Neuroscience Institute Dissertations

The Effects Of Early Corticosterone Treatment On The Development Of The Avian Song Control System

Mahin Shahbazi — Mon, 16 Jul 2012 13:08:00 PDT

Stress has long lasting effects on physiology, development, behavior, reproductive success and survival. These effects are mediated by glucocorticoids, such as corticosterone (Cort), via glucocorticoid receptors (GR), though the exact mechanisms underlying these effects are unknown. Early developmental stress affects the size of the avian song control nuclei (particularly HVC; proper name) and song quality in many songbirds, suggesting a direct link between brain and behavior. HVC is required for song learning and production. The complexity of the male zebra finch (Taeniopygia guttata) courtship song is important in female mate choice. Although the mechanisms behind the effects of developmental stress on song nuclei size and song quality are unknown, it is likely that elevated levels of Cort via GR within brain song nuclei play a significant role. We investigated the distribution, quantity, and subcellular-localization of GR- immunoreactive (GR-ir) neurons in the brains of male zebra finches 10 days post-hatch and in adulthood using immunohistochemistry. There was wide distribution of GR-ir neurons including two song nuclei HVC and robust nucleus of the arcopallium (RA). Distribution did not vary between the two ages but there were significant differences in the overall number of GR-ir neurons and their subcellular localization. We hypothesized that early Cort treatment would reduce song quality and HVC size in adult males. We inserted Cort implants in males at four days post-hatch and quantified the effects of early Cort treatment on adult song quality. Early Cort treatment decreased song similarity between the tutor and tutee’s songs and resulted in poorer copies of tutor song, but did not alter mean amplitude or song duration. Early Cort treatment reduced the HVC size in both juvenile and adult birds. This result suggests that the effect of developmental stress on the HVC size may be mediated through Cort via activation of GR within HVC as a mechanism by which HVC size and song quality are altered in developmentally stressed birds. These results suggest a potential role for Cort in mediating adverse effects of developmental stress in adult male zebra finches and highlight the developmental plasticity of the zebra finch brain.

Adult Neurogenesis in the Spiny Lobster, Panulirus Argus: Molecular, Cellular, and Physiological Changes of Olfactory Receptor Neurons

Tizeta Tadesse — Thu, 12 Jul 2012 13:05:17 PDT

Adult neurogenesis of olfactory receptor neurons (ORNs) occurs in diverse organisms including in decapod crustaceans. This dissertation describes the molecular, cellular, and physiological changes that occur during adult neurogenesis of ORNs in the antennular lateral flagellum (LF) of the spiny lobster Panulirus argus. Examination of the role of splash (spiny lobster achaete scute homolog) in adult neurogenesis and regeneration using in situ hybridization showed splash was not closely associated with the formation of sensory neurons under normal physiological conditions. Damage to the LF, which induces regeneration, enhanced splash expression, suggesting an association between splash with regeneration and repair. This study suggests that splash plays multiple roles in the olfactory organ of adult spiny lobsters. Examination of extracellular and intracellular Ca²⁺ in mediating spontaneous and odor-induced responses of ORNs, using calcium imaging showed that odor-induced Ca²⁺ transient responses and spontaneous Ca²⁺ oscillations in ORN somata are primarily mediated by an influx of extracellular Ca²⁺ through Co²⁺ -sensitive Ca²⁺ channels, but that intracellular Ca²⁺stores also have some contribution. These responses are independent of TTX-sensitive Na⁺ channels, suggesting that these Ca²⁺ responses may reflect receptor potentials. Examination of changes in odor specificity, sensitivity, and temporal responses in adult-born ORNs showed an increase in the percentage of odorant-responsive ORNs as they age from newly-born cells to mature, and a decrease in odorant-responsive ORNs as they senesce. As adult-born ORNs age, there was a decrease in the percentage of ORNs that undergo spontaneous Ca²⁺ oscillations and an increase in the amplitude of oscillation. ORNs became more broadly tuned as they senesce, and their response profile, defined by the most effective odorant, changed. Odor sensitivity changed with age. This study demonstrated that the physiological response properties of adult-born ORNs changed with functional maturation. Taken together, this dissertation reveals molecular, cellular and physiological changes in adult born ORNs and elucidates mechanisms of adult neurogenesis.

Peripheral and central mechanisms through which high energy diets impair hippocampal-dependent memory in male rats

Amy Patricia Ross — Thu, 14 Jun 2012 12:08:55 PDT

Over the past five decades, per capita caloric intake has increased by approximately 28% in the United States. A hallmark of the current standard American diet is an excess of energy sources from saturated fat and refined carbohydrates. High energy diets such as the “Western” diet cause numerous pathologies, including non-alcoholic fatty liver disease (NAFLD), high blood pressure, dyslipidemia, and peripheral insulin resistance. High energy diets also negatively impact the hippocampus, a brain area important for learning and memory. It is not surprising, then, that high energy diets impair hippocampal-dependent memory. The experiments in this dissertation investigate possible diet-induced consequences that may contribute to the impairing effects of high energy diets on hippocampal-dependent memory. Our initial experiments found that diet-induced NAFLD impairs hippocampal-dependent memory, but these cognitive deficits were not due to decreases in insulin-like growth factor-1 (IGF-1) or hippocampal insulin signaling. Next, we found that a high energy diet increased the ability of epinephrine to increase blood glucose concentrations, indicating a novel way in which high energy diets impair liver function. The final set of experiments found that high energy diets do not necessarily impair memory but instead may prevent the memory-enhancing effects of acute stress. Taken together, these results indicate that high energy diets interact with acute stress to negatively impact hippocampal-dependent memory, and that hippocampal insulin resistance and IGF-1are not likely involved.

Dissociated Functional Pathways for Appetitive and Consummatory Reproductive Behaviors in Male Syrian Hamsters (Mesocricetus auratus)

Laura E. Been — Tue, 06 Dec 2011 08:33:08 PST

In many species, including Syrian hamsters, male reproductive behavior depends on the perception of odor cues from conspecifics in the environment. Volatile odor cues are processed primarily by the main olfactory system, whereas non-volatile cues are processed primarily by the accessory olfactory system. Together, these two chemosensory systems mediate appetitive reproductive behaviors, such as attraction to female odors, and consummatory reproductive behaviors, such as copulation, in male Syrian hamsters. Main and accessory olfactory information are first integrated in the medial amygdala (MA), a limbic nucleus that is critical for the expression of reproductive behaviors. MA is densely interconnected with other ventral forebrain nuclei that receive chemosensory information and are sensitive to steroid hormones. Specifically, several lines of evidence suggest that MA may generate behavioral responses to socio-sexual odors via functional connections with the posterior bed nucleus of the stria terminalis (BNST) and medial preoptic area (MPOA). It is unknown, however, how these three nuclei act as functional circuit to adaptively regulate appetitive and consummatory reproductive behaviors. Therefore, the overarching goal of this dissertation was to determine how BNST and MPOA function, both uniquely and as a circuit with MA, to generate attraction to female odors and copulatory behaviors in male Syrian hamsters. We found that BNST is required for attraction to female odors, but not for copulation, in sexually-naïve males. In contrast, MPOA is required for both attraction to female odors and for copulation in sexually-naïve males. Surprisingly, prior sexual experience mitigated the requirement of BNST and MPOA for these behaviors. Next, we found that MA preferentially transmits female odor information to BNST and to MPOA, whereas BNST relays female and male odor information equivalently to MPOA. Finally, we found that the functional connections between MA and BNST are required for attraction to female odors but not for copulation, whereas the functional connections between MA and MPOA are required for copulation but not for attraction to female odors. Ultimately, these data may uncover a fundamental mechanism by which this ventral forebrain circuit regulates appetitive and consummatory reproductive behaviors across many species and modalities.

Attenuated Effects of Opiates in Adolescent vs. Adult Male Rats: Reinforcement, Relapse, and Withdrawal

James M. Doherty — Fri, 15 Jul 2011 06:57:50 PDT

Adolescence in humans is a vulnerable period for illicit drug use, and teenage onset of drug use is associated with long-term addiction. Adolescent sensitivity to drug reinforcement, relapse, and withdrawal has not been explored thoroughly in animal models, especially considering opiate drugs such as morphine and heroin. The present series of studies profiles adolescent sensitivity to opiates using adolescent and adult male rats to test for age differences in opiate self-administration, reinstatement, withdrawal signs, locomotor sensitization, and even brain activation during drug-seeking. To test for acute sensitivity to the reinforcing effects of morphine or heroin, we compared patterns of self-administration by adolescent vs. adult male rats on various schedules of reinforcement, drug doses, and daily access conditions. Using fixed ratio schedules and short daily access, adolescents self-administered less morphine than adults, an effect commonly interpreted as higher drug sensitivity. In contrast, escalation of morphine intake under long access conditions was similar across ages, as was heroin intake using fixed or progressive ratio schedules of reinforcement. To test for enduring effects of opiates, we compared opiate-seeking in the absence of the drug in tests of extinction responding and cue-induced reinstatement. Regardless of the acute effects of morphine or heroin, all adolescent treatment groups showed attenuated opiate-seeking compared to adults. Next we considered behavioral correlates of reinforcement, drug withdrawal and locomotor sensitization, during and after escalating doses of experimenter-administered heroin. Consistent with attenuated opiate-seeking, adolescents exhibited attenuated somatic and locomotor signs of withdrawal compared with adults, although locomotor sensitization was similar across ages. Finally, the medial prefrontal cortex (mPFC) is a brain region heavily implicated in drug reinforcement, so we used tissue levels of Fos-like immunoreactivity to compare activation of this region by heroin-seeking. Indeed mPFC activation was absent in rats that self-administered heroin as adolescents, but robust in adults. Together these behavioral and neuroanatomical results surprisingly suggest that adolescent male rats are less sensitive than adults to some acute and enduring effects of opiates, and may predict better response profiles among younger human addicts. Through future studies, adolescent rats may provide a new model to help identify treatments for drug abuse.

Chemical Defenses of Aplysia Californica and Sensory Processing by Predatory Fishes

Matthew Nusnbaum — Mon, 25 Apr 2011 13:37:27 PDT

In predator-prey interactions, prey species have complex defensive behaviors to protect themselves from predators. Chemical defenses are one tool that is employed to protect against predators, especially for slow-moving or otherwise susceptible prey. Many of these chemical defenses have been studied and the effective compounds identified, but few studies were performed on their mechanisms of detection.

In my research, I used the sea hare, Aplysia californica, as chemically defended prey. This slow moving mollusk is soft-bodied with no external shell, but it has adapted a number of defenses including chemical defenses. Ink is a sticky mixture of the products of the ink gland and the opaline gland which are mixed in the mantle cavity and released toward an attacker. I show that this ink secretion protects the sea hare from predation by a fish predator.

Because many deterrent compounds taste bitter, bitter taste receptors are thought to protect predators from ingesting harmful compounds in prey. Studies of deterrent taste detection have commonly utilized bitter compounds from human hedonics to study the responses in animals, such as fruit flies, fishes, rats, and monkeys. In my dissertation, I argue that the study of chemical defenses allows us to ask more questions about detection of relevant deterrents and interactions between predators and prey at the individual and population levels. My results show that diet-derived pigments in Aplysia ink, aplysioviolin and phycoerythrobilin, are strongly deterrent to fish predators. Electrophysiological analyses of the gustatory system show that these compounds are equipotent and cross-adapt each others’ responses completely. Aplysioviolin and phycoerythrobilin produced incomplete reciprocal cross-adaptation with amino acids and adapted bile salt responses but were not significantly adapted by these latter stimuli. These results showed multiple pathways that are sensitive to aplysioviolin and phycoerythrobilin, which may have different effects on the physiology and behavior of the predatory fish. My findings demonstrate the value to the fields of chemical ecology and chemosensory biology of studying sensory processing of relevant deterrent compounds. This work lays the foundation for how a diet-derived photopigment is adapted by a species to protect itself from predators by stimulating their chemosensory systems.

Functional Substrates of Social Odor Processing within the Corticomedial Amygdala: Implications for Reproductive Behavior in Male Syrian Hamsters

Pamela Mary Maras — Tue, 15 Jun 2010 10:15:13 PDT

Adaptive reproductive behavior requires the ability to recognize and approach possible mating partners in the environment. Syrian hamsters (Mesocricetus auratus) provide a useful animal model by which to study the neural processing of sexual signals, as mate recognition in this species relies almost exclusively on the perception of social odors. In the laboratory, male hamsters prefer to investigate female odors compared to male odors, and this opposite-sex odor preference provides a sensitive measure of the underlying neural processing of sexual stimuli. In addition to chemosensory cues, reproductive behavior in hamsters also requires sufficient levels of circulating gonadal steroid hormones, which reflect the reproductive state of the animal. These chemosensory and hormone signals are processed within an interconnected network of ventral forebrain nuclei, and within this network, the posteromedial cortical amygdala (PMCo) and medial amygdala (MA) are the only nuclei that both receive substantial chemosensory input and are also highly sensitive to steroid hormones. Although a large body of evidence suggests that the MA is critical for generating attraction to sexual odors, the specific role of the PMCo in regulating odor-guided aspects of male reproductive behavior has never been directly tested. Furthermore, detailed analyses of the MA suggest that separate, but interconnected sub-regions within this nucleus process odors differently. Specifically, the anterior MA (MeA) receives the majority of chemosensory input and responds to a variety of social odors, whereas the posterodorsal MA (MePD) receives less chemosensory input but contains the vast majority of steroid receptors. In order to further elucidate how the PMCo and/or MA process sexual odors, this dissertation addressed the following research questions: (1) Is the PMCo required for the expression of either opposite-sex odor preferences or male copulatory behavior? (2) Are functional interactions between MeA and MePD required for the expression of opposite-sex odor preferences? (3) How do MeA and MePD regulate odor responses within the MePD and MeA, respectively? (4) Are odor and/or hormone cues conveyed directly between MeA and MePD? Together, these experiments provide a comprehensive analysis of the functional and neuroanatomical substrates by which the brain processes sexual odors and generates appropriate behavioral responses to these stimuli.