Browsing by Subject "Neuroplasticity"

Now showing 1 - 9 of 9
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    Naturally Motivated Behavior and Neuroplasticity: How Sexual Experience Affects Neural Activation During Sexual Behavior in Female Syrian Hamsters
    (2016) Caron, Madeline F.; Been, Laura
    Naturally motivated behaviors, like sexual behavior, are subject to behavioral plasticity, which can affect neuronal function. The purpose of this study was to investigate the plasticity of sexual behavior and neural circuits related to sexual behavior in female Syrian hamsters. We hypothesized that lordosis latency would decrease and lordosis duration would increase with sexual experience. We also hypothesized that sex experience would increase the activation of the projections from the prefrontal cortex (PFC) to the nucleus accumbens (NAc) during sexual behavior. We tested our hypothesis by ovariectomizing and hormone priming all subjects and giving half of the subjects six weeks of sex experience while the other half remained sexually naïve. All subjects then received an injection of a retrograde tracer into their NAc and a final sexual experience. All subjects were then sacrificed, and their brain tissue was collected and stained using immunohistochemical techniques. Our data did not support our hypotheses about lordosis latency or duration, and we were unable to test our neuroplasticity hypothesis due to unquantifiable staining. Limitations and possible troubleshooting techniques are discussed in the context of directions for future research.
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    Neuroplasticity after Sexual Experience in the Nucleus Accumbens of Syrian hamsters
    (2016) Acabá, Luis; Been, Laura
    Research over the past three decades has demonstrated that many neural changes occur in response to rewarding stimuli and behavior. However, most of this research has focused on the changes that occur following drug use and their role in addiction. Less research has investigated the neural changes in response to everyday rewarding behaviors such as eating, exercising, and sexual behavior, and even less has explored whether these changes differ in male and female brains. The goal of this study was to investigate the changes in brain circuitry that occur in Syrian hamsters after exposure to sexual experiences and to identify any possible sex differences involved. Specifically, levels of delta FosB, a transcription factor that is important for long-term neural plasticity following rewarding experiences, was measured in the Nucleus Accumbens (NAc) as a way to quantify these neural changes. This study also aimed at investigating whether the efficiency with which hamsters mate is improved with experience, as measured by the time the hamsters are actively having sex and the amount of sex-related behaviors they perform. It was expected that sexual experiences would lead to an up-regulation of delta FosB in the NAc, that this up-regulation would not differ between the sexes, and that mating efficiency would improve with experience. The results demonstrated that sexual experience led to higher delta FosB levels in the NAc than controls, and that there were no differences in delta FosB levels between males and females of the same group. This study also found that mating efficiency was not improved with experience. The results obtained in this study suggest that the normal rewarding behavior of sexual experience leads to neuroplastic changes in the NAc of Syrian hamsters and that male and female Syrian hamsters likely have similar neuroplastic changes following sexual experiences. This research has the potential to provide a better understanding of how drugs of abuse take advantage of reward pathways, and eventually lead to better treatments for addiction.
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    Oxytocin Receptor Plasticity Following a Hormone-Simulated Pregnancy in Syrian Hamsters: Implications for Postpartum Mood Disorders
    (2018) Benedetto, Lauren E.; Been, Laura
    Despite the fact that approximately 15‒20% of women develop postpartum depression and/or anxiety, and that the resulting outcomes for both the mother and her child are negative, the underlying neurobiological mechanisms of the disorders remain poorly understood. Previous research suggests that ovarian hormone fluctuations as well as changes in oxytocin signaling that occur at parturition and in the postpartum likely play a role in the etiology of these disorders. Given the increase in oxytocin-producing neurons in the paraventricular nucleus (PVN) of the hypothalamus following a hormone simulated pregnancy, Experiment 1 sought to examine oxytocin receptor levels in PVN efferents, particularly in the medial amygdala (MeA), nucleus accumbens (NAc), bed nucleus of the stria terminalis (BNST), and raphe nuclei. Results indicate an increase in oxytocin receptor density in the raphe nuclei among hormone-withdrawn animals as compared to controls, suggesting that the region could be implicated in the etiology of anxiety-like behavior during the postpartum period. Unexpectedly, behavioral results indicate reduced non-specific locomotor ability as measured by the Open Field Test and increased anxiety-like behavior as measured by the Elevated Plus Maze in hormone-withdrawn animals. Experiment 2 sought to explore whether neurodegeneration was responsible for the decreased oxytocin-producing neurons found in hormone-sustained animals. Unexpectedly, cell death is visible in hormone-withdrawn and not hormone-sustained animals, suggesting that some neuroplasticity may be taking place. Overall, these two experiments add to our understanding of the brain and behavior following hormone-simulated pregnancy in hamsters, which may inform our understanding the postpartum period in humans.
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    Plasticity of Oxytocin Receptors in the Postpartum Period Using a Hamster Model
    (2018) Taveras, Shantal; Been, Laura
    The deleterious consequences of postpartum depression and anxiety (PPD) on the mother-child dyad has greatly incentivized more research in the neurobiological mechanisms during the peripartum period. Several studies have stipulated that neurobiological and hormonal components may lead to the etiology of PPD. However, a greater understanding of the complexities of PPD will not unfold until knowledge on the typical patterns of puerperium is prioritized. In the current study, we simulated pregnancy in a hamster model to investigate changes in oxytocin receptor density in the efferents of the paraventricular nucleus (PVN). For the four regions of interest, we predicted a decrease in oxytocin receptors density for the estrogen-withdrawn hamsters within the postpartum period. The raphe nucleus (RN) was the only region of interest that attained statistical significance. Contrary to our hypothesis, the estrogen-withdrawn group exhibited a significant increase of oxytocin receptors compared to the control group in this region. Utilizing an open field test and elevated plus maze, we also expected to observe less anxiety-like behaviors from the estrogen-withdrawn group. However, our results did not reveal any statistical significance for anxiety-like behaviors. Following previous results, this study also investigated the overall neurodegeneration within the PVN, specifically an increase of cell-death in the estrogen-sustained group. After qualitative analysis, we visualized greater fluoro-jade staining, a measure of neurodegeneration, within the estrogen-withdrawn group. By gaining greater comprehension of the estrogen and oxytocin pathway, it will lead to a greater understanding of the typical postpartum period and, thereby, the intricacies involved in the peripartum period.
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    Postpartum Oxytocin Receptor Plasticity And Anxiety-Like Behavior in Syrian Hamsters: The Potential Role of the Dorsal Raphe Nuclei
    (2018) Levine, Taylor; Been, Laura
    The postpartum period is a time of high vulnerability for females to develop depression. Not only does postpartum depression significantly hinders the motivation and enjoyment that a mother feels in her new role, but also the development of the offspring, doubling the impact of this unique affective disorder. Oxytocin, a hormone involved in birth, maternal behavior, depression, and anxiety may help to untangle the link between postpartum hormonal levels and the occurrence of postpartum depression. The present study examined oxytocin receptor plasticity in efferents of the paraventricular nucleus, the main source of central oxytocin, in an animal model following a hormone-simulated pregnancy. Estrogen-withdrawn females exhibited a significantly greater density of oxytocin receptors in the dorsal raphe nuclei and there were no significant differences in receptor density between hormonal treatment groups in other efferents examined. Estrogen-withdrawn females also displayed higher levels of anxiety-like behavior than estrogen-sustained animals in the Elevated Plus Maze. Ultimately, the present study aimed to understand the role of oxytocin signaling in postpartum mood disturbances and how oxytocin may meet the demand as a novel, targeted treatment for postpartum depression.
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    Postpartum oxytocin receptor plasticity in Syrian hamsters: Implications for the treatment of peripartum mood disorders
    (2018) Heaton, Elizabeth C.; Been, Laura
    Peripartum mood disorders, if left untreated, result in negative outcomes for both the mother and child. Despite these severe consequences, the neurobiology of peripartum mood disorders is not well understood. The present study aims to build upon previous research investigating the role of oxytocin in neuroplastic and behavioral changes during the peripartum period. Past work found a significant increase in oxytocin-immunoreactive neurons in the PVN as a result of hormone withdrawal in a hormone-simulated pregnancy model conducted in Syrian hamsters. Using the same model, we studied post-synaptic plasticity: specifically, we assessed which PVN efferents, if any, experienced changes in oxytocin receptor expression using receptor autoradiography. The regions of interest in this study were medial amygdala (MA), nucleus accumbens (NA), bed nucleus of the stria terminalis (BNST), and the raphe nuclei as each of these four areas are heavily involved in the production of maternal behavior. There was a significant increase in OTR density in the dorsal raphe in the hormone withdrawn group as compared to oil control. Changes in OTR density in the dorsal RN, which regulates serotonergic activity and anxiety- and depression-related behavior in humans and rodents, may play a role in the development or sustainment of peripartum mood disorders.
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    The Relationship Between Neurogenesis and Pain Behavior
    (2008) Alspector, Emily; Sternberg, Wendy
    One of the most prominent discoveries of recent neuroscience is the finding that neurogenesis, the formation of new neurons, can occur in the adult brain. While it was previously thought that neurogenesis occurs only in developmental stages, recent breakthrough research has revealed novel analyses about the brain, specifically its inherent plastic nature. Plasticity is not just an attribute of the brain; many bodily mechanisms exhibit plastic properties, as well, including the pain pathway. Sensitization, or the lowered sensitivity threshold of pain-responsive receptors with increased stimulation, is one such example of plasticity in the pain response. Interestingly, mechanisms of pain and neurogenesis have been shown to be connected. Research indicates an inverse relationship between pain and neurogenesis: fewer neurons will form as pain is enhanced. Patients with Alzheimer’s disease, a disease in which adult neurogenesis occurs at a slower rate than normal, report a higher pain tolerance. The present study was designed to investigate if the administration of galantamine and nicotine, both of which are acetylcholine agonists but have opposing effects on neurogenesis, have effects on pain behavior associated with varying degrees of neurogenesis. We hypothesize that if neurogenesis increases with galantamine administration and decreases with administration of nicotine, the mice should display significantly more pain behavior in galantamine conditions when compared to both nicotine subjects and controls because of the increased number cells involved in the pain pathway that form in conjunction with new neurons. Such findings would establish a correlation between either increased pain threshold or analgesia and drug-induced neurogenesis. The general trend observed indicated that with increased neurogenesis, the subject exhibited more pain during the formalin test. Limitations and future research are discussed.
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    The Role of Mesolimbic Estrogen Receptors in Modulating Peripartum Estradiol Withdrawal Effects on Neuroplasticity
    (2024) Barrett, Annie; Been, Laura
    Postpartum Depression (PPD) has many biological and sociocultural contributors as well as significant implications. One biological contributor is the fluctuation in peripartum hormones, particularly the significant increase in estradiol during pregnancy, followed by a rapid decrease following childbirth, known as postpartum estradiol withdrawal. These hormone changes impact the mesolimbic dopamine pathway, which consists of dopaminergic projections from the Ventral Tegmental Area (VTA) to the Nucleus Accumbens (NAc). Recent evidence has shown that Estrogen Receptors (ERs) in the VTA may mediate this relationship between estradiol withdrawal and mesolimbic dopamine transmission. These changes may be measured by ΔFosB, a transcription factor in the NAc that is associated with long-term neuroplasticity and has implications for depressive-like behaviors in rodent models. We silenced ERs in the VTA using a stereotaxic injection of lentiviruses carrying short-hairpin RNA (shRNA), then we used a hormone-simulated pseudopregnancy (HSP) method to simulate the estradiol and progesterone changes during pregnancy. Finally, we used an immunohistochemistry protocol to determine the role of ERs in the VTA in modulating the effect of postpartum estradiol withdrawal on ΔFosB levels in the NAc in adult female C57BL/6 mice. We found no significant effects of the virus condition, hormone condition, or the interactions between virus and hormone conditions in the NAc Core or Shell. This study will be concluded this summer to include more scrambled control animals and a study of ESR2 knockdown. Future research would differentiate between the injected and non-injected side of the brain, and may consider interactions between ERɑ and ERβ and behavioral implications. Keywords: neuroplasticity, postpartum depression, estrogen receptors, hormone-simulated pseudopregnancy, ventral tegmental area, nucleus accumbens
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    The Shaping of Sex Behavior, Odor Perception, and Neural Activation by Sex Experience: The Role of the Bed Nucleus of the Stria Terminalis’s Projections to the Nucleus Accumbens
    (2016) Williams, Alexis; Been, Laura
    Research has demonstrated that drugs of abuse lead to changes in both behavior and in neural activation. Drugs of abuse activate the same reward pathway in the brain as natural rewards, such as sex behavior. In order to better understand drug addiction, it is important to study how behavior and the brain change in response to experience with natural rewards. In the model organism of the Syrian hamster, sex behavior depends critically on the processing of odors. The bed nucleus of the stria terminalis (BNST), the medial amygdala (ME), and the medial preoptic area (MPOA) all process conspecific odors that help guide and reward sex behavior. There is plasticity in this brain region, and in particular sexual experience has been shown to modify the BNST’s involvement in opposite sex odor preference. It is unclear whether the number of activated projections is modified by experience. Thus, this research investigated how sex experience may change the neural response to a sexual odor in BNST neurons that project to the nucleus accumbens (NAc) in male Syrian hamsters. Hamsters were divided into a group that received no sexual experience or into a group that received eight ten-minute sexual experiences with a female hamster. Both groups of hamsters were injected with a retrograde tracer, Cholera Toxin B (CTB), into the NAc. The groups were given an odor experience and sacrificed. Immunohistochemistry was used to visualize CTB as well as c-Fos, a measure of recent neuronal activity. However, the neurons were not able to be visualized due to a hypothesized problem with over-fixation of the tissue. The research demonstrated that the number of mounts, intromissions, ejaculations, and the efficiency rate (mounts/intromissions) did not significantly differ over repeated sexual experiences. Future work utilizing correct staining of the tissue will help provide an understanding of how experiences that occur as part of an individual's everyday life can change the brain's reward system and impact future behavior.