Neuroscience and Behavior Masters Theses Collection

The Effects Of Adolescent Binge Drinking On Corticotropin-Releasing Factor Cells In The Amygdala And Social Predictors Of Alcohol Intake In Male And Female Rats

Karanikas, Chrisanthi — Fri, 23 Nov 2012 07:23:39 PST

Alcohol is one of the most common drugs of choice among adolescents. Normally, the method of consumption is drinking large quantities of alcohol in short periods of time, otherwise known as “binge drinking.” Corticotropin releasing factor (CRF) stress peptide producing cells in central nucleus of the amygdala (CeA) has been implicated in behavioral responses to stress and addiction. The goals of this thesis were to determine the effects of voluntary binge drinking in adolescence and vapor-induced alcohol dependence in adulthood on CRF cells in the CeA. These studies were done using an operant model of voluntary binge drinking in rodents in which adolescent animals are allowed to orally self-administer sweetened alcohol intermittently (or sweetened water for controls) during early adolescence. The current findings demonstrate that binge drinking during adolescence decreases the number of CRF-ir cells in the CeA. This decrease in cell number is long-term, lasting well into adulthood and dependence does not exacerbate this effect. A second goal was to determine whether certain behaviors could be used as a predictive measure for adolescent binge drinking. The current findings indicated that frequency of self-grooming, can be used as a predictive measure for adolescent binge drinking. Specifically, increased frequency of self-grooming predicts lower alcohol self administration during adolescence.

A Novel Role for wnt5b in Regulating Proliferation of Radial Glial Cells

Burton, Sean W. — Wed, 24 Aug 2011 09:54:37 PDT

The wnt family of secreted glycoproteins perform diverse roles from development through adulthood in both vertebrate and invertebrate organisms. These roles include the establishment of multiple body axes, cell polarity and migration during gastrulation, and prevention of tumorigenesis during adulthood. Much research has been performed to examine the function of the different wnt genes, however, some have received relatively little investigation.
One of the relatively unknown wnt genes is wnt5b. My work has been characterizing a zebrafish with a mutation in the wnt5b gene, looking for mutations that caused defects in axonal and glial patterning during embryonic development. Previously, wnt5b has been shown to influence planar cell polarity, and has been found to inhibit zebrafish fin regeneration and implicated as an inducer of type II diabetes. However, little research has been performed to investigate its role in the development of the nervous system.
Here I show that wnt5b plays a direct role in regulating proliferation of radial glial cells in the embryonic zebrafish spinal cord. Zebrafish with mutations in this gene have a increased number of radial glial cells that are in m-phase, compared to wild type embryos. I also show that wnt5b gain of function is sufficient to reduce this number well below wild type levels. Here I will present findings that, when combined with what has been previously found about the roles of wnt5b and its link to leukemia and mammary tumors, suggests that wnt5b may be a candidate for further study as a route to cancer therapy.

The Effects of Testosterone on Emotional Processing in Male Rhesus Monkeys (Macaca Mulatta)

King, Hanna M. — Fri, 05 Nov 2010 09:19:44 PDT

The effects of testosterone (T) extend beyond reproductive behavior to the areas of cognitive and emotional functioning. While T effects on cognition have been extensively investigated, less is known about the role of T in the processing of emotional stimuli. Considering the role that T plays in aggressive behavior and dominance status, it is of particular interest to determine whether T modulates the processing of social threat. Due to their similarities to humans in brain organization, reproductive endocrinology and affective regulation, rhesus monkeys (macaca mulatta) provide an excellent model to investigate this relationship. In a within-subjects design, six male rhesus monkeys underwent treatment to suppress endogenous T and received either T or oil replacement. Tests of anxiety, attention and memory for social and non-social emotional stimuli, and risk-taking were administered to animals during both treatments. Data analyses indicate that T treatment resulted in faster response times, but had no effect on anxiety, attention or memory for emotional stimuli, or on risk-taking behavior. There are several limitations to this study that may account for the lack of effect of T and therefore, further investigation of the relationship between T and emotional processing is warranted.

Regulation of Trio Splice Variants by 17Β-Estradiol and 2,3,7,8-Tetrachlorodibenzo-p-dioxin

Cunningham, Michael J. — Mon, 05 Apr 2010 12:13:18 PDT

The anteroventral periventricular nucleus (AVPV) is a sexually dimorphic preoptic structure that is nearly three times larger in the female rat. Estradiol (E2) exposure during development decreases AVPV volume through apoptosis, a process which normally occurs preferentially in male. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disrupter that interferes with E2-dependent sexual differentiation of the AVPV. Whole-genome microarrays were used to identify sex-specific genes regulated by E2 and TCDD in postnatal day 2 (P2) AVPV punches from untreated males and females, males treated with TCDD or vehicle, and females treated with E2 or vehicle. Trio emerged as a gene target regulated by E2 and TCDD, and this gene is essential for neurite outgrowth which is sexually dimorphic in the AVPV. My goal was to verify microarray data that Trio was expressed in the P2 AVPV and to test whether expression was affected by sex, E2 and TCDD. The microarray did not discriminate among Trio splice variants, 9S, 9L and Duet, so I mapped each of these in the P2 AVPV using in situ hybridization. I used quantitative real-time PCR to examine the effects of sex, E2 and TCDD on mRNA levels encoding each splice variant. I found that the AVPV expressed 9S and 9L at moderate levels and Duet at low levels. The expression of 9S and 9L mRNA was increased by E2 in females. However, only 9S expression differed between sexes and it was lower in males. TCDD had no effect on expression of any of the splice variants. This work provides the first evidence that Trio splice variants are independently regulated and that Trio may mediate effects of E2 in the developing AVPV.

MDMA and Methamphetamine: An Investigation of a Neurochemical and Behavioral Cross-Tolerance in the Rat

Henderson, Christina S. — Wed, 13 Jan 2010 11:36:18 PST

We previously found that intermittent administration of 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) to adolescent male rats protected against the behavioral and serotonergic neurotoxic effects of a subsequent MDMA binge. Similar results have been reported for the dopamine (DA) neurotoxin methamphetamine (METH). The present study tested the hypothesis that intermittent adolescent MDMA exposure would protect against the DA neurotoxic effects of a METH binge. Male Sprague-Dawley rats were injected s.c. with MDMA (10 mg/kg x 2; 4-h interdose interval) or saline every fifth day from postnatal day (PD) 35 through PD 60. The animals were then challenged with either a low- or high-dose METH binge (4 or 8 mg/kg x 4; 2- h interdose interval) or saline on PD 67. Activity was measured 1 day after the binge, and regional serotonin transporter (SERT) and dopamine transporter (DAT) expression were analyzed at PD 74 by radioligand binding. All animals treated with METH on the challenge day became hyperthermic, independent of pretreatment conditions. Both MDMA-pretreated and drug-naïve rats also showed a dose-dependent hypoactivity 24 h after the first dose of the METH binge. The SERT binding results indicated that adolescent pretreatment with MDMA provided full or partial protection (depending on the brain region) against the serotonergic deficits produced by METH in previously drug-naïve animals. In contrast, MDMA pretreatment failed to protect against METH-induced decreases in striatal DAT binding. These results suggest that the neuroprotective 2 effects of adolescent MDMA pretreatment are confined to the serotonergic system, possibly reflecting a selective upregulation of antioxidant mechanisms in that system.

Behavioral Alterations in Prairie Voles (Microtus ochrogaster) after Parent-Pup Separation

Yamamoto, Mihoko — Wed, 02 Dec 2009 10:23:40 PST

The prairie vole (Microtus ochrogaster), a highly social species, offers a unique opportunity to examine the effects of parent-pup separation in a biparental family system similar to humans. We hypothesized that 1) repeated separation from pups affects parental behavior and emotionality in parents, and 2) neonatal parental separation affects emotional and physiological development in pups, and thus induces altered adult parental, emotional, and social behaviors. During postnatal day (PND) 1-10, pups were removed from their parents for 0, 15, or 360 min and housed either individually or with siblings. Unhandled controls experienced only daily lid opening. Tests for parental responsiveness and emotionality were conducted on PND11 for parents and PND90-92 for their offspring. Emotionality tests included the elevated plus maze, open field, and forced swim tests. Starting at PND150, half of each litter was paired with an opposite-sex vole for 24 hours and tested for partner preference. Additionally, behavioral response to stress was measured in all animals 0, 30, or 60 min after exposure to a forced swim. Generally, the behavior of the parents and adult offspring was influenced by daily handling, the length of the separation, and presence of siblings. Parental behaviors in parents did not differ among groups, while their anxiety- and depression-like behaviors were influenced by pup separation. For the adult offspring, separation treatment altered parental behavior, emotionality, partner preference, and stress response. Our results demonstrated that parent-pup separation affects emotional and social behaviors in prairie vole parents and adult offspring.

Event-Related Potential Indices of Attentional Gradients Across the Visual Field

Richiedei, John C. — Thu, 27 Aug 2009 06:18:45 PDT

Our lives are dominated by a complex visual world, and spatially selective attention allows us to process only the most relevant information. Previous evidence suggests that if possible locations of stimulus presentation are delineated, attention affects processing in a spatially graded manner. This gradient is seen in both behavioral measures and in visual evoked potentials (VEPs). Stimuli presented close to cued regions elicit faster responses and larger VEPs than those presented farther away. However, both position in the visual field and allocation of attention may contribute to the observed gradients. These relative contributions can be distinguished by comparing responses on physically identical trials when attention is directed to locations at various distances from the stimuli. In the current study, participants attended to one of 12 squares arranged in a circle around fixation. Letters appeared individually, each in one of the squares; 80% were O’s (standards) and 20% were X’s (deviants). Participants were instructed to press a button when an X appeared at the attended location. The largest amplitude N1s (150-200 ms) were observed when participants attended to the location where a standard was presented. VEPs elicited by standards showed evidence of asymmetric attentional gradients. Specifically, the gradient of facilitation spread down more than up. Results also showed that attention had differential effects on the stages of processing indexed at specific time windows. These results confirm that attention can be applied to visual processing in a spatial gradient, reveal its asymmetric distribution, and elaborate on the timing of its selectivity.

Sexually Differentiated Object Preference in Rhesus Monkeys (Macaca mulatta)

Berkowitz, Jamie — Fri, 03 Apr 2009 11:22:29 PDT

Children have strong preferences for sex-typed toys; boys prefer trucks, whereas girls prefer dolls. These preferences appear to be driven by complex interactions of hormones and the socio-cultural environment. The relative contribution of each of these factors in children is impossible to isolate given ethical limitations. Non-human primate species afford the opportunity to examine preferences in the absence of societal values and influences that children experience. In two previous studies with non-human primates, one with vervet monkeys and one with rhesus monkeys, monkeys showed sex-typed object preferences that paralleled those of children. However, several uncontrolled variables could have influenced these preferences. Our study considered object characteristics and we controlled for possible color preferences. We also tested monkeys individually to eliminate the effects of social facilitation and dominance rank. In experiment 1, monkeys were given a choice between similar objects of different colors (Phase A) and moving vs. non-moving objects (Phase B). In experiment 2, monkeys were given a choice between dolls and trucks (Phase A) and subsequent phases looked at the influence of moving wheels (Phase B) and hardness (Phase C). Contrary to previous findings, monkeys did not show sex-typed object preferences. Instead, the monkeys preferred blue objects, hard PVC objects such as trucks and hard dolls, and dolls with wheels. The influence of previous reward based cognitive testing, familiarity of substrate materials, and rearing condition are considered as possible explanations for these findings.

Combined Treatment With NPY Y5 Antagonists and NAN-190 Attenuates Transients in Light-induced Phase Shifts and Potentiates Phase Shifts Only During the Late Subjective Night

Costello, Mary K. — Mon, 15 Dec 2008 07:37:29 PST

Circadian rhythms in physiology and behavior are synchronized by a central pacemaker, the suprachiasmatic nuclei (SCN) of the hypothalamus. Shift work, jet lag and sleep disorders can disrupt circadian rhythms, negatively impacting health and well-being. The SCN pacemaker resets rapidly in response to changes in the daily light cycle, however, adjustment of peripheral oscillators to changing time zones or work shifts is more gradual, leading to internal desynchrony. In addition, many diseases can impair the SCN’s ability to adjust to changes in the light cycle. My research investigated whether combined pharmacological inhibition of neuropeptide Y and serotonin could enhance resetting and attenuate transient cycles in locomotor activity following a sudden change in light exposure. I found that simultaneously blocking neuropeptide Y and serotonin receptors potentiated phase shifts during the late subjective night and significantly reduced transient cycles of locomotor activity in hamsters. Development of treatments that enhance the circadian system’s response to light may alleviate some of the negative health consequences experienced by travelers, shift workers and individuals with disease-related circadian desynchrony.

Deletion of the Bax Gene Severley Impairs Sexual Behavior and Modestly Impairs Motor Function In Mice

Jyotika, Jigyasa — Mon, 15 Dec 2008 07:27:49 PST

During neural development, nearly 50% of all newly generated neurons undergo cell death after making provisional contact with their target cells. The functional consequences of eliminating this neuronal cell death are not known. Bax, a pro-apoptotic protein, is required for cell death in many neural regions. A null mutation of the Bax gene in mice has been shown to increase overall cell number and eliminate the sex differences in neuron number in the anteroventral periventricular nucleus (AVPV) and the principal nucleus of the bed nucleus of the stria terminalis (BNSTp). The aim of my Master’s thesis was to study male and female sexual behaviors and motor behavior in Bax -/- mice and their wild-type siblings. Animals were gonadectomized in adulthood and provided with ovarian hormones or with testosterone for tests of female and male sexual behaviors, respectively. Wild-type mice exhibited a sex difference in feminine sexual behavior, with high lordosis scores in females and low scores in males. This sex difference was eliminated by Bax deletion, with very low receptivity exhibited by both male and female Bax -/- mice. Male sexual behavior was not sexually dimorphic among wild-type mice, but mounts and pelvic thrusts were nearly absent in Bax -/- mice of both sexes. The knockouts did not display deficient motor strength or performance at low speeds on a RotaRod apparatus compared to wild type mice. At high speeds, however, Bax -/- animals exhibited impairments on the RotaRod. Therefore, developmental cell death may be required for exhibition of male and female sexual behaviors, and for coordination of relatively difficult motor tasks.