Nicotine addiction is a multifaceted disease that can be influenced by several factors. Emerging evidence indicates that the neural substrates of nicotine addiction overlap with the neural substrates of learning and memory. Nicotine modulates various types of learning and memory and the ability of nicotine to alter cognitive processes may contribute to its addictive liability. Acute nicotine enhances contextual conditioning in mice, tolerance develops to this effect with chronic administration, and withdrawal from chronic nicotine produces cognitive deficits. While tolerance and withdrawal deficits both occur following chronic administration, it is unknown if they share similar mechanisms. The series of experiments in Chapter 2 were designed to provide evidence that tolerance and withdrawal are dissociable. C57BL/6J mice were implanted with osmotic minipumps that delivered constant nicotine or saline for various durations and then were trained and tested in contextual conditioning either during chronic nicotine administration or 24 hours after pump removal. Chronic nicotine enhanced contextual conditioning in a dose- and time-dependent manner. Tolerance developed quickly to the enhancing effect of chronic nicotine. Furthermore, the duration of chronic nicotine treatment required to produce cognitive deficits upon cessation of treatment differed than that required to produce tolerance, which suggests that tolerance and withdrawal are mediated by separate mechanisms. Chapter 2 concludes by presenting a model that integrates nicotinic acetylcholine receptor desensitization and upregulation to explain the present findings. The model presented in Chapter 2 predicts that there will be enhanced sensitivity to acute nicotine during a period of nicotine withdrawal. Previous research indicates that prior exposure to nicotine enhances sensitivity to acute nicotine injections, but it is unclear if this enhanced sensitivity is due to prior nicotine exposure or enhanced sensitivity to nicotine during withdrawal. Therefore, the experiments in Chapter 3 were designed to determine if prior exposure to nicotine or nicotine withdrawal altered sensitivity to acute nicotine injections. This was accomplished by assessing the effects of acute nicotine on contextual conditioning immediately after cessation of chronic nicotine treatment and two weeks later, a time period not associated with withdrawal-related changes in cognitive function. Results of the study showed that acute nicotine enhanced contextual conditioning across a wide range of doses in both saline- and nicotine-withdrawn mice. However, a greater enhancement of contextual conditioning was observed in mice withdrawn from chronic nicotine treatment for 24 hours than all other withdrawal groups, suggesting enhanced sensitivity during withdrawal. The enhanced sensitivity to acute nicotine suggests altered nAChR function during withdrawal. In addition, the lowest dose of acute nicotine did not enhance contextual conditioning in groups that received chronic nicotine but did in other groups. The simultaneous observation of a hyper and hyposensitive nAChR system during withdrawal suggests that there may be a phasic response to chronic nicotine. Together, the results of the present study suggest that tolerance and withdrawal operate under separate mechanisms, and that there is overall enhanced sensitivity to nicotine during periods of nicotine withdrawal. / Psychology

Animals coordinate their behavior with each other during cooperative and agonistic social interactions. Such coordination often adopts the form of “turn-taking”, in which the interactive partners alternate the performance of a behavior. Apart from acoustic communication, how turn taking is coordinated, is not well known. Furthermore, the neural substrates that regulate persistence in engaging in social interactions are poorly studied. Here, we use Siamese fighting fish (Betta splendens), to study visually-driven turn-taking aggressive behavior. Using encounters with real conspecifics and with computer animations, we discover the visual cues from an opponent and the behavioral dynamics that generate turn taking. Through a brain-wide screen of neuronal activity during aggressive behavior, followed by targeted brain lesions, we then discover that the caudal portion of the dorsomedial telencephalon, an amygdala-like region, promotes continuous participation in aggressive interactions. Our work highlights how dynamic visual cues shape the rhythm of social interactions at multiple timescales and points to the pallial amygdala as a region controlling the drive to engage in such interactions.

The naked mole-rat (Heterocephalus glaber) is one of the most social mammals on the planet. These animals live in underground colonies consisting of a breeding female (the “queen”), 1 to 3 breeding males and up to 300 nonreproductive “workers” organized in a dominance hierarchy. In addition to their eusociality, naked mole-rats have evolved many extreme biological characteristics including an exquisite sense of touch and insensitivity to certain types of pain. However, the overlap between the social and somatosensory abilities of naked mole-rats remains mysterious. In this work, we show that naked mole-rats exhibit caste-like behavioral signatures linked to eusociality, predominantly utilize snout-to-snout interactions in social behavior and possess a somatosensory profile to mechanical stimuli distinct from mice. In the first chapter of this work, we leveraged machine learning and molecular biology tools to create a behavioral atlas of naked mole-rat behavior. We first utilized a computational pipeline of pose-tracking using SLEAP and behavioral segmentation using keypoint-MoSeq to identify 20+ behavioral syllables. This showed that the queen naked mole-rat has a distinct behavioral phenotype from the workers, consisting of faster movements, less anxiety-like freezing, and less colony maintenance behaviors such as digging. We next showed that behavioral differences exist between the workers and that the dominance rank of a given individual could be predicted by its spontaneous behaviors in an open field. Relative rank differential appeared to have relevance for social behaviors: during a tube test for dominance, pairings of a high-ranked and low-ranked animal occurred more quickly and were won more frequently by the dominant animal. Snout touch played an integral role in these dominance tests (perhaps in the communication of individual ID information). This prompted us to investigate snout-to-snout interactions in the open field. We found that two familiar naked mole-rats from the same colony engaged in hundreds of snout interactions in a 10-minute period, and the number of interactions was nearly twice as high between two foreign animals. Follow-up experiments explored the molecular basis of this snout touch and showed that mechanosensory channels (e.g. Piezo2) are likely involved in social snout-to-snout interactions. Furthermore, trimming the sensory whiskers of naked mole-rats disrupts their ability to recognize conspecifics and alters their relative dominance relationships. These findings uncover face touch as a prominent social behavior in naked mole-rats that is intimately linked to social recognition. In the second chapter of this work, we more deeply investigated naked mole-rat somatosensation by using high-speed videography. We began by determining how naked mole-rats respond to both innocuous stimuli (cotton swab, dynamic brush) and noxious stimuli (light and heavy pinpricks) when given to the hindpaw. Compared to mice, naked mole-rats showed a distinct hindpaw phenotype, never responding to innocuous touch stimuli, responding to light pinprick, but rarely responding to heavy pinprick (normally the most noxious stimulus that elicits the strongest pain response in mice). Interestingly, naked mole-rats do respond to brush stimuli to the back skin with a dorsiflexion posture. These animals also exhibit an idiosyncratic withdrawal response to a brush applied to the snout skin which appears to be highly aversive. Interestingly, the velocity of this aversive snout withdrawal appears to be socially modulated and is decreased in the presence of another naked mole-rat in the testing chamber. This phenotype does not occur in mice and provides additional evidence that the naked mole-rat snout is not only extremely sensitive but plays a role in processing socially relevant information.

Neuroscience as a field is collecting more data than at any other time in history. The scale of this data allows us to ask fundamental questions about the mechanisms of brain function, the basis of behavior, and the development of disorders. Our ambitious goals as well as the abundance of data being recorded call for reproducible, reliable, and accessible systems to push the field forward. While we have made great strides in building reproducible and accessible machine learning (ML) systems for neuroscience, reliability remains a major issue. In this dissertation, we show that we can leverage existing data and domain expert knowledge to build more reliable ML systems to study animal behavior. First, we consider animal pose estimation, a crucial component in many scientific investigations. Typical transfer learning ML methods for behavioral tracking treat each video frame and object to be tracked independently. We improve on this by leveraging the rich spatial and temporal structures pervasive in behavioral videos. Our resulting weakly supervised models achieve significantly more robust tracking. Our tools allow us to achieve improved results when we have imperfect, limited data while requiring users to label fewer training frames and speeding up training. We can more accurately process raw video data and learn interpretable units of behavior. In turn, these improvements enhance performance on downstream applications. Next, we consider a ubiquitous approach to (attempt to) improve the reliability of ML methods, namely combining the predictions of multiple models, also known as deep ensembling. Ensembles of classical ML predictors, such as random forests, improve metrics such as accuracy by well-understood mechanisms such as improving diversity. However, in the case of deep ensembles, there is an open methodological question as to whether, given the choice between a deep ensemble and a single neural network with similar accuracy, one model is truly preferable over the other. Via careful experiments across a range of benchmark datasets and deep learning models, we demonstrate limitations to the purported benefits of deep ensembles. Our results challenge common assumptions regarding the effectiveness of deep ensembles and the “diversity” principles underpinning their success, especially with regards to important metrics for reliability, such as out-of-distribution (OOD) performance and effective robustness. We conduct additional studies of the effects of using deep ensembles when certain groups in the dataset are underrepresented (so-called “long tail” data), a setting whose importance in neuroscience applications is revealed by our aforementioned work. Altogether, our results demonstrate the essential importance of both holistic systems work and fundamental methodological work to understand the best ways to apply the benefits of modern machine learning to the unique challenges of neuroscience data analysis pipelines. To conclude the dissertation, we outline challenges and opportunities in building next-generation ML systems.

Contemporary machine learning models exhibit unprecedented performance in the text, vision, and time-series domains, but at the cost of significant computational and human resources. Applying these technologies for science requires balancing accuracy and resource allocation, which I investigate here via three unique case studies. In Chapter 1, I present a deep learning system for animal pose estimation from video. Existing approaches rely on frame-by-frame supervised deep learning, which requires extensive manual labeling, fails to generalize to data far outside of its training set, and occasionally produces scientifically-critical errors that are hard to detect. The solution proposed here includes semi-supervised learning on unlabeled videos, video-centric network architectures, and a post-processing step that combines network ensembling and state-space modeling. These methods improve performance both with scarce and abundant labels, and are implemented in an easy-to-use software package and cloud application. In Chapter 2, I turn to the Gaussian process, a canonical nonparametric model, known for its poor scaling with dataset size. Existing methods accelerate Gaussian processes at the cost of modeling biases. I analyze two common techniques -- early truncated conjugate gradients and random Fourier features -- showing that they find hyperparameters that underfit and overfit the data, respectively. I then propose to eliminate these biases in exchange of increased variance, via randomized truncation estimators. In In Chapter 3, I investigate continual learning, or "finetuning", in large language models (LLMs) with billions of weights. Training these models requires more memory than typically available in academic clusters. Low-Rank Adaptation (LoRA) is a widely-used technique that saves memory by training only low rank perturbations to selected weight matrices in a so-called "base model'". I compare the performance of LoRA and full finetuning on two target domains, programming and mathematics, across different data regimes. I find that in most common settings, LoRA underperforms full finetuning, but it nevertheless exhibits a desirable form of regularization: it better maintains the base model's performance on tasks outside the target domain. I then propose best practices for finetuning with LoRA. In summary, applying state-of-the-art models to large scientific datasets necessitates taking computational shortcuts. This thesis highlights the implications of these shortcuts and emphasizes the need for careful empirical and theoretical investigation to find favorable trade-offs between accuracy and resource allocation.

No description available.

The purpose of this experiment was to compare the effects of combining negative reinforcement and positive reinforcement during teaching with the effects of using positive reinforcement alone. A behavior was trained under two stimulus conditions and procedures. One method involved presenting the cue ven and reinforcing successive approximations to the target behavior. The other method involved presenting the cue punir, physically prompting the target behavior by pulling the leash, and delivering a reinforcer. Three other behaviors were trained using the two cues contingent on their occurrence. The results suggest that stimuli associated with both a positive reinforcer and an aversive stimulus produce a different dynamic than a situation that uses positive reinforcement or punishment alone.

ambiente subterrâneo oferece rotas de deslocamento entre pontos de forrageamento ou local de estoque de alimentos e abrigo contra predadores e frio ou calor intensos. Dentre os roedores, cerca de 250 espécies usam o espaço subterrâneo (11%). Algumas dessas espécies são \"subterrâneas estritas\", mas a maioria são \"fossoriais\" em diferentes graus de dependência do subterrâneo, como o Clyomys bishopi que forrageia sobre a terra. O objetivo deste trabalho foi caracterizar o sistema subterrâneo dessa espécie endêmica do cerrado paulista, e correlacionar com aspectos distais e proximais do comportamento de escavação. No primeiro capítulo, são descritos os sistemas subterrâneos e verificadas suas relações com variáveis ambientais. No segundo, o uso do espaço pela espécie é investigado a partir da dinâmica de abertura das bocas de tocas de sistemas ao longo de dois anos. No terceiro capítulo, a temperatura interna dos sistemas é caracterizada e investigada quanto à sua relação com variáveis ambientais. Finalmente o último capítulo apresenta uma revisão sistemática sobre o uso de sistemas subterrâneos em Rodentia. Os sistemas subterrâneos de C. bishopi são complexos, com diversos túneis, bocas e câmaras de estocagem de sementes e com material de ninho. Os sistemas são maiores e mais profundos na estação seca do que na chuvosa. A espécie abre e fecha as bocas de seus sistemas ao longo do ano, e o maior número de abertura de bocas foi encontrado na estação seca em paisagem aberta, apoiando a hipótese de que os sistemas subterrâneos para a espécie funcionam principalmente como rotas de deslocamento entre áreas de forrageamento, protegidos de predadores. A temperatura apresenta um ciclo circadiano com acrofase após o pôr do sol sem distinção entre as estações climáticas, têm relações com a paisagem em que estão inseridas, sendo menores nas paisagens fechadas e mais elevadas na chuva, com temperatura mais elevada dentro da toca durante a noite e início da manhã. Os hábitos subterrâneos carregam sinais filogenéticos e tem relação com hábitos sociais, interações com o ambiente e a disponibilidade de alimento nos dois sentidos, seja no ganho ou na perda da socialidade. A manutenção da vida social numa espécie e a complexidade dos sistemas relacionam-se também com a maior compactação do solo. A hipótese das relações evolutivas entre a formação de colônias de sistemas subterrâneos, com seus usos e a vida social pode ser testada em trabalhos futuros / The subterranean environment provides displacement routes between foraging points or food storage locations and shelter from predators and intense heat or cold. Among rodents, about 250 species use underground space (11%). Some of these species are strictly subterranean, but most of them are \"fossorial\" in varying degrees of subterranean dependence, such as the Clyomys bishopi that forages above ground. The aim of this study was to characterize the burrow system of this species (that is endemic to cerrado of São Paulo) and to correlate with distal and proximal aspects of the burrowing behavior. In the first chapter, the burrow systems are described and their relationships with environmental variables are verified. In the second, the use of space by the species is investigated from the dynamics of opening and closing burrow systems entrances over two years. In the third chapter, the internal burrow\'s temperature is characterized and it is investigated in relation to the environmental variables. Finally, the last chapter presents a systematic review about the use of burrow systems in Rodentia. Burrow systems of C. bishopi are complex, with several tunnels, entrances and chambers of food storage and nest material. The systems are larger and deeper in the dry season than in the rainy one. The species opens and closes the entrances of its systems throughout the year, and the largest number of entrance openings was found in the dry season that are in open landscape, supporting the hypothesis that this species uses the burrow systems mainly as displacement routes between foraging areas, protected from predators. Temperature exhibits a circadian rhythm with acrophase after sunset without distinction between climatic seasons. This rhythm has relations with the landscape in which they are inserted: smaller in the closed landscapes and more elevated in the rain with higher temperature inside the burrow during night and early in the morning. Subterranean lifestyle carries phylogenetic signals and is related to social habits with interactions between the aridity and the availability of food and sociality on both directions: gain or loss of sociality. Also there are relations soil hardness, burrow\'s complexity and the maintenance of sociality among species. The hypothesis of the evolutionary relationships between the formation of burrow systems colonies with their uses and sociality can be tested in future studies

The cues used by marine turtles to locate foraging areas in the open ocean are largely unknown though some species (especially the green turtle [Chelonia mydas], the loggerhead [Caretta caretta], and the leatherback [Dermochelys coriacea]) somehow locate areas of high productivity. Loggerheads can detect airborne odors, but a capacity to orient has not yet been investigated. In this comparative study, tethered loggerheads and leatherbacks were exposed to dimethyl sulfide (DMS) or food odors in a laminar flow of air. Turtles did not orient into the air current. Free-swimming loggerheads and green turtles were also exposed to air- or waterborne food (squid) odor plus a neutral visual stimulus. Both species showed increases in swimming activity and biting behavior to both stimuli. These results suggest that airborne odors are likely not used to locate distant areas, but that they are used in localized food searching efforts. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

A forma como as formigas se dispersam pelo espaço está relacionada tanto à processos coletivos de formação de trilhas preferenciais de forrageamento por meio de marcação feromonal quanto à fatores individuais como orientação por ângulos, distância e direção da colônia, o comportamento em bifurcações e memória individual. Entretanto a compreensão de como esses mecanismos se articulam na produção de uma resposta da colônia frente à uma tarefa espacial poucas vezes foi focado. Além disso, assim como no forrageamento, a forma como se dá a dispersão pelo espaço na exploração também é crítica. Sendo assim, a dispersão das formigas pelo espaço representa um ponto de balanço entre a exploração e o forrageamento, em que os fatores individuais e coletivos compõem conjuntamente uma resposta ao desafio espacial. No entanto, na medida em que o uso do espaço é frequentemente observado pelo ponto de vista da otimização do forrageamento, esse balanço é pouco explorado. O objetivo do trabalho foi avaliar como a dispersão espaço-temporal das formigas de uma colônia, produzida por mecanismos coletivos e individuais, reflete tanto o esforço exploratório quanto o de forrageamento. Para isso, foi criado um labirinto hexagonal duplo concêntrico e foram comparadas as dispersões das formigas em duas condições: com alimento numa posição específica, e em uma condição controle, em que o alimento era oferecido junto à colônia de forma que a dispersão fosse uma exploração desvinculada do forrageamento. Para a observação das formigas no labirinto, foram dispostas câmeras de vídeo sobre os corredores e foi desenvolvido um software de análise de vídeo para a contagem de formigas. Embora a dispersão decorrente do forrageamento e da exploração sejam indissociáveis, através da simulação computacional com modelos de referência em que predominam um dos casos foi possível avaliar o grau de contraste com dispersões observadas experimentalmente. Observamos que, de fato, os controles são mais próximos do modelo nulo de exploração e os experimentos com folhas do modelo de forrageamento. Embora o caminho preferencial observado tenha divergido do modelo, são mais próximos do modelo de forrageamento, mostrando a relação entre a forma da dispersão e os comportamentos subjacentes. Além disso, houve uma baixa convergência nos controles, ao passo que nos experimentos com folhas a formação de trilhas preferenciais apresentou graus variados de convergência. Na condição experimental a formação de trilhas preferenciais decorrente da marcação feromonal coletiva, em conjunto com o comportamento individual nas bifurcações assimétricas e o próprio desenho do labirinto favoreceram a separação entre as trilhas de ida e volta do alimento. Enquanto o caminho de ida permaneceu o mais provável dado o labirinto, o caminho de retorno foi otimizado, estabelencendo um caminho mínimo contralateral ao caminho de ida. Assim, a relação entre os mecanismos coletivos e individuais fornece um cenário apropriado para a análise do balanço entre o forrageamento e a exploração / The means by which ants disperse is given by collective processes of preferential foraging trail formation by means of pheromone marking as well as by individual factors such as orientation by features\' angles, colony distance and direction, choices at bifurcations and individual memory. However, how these mechanisms interact in producing a colony response given a spatial task has rarely been the focus of studies. In addition, as in the case of foraging, the spatial dispersal pattern for exploration is also critical. So, the ants dispersal in space represents a balance point between exploration and foraging, in which the individual and collective factors together compose a response to the spatial challenges. However, as the space occupation is frequently studied regarding foraging optimization, this balance is disregarded. The objective of this study is to understand how the spatio-temporal dispersal of ants in a maze, as produced by such collective and individual mechanisms, reflects both the exploratory and foraging efforts. With that aim, I created a double concentric hexagonal maze and compared the ants dispersal in two conditions: in the offering of food in a specific place, and in a control condition, food was given in the same place as the colony such that its dispersal is unrelated to foraging. In order to observe the ants behaviour, video cameras were set on top of each maze connection and a software was developed to count the passage of the ants. Although the dispersal due to foraging and from exploration are inseparable, using computer simulations of reference theoretical models of each case it was possible to contrast and measure the differences to the experimentally observed dispersals. We observed that indeed, the experimental group was closer to the foraging model while the control was closer to the null model of exploration. Although the observed preferential path was different from that of the foraging model, it was still closer, showing the relationship between the observed dispersal and the underlying behaviours. Moreover, there was a low convergence in the control group, while various degrees of convergence were observed in the experimental group. In the experimental group, the formation of preferential paths by means of collective pheremonal markings, together with individual preferences at asymmetric bifurcations and the design of the maze, favoured the separation between outbound and inbound paths. Whilst the outbound path remained the most probable given the geometry of the maze, the inbound path was optimised, establishing a minimal path on the opposite side of the outbound path. Thus, the relationship between the collective and individual mechanisms provide a more than appropriate scenario for the analysis of the balance between foraging and exploration