg cocaine. The hypothesis was supported because each group did react differently to cocaine. High fat food decreased sensitivity to cocaine whereas being placed on a diet after exposure to high fat food increased sensitivity.
HUMAN RETINAL PROGENITOR CELLS AS A THERAPY FOR DEGENERATING PHOTORECEPTOR CELLSGeorge Villatoro, Geoffrey Lewis.
University of California, Santa Barbara, Santa Barbara, CA.
Retinal photoreceptor degeneration is the common cause of blinding conditions such as retinitis pigmentosa that, up to date, has no true treatment. Our lab is focusing on the effect that human retinal progenitor cells have on existing photoreceptor cells in retinas that are suffering from photoreceptor degeneration. We expect the hRPC (human retinal progenitor cells) will have therapeutic effects on the retina by salvaging photoreceptor cells that would have otherwise degenerated. We will be using the animal model RCS (Royal Collage of Surgeons) rats as subjects, which exhibit the characteristic of a heritable gene mutation responsible for retinal cell degeneration. These rats are going to be injected with hRPC on postnatal day 30. On postnatal day 90, we will examine the effects that the hRPC had on the subject’s retina by first embedding the eyes in OCT and then cutting frozen sections of the retina. We will use methods of immunohistochemical labeling (anti-human antibody) to identify the progenitor cells and the nuclear stain hemotoxylin and eosin to tally the remaining photoreceptor nuclei. In an inflicted subject, most of the photoreceptor cells will have degenerated by postnatal day 90 so we could examine if the presence of the hRPC had an effect by counting how many photoreceptor cells have been preserved in the animal retina. We then are able to determine if the hRPC had a therapeutic effect on the inflicted retinas. The progenitor cell’s rescue potential can then be determined.
C. ELEGANS MODEL OF AMYOTROPHIC LATERAL SCLEROSIS: UNDERSTANDING THE ROLE OF TDP-43
AGGREGATION AND ITS EFFECTS ON HSN MOTOR NEURONSZelene Figueroa, Cindy Voisine.
Northeastern Illinois University, Chicago, IL.
Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) also known as Lou Gehrig’s disease, are often characterized by a loss of neurons that lead to death. It is hypothesized that the aggregation of the protein TDPis what leads to degeneration of motor neurons. The nematode C. elegans provides a neurodegenerative model for ALS that can be used to perform behavioral assays that monitor motor neuron function. This model was made by cloning the human version of the TDP-43 gene under a pan-neuronal promoter. Taking advantage of the transparency of C. elegans, the human TDP-43 was tagged with a YFP (yellow fluorescent protein) to provide visual representation
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of its aggregation during development and aging. Behavioral assays were performed to monitor TDP-43 and the effects of its aggregation in hermaphrodite specific neurons (HSN), which are responsible for the reproductive success of C. elegans. According to the preliminary data obtained, there are changes in egg laying rates between wild-type animals and animals expressing TDP-43. Observed changes in egg laying rates suggest defects in HSN motor neurons. The data supports the hypothesis that TDP-43 aggregation leads to neurodegeneration. Our studies using this C. elegans model will enhance our understanding of TDP-43 and neuronal defects associated with ALS.
PROLONGED HABITUATION: LONG PULSE RAMP WAVE ELICITS FEEDFORWARD INHIBITORY CIRCUIT IN
ZEBRAFISH LARVAECindy Martinez Juarez1, Ulysses Savage2, Adam Roberts3, David Glanzman3.
San Jose State University, San Jose, CA, 2Center for Neural Repair, University of California, San Diego, La Jolla, CA, 1
University of California, Los Angeles, Los Angeles, CA. 3
Zebrafish larvae are beneficial model organisms for investigating the neurobiological basis for elementary learning.
Zebrafish are especially useful because of their rapid development and reproduction. Their transparency in the larval stage makes them appropriate for investigating neuronal function using optogenetics. Zebrafish larvae demonstrate a rapid escape reflex (the C-start), which is mediated by a simple neural circuit located in the brainstem and spinal cord consisting of Mauthner (M) cells. This neural circuit readily lends itself to neurophysiological analyses because of its relative simplicity. Previous research established distinct forms of habituation of the C-start reflex in response to auditory stimuli. Habituation is a nonassociative type of learning in which an organism’s responsiveness to a stimulus is decreased after repeated exposure to that particular stimulus. The current research uses a long-duration tone that gradually increases in intensity instead of a short tone burst to induce longer lasting habituation. These long duration tone bursts may elicit a feedforward inhibitory neural circuit that is not elicited by short tone bursts. A highspeed camera captures the images of the larvae while they are exposed to this long duration tone to determine if the larvae exhibit a C-start reflex. Preliminary results indicate that the use of a long-duration tone causes an increase in the strength and duration of habituation. This research may yield insights into the role of inhibition in simple forms of learning and memory.
MECHANICAL CHANGES CAUSED BY CORTICAL SPREADING DEPRESSIONNicholas Sun Child2, Kevin Christopher Brennan1, Jorge Mendez1, Jeremy Theriot1.
University of Utah, Salt Lake City, UT, 2University of Montana, Missoula, MT.
1 Cortical spreading depression (CSD) is a slowly propagating wave of neuronal and glia depolarization involved in several neurological disorders including migraine, stroke, and brain injury. The physical displacement of the neural tissue associated with the wave is an important component of CSD that has not been previously quantified. Regarding mechanical changes at the cellular level, it was shown that CSD causes neuronal and astrocytic swelling but only for a short time after the passage of the depolarizing wave has been analyzed, even though the effects of CSD on brain tissue last at least an hour. In this work, we characterized physical changes in the brain as a result of CSD using in vivo, 2-photon excitation microscopy. Genetically modified animals expressing green fluorescent protein in interneurons (GAD67-GFP Δneo) allowed tracking of the position of interneurons as the wave progresses. In addition, the use of a dye that is specifically taken up by astrocytes (sulforhodamine 101) allowed simultaneous measurements of cell volumes in interneurons and in astrocytes. Three dimensional images at different time points before and after CSD were reconstructed from Z-stacks of an area with several interneurons and astrocytes. Images were processed in ImageJ by manually thresholding the local area around each cell, and their volumes were calculated 5 s, 30 s, and 1 h after CSD. This study is providing important information regarding the amplitude and duration of the mechanical changes at a cellular level after CSD. Our results could help explain the effects of CSD in migraine, stroke, and brain injury.
DETERMINING THE FUNDAMENTAL UNIT OF SONG IN ZEBRA FINCHESJennifer Watts, Todd Troyer.
University of Texas at San Antonio, San Antonio, TX.
Most complex actions, such as speech, are composed of sequences of more basic motor gestures such as syllables or words. Songbirds have emerged as a leading model system for studying how brain circuits produce
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Biological Sciences such complex sequences. The song of the most widely studied songbird, the zebra finch, consists of repeats of a stereotyped sequence of 100- to 250- millisecond-long vocal gestures known as syllables. Birds startled by flashes of light interrupt their song between syllables, suggesting that syllables are units of song behavior. However, electrophysiological recordings reveal that individual neurons producing 5 to 10 millisecond bursts of action potentials aligned to the song with millisecond precision. Furthermore, there is no evidence that these bursts are organized into syllable-sized units. Our lab has developed software that extracts acoustic features from each 5 to 10 millisecond long slice of song, allowing variations in song behavior to be measured at the time scale of neural bursts. We hypothesize that, if the syllable is the fundamental unit of song, then the song-by-song feature correlations between slices in the same syllable will be stronger than feature correlations between slices in different syllables. We will record a large collection of adult zebra finch songs (90 days of age, 500 songs per bird), use computer aided software to identify song syllables, and then determine feature correlations. If our hypothesis is correct, it will indicate the presence of currently unknown neural mechanisms that serve to link neural bursts into syllable-based units. (Partially supported by NSF IOS-0951310 and NIH/NIGMS MBRS-RISE GM06065).
DRIED PLUMS’ ABILITY TO PROTECT FROM POST-MENOPAUSAL WEIGHT GAIN DUE TO ALTERATIONS IN
GUT MICRO FLORANataly Daggy, Brenda Smith.
Oklahoma State University, Stillwater, OK.
In less than 40 years, the prevalence of obesity in the US has increased by over 50%. In the female population, a deficiency in estrogen due to menopause is similarly responsible for increased adiposity, increasing chances of cardiovascular disease. Studies have shown that body weights of ovariectomized mice fed dried plum were lower than mice fed a controlled diet. Recently, studies suggest that microflora may play a vital role in obesity through their impact on metabolism and energy storage. It has been shown that normal-weight, germ-free mice inoculated with microflora from obese mice had an increase in adipose tissue despite following a low fat diet. The purpose of our experiment is to understand why ovariectomized mice on a controlled diet are experiencing weight gain and increased adiposity, while ovariectomized mice on the dried plum diet are not experiencing these detrimental effects of hormone deficiency. In this study X-week-old mice will either be Sham operated (Sham = 1 Group) or overiectomized (OVX = 5 groups) and assigned to the following treatments: groups 1 (sham) and 2 (OVX) on a control diet, group 3 with a 25% DP diet, group 4 with DP polyphenol extract diet, group 5 with a DP carbohydrate extract diet, and group 6 a DP polyphenol and carbohydrate extract diet. All 5 diets are isocaloric and contain the same amount of macronutrient.
Body composition will be analyzed, food intake will be recorded, and fecal content will be collected and analyzed.
EFFECTS OF DIETARY CHOLESTEROL AND JOJOBA SEED OIL ON HIGH-DENSITY LIPOPROTEIN
SUBCLASSES IN NEW ZEALAND WHITE RABBITSTarek Karam, Raymond Garcia.
California State University, Los Angeles, Los Angeles, CA.
Atherosclerosis is the leading cause of cardiovascular disease in America. The body’s defense against atherosclerosis is the reverse cholesterol transport pathway (RCT), a multistep process that results in the net movement of cholesterol esters by high-density lipoproteins (HDL) from the peripheral tissues to the liver. The characteristic decrease of serum HDL concentrations in hypercholesterolemic New Zealand White (NZW) rabbits is hindered by dietary jojoba oil.
We hypothesize that differences among the two main HDL subfractions, HDL2 and HDL3, that maintain HDL level is due to regulation of HDL2 cholesterol esters (HDL2-CE). NZW rabbits were divided into four experimental groups and placed on either a normal chow diet or a normal diet supplemented with either 3% jojoba oil, 1% cholesterol, or 1% cholesterol + 3% jojoba oil. Cholesterol esters were measured one week after the diets were administered. Our results show a significant interaction between the HDL2-CE concentrations and total serum HDL concentration in the cholesterol and the cholesterol + jojoba oil diets, suggesting that the effects of jojoba oil on HDL concentration are due to the regulation of HDL2. (CSU-LSAMP is supported by the National Science Foundation under Grant No. HRDand the CSU Office of the Chancellors.)
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SCIENCE IDENTITY MEDIATES THE EFFECTS OF TRADITIONAL ELDER SUPPORT IN A STEM COURSE ON
STUDENT LEARNING OUTCOMESPriscila Angeles Rojas1, Sarah Alkholy1, Tanya Dahms2, Fidji Gendron3, Maria Pontes Ferreira1.
Wayne State University, Detroit, MI, 2University of Regina, Regina, SK, CA, 3First Nations University of Canada, 1 Regina, SK, CA.