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Publication Interaction between Time of Day and Corticosterone on Neuroimmune Responses(2024-05) Santos, NathanThe circadian clock governs many physiological processes, including immune responses which show time of day variations. Here we investigated the impact of time of day on immune responses to acute viral like pathogens using intranasal poly(I:C). We found that the transcriptional profile in the olfactory bulb, a key entry point for viral pathogens, varied significantly depending on the time of challenge. At (Zeitgeber time) ZT12, immune related transcripts were upregulated, indicating enhanced immune surveillance and response to viral infection. Conversely, at ZT0, transcripts associated with inflammation were downregulated, suggesting a dampened immune response. Additionally, we explored the role of acute stress induced corticosterone release in modulating time of day immune responses. Inhibition of corticosterone production with metyrapone altered the expression of clock gene nr1d1 to poly(I:C) in a time-of-day dependent manner, highlighting the interconnection between the circadian clock and acute stress hormone. This study has implications for further understanding of disease states in the context of both circadian and stress biology.Publication How Perception of Decision Environment and Future Information Affects Changes in Delay Discounting Rates: Differences Across U.S. and China, Differences Before and After the U.S. 2018 Midterm Elections(2019-09) Walsh, FranIn this thesis, I will explore the idea that choices between present, smaller value options and future, larger value options depend on how much individuals trust the future to deliver the reward. Due to this aspect of trust, the individual must build their estimate of trust based on information for their present environment and their future expectations. This estimate of future trust can change across different time points in the same environment (i.e., before and after a national election) and between environments in the same time point (i.e., between two countries experiencing different economic rates of change). In this set of presented experiments, I will explore the link between decision environment and delay discounting, as well as the relationship between the contents of future perception and delay discounting. These two experiments will test differences in delay discounting (a) across two economic systems (China and the U.S.), as well as (b) before and after a national election (2018 U.S. Midterms). The results of the different decision environments study show that the delay discounting rates are significantly different across the two countries, specifically within the framing of present and future. These differences are not explained by differences in culture effects or individual differences in personality traits, suggesting that difference in environment is driving the effect. The results from the Midterm election experiments show evidence for differences in delay discounting between political identities and income groups. There are also differences in how these two groups perceive the contents of their future before and after the election. Specifically with evidence that negative future projection corresponds with increased delay discounting. Overall, these experiments show that delay discounting can be affected by the way information is framed within an environment and how we expect our environments to change over time.Publication Sex Differences in Oligodendrocyte Development: Potential Implications for the Effect of Alcohol Drinking on Myelin.(2019-09) Scott, SamuelAdolescence is a period of time when the brain undergoes profound development. Myelination is a maturational process in which oligodendroglia project out lipid-rich ramifications which wrap and insulate axons. This is crucial for effective neurotransmission between brain regions and, if compromised by pharmacological insults such as alcohol, can have long-term implications on behavior and cognition. We have previously shown that adolescent alcohol impacts males and females differentially, however it remains unknown how alcohol impacts oligodendroglia during development. The goal of this study was to determine the cellular dynamics of the oligodendroglia in male and female mice through development with and without alcohol exposure. Our results suggest that sexually dimorphic temporal dynamics exist within oligodendroglia. Specifically, this population of cells is notably dynamic during adolescence in males while stable in females. In addition, preliminary studies show that alcohol may cause a restriction on differentiation of oligodendroglia in male but not female mice. Further understanding of sex differences in the mechanisms of alcohol-induced change to oligodendroglia development could create the foundation for targeted, specific therapeutic agents and allow for individualized treatment of patients suffering from alcohol use disorders and potentially other addictions.Publication Relationship of Maternal and Infant Cortisol Matrices with Later Infant Behavior and Temperament(2020-09) Perris, AnastasiaPrenatal stress has been correlated with adverse developmental outcomes affecting infant cognition and behavior. Previous studies have shown that prenatal stress can lead to increased susceptibility to adult disease but few studies have looked at the physiological stress response system by measuring the activity of the hypothalamicpituitary-adrenal (HPA) axis. Cortisol, the output of the HPA axis can be secreted in many different matrices (saliva, blood, urine, feces and hair). Most studies that do, only look at one measure of hormone production instead of examining multiple matrices. Additionally these studies do not look at the relationship between matrices. Hair provides a long-term assessment of cortisol hormone production as related to infant behavior. Four measures of cortisol representative of prenatal and postpartum periods were collected in a sample population of rhesus macaques at the NIH facility. No stress was applied to these animals and cortisol concentrations were assessed in maternal hair, infant hair, amniotic fluid, and mothers’ milk. These cortisol measures were then analyzed first to determine vii the relationships between the four measures and second to relate these cortisol values to infant behavior in the primate neonatal neurobehavioral assessment. Subjects of this study were 30 mothers and infants from the 2015 and 2016 breeding cohort. 25 of which, were unique dyads. Using four statistical analyses and 3 groupings of behavior, we found that maternal hair cortisol concentrations were correlated with different temperaments of infants, while milk cortisol concentrations were correlated with infant’s visual exploration of the environment. Additionally, an inverse relationship was found between hair cortisol concentrations and both hair cortisol concentrations with amniotic fluid cortisol. Together, the four statistical analyses show that Maternal HPA axis activation during and after pregnancy affects infant behavioral development 1 month postpartum.Publication Relationships Between Personality Type and Cognitive Ability in Marmoset Monkeys (Callithrix jacchus)(2020-09) Marciano, ZacharyPersonality refers to multiple traits that are thought to be stable over time and across situations. It is recognized that personality has a neural basis and is associated with health outcomes. Whether personality is also associated with cognitive ability, however, is still a matter of intense debate. One way to examine these potential relationships is to use a nonhuman primate model for which complexities present in humans can be minimized. Recent research into the varying personality types of marmoset monkeys suggests that there are predominantly three to five core primary domains that most marmosets and other primates can be categorized into, such as dominance, sociability, and neuroticism. The aim of the proposed study was to categorize a small colony of marmosets into respective personality domains, and to examine correlations between the monkeys’ personalities and their cognitive ability. This study was be conducted on 27 marmoset monkeys (14 male, 13 female) housed in the Lacreuse lab at the University of Massachusetts Amherst. A personality survey based on Koski (2015) containing 55 personality traits was utilized by 8 human judges, all of whom have been working with these monkeys daily for at least one year. Each judge rated each individual monkey on each individual trait on a 1 to 7-point scale; 1 indicating total absence of a trait and 7 indicating extreme presence of a trait. Once the survey data was compiled, a principal component analysis (PCA) was conducted to condense the myriad of ratings into smaller distinguishable personality domains. Three personality types were identified in this population, consistent with other non-human primate species. An ICC(2) was performed to ensure the interrater reliabilities of the 8 judges were consistent enough to be considered. Lastly, a linear regression was conducted to reveal possible correlations between the observed personality domains and cognitive performance achieved in a reversal learning task. The results of this experiment showed no statistically significant relationships between any of the three personality domains: Assertiveness, Neuroticism, and Inquisitiveness with the reversal learning cognitive scores. Although these findings suggest that personality and cognitive flexibility are independent in marmosets, we cannot rule out that personality may influence other cognitive domains. Additional studies are needed to examine this possibility.Publication SEX SPECIFIC ELECTROPHYSIOLOGY OF AROMATASE NEURONS IN THE MEDIAL AMYGDALA(2019-09) Correia, Marcelo HenriqueThe medial amygdala (MeA) is a central node in the interwoven circuits that regulate social behavior based on pheromones. Aromatase-expressing (arom+) neurons in the MeA are key for the establishment and maintenance of sex differences. Here, we characterized the intrinsic electrophysiological properties of arom+ neurons and non-aromatase (arom-) neurons in the MeA of male and female mice. Most electrophysiological properties were similar for arom+ neurons in the MeA between sexes, but the relative refractory period was twice as large in female mice. We also show that the firing pattern and firing frequency is markedly different between arom+ and arom- neurons. The activity of MeA neurons could be modulated by estradiol, which reduced activity in arom+ neurons in males. The differences between arom+ and arom- neurons were observed in both sexes suggesting that aromatase expression delineates a neural population in the MeA with similar and unique electrophysiological properties.Publication Changes in Color Guidance over the Course of a Complex Visual Search(2019-05) Papargiris, RyanWhen searching for an object, we store a mental representation of the target, which guides our search through the use of attention. The effectiveness of this search guidance varies depending on the task and the relationship between target and distractors. With a better understanding of how search guidance changes over time within a trial, we can better compare the differences between experimental conditions. Eye tracking data from a variety of search tasks were analyzed to determine how color guidance varied over the course of the trial. Color guidance for a given fixation was evaluated based on the distance in color space between the nearest object and the target color. These color differences were averaged over all of the trials and plotted based on when the fixation occurred in the trial. The results indicate that color guidance does not begin working at maximum effectiveness immediately. As the trial progresses, the average color difference decreases. After this initial decrease, if the target is not present, guidance becomes less selective and target dissimilar distractors are increasingly fixated. The color distance graphs were compared between experiments to reveal significant differences arising from the experimental conditions.Publication One Year Change in Cognitive Function in Male and Female Common Marmosets (Callithrix jacchus)(2019-05) Healey, BriannaLong term cognitive studies in humans and nonhuman primates such as macaques are difficult because of their long lifespan. The common marmoset (Callithrix jacchus) is a non-human primate who shares with humans many features characteristic of primates, including a complex brain and cognitive function. They also have a short lifespan (~10 years) that makes them a great model in studies of cognitive aging. This study focuses on the rate of decline in cognitive function in male and female marmosets based on performance on reversal learning tasks over 2 years of testing. We found that marmosets improved their overall performance from Year 1 to Year 2 due to practice effect, but that females exhibited an impairment in reversal learning compared to males in both years. We also found important individual differences, with some monkeys showing decline in Year 2 compared to Year 1 while most monkeys maintained or improved their performance in reversal learning over the two years. We conclude that (1) cognitive flexibility, as assessed by reversal learning, is impaired in middle-aged female marmosets compared to males, likely due to sex differences in habitual vs. goal-directed behavior, and (2) that reversal learning is a sensitive measure that can capture one year individual changes in cognitive function.Publication Frequency Selectivity is Conferred by Membrane Resonance in a Sensory System of Non-mammalian Vertebrate, Rana Castebiana(2019-05) Frolov, DaniilIn the amphibian auditory system, a subset of hair cells is known to be frequency tuned via electrical resonance. This tuning is thought to contribute to frequency selectivity of the information leaving the auditory periphery via the auditory afferent fibers. At the same time, while most, if not all, afferent fibers are shown to be frequency tuned, electrical resonance has only been experimentally demonstrated in a subset of amphibian auditory hair cells. In this thesis, we validate and use a novel Zap current method to probe the electrical resonance of the bullfrog amphibian papilla hair cells. We uncover the existence of two previously unknown types of electrically resonant auditory hair cells. We then show the existence of resonant hair cells across the length of amphibian papilla, with the range of frequency tuning that is nearly indistinguishable from that previously reported in the of auditory fibers. Therefore, this work further validates amphibian hair cell frequency resonance as the possible mechanism underlying frequency selectivity of the subsequent stages in auditory signal transduction.Publication Sex, Motivation, and Reversal Learning in the Common Marmoset (Callithrix jacchus)(2019-05) Carlotto, AlyssaThis study examined the relationships between motivation and cognitive performance in male and female common marmosets (Callithrix jacchus). This question was driven by prior data from the Lacreuse lab showing a robust female impairment in reversal learning, as assessed by the number of trials needed to acquire a reversal following a simple discrimination between two stimuli. This thesis tested the hypothesis that the female impairment in reversal learning was mediated by deficits in motivation. Two sets of measures were used to test this hypothesis. I evaluated physical effort via testing on the progressive ratio (PR), a test that requires animals to produce an increasing number of responses to get a reward. Cognitive effort was evaluated through the number of refusals (aborted trials) produced during performance of a reversal. Because estrogen replacement was previously shown to impair reversal learning in ovariectomized females, I also examined whether PR performance was affected by estrogen levels in a subset of female subjects. Contrary to my hypothesis, reversal learning was not significantly associated with cognitive or physical effort in either males or females. Estrogen levels did not significantly affect physical effort, but there was too much variability in a small sample of females for these results to be compelling. We conclude that the sex difference in reversal learning performance is unlikely to be mediated by sex differences in motivation. Instead females may be more likely than males to engage in habitual processes implicating the dorsal striatum, likely through the action of estrogens on this brain region.Publication Does Lactobacillus reuteri Probiotic Treatment Improve Sleep Quality in Rhesus Macaques (Macaca mulatta) Displaying the Self-injurious Phenotype?(2019-02) McGinn, PeterSelf-injurious behavior (SIB) is a complex phenotype that occurs with an increasing prevalence of about 7-34% in humans and 10-12% in non-human primates (NHPs). This study evaluated the efficacy of probiotic Lactobacillus reuteri as a treatment for self-injurious behavior (SIB) and sleep disruption in rhesus macaques. The treatment was proposed to alleviate mild self-biting, sleep disruption, and reduce chronically elevated hypothalamic-pituitary-adrenocortical (HPA) axis activity, all hallmark features of monkeys with this condition. The probiotic preparation included two strains of L. reuteri (L. reuteri ATCC PTA 6475 & L. reuteri DSM 17938) containing on average 200 million colony forming units per chewable tablet. The study was conducted on 14 rhesus macaque monkeys (9 males) housed at the University of Massachusetts Amherst. To our knowledge this is the first time that a Lactobacillus strain has been used as a treatment for SIB in rhesus macaques. This study utilizes motion-activated infrared camera technology, modified enzyme-immunosorbent-assays (EIAs) techniques to measure hair cortisol concentrations, and daily behavioral observations to provide an overall assessment of the behavioral, physiological, and sleep associated implications of probiotic treatment on SIB and control non-human primates (NHPs). Administration of L reuteri modestly decreased biting behavior in monkeys with SIB (F(2,12) = 5.64, p= 0.02) and showed overall decrease in nighttime activity across all subjects but did not normalize SIB to nonSIB values. Hair cortisol values are pending. These findings and the findings of previous work further strengthen the argument for probiotics as an efficacious treatment for SIB behavior.Publication Mapping a Pup-responsive Pathway from the Medial Preoptic Area to the Ventral Tegmental Area.(2018-09) Andina, MatiasMaternal behavior is the complex array of caregiving behaviors females display towards offspring. In rats, the transition to motherhood depends on the action of various hormones, especially estradiol near parturition, which primes the maternal circuitry to respond to pups upon first encounter at parturition with appropriate maternal behavior. Although virgin rats avoid pups, new mothers are highly motivated to interact with pups, and their maternal behavior depends on the functional interaction between the medial preoptic area (mPOA) and the ventral tegmental area (VTA). However, a precise mapping of the VTA-projecting mPOA neurons remains to be elucidated. To determine whether pup-responsive neurons in the mPOA project to the VTA, we injected the retrograde tracer Fluorogold (FG) into the VTA of new mother and virgin female rats. Six days later, females were exposed to 3 pups for 5 minutes, and their brains processed to visualize FG and c-Fos immunostaining. In addition, we further characterized the molecular phenotype of these neurons by performing immunohistochemistry against estrogen receptor alpha (Esr1). As expected, the behavior of postpartum and virgin females toward pups was different. Mothers readily approached pups and displayed maternal behavior, whereas virgins avoided interaction with pups. Despite these disparate responses to pups, no differences were found in the number and distribution of mPOAc-Fos→VTA neurons. In addition, in both postpartum and virgin females, a significant proportion of these pup-responsive mPOA→VTA projecting neurons also express Esr1. Further functional interrogation of these c-Fos+/Esr1+ mPOA→VTA neurons in virgins and mothers might elucidate distinct circuit dynamics potentially underlying their behavioral differences towards pups.Publication A Precise Steroid-responsive Centrifugal Feedback Projection to the Accessory Olfactory Bulb(2018-09) Inbar, TalThe accessory olfactory bulb (AOB) processes pheromonal signals which in turn drive social behaviors. Here we identify a tract of aromatase-expressing (arom+) fibers in the dorsal lateral olfactory tract (dLOT) which terminate in the granule cell layer (GCL) of the AOB. We utilized a retrograde tracer in aromatase reporter animals to delineate the source of these fibers. We show that these input fibers emerge almost exclusively from a contiguous population of arom+ neurons that spans the bed nucleus of the accessory olfactory tract (BAOT) and posterioventral subnucleus of the medial amygdala (MeApv). This population of neurons expresses the estrogen receptor alpha and contains more aromatase neurons in male mice than female mice. Thus, this population of feedback neurons can detect neuroendocrine changes and modulate the output of AOB projection neurons in a way that is sexually dimorphic and could influence every downstream target of the AOB.Publication The Role of Hypothalamic Vasopressin Cells in Male Sociability and Anxiety-Linked Behavior(2018-09) Nanda, PrakrutiThe vertebrate hypothalamus is a central node within multiple interwoven neural networks that integrate external and internal cues to control homeostasis, endocrine functions and social behavior. The neuropeptide hormone arginine-vasopressin (AVP) is produced in both the supraoptic and paraventricular nuclei of the hypothalamus. Expression within these nuclei is conserved across species, and species differences in the expression of AVP and its cognate receptors correlate with differences in social behavior. As a central node within the social behavior network, chemogenetic manipulation of AVP+ cells in the paraventricular nucleus (pvn) of the hypothalamus provides a unique opportunity to investigate the relationship between social behavior and the regulation of stress responses. Here, we show that reversibly inducing excitatory activity in vasopressin neurons in the PVN results in reduced motivation for social interaction and increased grooming behavior in males. Chronic activation of PVN AVP neurons reduced social motivation in male mice that persisted even without CNO administration. These results highlight the role PVN AVP+ neurons play in the modulation of male social motivation.Publication Vocal Communication During Early Mother-Infant Interaction: Studies Using the Wistar-Kyoto Rat Model of Depression(2018-05) Tuncali, IdilPostpartum depression is a serious psychiatric condition that has deleterious effects on the mother and poses a risk for the mother-infant relationship and ultimately the infant’s development. Maternal anhedonia and social communication deficits are two major clinical features central to postpartum depression that likely contribute to deficits in parenting. The present study used Wistar-Kyoto (WKY) mother rats, an animal model of depression which we have developed to examine the postpartum disorder, to investigate the relationship between maternal anhedonia, social communication deficits and parenting disturbances. Rats produce ultrasonic vocalizations (USVs) in different social contexts, and USVs are becoming an increasingly valuable assay for behavioral phenotyping. Alterations of the ultrasound patterns have been reported in several models of neuropsychiatric disorders, including those associated with communicative/social deficits, and can also provide reliable insight into the affective state of the mother rat during social interactions with her litter. In the first study, WKY and control Sprague-Dawley (SD) postpartum females were examined for their affective responses to social cues from pups, as measured by their ultrasonic vocalizations (USVs) during a 30-minute maternal behavior test following 20 minutes of mother-litter separation. Total number of calls, acoustic frequency and duration of calls, and individual USV profiles were analyzed in conjunction with maternal behavior. Both WKY and SD mothers predominantly produced ~50 kHz USVs when interacting with the pups in the maternal behavior test. WKY mothers emitted more trill-type USVs as is compared with SD mothers. Similarly, WKY mothers exhibited substantial disturbances in theirmaternal behavior. A second experiment evaluated the therapeutic efficacy of adenosine A2A receptor antagonism as a novel treatment strategy for postpartum depression. Emerging evidence indicates that the neuromodulator adenosine, particularly through actions on adenosine A2A receptors, modulates behavioral functions associated with the mesocorticolimbic DA system, including cognitive and motivational processes. Results indicate that acute MSX-3 administration did not attenuate the parenting disturbances of WKY or affect the USV emissions of either strain. Taken together, these results provide evidence for the presence of maternal USVs during motherlitter interactions, and further suggest that variations in USVs produced by mothers during social interaction with their pups may function as an index of their affect. Rat USVs may be used to study the neurobiological mechanisms underlying maternal affect in animal models of postpartum disorders.Publication Effort-Related Motivational Dysfunctions: Behavioral and Neurochemical Studies of the Wistar-Kyoto Rat Model of Depression(2018-05) Abbott, BrendanDepression and related disorders are characterized by motivational dysfunctions, including deficits in behavioral activation and exertion of effort. Animal models of relevance to depression represent a critical starting point in elucidating the neurobiological mechanisms underlying motivational dysfunctions. The present study explored the use of the Wistar-Kyoto (WKY) animal model of depression to examine effort-related functions as measured by voluntary wheel running and performance on a mixed fixed ratio 5/progressive ratio (FR5/PR) operant task. Given the known link between activational aspects of motivation and the mesocorticolimbic dopamine (DA) system, the behavioral effects of d-amphetamine (0.5 and 1.0 mg/kg, IP), a psychostimulant that increases DA release, were evaluated in WKY and control Sprague-Dawley (SD) male and female rats responding on a mixed FR5/PR task. An additional experiment assessed intracellular content of monoamine neurotransmitters and their metabolites in relevant mesocorticolimbic brain regions, including the medial prefrontal cortex, the nucleus accumbens and the ventrolateral striatum using HPLC-ED. WKY rats demonstrated initial effort-related deficits in FR5/PR responding compared to SD controls, which ameliorated with training. Amphetamine significantly decreased FR5 work output, but increased responding on the PR phase in both SD and WKY rats. This effect was more pronounced in SD rats compare to WKY rats. In addition, sex differences were evident both in FR5/PR performance and in the behavioral response to amphetamine treatment. Moreover, females demonstrated higher levels of voluntary wheel-running than males. Finally, tissue concentrations of dopamine were lower in the NA and VLS of WKY compared to SD rats. Taken together, results suggest dysfunctions in mesolimbic DA neurotransmission in the WKY strain, likely underlying the depressive phenotype. The present study represents an important initial step in validating the WKY strain as a rat model of effort-related dysfunctions relevant to depression and other neuropsychiatric disorders.Publication Explicit Learning of Phonotactic Patterns Disrupts Language Learning(2017-09) Hare, EvanLearning environment has been proposed to be a cause of age of acquisition effects in second language acquisition. Explicit learning in adults is linked to fast initial gains but poorer ultimate attainment whereas implicit learning in children requires more input but leads to greater proficiency in the long run. The current study used ERP measures to determine if explicit learning of a phonotactic pattern interferes with implicit learning of that same pattern in adults. Listeners were told to figure out the pattern of consonants that can go together in a word by listening to 16 CVCV nonsense words in which the two consonants all matched in voicing or never matched in voicing. Listeners rated novel items that fit the pattern presented in training as far more likely to fit the rule than novel items that violated that pattern, indicating that they did indeed learn the pattern. For participants who heard the voicing-mismatch language, novel items that violated the pattern elicited a larger negativity 200-400 ms after onset compared to novel items that fit the pattern. This effect was entirely distinct from what was previously observed under implicit learning conditions. Further, three patterns of data suggest that difficult explicit learning of a phonotactic pattern decreased language learning. First, differences in N400 amplitude across training blocks were reduced compared to what was observed with implicit learning. Differences in N400 amplitude in response to trained and novel items were limited to the more easily learned matched-voicing language. Second, the ERP index of implicit phonotactic learning, a larger Late Positive Component (LPC) in response to novel items that violate compared to fit the pattern, was absent under explicit learning conditions. Third, and supporting the idea that an absence of an LPC effect indicates an absence of implicit learning, the only hint of an LPC-like effect was evident for the more easily learned matched-voicing pattern. These patterns of data suggest that, at least for patterns that native speakers have exclusively implicit knowledge of, challenging explicit learning can interfere with other aspects of language learning. Adults who approach second-language acquisition with class-room style explicit learning strategies may compromise implicit learning of complex patterns that are necessary for higher levels of ultimate proficiency.Publication An Adult Zebrafish Brain Atlas To Investigate Shh Mediated Cell-Cell Signaling In Neurogenic Zones(2017-02) Lutservitz, Alyssa PAdult neurogenesis occurs in proliferative zones of the brain that contain neural progenitor cell populations capable of differentiating into specific cell types. However, we remain limited in our understanding of the signals that regulate neural progenitor cell proliferation and differentiation in adults. Recently zebrafish (Danio rerio) have emerged as an excellent model for studying the molecular mechanisms behind adult neurogenesis, because sixteen proliferative zones remain active in the adult brains. Thousands of fluorescent transgenic reporter lines have been generated in zebrafish that reveal gene expression patterns of cell-cell signaling systems, some of which may regulate neurogenesis in these brain regions. Using a new tissue clearing technique and whole brain imaging with fluorescent light sheet microscopy (FLSM) we have generated the first 3-Dimensional atlas of gene expression in an intact adult zebrafish brain. So far we have created a reference brain image and have aligned the expression patterns from three transgenic lines. This work is a preliminary step in the generation of a new, open access brain atlas called the Zebrafish Adult Brain Browser (ZABB). While generating this atlas we focused on documenting the adult brain regions responsive to Sonic Hedgehog (Shh), a cell-cell signaling system known to regulate neurogenesis during embryonic development. We used two Shh-reporter lines to create another atlas comparing reporter transgene expression in whole brain and sectioned tissue to the expression of the Hedgehog (Hh) target gene ptch2 using in situ hybridization. We show that the reporter lines reveal different Hh responsive domains, but together identify fourteen Hh responsive regions in the brain, nine of which are known proliferative zones. Thus, it appears that subsets of both proliferating neural progenitors and non-proliferative cells remain Hh responsive in adult brains. Our data suggests that Hh signaling contributes to the regulation of neural progenitor cells in nine of the sixteen proliferative zones. Uncovering the molecular mechanisms behind adult neurogenesis and forming a greater understanding of adult neural stem cell regulation has the potential to influence the treatment of many neurodegenerative diseases and cancers.Publication Chemosensory Receptors in Berghia stephanieae: Bioinformatics and Localization(2022-09) Watkins, Kelsi L.Chemosensation is achieved through the binding of chemical signals to chemoreceptor proteins embedded in the membranes of sensory neurons. The molecular identity of these receptors, as well as the downstream processing of chemosensory signals, has been well studied in arthropods and vertebrates. However, very little is known about molluscan chemosensation. The identity of chemoreceptor proteins in the nudibranch mollusc Berghia stephanieae are unknown. Data from other protostome and molluscan studies suggest Berghia may use ionotropic receptors for some forms of chemoreception. This study used a bioinformatics approach to identify potential chemosensory ionotropic receptors in the transcriptome of Berghia. A hidden Markov model program was used to generate molecular profiles of previously identified chemosensory receptors in other animals. A Berghia transcriptome was then searched for likely homologous sequences. Candidate sequences were investigated using protein prediction tools and molecular phylogenies. Fourteen ionotropic glutamate receptors (likely synaptic) and five divergent ionotropic receptors were identified. One of these divergent ionotropic receptor sequences, IR-D, may encode a chemosensory receptor and was therefore selected to determine its cellular expression in sensory and brain tissue using in situ hybridization chain reaction. Expression was seen in the rhinophores and oral tentacles of Berghia, as well as in the rhinophore ganglion, cerebral-pleural ganglion, and pedal ganglion. Similar expression patterns were obtained with tissue-specific transcriptomic data. This was the first study to investigate IR-D as a potential chemosensory receptor in molluscs, and thus has helped identify a new family of possible ionotropic chemoreceptor proteins in molluscs. These results have laid the groundwork for continued investigation of Berghia’s chemosensory system.Publication Emotional Effect on Culture Difference in Economic Decision Making(2022-05) Ba, LanIt is well known that cultural difference could affect people’s attitude, behavior and cognitive processes. Previous studies have shown a cross-cultural difference on self-construal between Western Caucasian (WC) and East Asian (EA), as well as their culturally distinguished motivational strategies, cognitive and emotion regulation methods. “Cushion hypothesis” (Hsee & Weber 1999) has suggested that WC were more risk aversive than EA during economic decision, because of dissimilar familial-social economic supporting system between two cultures. The current study digs in depth to these differences in emotional experience associated with decision making and discovers how cultures effect people’s counterfactual emotions—the “what if” emotion—during economic decision making. There are two types of counterfactuals thoughts we are looking at: regret and relief. Regret is triggered if an alternative action would have led to a better outcome, while relief is triggered if an alternative action would lead to equal or worse outcome. WC are expected to be more self-reliance, therefore would be more conservative about financial decision, and greater vigilant at economic choices prompting WC to process prior decision that led to least undesirable economic outcome; while EA are easier to get financial help form their families, would hold a relatively more relax attitude, compare to WC, about risk-taking behavior on economic decision, and be more chilled after receive preferable outcome than WC. Current study will use electropherogram (EEG) to record different event-relative potential (P2, P3 and LPP) and both FC (frontal central lobe) and CP (central parietal lobe) regions to examined how cultural difference affects counterfactual emotions during economic decision making, at both initial spontaneous arousal stage, P2 and conscious effortful emotional appraisal stage, LPP. Additionally, self emotional rating was included in the present study to consolidate validity of the task. In our results, all subjects rated happier on Relief than Regret, and Certain than Gamble conditions, only in Relief condition WC rated happier than EA, and only WC rated happier on Certain condition than Gamble condition. The emotional effect showed at P2 in FC suggested that positive result in regret condition could lead a more intensive immediate emotion arousal. Coincidently, the main effect of emotion at LPP, in the opposite direction compared to P2, at FC, might suggest an overall convoluted counterfactual emotional processing. At P3, choices by culture interaction presented at both region, further, only EA, but not WC, had a greater arousal in gamble condition than certain. This suggested a difference in cognitive processing of choices was different between two cultures. Interestingly, a three-way interaction was found at CP during P3, indicate a complexity of culture discrepancy of emotional process. Finally, a co-relation test between LPP signal and self-emotional rating was conducted, for the coincident of result of main effect of choices plus a marginal choices by culture interaction between behavioral rating and LPP. As the result, only in EA, at both choices conditions, the rating is positively related to LPP amplitude. Overall, both at P3 and LPP we found cultural specialized results correlated with choices condition, which indicated a obscure cultural effect on cognitive process. Moreover, the marginal three-way interaction at P3, CP, may suggest a cultural effects on both economic decision-making related cognitive process and emotional response.