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Structural plasticity mediated by addition and elimination of dendritic spines is thought to underlie the formation of long-term memory. However, the spatial relationship of those structural activities during learning and memory remains unclear. Using in vivo two-photon microscopy, I track spine dynamics in mouse retrosplenial cortex (RSC) during contextual and spatial learning. I report that learning leads to addition of new spines that are spatially clustered, and the amount of clustering is predicted by spine turnover prior to learning. Both spine measures are correlated with learning and memory performance. Accordingly, a genetic manipulation by heterozygous mutation of Ccr5 that enhances pre-learning spine turnover also enhances learning-related spine clustering, as well as future learning and memory performance. New spines related to one memory do not form cluster with spines related to a distinct memory. In contrast, spines gained from one repetitive task tend to cluster with each other. Remarkably, clustered new spines are usually added on dendritic segments with rapid spine turnover, revealing the presence of hotspots on dendritic tree where elevated rates of spine turnover facilitate clustered spine addition associated with memory. One implication of these findings is that increased spine turnover may allow neurons to more efficiently sample the synaptic space during learning in order to optimize information acquisition. Once acquired, spine clustering may stabilize this information, thus strengthening memory circuits.

This work seeks to advance understanding of how to construct and control tensegrity spines: highly compliant robots with many degrees of freedom inspired by biological spines. Tensegrity describes systems of rigid bodies stabilized by cables, where on a simulated twelve segment robot up to 72 degrees of freedom require constraints or control. To coordinate the high number of actuators, central pattern generator (CPG) based controllers provide goal directed, adaptive trajectories for movement on rough terrain. As a result, this work details, to the author's knowledge, the first CPG based robotic control capable of goal directed locomotion on rough terrain. This control scheme is implemented on four different tensegrity spine designs.Prior to this work, tensegrity spines were passive, hand constructed models; the open source NASA Tensegrity Robotics Toolkit (NTRT) was created to develop robots inspired by these and other tensegrity models using physics based simulation. This work also discusses the development and implementation within NTRT of a cable model with contact dynamics and realistic forces. Finally, the simulations are validated against the forces measured in the hardware implementation of a three segment tensegrity spine robot.

The anterior cingulate cortex (ACC) plays an important role in reward-based decision-making, linking higher-order thinking and emotions. Because of this area's dense connectivity it is important to study the properties of the excitatory and inhibitory network that governs ACC output. The aim of this study was to characterize the morphology of dendritic excitatory postsynaptic sites and inhibitory inputs on layer 2 and layer 3 ACC pyramidal neurons, the principal intracortical projection neurons of the cortex. Using biocytin-filling and high-resolution confocal imaging, we quantified the distribution of dendritic spines, the major sites of excitatory input, on pyramidal cells. We visualized inhibitory inputs apposed to specific pyramidal cell compartments, including the axon initial segment, soma, dendrites, and dendritic spines, through immunohistochemical labeling of vesicular γ-aminobutyric acid transporter. Layer 2 and layer 3 cells had similar spine densities on their apical and basal dendritic compartments, with a maximum spine density occurring in their middle apical and middle basal compartments. Axon initial segments of layer 3 cells had a higher density of inhibitory input compared to the layer 2 cells (0.84 vs 0.66 apps/μm). The apical dendritic shaft had a higher apposition density than the basal dendritic shaft in an individual layer (layer 2, 0.50 vs 0.32; layer 3, 0.50 vs 0.28 apps/μm) with the majority of the innervation occurring on the proximal compartments of both apical and basal segments. Although located in different laminae, these cells showed similar inhibitory input distributions, with higher amounts of inhibition proximally. Finally, these inhibitory inputs also occurred on dendritic spines, with the highest density on thin spines. However, proportionally, mushroom spines had the highest level of innervation, with up to 44% of these spines receiving inhibitory input. These findings add to the understanding of how inhibition at the cellular level can affect the output of the ACC and begin to uncover important relationships between cellular structure and function in this brain region.

Using a dietary model in Sprague Dawley rats of gestational/neonatal iron deficiency, our lab has demonstrated structural, biochemical, electrophysiological and behavioral changes in the developing hippocampus. The high energy demands of the developing hippocampus make it particularly vulnerable to iron deficits. At gestational day two, the pregnant dams were given iron deficient (ID) chow to induce approximately 50 % brain iron deficiency by postnatal day (P)15. Our dietary model allowed us to observe changes during ID at P15 and P30 and also after iron repletion at P70. Dendritic changes have been demonstrated with MAP-2 staining, but this stain only allowed for measurement of the first portion of the apical dendrite. Therefore, the Golgi stain was used to allow for tracing of the entire apical dendritic trees, with quantification using Sholl analysis to observe the growth trajectory. The objective was to determine how apical dendrite growth is altered, short term and long term, by early iron deficiency. Approximately 20 neurons were traced from each of the three time points and two dietary conditions. Four or more animals were used from each group. Results show early iron deficiency altered dendritic developmental trajectory. Distance to peak branching was shorter in the ID and formerly ID animals as well as thinner third generation branches at P15. Also at P70 in FID animals, peak branching density was decreased. Decreased transcript levels were seen in the IDA and formerly IDA animals. Altered transcript levels of various cytoplasmic and transmembrane proteins critical to structural growth (RhoA, Rac1, Cdc42, Cypin, Cofillin, Profilin, Crmp1, Cxcr4) support altered morphology and contribute to reduced plasticity of the system. Early iron deficiency affects apical dendrite development and results in long term decreased cytoskeletal plasticity, these findings may underlie some of the functional deficits seen in this condition.

The understanding of human memory is one of the greatest challenges facing neuroscience today. The brain's extraordinary ability to integrate information and appropriately adapt in response to various stimuli is at the core of learning and memory. At a cellular and molecular level, learning and memory relies on a neuron's ability to facilitate activity-dependent changes in synaptic efficacy. In order to better understand the mechanism behind such changes, we investigate the function of Arc, an immediate-early gene essential for both long-term and homeostatic plasticity. We find that through AMPA receptor endocytosis, Arc expression modulates spine morphology to favor more plastic thin spines and filopodia. Thus, Arc expression simultaneously reduces synaptic efficacy through AMPA receptor endocytosis while increasing structural plasticity by favoring thin spines. Supporting this, we find that loss of Arc in vivo leads to a decrease in the proportion of thin spines as well as neural network hyperexcitability. Given Arc's role in spine morphology we also investigate possible actin-regulating Arc-binding partners. We find that Arc directly binds to Wave3, an actin-nucleating factor, in neurons. We further demonstrate that reduction of Wave3 expression leads a marked decrease in primary dendrite length. In mature neurons, reduction of Wave3 results in decreased spine density and increased filopodia. Finally, Arc expression partially rescued these reductions in primary dendrite length and spine density, supporting a functional role for the Arc-Wave3 interaction. Thus, our investigations of Arc and Wave3 have contributed to the understanding of synaptic plasticity, and suggest new links between synaptic efficacy, structural plasticity, homeostasis and memory.

In the digital entertainment industry, cities are one of the largest artifacts modeled by artists. One alternative to modeling an entire city by hand is to use an urban simulation. Often, those simulations use a gridded terrain representation. Translating gridded simulation results into a more continuous, realistic representation can often be difficult. Our vectorization process transforms gridded urban land use data into a representation that mimics what might be seen in GIS or online mapping tools. Our method consists of three major phases. In the first phase, the raster data is is analyzed and the transportation layer is abstracted and filtered. Next, the city blocks are constructed from the raster data. Third, the blocks are subdivided and land use and density are assigned to each constructed parcel. The result is scored and compared with the output from the simulation to match location, sizes, and proportions.

Conventionally, spines on bivalves and other organisms are thought to serve an antipredatory function; however, this has been tested minimally for epifaunal bivalves, and completed research is contradictory. It is possible that spines do not serve an antipredatory function directly, but provide a substrate for epibionts, those organisms that encrust the outer surface of the bivalve’s shell. Although potentially harmful, coverage by epibionts would benefit the bivalve by concealing it from potential predators. The first portion of this project examined the mechanical behavior of crushed spined and un-spined shells of one epifaunal bivalve (Spondylus regius) in order to ascertain if spines increase the amount of work or force required to fail a shell, elucidating a potential protective function of the spines. A second study demonstrated that epibiont acquisition on various morphologies (including spined, ribbed and smooth varieties) of epifaunal bivalve shells is differential with respect to epibiont species richness and percent coverage. A third study examined the shell morphology of epifaunal bivalves to determine if any correlations exist between this and latitude (and theoretically with predation intensity). To further examine the evolution of interactions between bivalves and their predators with respect to spine development, data were compiled from museum specimens and the paleontological and ecological literature to document changes in bivalve ornamentation through time, water depth and habitat preference. In general, the results here presented indicate that spines and other shell ornamentations likely enhance epibiont coverage and possibly afford some direct physical protection against predators. However, the lack of clear progression in spine characteristics along purported predation gradients may also indicate that hypothesized predation gradients need to be reexamined.

Predation is recognized as a significant agent of natural selection in marine environments from the Cretaceous to the Recent, but older predator-prey systems have been studied only rarely. Predator diversity and drilling predation frequency both increased during the Mid-Paleozoic. Productidine brachiopods, which possessed spines, also experienced a major radiation during this time. The evolution of spines may have been a response to predation. Because some productidines lived in muddy environments, their spines have been interpreted to enable the animal to rest on soft substrates, but this may not be the only function of spines. Environmental distribution of Devonian spinose brachiopods from New York, including a productidine, indicates that these brachiopods preferred sandy environments, suggesting that functional hypotheses other than the soft-substrate hypothesis need to be considered. In a study of a Devonian assemblage of drilled brachiopods from Iowa, drilling stereotypy is significant, suggesting that the boreholes are predatory or parasitic in origin. Moreover, drilling success against a productidine was significantly lower than against a non-spinose, but morphologically similar, species. This is the first quantitative evidence that brachiopod spines could deter certain predators. Because the productidine brachial (dorsal) valve was uppermost in life, dorsal spines may have been anti-predatory. The most parsimonious hypothesis of productidine evolution, developed using stratocladistics, suggests that dorsal spines evolved independently in four productidine lineages. Such convergence suggests strong selective pressure to evolve this feature. In modern oceans, a latitudinal gradient in shell ornament exists due to greater predation pressure in the tropics. If predation was intense enough in the Mid-Paleozoic to influence prey communities, a latitudinal gradient in prey ornament also should exist at that time. A paleogeographic study of Devonian productidines and their non-spinose relatives documents a strong correlation between the distribution of Devonian ornament and paleolatitude. These results suggest that productidine evolution may have been influenced partly by increased predation intensity. This constitutes an example of escalation, an evolutionary response to increasing biotic hazards, distinct from that studied in the Recent, as Mid-Paleozoic predators and prey are only distantly related to their modern analogs. Biotic interactions may conform to certain patterns independent of lineage.