Bushmire, Victoria E.
May 2006
Double Major: Neuroscience/Psychology
First Reader: Clark
Second Reader: Cross
Effects of Punished Responding of Feeding Behavior in PVN Lesioned Rats
Abstract: A physiological punishment paradigm may exist in the naturally produced satiety signals one experiences after sufficient food intake to eliminate continued eating. Stomach and gastric distention felt after eating may serve as physiological signals to reduce food intake because, if one is full, food should no longer be reinforcing. However, with the overwhelming prevalence of obesity, it perhaps can be concluded that satiety signals no longer control feeding behavior and overeating and weight gain is a result. The current study investigates the effects of punished behavior on feeding behavior in PVN lesioned rats. Before and after bilateral electrolytic lesions, lever pressing behavior was observed in an alternating schedule of food and shock presentation. Although previous research suggests that PVN lesioned rats make more punished responses for reinforcement, similar results were not found in this study. Furthermore, the results also contradict other research that suggests when paired with food, shock may actually serve to increase response rates. It should be noted, however, that PVN lesions were not successful and the experimental procedure was not similar to those used in previous studies,
possibly explaining the obtained results. Funding: Allegheny College Neuroscience Program.
Ferris, Katheryn E.
May 2006
Major: Neuroscience
Minor: Science, Health, and Society / Chemistry
First Reader: Coates
Second Reader: Clark
Effects of Topical Nasal Carbonic Anhydrase Inhibition on CO2 Detection Threshold in Rats
Abstract: A previous study by Youngentob et al. (1991) reported that Long-Evans rats have the ability to discriminate inspired CO2 concentrations as low as 0.5%. The first objective of this study was to determine CO2 detection thresholds for Sprague Dawley and Zucker rats. The rats were operantly trained to discriminate between CO2 and control air (0% CO2) and then were subjected to various CO2 concentrations (0.5-12.5%) to determine their threshold. It was found that there was a difference between strains with Zucker rats having an average threshold of 1.32% CO2 and Sprague Dawley rats having an average threshold of 0.53% CO2. A second objective of the study was to determine if the carbonic anhydrase (CA) inhibitor, methazolamide, would affect the CO2 threshold. CA is found in a small number of olfactory neurons in rats and may play a role in the discrimination of CO2. The thresholds of seven Zucker rats were determined and then retested after the CA inhibitor was applied topically to the nasal mucosa. The CO2 detection threshold was 5.9% after inhibition, which was significantly different than the 0.47% CO2 detection threshold found at baseline (p<0.001). These findings indicated that CA is required for the detection of low concentrations of nasal CO2. Funding: Heuer Foundation and Allegheny College Neuroscience Program.
Flynn, Sean P.
May 2006
Major: Neuroscience
Minor: English
First Reader: Hollerman
Second Reader: Cross
Effects of Haloperidol, Clozapine, and Combined 8-OH-DPAT/Haloperidol Treatment on Prepulse Inhibition in the Rat Neonatal Ventral Hippocampal Lesion Model of Schizophrenia
Abstract: Schizophrenia is one of the most common mental disorders affecting approximately one percent of the world’s population. Diagnosis involves a complex symptomology including positive, negative and cognitive-attentional symptoms. Thought disorder, a cognitive-attentional symptom, can be quantitatively measured though prepulse inhibition (PPI) of the acoustic startle response, a form of plasticity of the startle reflex mediated via sensorimotor gating, which is decreased in schizophrenic patients. Neonatal ventral hippocampal ibotenic-acid lesions (NHVL), an animal model of schizophrenia, exhibits deficits in PPI after postnatal day (PND) 56. Typical and atypical antipsychotic drugs are the most common treatment of schizophrenia, but have deleterious side effects including extra-pyramidal side-effects and hemotoxicity, respectively. Antipsychotic drugs with a D2/5-HT1A receptor profile have shown promise in the treatment of schizophrenia. The 5-HT1A agonist 8-OH-DPAT (0.03 mg/kg) was given in conjunction with haloperidol (0.1 mg/kg) and compared to haloperidol (0.1 mg/kg) and clozapine (2.5 mg/kg) for reversal of NVHL-induced PPI deficits. NVHL animals exhibited no deficits in PPI on PND 56, inhibiting examination of antipsychotic drug effects. The inability to produce PPI deficits may result from adult hippocampal neurogenesis, insufficient hippocampal damage, PPI measurement systems, rodent substrain or genetic differences at the D2 receptor. Funding: Keck Foundation and Allegheny College Neuroscience Program.
Geffert, Laura M.
May 2006
Double Major: Neuroscience/Psychology
First Reader: Cross
Second Reader: Hollerman
Comparison of Startle Response in Spontaneously Hyperactive Rats (SHR) after injection of treatments that affect the 5-HT, NE, and DA systems.
Abstract: Attention Deficit Hyperactivity Disorder is a frustrating disorder because it is not yet understood why children and adults manifest behavior problems. Stimulants increase locomotor activity in non-ADHD children but decrease locomotor activity and increase attention in children with ADHD. Neurochemically, psychostimulants are thought to interact with plasma membrane monoamine transporters, especially the dopamine, serotonin, and norepinephrine transporters. Antidepressents that increase the release or decrease the reuptake of 5-HT have been studied for their therapeutic possibilities due to serotonin’s inhibitory effects on some excitatory neurotransmitters such as norepinephrine and their behavioral disinhibition of impulsivity. The high incidence of male diagnoses of ADHD is discussed and different treatments are proposed for each sex. In combination with pharmacological procedures, the prepulse inhibition test allowed for examination of the neurochemical and neuroanatomical systems that are in control of sensorimotor gating, which appears to be abnormal in those diagnosed with ADHD. Spontaneously hypertensive rats were used as the animal model for ADHD to study the difference of effects of methylphenidate (10mg/kg), nicotine (0.4 mg/kg), atomoxetine (1.5 mg/kg), and fluoxetine (5 mg/kg). The startle reactivity of the subjects was significantly lower in the methylphenidate or nicotine groups than in the atomoxetine or fluoxetine groups. Prepulse intensities of 75 and 85 decibels yielded more inhibition than 65 decibels or non-prepulse iterations. Females had significantly lower startle responses than males and showed more inhibition in the methylphenidate, atomoxetine, and fluoxetine groups than males. Nicotine did not show a significantly different startle response between genders, but indicated similar inhibition properties of methylphenidate. Funding: Allegheny College Neuroscience Program.
Geiser, Kyle S.
May 2006
Double Major: Neuroscience/Psychology
First Reader: Cross
Second Reader: Hollerman
Neonatal Ethanol Exposure and Treatment with the 5-HT1A Agonist Buspirone in an Animal Model of Fetal Alcohol Syndrome
Abstract: In the present study the effects of early postnatal exposure to ethanol (6.6% v/v; i.p.) and buspirone (4.5mg/kg; i.p.) on 5-HT1A receptor densities within the dorsal raphe was investigated. Rat pups were placed into one of three experimental groups: ethanol only, ethanol and buspirone, or control. The animals were subjected to either drug daily during the first eight postnatal days. Perfusions were done with a 4% paraformaldehyde solution on postnatal day 59. Immunocytochemistry was used to stain the receptors, which were quantified under a microscope with a magnification of 40X. The means were calculated and compared between the three groups. The ethanol only group had the lowest average number of 5-HT1A immunoreactive cells (13) per section/dorsal raphe. The ethanol and buspirone group had a mean of 20.8 while the control group had a mean of 23.45. Funding: Allegheny College Neuroscience Program.
Grant, Abigail R.
May 2006
Major: Neuroscience
Minor: German Studies
First Reader: Coates
Second Reader: French
The effects of temperature on the ventilatory responses of Sprague-Dawley rat pups to carbon dioxide and the implications for sudden infant death syndrome
Abstract: Increased temperature and accumulation of CO2 are both risk factors associated with sudden infant death syndrome. The purpose of the present study was to examine the effects of temperature on the ventilatory response of Sprague-Dawley rat pups to CO2. Thirty-nine rat pups from four litters were divided into three temperature groups: low (23-25C), medium (32-35C), and high (37-41C). Rat pups were tested on days 1, 2, 3, 5 and 7 following birth. Each weighed rat was placed in a plethysmograph chamber for detection of pressure changes during ventilation recordings. A 15-minute air sequence, including exposure to control air and 8% CO2, was delivered to each rat pup. Ventilatory traces were recorded with BIOPAC software and analyzed to determine breathing frequency, minute ventilation, and tidal volume. The results of this study suggest increasing or decreasing temperature from thermal neutrality may increase responsiveness to CO2. These results support the proposed association between temperature and increased risk of SIDS and suggest a thermally stressed infant may be overly sensitive to accumulation of CO2. Funding: Allegheny College Neuroscience Program.
Groth, Daniel C.
May 2006
Major: Neuroscience
Minor: History
First Reader: French
Second Reader: Nelson
Conus venom mediated effects on a Voltage-gated K+ channel found in the STG of the spiny lobster Panulirus interruptus
Abstract: In recent years a lot of research has been put into an organism known as the Cone Snail, a predatory snail with potent venom comprised of many short proteins known as Conus peptides. Conus peptides, or conotoxins, are able to target specific biological sites such as specific voltage-gated ion channels and ligand-gated ion channels. Relatively few conotoxin peptides have been identified that interact with voltage-gated K+ channels in comparison to Na+ and Ca2+ channels. Shal, a member of the Shaker family, is a gene that encodes a voltage-gated K+ channel that mediates A-type transient current, which is known to regulate neuronal membrane excitability as well as participate in many other functions. Little research has been put into the targeting of voltage-gated K+ channels such as Shal, and no conotoxin has been found to target this channel. In this experiment, shal RNA from the spiny lobster, Panulirus interruptus, was injected into Xenopus oocytes in order to determine if there was a significant difference in resting membrane potential and current generated when Conus venom was present. Over this study, the health of isolated oocytes was called into question. Many parameters were changed in order to insure greater oocyte survival rate, which included changes in the ND96 solution and injection electrodes. From voltage-steps and current traces, it was seen that the peak current at + 60mV was 3mA for shal-injected oocytes, and around 0.15mA at +55mV for water-injected oocytes. Due to time constraints, health of oocytes and difficulties with the electrophysiological apparatus, the addition of Conus Venoms was unable to be performed. Funding: Allegheny College Neuroscience Program.
John, Tamara N.
May 2006
Double Major: Neuroscience/Psychology
Minor: Spanish
First Reader: Cross
Second Reader: Clark
A comparitive study on the effects of Valporate, Carbamazepine, and Lamitrogine in PTZ- induced seizure rats
Abstract: Seizures occur across a vast spectrum of degenerative and psychological disorders. To maintain control over the various types of seizures there are many types of anti-epileptic drugs (AED) in use today. However, with each medication there are serious side effects to cortical areas, mainly the hippocampus. This study used Spontaneously hypertensive rats (SHR) to analyze the extent of damage within the hippocampus and other cortical areas due to the administration of various anti-epileptic drugs. Pentylenetetrazol (PTZ) was used to create the animal model of human absence seizures. Valporic Acid (VPA), Carbamazepine (CBZ), and Lamotrigine(LTG) were shown to cause significant damage to the hippocampus and amygdala regions by using an epifluorescent microscope with a blue light filter to analyze the slides. Both the Startle Response and Shuttle Box test showed statistical significance between drugs. VPA was statistically significant in the Startle Response test, while the LTG group was significant in the Shuttle Box test compared to the other drug groups. It can be concluded that while PTZ-induced seizures did cause serious damage to the brain, the medication used to treat the seizures caused further damage to both the hippocampus and the amygdala. Funding: Allegheny College Neuroscience Program.
Knaus, Eric R.
May 2006
Double Major: Neuroscience/Psychology
First Reader: Cross
Second Reader: Clark
Pre and Post-surgical Administration of Minocycline for Increasing Efficacy of Fetal Dopamine Grafts to Alleviate Parkinsonian Symptoms in 6-hydroxydopamine Lesioned Rats
Abstract: Parkinson’s disease is a neurological disorder characterized by the progressive degeneration of the nigrostriatal dopamine pathway. Limitations in pharmacological treatments have spurred examination of alternative treatments, such as dopaminergic cell grafts. The robustness of dopaminergic fetal cell grafts makes this type of graft an especially promising option. Excitotoxicity and immunological responses in the brain are likely barriers to greater efficacy of grafted tissue. Minocycline has been noted to be effective in treating and reducing the effects of neurological insult. This experiment explored the potential of minocycline use in increasing the survival and efficacy of fetal cell grafts. Rats given 6-hydroxydopamine lesions of the substantia nigra, and split into different groups to be treated pre and post-transplantation with intravenous doses of minocycline, showed no significant behavioral differences between minocycline administration groups and control after a complex analysis of variance. Histological data exhibited subtle, but notably better results in post-administration animals. Funding: Allegheny College Neuroscience Program.
Kozlosky, Heather L.
May 2006
Double Major: Neuroscience/Psychology
First Reader: Cross
Second Reader: Dale
The Antinociceptive Effects of Massage-like Stimulation on the Zucker Rat: An Investigation of the Involvement of Endogenous Oxytocinergic Mechanisms
Abstract: The use of massage therapy as a holistic approach to pain management has been found to employ methods that utilize the body’s own mechanisms in the relief of pain. The purposes of this study were to determine the effects of massage in the body based on review of earlier research and current experimentation, and to supply a neurological basis for the central mechanisms providing for its analgesic effect. Non-noxious somatosensory stimulation, i.e. massage, has been shown to produce an analgesic effect by stimulating a release of oxytocin, and oxytocinergic terminals have been identified in the pain modulation areas of the brain, specifically, the periaqueductal gray matter. All nine rats received chronic cannula implantations to the PAG prior to the start of the experiment. After recovery, massage treatments were carried out for 3 weeks, following with nociceptive tests designed to measure how quickly rats removed their tails from the painful stimulus, hot water. Rats then received 3 treatments of intra-PAG injections of OT and were used as comparison against the massage treatments. The increases in tail flick latencies demonstrated that animals undergoing massage therapy and OT treatment, respectively, were able to withstand more pain for longer periods of time than prior to treatment. This effect was diminished with the non-selective opioid receptor antagonist naloxone. Funding: Allegheny College Neuroscience Program.
Marlowe, Autumn K.
May 2006
Double Major: Neuroscience/Psychology
Minor: Music Theory
First Reader: Cross
Second Reader: Clark
Testing the Mirror Neuron Hypothesis of Autism Using Observational Learning and an Animal Model.
Abstract: The current study examined the validity of the mirror neuron hypothesis of autism and attempted to provide support for this hypothesis using an animal model. The Sprague-Dawley subjects were injected with valproic acid at 12.5 days of gestation. This interferes with neuronal development and causes symptoms very similar to those seen in autism. This study attempted to use behavioral and social recognition tests to assess the social deficits of the rats. The assessments used were social recognition based on olfactory cues and a water maze test where the route to a platform was learned by observing a test animal.
Normality of the controls and abnormality of the VPAs was determined by their performance in the olfactory cues social recognition test. These tests showed that the VPAs spend less time investigating, however they follow the general pattern expected when presented with a new animal. Observational learning abilities of the controls and VPAs were assessed using the water maze test. Results of this test indicated no deficit in the observational learning of the VPAs, who actually performed better than the controls. Overall, no evidence was found to support the mirror neuron hypothesis of autism. Funding: Allegheny College Neuroscience Program.
McIlvried, Lisa A.
May 2006
Double Major: Neuroscience/Psychology
First Reader: Cross
Second Reader: Hollerman
Treatment potential of minocycline in solid fetal tissue grafting for Parkinson’s disease
Abstract: Parkinson’s disease is one of the most common neurodegenerative disorders in the United States. It results in the progressive and selective loss of dopamine neurons in the nigrostriatal pathway, leading to motor deficits. There is currently no known successful, long-term therapy. Mesencephalic fetal cell transplantation has possible therapeutic benefits because it strives to replace the dopamineric neurons and repair the underlying degeneration. However, in experiments so far only 5-10% of transplanted cells survive. The inflammatory response created by microglia, the brain’s immune system, could be a main factor in tissue death. It is possible to ameliorate these conditions by specifically inhibiting microglia with minocycline, which has neuroprotective and restorative properties. This study aimed to test the potential of minocycline for improving the grafting technique. Rat solid fetal mesencephalic tissue was treated with minocycline or saline (control) and grafted next to the caudate nucleus using the unilateral 6-OHDA rat model of Parkinson’s disease. Survival of the graft was assessed behaviorally as well as histologically. While no statistical significance was found, results of individual rats suggested that grafts were behaviorally beneficial for improvement in motor skills associated with PD. It is possible that minocycline increased integration of grafts but did not necessarily improve behavioral deficits. Funding: Allegheny College Neuroscience Program.
McShea, Megan E.
May 2006
Major: Neuroscience
Minor: Writing
First Reader: French
Second Reader: Nelson
Continuing the search for Conus venom peptides specific to the Ca2+- and voltage-gated K+ channel, hSlo
Abstract: The discovery of highly specific, relatively short peptide chains from the venoms of predatory Conus snails have ushered in a new era of pharmacologic research, with immense potential for hSlo K+ channel investigation. In humans the channel is distributed throughout several tissues, including the brain and smooth muscle, and plays an increasingly understood role in maintaining tissue ‘tone’ and homeostasis (McCobb et al., 1995; Tanaka et al., 1997). The development of specific pharmacologic agents using Conus venoms promises to improve our understanding and control of the channel in both laboratory and clinical settings. Within this study, hSlo was expressed in the membrane of Xenopus laevis oocytes and current was measured using two-electrode voltage clamping. Difficulty with oocyte health prevented Conus venom application; otherwise the effects of Conus striatus would have been explored. Changes to the oocyte protocol were made, and further changes were suggested to optimize oocyte health for future experiments. However, despite oocyte difficulties the hSlo channel was expressed in this model system, which shows great potential for future hSlo exploration.
Funding: Keck Foundation and Allegheny College Neuroscience Program.
Medwid, Valery A.
May 2006
Major: Neuroscience
Minor: Economics
First Reader: Cross
Second Reader: Hollerman
Effects of Castration and Subsequent Hormone Replacement Therapy on the Sexually Dimorphic Brain Structures and Sexual Orientation of the Sprague-Dawley Rat
Abstract: Volumetric differences in certain brain structures are believed to contribute to the sexual orientation and behavior of an individual. Research conducted on homosexual male brains show that a main structure responsible for sexual behavior (INAH-3) is smaller in homosexual men than in heterosexual men. The reduced size of the INAH-3 is seen in both homosexual men and women, leading researchers to believe that the brain of a homosexual man is similar to that of a female. The cause of this volumetric difference between homosexual and heterosexual men is not certain, but prenatal stress and the circulation of testosterone are two possible contributing factors. The purpose of this study was to investigate whether testosterone levels reduced by castration would cause male rats to exhibit homosexual behavior. This would include the loss of attraction to females and increased attraction to males. This study further investigated whether injections of testosterone in the castrated male rats would reinstate sexual attraction to females. Results showed that male rats did indeed show a decrease in sexual attraction to female rats after castration, but no increased attraction toward males. Testosterone replacement proved to reverse the effects of castration and bring the males back to their sexual orientation prior to surgery. These findings relate to assumption that hormone imbalance and reduction in the size of certain brain structures is responsible for homosexual behavior. Funding: Allegheny College Neuroscience Program
Mickley, Katherine R.
May 2006
Double Major: Neuroscience/Psychology
Minor: English
First Reader: Dale
Second Reader: Wiseman
Title: An Electrophysiological Comparison of the Retrieval of Words in Emotional and Non-emotional Context
Abstract: A major approach to the understanding of emotion and cognition has been the study of memory of emotional events. However, the cognitive and neural mechanisms responsible for the interaction of emotions and memory are still unclear. In order to understand the effects of emotional context on retrieval of memories and avoid the confound of emotion at retrieval, this study examined the brain’s event-related potentials (ERPs) elicited by the recognition of words that had been encoded in mentally imagined positive, negative, or neutral contexts. Neutrally valenced words were presented to participants in positive, negative, or neutrally valenced sentences, and participants were asked to create a visual mental image of the sentence. At test, participants made old/new recognition judgments for these words while ERPs were being recorded via an electroencephalogram. Words encoded in positive contexts, but not those encoded in negative contexts, were recognized at lower rates than those encoded in neutral contexts. In addition, words from negative, but not positive sentences across all classes of items elicited late (1000-1600ms) positivity in the right frontopolar scalp region. Late frontopolar positivity changed as a function of class (emotional hit, neutral hit or correct rejection) and valence in that it was not present in the right hemisphere for neutral hits, emotional hits or correct rejections. A significant quadratic effect was also found in the right hemisphere across locations of electrodes for emotional hits, neutral hits and correct rejections from the negative emotion group. This may indicate that the brain using spatially distributed electrical changes to reflect retrieval of a certain piece of information. These findings suggest that the memory retrieval for positive and negative contexts have different cortical signatures. Funding: Allegheny College Neuroscience Program.
Myers, Wayne P.
May 2006
Double Major: Neuroscience/Psychology
First Reader: Hollerman
Second Reader: Cross
Behavioral Evaluation of Neurotoxin-Induced Dopamine Neuronal Death in Caenorhabditis elegans.
Abstract: Parkinson’s disease is a complex neurodegenerative disorder characterized by the death of neuronal dopamine. The recent completion of the Caenorhabditis elegans genome has made it a popular animal in the research of numerous diseases, including Parkinson’s disease. The neurotoxin 6-hydroxydopamine (6-OHDA) causes the degeneration of dopamine neurons and is used to create a neurotoxin induced Parkinsonian experimental model. The 6-OHDA induced Parkisonian model has been used to study the dopamine circuitry of C. elegans. Recent studies have used genetic and pharmacological evaluations to study 6-OHDA induced dopamine degeneration in C. elegans. Other studies have used genetic manipulations to reveal that the C. elegans dopamine circuitry is involved in various behaviors. Behaviors such as egg laying, mediation of locomotion rate in accordance to food availability (basal slowing response), and in avoidance responses (touch transducing response). This study showed that C. elegans exposed to the neurotoxin 6-OHDA were unable to execute normal egg laying behaviors and loss their ability to mediate their locomotion rate in accordance to food availability. Funding: Allegheny College Neuroscience Program.
Nguyen, Hanh T.
May 2006
Major: Neuroscience
Minor: Spanish
First Reader: Cross
Second Reader: Dale
The neuroprotective effects of isoflurance in awake ischemic vs. anesthetized ischemic animals using diffusion and perfusion imaging.
Abstract: Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) can rapidly detect lesions in acute ischemic stroke animal model. These methods were used to investigate the neuroprotective effects of isoflurane on the temporal evolution in transient (60 minutes) focal ischemic brain injury in rats via middle carotid artery occlusion (MCAO). The gold standard 2,3,5-triphenyltetrazolium chloride (TTC) staining method was used to compare infarct volume at 48 hours in three different animal groups (anesthetized with isoflurance, awake and restrained, and awake in cage)
The results show that the mean infarct volume in group A (awake and restrained during imaging, n = 4) tended to be larger than the Group B and C (anesthetized on the bench and wake up in the cage, respectively, n = 6). As expected, the TTC-defined infarct volume in Group A at 48 hours post-ischemia was significantly different with that in Group B and C (197.206±71.82 vs. 92.267±27.96mm3, P=0.01; 197.206±71.82 vs. 91.77±37.0246mm3, P=0.01, respectively). The mean infarct volumes in group B and C were similar. Surprisingly, the TTC-defined infarct volumes in Group B and C after 48 hours were not significantly different (92.267± 27.956 vs. 91.77±37.02 mm3, P=97.9).
In conclusion, quantitative diffusion and perfusion imaging during the acute phase after transient suture MCAO demonstrated substantial differences in the temporal evolution of the ischemic lesion in awake animal. The mean TTC-derived infarct volume of the awake and restrained ischemic animals is significantly higher than anesthetized ischemic animals. This result is contradicted by the lack of significant difference between the anesthetized ischemic animals and awake in the cage ischemic animals. Funding: Yerkes Imaging Center and Allegheny College Neuroscience Program.
Pajak, Chelsea E.
May 2006
Double Major: Neuroscience/Psychology
First Reader: Cross
Second Reader: Clark
Comparing the treatment effects of direct GABA agonist and NMDA partial agonist for the treatment of pilocarpine induced seizures
Abstract: Seizure disorders and epilepsy are the number one neurological disorder in canines. There are many treatment options for seizure disorders. They fall into three main groups: GABA agonists, partial NMDA agonists, and NMDA antagonists. The present study compared the effects of GABA agonist, Valproic Acid, and NMDA partial agonist, D-cycloserine, in terms of time of onset of the seizure and the severity of the seizure. Pilocarpine (10 mg/kg) was used to induce the seizure through an intraperitoneal injection. First the animal was pretreated with either saline (control group), Valproic Acid (200 mg/kg) or D-cycloserine (160 mg/kg). After seven minutes the pilocarpine was injected and timing began. The time that the first sign of seizure activity began was recorded. Also the severity, according to a modified Racine Scale, that the seizure reached within 15 minutes was recorded. The seizure was then stopped using the same dose of the same drug used during pretreatment (Valproic Acid in the control group). The results were not significant, but found that the control group had an overall higher time of onset and the D-cycloserine group had the lowest time of onset. Week two had the highest time of onset and week three had the lowest time of onset. Lastly, the control group reached the highest level of seizure severity and the valproic acid group had the lowest level of severity. The highest average seizure severity occurred in week one and was the lowest in week three. Funding: Allegheny College Neuroscience Program.
Paravati, Anthony J.
May 2006
Major: Neuroscience
Minor: economics
First Reader: Coates
Second Reader: Kleinschmidt
Gene Expression for Carbonic Anhydrase Isoenzymes in Rat Olfactory Epithelium
Abstract: Carbonic Anhydrase (CA) is physiologically important throughout the mammalian body as the catalyst of reversible hydration of CO2. There are a number of CA isoenzymes (CA I-XIV) with varying degrees of activity. Carbonic anhydrase mediated chemoreception is thought to be the physiological mechanism behind responses to elevated [H+] produced by delivery of CO2 and acidic odorants to the olfactory epithelium. CA enzymatic activity has been demonstrated in many tissue types, including the olfactory epithelium, using immunohistochemical techniques. However, the present study investigates relative expression of CA isoenzymes (CA I IV) at the transcriptional level in total olfactory epithelium harvested from 6 young-adult Sprague-Dawley rats (4 female; 2 male). Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed using primers for each gene coding for CA I through CA IV and the housekeeping gene GADPH to determine the relative expression of CA isoenzymes. In addition to GADPH, amplification products of CA II and CA IV were the most consistently detected CA genes in both male and female olfactory epithelium. The results suggest that CA II, followed by CA IV, is the most abundant CA mRNA in the olfactory epithelium and the kidney. Inter-individual variability and variability between sexes was also seen in the expression of CA isoenzymes in the rat olfactory epithelium. This variability may contribute to differences between individuals in olfactory chemosensitivity to CO2. Funding: Allegheny College Neuroscience Program.
Parker, October L.
May 2006
Major: Neuroscience
Minor: Writing
First Reader: Cross
Second Reader: French
The Effects of a-MSH on the Weight and Food Consumption in MSG- treated Zucker Rats
Abstract: The health complications that accompany obesity have induced several studies seeking to reverse the syndrome. The hormones that affect feeding and energy homeostasis have emerged as key players in obesity. Specifically, the hormones released by POMC neurons that are activated by leptin, have been shown to have significant effects on obese subjects. One set of POMC neurons is inhibited by leptin, and the other set are activated by leptin. Leptin activates a-MSH, which causes an increase in energy expenditure and a decrease in energy intake. Several researchers have found that mutation and desensitization of POMC neurons leads to obesity by unresponsiveness to anti-obesity signals. In this paper, it is hypothesized that injections of a-MSH into the Lateral Hypothalamus of MSG-obesity induced Zuckers will lead to weight loss. The results, however, reveal that a-MSH injections did not produce significant decreases in the weight of test subjects.Funding: Allegheny College Neuroscience Program.
Reoli Rachel A.
May 2006
Double Major: Neuroscience/Psychology
First Reader: Cross
Second Reader: Hollerman
An examination of the neuroprotective properties of 5-HT1A receptor agonist, BAY x 3702, on hippocampal CA1 neurons in a rat model of transient global ischemia
Abstract: 5-HT1A receptor activation has been proposed to provide neuroprotective properties (Kline, 2001) and aid in the extension of neuronal processes (Azmitia, 2001). The current study examined the neuroprotective effects of the 5-HT1A receptor agonist Repinotan, focusing on its proposed ability to reduce tissue damage of hippocampal CA1 neurons immediately following a rat model of transient global ischemia (TGI) (Kline, 2001). Through behavioral testing, a significant decrease in both total and dominant paw responses for food retrieval of the control subjects was found when comparing pre-surgical responses to post-surgical responses. However, no significant difference was observed in either the total paw responses or the dominant paw responses of the experimental subjects when comparing pre-surgical responses to post-surgical responses. Thus, the subjects treated with Repinotan immediately following TGI were found to show an increase in behavioral performance, unlike the subjects that did not receive treatment with Repinotan following TGI. Contrary to the behavioral results, histological findings showed that subjects treated with Repinotan possessed an increased amount of neuronal tissue damage when compared to the control subjects. This inconsistency may be due to a lack of reliability observed with the behavioral tests. Thus, deviating from the expectations that Repinotan possesses neuroprotective properties, the current study found that Repinotan does not act as a neuroprotectant when administered immediately following TGI. Funding: Allegheny College Neuroscience Program.
Rogerson, Ashley L.
May 2006
Double Major: Neuroscience/Psychology
First Reader: Coates
Second Reader: Hollerman
The Effects of Carbonic Anhydrase Inhibition on pH Response to CO2 in Rats
Abstract: The role of CO2 as an exogenous stressor in SIDS deaths has prompted research investigating the physiology of CO2 detection at the cellular level. The effects of CO2 application on pH change in nasal mucosa was investigated using the rat as an animal model. Carbonic anhydrase (CA) is the enzyme in the nasal mucosa and within olfactory receptor neurons (ORNs) that facilitates the hydration of CO2, resulting in its dissociation to H+ and HCO3-. Acid-sensitive ion channels are then activated by the increased concentration of protons ([H+]) and signal transduction is initiated. After observing a positive correlation between the magnitude of pH response and concentration of CO2 ([CO2]) applied, quaternary ammonium sulfide (QAS) and acetazolamide (AZ) were used to inhibit CA. pH responses before and after the application of the CA inhibitor were then compared. QAS, the membrane impermeable CA inhibitor, did not cause the pH responses to diminish at any [CO2] 10-20 minutes post-inhibition. These results were similar to those in the control group, which used mammalian ringers (MR) solution in place of a CA inhibitor. The trend of pH responses following AZ application indicated that this membrane permeable CA inhibitor caused pH responses to diminish 10-20 minutes after CA inhibition, though statistical significance was lacking. The hypotheses that AZ would cause a more robust decrease in pH response than QAS and that the QAS group would produce results similar to the MR control group were supported. These results indicate that H+-sensitive ion channels in the olfactory pathway may be responsible for CO2 detection and have possible implications in investigating the underlying causes of SIDS deaths. Funding: Heuer Foundation and Allegheny College Neuroscience Program.
Rongo, Eleonor P.
May 2006
Double Major: Neuroscience/Psychology
First Reader: Cross
Second Reader: Searle-White
Investigation of the Effects of Prenatal Stress on the Sexual Behavior and the Sexually Dimorphic Nucleus of the Sprague-Dawley Rat.
Abstract: The present study was designed to determine the effects of prenatal stress on the sexually dimorphic nucleus (SDN) of the medial preoptic area of the hypothalamus and to determine its potential relationship in male sexual behavior. Corticosteroid (2.5 mg) or restraint stress were induced during critical days of brain masculinization (18-19) or critical days up to delivery (18-21). Restraint stress was comprised of plexiglass holder while exposed to bright lights and a blowing fan induced for 2 one hour periods (30 min break in between). Groups (n=4) were identified according to appropriate treatments. The control (n=2) were left undisturbed. Feminization of sexual behavior was determined through four mechanisms: behavioral observations, estradiol and progesterone priming, castration/priming, and measurement of SDN area. Possible demasculinization from prenatal stress was determined due to absence of copulation with either male or female stimuli. Hormonal priming indicated some feminization of male brain circuitry due to observed lordosis in one animal from 4 day restraint, 2 day restraint and 4 day corticosteroid treatments. Significant feminization of male SDN was not determined due to limited data recovered. Of the data obtained, stressed groups were smaller compared to controls. Differences in area may simply be indicate variation in brain morphology. Overall, prenatal stress failed to produce immediate feminization of male sexual behavior. However, hormonal priming suggests some brain feminization. Hypothesis was refuted, where both corticosteroid and restraint (4 days) would exhibit immediate feminized sexual behavior and feminized SDN compared to control male. Funding: Allegheny College Neuroscience Program.
Schuh, Laura C.
May 2006
Double Major: Neuroscience/Psychology
First Reader: Cross
Second Reader: Hollerman
The Effects of MK-801 and PCPA on the Developing Neuromuscular Junctions in Mice
Abstract: The developing neuromuscular junction goes through a series of synaptic eliminations before it is considered mature. At birth, muscle fibers are innervated by many neurons, however, during late embryonic and postnatal periods, many neurons pull away, resulting in a muscle fiber innervated by only one neuron. During this process, only the most active inputs are maintained, while the least active draw back and are eliminated. Therefore, correlated activity in the nervous system reduces competition and causes a delay in development. Correlated activity, or gap junctional coupling, is increased with the pharmacological blocker, MK-081. The purpose of this study is to examine the effects of MK801 on the developing neuromuscular junction in mice. When treated with MK-801 mice show an increase in gap junctional coupling of connexins 40 and 45. Both of these connexins are usually down regulated, and eliminated during early postnatal development. Increased gap junctional coupling causes a decrease in motor neuron size (t-test, p<0.05). Funding: Allegheny College Neuroscience Program.
Stein, Kelly A.
May 2006
Double Major: Neuroscience/Psychology
First Reader: Cross
Second Reader: Clark
Treatment of Fetal Alcohol Exposure with 5-HT1A Receptor Agonist, Buspirone in order to Reverse Developmental Arrest
Abstract: Prenatal exposure to alcohol leads to a variety of fetal abnormalities including an underdeveloped brain, physical abnormalities, and cognitive and behavior dysfunction. These effects fall along a continuum of severity from mild cognitive or behavior problems to severe defects in appearance. One of the systems that alcohol is known to interfere with during prenatal development is the serotonin receptor system. The effect of a serotonin receptor agonist, buspirone, on the development of the serotonin system during prenatal alcohol exposure was tested using immunocytochemistry. There were significantly less cells containing 5-HT1A receptors in the animals exposed to ethanol during development, but more importantly animals treated with buspirone for ethanol exposure had significantly more cells containing receptors than the ethanol exposed animals without any treatment. The results of the study indicate that treatment of fetal alcohol exposure with a 5-HT1A receptor agonist is effective at reducing the negative effects on development. Funding: Allegheny College Neuroscience Program.
Stotsky, Bradley A.
May 2006
Double Major: Neuroscience/Psychology
First Reader: Cross
Second Reader: Hollerman
The Effects of Testosterone Propionate and Progesterone Steroid Treatment on Acoustic Startle Response in the Rat
Abstract: The present study examined acoustic startle response in three different groups of Sprague-Dawley adolescent male rats. Testosterone propionate (5.0 mg/kg) was administered for ten days to group TP, n=5 while progesterone (5.0 mg/kg) to group P, n=5, for the same amount of time. Controls, n=5, were treated for the same length with saline injections. Acoustic startle response at five different sound amplitudes was measured on Responder X software (Columbus Instruments). Animals were tested on day 1 of injections for acute effects drug treatment, day 10 of injections for subchronic effects of drug treatment and three days after the rat’s last injection to test for withdrawal effects of drug treatment. Using the data collected from startle response peak amplitude results indicate that as sound burst amplitude increased, startle response increased for all drug conditions. A conditioning response was seen in all drug treatments indicating habituation to testing apparatus. Significantly higher startle response amplitudes was seen among group P when compared to controls. This differs from previous studies that demonstrate anxiolytic effects from progesterone treatment due to the metabolism of progesterone into allopregnanolone (ALLO). This neuroactive steroid is a potent ligand of GABA receptors, the principle inhibitory neurotransmitter. Funding: Allegheny College Neuroscience Program.
Thomas, Michael G.
May 2006
Major: Neuroscience
Minor: Vocal Performance
First Reader: Cross
Second Reader: Hollerman
Evaluating Advanced Neuroprotective Strategies in Response to Stroke: developing an extended pharmaceutical timeline.
Abstract: Stroke is the third leading killer among all adults in the United States. Recent neuroprotective treatment approaches have been proven successful at the onset of the stroke in minimizing or eliminating neural damage. While the effects of stroke can be blocked with neuroprotectants, it is not practical or useful to administer these methods at the exact time of onset in humans, as most stroke patients are unable to communicate they are having an ischemic attack. This research investigated several advanced neuroprotective strategies to establish a pharmaceutical timeline of three hours in which neuroprotective drugs could be administered to block the negative effects. Combinations of Clenbuterol, Memantine, Magnesium Sulfate, and Minocycline were administered to stroke-model rats to determine the success of an extended pharmaceutical timeline. Behavioral and histofluorescent tests were used to assess the damage. This study resulted in the conclusion that a neuroprotectant combination of Magnesium Sulfate and Minocycline was most effective at blocking the negative effects even after three hours following the stroke. Various combinations of all neuroprotectants were effective when administered at the onset of the stroke, but the data suggest that Magnesium Sulfate and its neuroprotective properties are best suited for long-term (more than three hours) stroke treatments. Funding: Allegheny College Neuroscience Program.