Male survivors of abuse who become fathers themselves face challenges different from female survivors, such as conceptualizing their roles as providers and heads of households after the traumatic and often belittling experiences of abuse. However, very few researchers have studied the connection between child abuse and fatherhood, and none specific to young African American fathers. An interpretative phenomenological approach enabled exploration of how African American fathers who were abused as children, conceptualized and perceived their own experiences with fatherhood. The theoretical framework for this study was identity theory, which indicates that how people conceptualize a social role influences their actions in that role. Research questions centered on how young African American fathers, who were abused as children, conceptualized fatherhood and carried out their roles as fathers. Data collected from 11 young African American fathers came through in-depth, semistructured interviews. Key findings showed participants conceptualized fatherhood as being present for, providing for, and protecting their children. These fathers worked to break the cycle of abuse they had experienced and to show support for their children. Implications to promote social change include use of study findings to develop parenting programs that address childhood trauma. Other benefits may come from developing groups for father with children in the foster care system, helping these men to understand why they parent the way they do and to break the destructive cycle of parenting they had experienced. Findings may also contribute to the establishment of fatherhood programs that match fathers with supportive role models who help in navigating the father role.

Previous studies completed with humans have revealed insight into the effects of anxiety on attention tasks such the dot-probe task, but there is little information about such effects on non-human primates. This study aimed to assess whether anxiety or anxious behaviors would impact rhesus macaque performance on a three stimuli paradigm similar to the dot-probe task. Utilizing images of conspecifics (strong threat, mild threat, and neutral), eight monkeys were video recorded completing a task that required them to slide two doors, which held these images, to the side to obtain a treat. We hypothesized that behavioral phenotype (high or low anxiety) would affect attention on this modified dot-probe task. Additionally, we predicted that time spent looking at mildly threatening stimuli would be positively correlated with high levels of anxious behaviors (e.g., scratching, yawning, pacing, self-biting) and cortisol concentrations over a four month period. We also predicted that a higher percentage of the mildly threating stimuli as a first choice would be positively correlated with high levels of anxious behaviors and cortisol concentrations. However, anxious behaviors and cortisol concentrations did not affect performance on this task. Interestingly, a sex difference was found for the mild threat stimuli, with females taking significantly more time to complete the task when presented with the mild stimuli (p = 0.01), and also looking at the mild stimuli longer than males (p = 0.03). These data suggest that males and females interpret ambiguous facial expressions differently, possibly indicating the significance of attention in female dominance hierarchies in macaque social groups.

Maternal 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.

The 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.

Although cannabis is widely consumed by humans for the intoxicating effects that are mediated by delta-9 tetrahydrocannabinol (THC), pre-clinical models of THC self-administration have been difficult to establish. We hypothesized that THC may have reinforcement enhancing effects comparable to other drugs (e.g., nicotine and caffeine), which are also widely consumed by humans but difficult to establish as primary reinforcers in non-human animals. To investigate whether THC is a reinforcement enhancer, male (M, n=8) and female (F, n=8) rats were shaped to self-administer a reinforcing saccharin (SACC) solution (0.2% w/v) in standard operant chambers equipped with infrared beams to monitor locomotor activity. At baseline, we found a significant sex difference for active lever responses and reinforcers earned (F

Neuropeptide signaling play critical roles in maintaining distinct behavioral states and orchestrating transitions between them. However, elucidating the mechanisms underlying neuropeptide modulation of neural circuits in vivo remains a major challenge. The nematode Caenorhabditis elegans serves as an excellent model organism to study neuropeptide signaling mechanisms encoded in relatively simple neural circuits. We have used the C. elegans egg-laying circuit as a model to understand how neuropeptide signaling modifies circuit activity to generate opposing behavioral outcomes. C. elegans egg-laying behavior is composed of alternating cycles of two states – short bursts of egg deposition (active phases) and prolonged periods of quiescence (inactive phases). We have identified two neuropeptides (NLP-7 and FLP-11) that are locally released from a group of neurosecretory cells (uv1) and coordinate the temporal organization of egglaying by prolonging the duration of inactive phases. These neuropeptides regulate activity within the core circuit by inhibiting serotonergic transmission between its individual components (HSN motorneurons and Vm2 vulval muscles). This inhibition is achieved at least in part, by reducing synaptic vesicle abundance in the HSN synaptic regions. To identify potential downstream signaling components that mediate the actions of these neuropeptides, we have performed a forward genetic screen and have identified a strong candidate. In addition, we are trying to identify the receptor(s) of these neuropeptides by using a candidate gene approach. Together, we demonstrate that local neuropeptide signaling maintains the periodicity of distinct behavioral states by regulating serotonergic transmission in the core neural circuit.

Circadian rhythms are self-sustained 24-hour period oscillations present in most organisms, from bacteria to human. They can be synchronized to external cues, thus allowing organisms to anticipate environmental variations and optimize their performance in nature. In Drosophila, the molecular pacemaker consists of two interlocked transcriptional feedback loops. CLOCK/CYCLE (CLK/CYC) sits in the center and drives rhythmic transcription of period (per), timeless (tim), vrille (vri) and PAR domain protein 1 (Pdp1). PER and TIM negatively feedback on CLK/CYC transcriptional activity, forming one loop, while VRI and PDP1 form the other by regulating Clk transcription negatively and positively, respectively. Posttranscriptional and posttranslational regulations also contribute to circadian rhythms. Although much has been learned about these feedback loops, we are still far from understanding how stable 24-hour period rhythms are generated. My thesis work was to determine by which molecular mechanisms kayak-α (kay-α) and Ataxin-2 (Atx2) regulate Drosophila circadian behavior. Both genes are required for the precision of circadian rhythms since knocking down either gene in circadian pacemaker neurons results in long period phenotype. The work on kay-α constitutes the first half of my thesis. We found that the transcription factor KAY-α can bind to VRI and inhibit VRI’s repression on the Clk promoter. Interestingly, KAY-α can also repress CLK’s transcriptional activity on its target genes (e.g., per and tim). Therefore, KAY-α is proposed to bring precision and stability to the molecular pacemaker by regulating both transcriptional loops. The second half of my thesis focuses on ATX2, an RNA binding protein whose mammalian homolog has been implicated in neurodegenerative diseases. We found that ATX2 is required for PER accumulation in circadian pacemaker neurons. It forms a complex with TWENTY-FOUR (TYF)—a crucial activator of PER translation—and promotes TYF’s interaction with Poly(A)-binding protein. This work reveals the role of ATX2 in the control of circadian rhythms as an activator of PER translation, in contrast to its well-established role as a repressor of translation. It also further demonstrates the importance of translational regulation on circadian rhythms. Finally, it may help understanding how ATX2 causes neuronal degeneration in human diseases.

Dopamine (DA) is central to movement, reward, learning, sleep, and anxiety. The dopamine transporter (DAT) spatially and temporally controls extracellular dopamine levels by taking DA back up into the presynaptic neuron. Multiple lines of evidence from studies using pharmacological DAT blockade or genetic DAT deletion demonstrate that DAT availability at the plasma membrane is required for maintenance of homeostatic DA levels and DA tone. Therefore, intrinsic mechanisms that regulate the transporter’s availability at the plasma membrane may directly impact downstream DA signaling cascades and DA-dependent behavior. Acute, regulated DAT internalization in response to protein kinase C (PKC) activation has been well documented, however the physiological importance of this mechanism remains untested. Due to DAT’s critical role in regulating DA levels, It is essential to understand mechanisms that acutely regulate DAT function and surface expression, and further, how these mechanisms contribute to DA related behaviors. DAT has intracellular amino and carboxy termini, which contain domains for transporter phosphorylation, recruitment to and from the plasma membrane, and sites for protein-protein interactions. To test whether these domains work synergistically for DAT function and regulated endocytosis I made DAT/SERT chimeras, in which I switched DAT’s amino, carboxy, or both termini with that of SERT, a homologous transporter with highly divergent intracellular domains. I demonstrated that DAT’s amino and carboxy termini synergistically contribute to substrate and select competitive inhibitor affinities. Additionally, I demonstrated that the amino terminus is required for PKC-stimulated DAT endocytosis, and that both N- and C-termini are required for downstream Ack1-dependent regulation of DAT endocytosis. To test the physiological importance of PKC-stimulated DAT endocytosis in vivo, I knocked down Rin, a GTPase required for PKC-stimulated DAT trafficking, in mouse DA neurons. This study was the first to achieve AAV-mediated, conditional, and inducible gene silencing in neurons. Using this AAV approach, I demonstrated a critical role for Rin GTPase signaling and DAT trafficking in both anxiety and locomotor response to cocaine. Taken together, this thesis 1) adds to the understanding of DAT functional and endocytic mechanisms and 2) is the first to report the physiological impact of Rin signaling and DAT endocytosis in DA behavior.

Circadian rhythms are endogenous cycles that control physiological and behavioral changes that can be affected by environmental factors which allow most eukaryotic organisms to synchronize their daily activities with the 24-hour day. Parasteatoda tepidariorum,the common house spider, demonstrates a short-period circadian clock averaging 21.6 hours when left in constant darkness, yet they are able to entrain to a 24-hour light cycle. We tested whether these spiders were able to use non-photic Zeitgebers to entrain to the 24-hour day. Periodic presentation of food and disturbance were not found to be effective cues for the spiders’ entrainment. A few individuals were clearly able to entrain to an 8 oC amplitude temperature cycle, while most did not.

Until recently, society and science often ignored, erased, and avoided bisexual women and men and individuals with biracial and multiracial identities, and rarely considered these identities simultaneously. Prior research has shown that some lesbians and gay people of color exhibit resilience against sexual minority stress due in part to an inoculating effect of exposure to racism earlier in life. However, little is known about the lived experience of thriving, resilient bisexual multiracial individuals. In the tradition of positive psychology and context of intersectionality theory, this qualitative study explored how multiracial bisexual individuals develop and maintain flourishing well-€being despite sociocultural factors promoting chronic stressors. In-€depth, semistructured interviews were conducted with 6 multiracial bisexual participants. Interpretive phenomenological analysis revealed 6 key themes for developing and maintaining resilience: integration of intersecting social identities, social support, emotional openness, hope and optimism, meaningful life, and life/personal accomplishments. Deeper knowledge about resilience-€building in holders of multiple-€marginal identities may influence informed stakeholders (bisexual, biracial and multiracial individuals and their families, service providers, researchers, public institutions, and decision makers) to advance development of more effective counseling programs and influence more responsive and affirmative social policies. Subsequent social change involves the advance of sexual health, rights, and behaviors of bisexual, biracial and multiracial citizens.