The evolutionary emergence of neural organisation in computational models of primitive organisms

Over the decades, the question why did neural organisation emerge in the way that it did? has proved to be massively elusive. Whilst much of the literature paints a picture of common ancestry the idea that a species at the root of the tree of nervous system evolution spawned numerous descendants the actual evolutionary forces responsible for such changes, major transitions or otherwise, have been less clear. The view presented in this thesis is that via interactions with the environment, neural organisation has emerged in concert with the constraints enforced by body plan morphology and a need to process information eciently and robustly. Whilst these factors are two smaller parts of a much greater whole, their impact during the evolutionary process cannot be ignored, for they are fundamentally signicant. Thus computer simulations have been developed to provide insight into how neural organisation of an articial agent should emerge given the constraints of its body morphology, its symmetry, feedback from the environment, and a loss of energy. The first major finding is that much of the computational process of the nervous system can be ooaded to the body morphology, which has a commensurate bearing on neural architecture, neural dynamics and motor symmetry. The second major finding is that sensory feedback strengthens the dynamic coupling between the neural system and the body plan morphology, resulting in minimal neural circuitry yet more ecient agent behaviour. The third major finding is that under the constraint of energy loss, neural circuitry again emerges to be minimalistic. Throughout, an emphasis is placed on the coupling between the nervous system and body plan morphology which are known in the literature to be tightly integrated; accordingly, both are considered on equal footings

The persistence of memory

Distributing learning in time has the remarkable ability to enhance memory in a wide range of species and behavioral paradigms, a phenomenon termed the spacing effect. An extensive body of scientific work provides insight into the molecular and cellular processes that underlie the spacing effect. However, it is unclear how trial spacing alters the activity of the neuronal populations that store a specific memory. With my work presented in this doctoral dissertation, I explored the relationship between trial spacing, memory strength, and the pattern of in vivo neuronal activity. To achieve this aim, I executed two initial studies to address two outstanding methodological concerns. In the first study, I describe two nutritional restriction methods that balance mouse well-being and behavioral performance on an operant conditioning task. Nutritional restriction can be achieved by either food or fluid restriction and is typically necessary to ensure task engagement in mice. However, these procedures can have detrimental effects on mouse welfare if not executed diligently. I monitored the the effect of food or water restriction on mouse welfare as well as performance on a head-fixed two-choice visual discrimination task. In this study, both restriction regimen resulted in similar maximum learning performance while mouse discomfort was typically sub-threshold, providing a blueprint to the wider neuroscientific community to carry out similar experiments. In the second study, I compare a novel in vivo microscopy technique with the current golden standard for in vivo imaging of individual neurons, which is two-photon microscopy. Imaging using a miniaturized epifluorescence microscope is an efficient and effective approach to image hundreds of neurons while a mouse is engaged in a freely moving behavioral task, but does not achieve the same lateral and axial resolution as two-photon imaging. I performed in vivo calcium imaging of mouse primary visual cortex neurons expressing genetically encoded calcium indicators using both microscopy techniques while mice were presented with drifting gratings. I demonstrated that the response properties and tuning features of mouse visual cortex neurons to gratings of different orientations were quantitatively comparable in spite of qualitative differences between the two imaging methods. In the third and main study, I explore whether trial spacing affects memory strength and in vivo activity of a population of individual neocortical neurons. I addressed this question by examining two non-mutually exclusive hypotheses. Trial spacing could enhance the selective strengthening of the connections between neurons that store a preexisting memory. This would stabilize this neuronal ensemble, which would allow for more precise ensemble reactivation and thereby more effective memory retrieval. Alternatively, trial spacing could affect the recruitment of additional neurons that store new information from subsequent trials. This would increase the size of the neuronal ensemble, which would make the stored memory more resilient to destabilization. To explore these hypotheses, I trained mice on an everyday memory task, a delayed matching-to-place task that instilled episodic-like memories. Trial spacing promoted memory retrieval, yet surprisingly impaired memory encoding. Simultaneously, I measured neuronal activity using a miniaturized microscope in the dorsomedial prefrontal cortex, a neocortical structure that stored these memories as evidenced by the amnesic effect of chemogenetic inhibition of the dorsomedial prefrontal cortex during training. Trial spacing promoted reactivation of the neuronal ensemble but did not affect the size of the neuronal ensemble, thereby providing the first direct observation of the effect of trial spacing on the activity of neurons in the intact mammalian brain. In summary, the work presented in this doctoral dissertation used modern neuroscientific methods to study whether altered neuronal ensemble characteristics underlie the spacing effect, a phenomenon that was first described over a century ago

Construction and Utilization of Digital Brain Atlases in Larval Zebrafish

Rapid escape responses are critical for predator avoidance in fish. Yet, while short-latency C-start (SLCs) circuitry is well-known (e.g., Mauthner and related cells), neurons integral to long-latency C-starts (LLCs) remain uncharacterized. In this dissertation, I identify neurons critical for LLC through the genetic and laser ablations of neurons in transgenic lines. Although transgenic lines provide powerful tools for implicating neurons in behavior, they suffer a number of limitations. Transgene expression is frequently broad, incompletely mapped, or off-target, making it difficult to accurately compare en masse or to other modalities. I addressed this by designing a UAS reporter that suppresses off-target expression through microRNA binding and building a digital atlas from hundreds of transgenic zebrafish lines. By co-imaging and registering lines with a broadly expressed structural marker, the Zebrafish Brain Browser aligns expression to within approximately one cell diameter allowing rapid and accurate comparison of expression, identification of transgenes, and prediction of genetic overlap in almost any set of cells in the larval zebrafish brain. Other modalities (e.g., neural activity and anatomic segmentation) were also incorporated from Z-Brain, another popular zebrafish brain atlas, by a novel multichannel secondary registration. Together, this work increases the fidelity, interoperability, and accessibility of brain atlases and provides a powerful platform for the dissection of neural circuits in larval zebrafish. Using these tools to design and analyze genetic ablations, I performed a 'circuit-breaking' screen to identify neurons underlying LLC behavior. Three of the screened lines reduced LLC probability by >50%. These lines labeled two shared cell clusters: one adjacent to the locus coeruleus (LC) and another in the dorsal hindbrain. Through laser ablation and optogenetic stimulation, LC-adjacent neurons were shown to be both necessary and sufficient for LLC startle. Projections of individual LC-adjacent neurons were characterized by a novel genetic intersection approach. These neurons were strikingly homogeneous, projecting bilaterally to midbrain and hindbrain structures. From this work, I hypothesize that ipsilateral hindbrain projections activate premotor neurons, while contralateral neurites subserve reciprocal inhibition. For the first time, I have identified a core component of the circuit mediating long-latency C-starts, an ethologically important behavior in zebrafish

Using MapReduce Streaming for Distributed Life Simulation on the Cloud

Distributed software simulations are indispensable in the study of large-scale life models but often require the use of technically complex lower-level distributed computing frameworks, such as MPI. We propose to overcome the complexity challenge by applying the emerging MapReduce (MR) model to distributed life simulations and by running such simulations on the cloud. Technically, we design optimized MR streaming algorithms for discrete and continuous versions of Conway’s life according to a general MR streaming pattern. We chose life because it is simple enough as a testbed for MR’s applicability to a-life simulations and general enough to make our results applicable to various lattice-based a-life models. We implement and empirically evaluate our algorithms’ performance on Amazon’s Elastic MR cloud. Our experiments demonstrate that a single MR optimization technique called strip partitioning can reduce the execution time of continuous life simulations by 64%. To the best of our knowledge, we are the first to propose and evaluate MR streaming algorithms for lattice-based simulations. Our algorithms can serve as prototypes in the development of novel MR simulation algorithms for large-scale lattice-based a-life models.https://digitalcommons.chapman.edu/scs_books/1014/thumbnail.jp

Impacts des polluants métalliques sur l'abeille : de la colonie au cerveau

Les abeilles sont des pollinisateurs essentiels. Une pléthore de facteurs de stress environnementaux, tels que les produits agrochimiques, a été identifiée comme contribuant à leur déclin mondial. En particulier, ces facteurs de stress altèrent les processus cognitifs impliqués dans les comportements fondamentaux. Jusqu'à présent, cependant, on ne sait pratiquement rien de l'impact de l'exposition à des métaux lourds, dont la toxicité est avérée chez de nombreux organismes. Pourtant, leurs émissions mondiales résultant des activités humaines ont élevé leurs concentrations bien au-dessus des niveaux naturels dans l'air, le sol, l'eau et la flore, exposant ainsi les abeilles à tous les stades de leur vie. Le but de ma thèse était d'examiner les effets de la pollution métallique sur l'abeille domestique en utilisant une approche multi-échelle, du cerveau à la colonie, en laboratoire et sur le terrain. J'ai d'abord observé que les abeilles exposées à une gamme de concentrations de trois métaux communs (arsenic, plomb et zinc) en laboratoire étaient incapables de percevoir et éviter des concentrations usuelles, néanmoins nocives, de ces métaux dans leur nourriture. J'ai ensuite exposé de façon chronique des colonies à des concentrations réalistes de plomb dans la nourriture et démontré que la consommation de ce métal altérait la cognition et le développement morphologique des abeilles. Comme les polluants métalliques se trouvent souvent dans des mélanges complexes dans l'environnement, j'ai exploré l'effet des cocktails de métaux, montrant que l'exposition au plomb, à l'arsenic ou au cuivre seul était suffisante pour ralentir l'apprentissage et perturber le rappel de la mémoire, et que les combinaisons de ces métaux induisaient des effets négatifs additifs sur ces deux processus cognitifs. J'ai finalement étudié l'impact de l'exposition naturelle aux polluants métalliques dans un environnement contaminé, en collectant des abeilles à proximité d'une ancienne mine d'or, et montré que les individus des populations les plus exposées aux métaux présentaient des capacités d'apprentissage et de mémoire plus faibles, et des altérations de leur développement conduisant à une réduction de la taille de leur cerveau. Une analyse plus systématique des abeilles non exposées a révélé une relation entre la taille de la tête, la morphométrie du cerveau et les performances d'apprentissage dans différentes tâches comportementales, suggérant que l'exposition aux polluants métalliques amplifie ces variations naturelles. Ainsi, mes résultats suggèrent que les abeilles domestiques sont incapables d'éviter l'exposition à des concentrations réalistes de métaux qui sont préjudiciables au développement et aux fonctions cognitives, et appellent à une révision des niveaux environnementaux considérés comme "sûrs". Ma thèse est la première analyse intégrée de l'impact de plusieurs polluants métalliques sur la cognition, la morphologie et l'organisation cérébrale chez l'abeille, et vise à encourager de nouvelles études sur la contribution de la pollution métallique dans le déclin signalé des abeilles, et plus généralement, des insectes.Honey bees are crucial pollinators. A plethora of environmental stressors, such as agrochemicals, have been identified as contributors to their global decline. Especially, these stressors impair cognitive processes involved in fundamental behaviours. So far however, virtually nothing is known about the impact of metal pollutants, despite their known toxicity to many organisms. Their worldwide emissions resulting from human activities have elevated their concentrations far above natural baselines in the air, soil, water and flora, exposing bees at all life stages. The aim of my thesis was to examine the effects of metallic pollution on honey bees using a multiscale approach, from brain to colonies, in laboratory and field conditions. I first observed that bees exposed to a range of concentrations of three common metals (arsenic, lead and zinc) in the laboratory were unable to perceive and avoid, low, yet harmful, field-realistic concentrations of those metals in their food. I then chronically exposed colonies to field-realistic concentrations of lead in food and demonstrated that consumption of this metal impaired bee cognition and morphological development, leading to smaller adult bees. As metal pollutants are often found in complex mixtures in the environment, I explored the effect of cocktails of metals, showing that exposure to lead, arsenic or copper alone was sufficient to slow down learning and disrupt memory retrieval, and that combinations of these metals induced additive negative effects on both cognitive processes. I finally investigated the impact of natural exposure to metal pollutants in a contaminated environment, by collecting bees in the vicinity of a former gold mine, and showed that individuals from populations most exposed to metals exhibited lower learning and memory abilities, and development impairments conducing to reduced brain size. A more systematic analysis of unexposed bees revealed a relationship between head size, brain morphometrics and learning performances in different behavioural tasks, suggesting that exposure to metal pollutants magnifies these natural variations. Hence, altogether, my results suggest that honey bees are unable to avoid exposure to field-realistic concentrations of metals that are detrimental to development and cognitive functions; and call for a revision of the environmental levels considered as 'safe'. My thesis is the first integrated analysis of the impact of several metal pollutants on bee cognition, morphology and brain structure, and should encourage further studies on the contribution of metal pollution in the reported decline of honey bees, and more generally, of insects

2020 GREAT Day Program

SUNY Geneseo’s Fourteenth Annual GREAT Day.https://knightscholar.geneseo.edu/program-2007/1014/thumbnail.jp

Chemical Defenses of Aplysia Californica and Sensory Processing by Predatory Fishes

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

Activation of the pro-resolving receptor Fpr2 attenuates inflammatory microglial activation

Poster number: P-T099 Theme: Neurodegenerative disorders & ageing Activation of the pro-resolving receptor Fpr2 reverses inflammatory microglial activation Authors: Edward S Wickstead - Life Science & Technology University of Westminster/Queen Mary University of London Inflammation is a major contributor to many neurodegenerative disease (Heneka et al. 2015). Microglia, as the resident immune cells of the brain and spinal cord, provide the first line of immunological defence, but can become deleterious when chronically activated, triggering extensive neuronal damage (Cunningham, 2013). Dampening or even reversing this activation may provide neuronal protection against chronic inflammatory damage. The aim of this study was to determine whether lipopolysaccharide (LPS)-induced inflammation could be abrogated through activation of the receptor Fpr2, known to play an important role in peripheral inflammatory resolution. Immortalised murine microglia (BV2 cell line) were stimulated with LPS (50ng/ml) for 1 hour prior to the treatment with one of two Fpr2 ligands, either Cpd43 or Quin-C1 (both 100nM), and production of nitric oxide (NO), tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) were monitored after 24h and 48h. Treatment with either Fpr2 ligand significantly suppressed LPS-induced production of NO or TNFα after both 24h and 48h exposure, moreover Fpr2 ligand treatment significantly enhanced production of IL-10 48h post-LPS treatment. As we have previously shown Fpr2 to be coupled to a number of intracellular signaling pathways (Cooray et al. 2013), we investigated potential signaling responses. Western blot analysis revealed no activation of ERK1/2, but identified a rapid and potent activation of p38 MAP kinase in BV2 microglia following stimulation with Fpr2 ligands. Together, these data indicate the possibility of exploiting immunomodulatory strategies for the treatment of neurological diseases, and highlight in particular the important potential of resolution mechanisms as novel therapeutic targets in neuroinflammation. References Cooray SN et al. (2013). Proc Natl Acad Sci U S A 110: 18232-7. Cunningham C (2013). Glia 61: 71-90. Heneka MT et al. (2015). Lancet Neurol 14: 388-40

Arbovirus and mosquito vector: behaviour and neurophysiological interactions

This study investigated the behavioral and neurophysiological consequences of flavivirus infection in the mosquito vector. The multidisciplinary study included novel methods and original research in its field. The findings revealed the importance to study viral infection in mosquitoes, which could lead to better virus outbreak management and new drug discoveries