Sheet Illumination microscopy is a well developed tool in the bio-imaging community due to many inherent advantages. Increased photonic efficiency allows for lower power light sources to be used, which in turn reduce phototoxic damage at the sample over time. High fidelity, high SNR data can be collected from these systems due to their optical sectioning capabilities, and as such, many have been designed to operate within a limited parameter space. These instruments often follow traditional design logic, for specialization in one imaging condition, to observe only a single type of scientific data. This mentality yields high resolution results for a particular class of data, yet is limited in terms of flexibility. Here, the design and development of a user-configurable light sheet microscope is discussed, which uses a spatial phase modulator to dynamically shape and optimize the incident light sheet to perform highly in a number of temporal and spatial scales. The result is a general purpose microscopy platform for the observation of many biological phenomena.

If we are to understand how nature formulates complex animal behavior, we must develop the tools that have the capabilities to capture these processes in their full capacity. I have created Transverse-Sheet Illumination Microscopy (TranSIM), a highly customizable, single objective microscope, with micron level resolution (0.7 um, 1.1 um, 1.6 um in x, y, and z, respectively) with the ability to image extended three dimensional volumes (750 um x 560 um x 160 um) at 200 volumes per second. For Danio rerio, approximately 10^5 neurons were imaged in 3D, opening an unparalleled view into the animal's complex processes at near millisecond temporal resolution. Fast intra-planar and inter-planar processes were observed signaling that utility of TranSIM. Overall, a 10-fold increase in the total volumetric imaging rate is achieved compared to any system currently available, and still with ample room for improvement.

Direct dark matter detectors are currently probing the favored supersymmetric theoretical phase space for weakly interacting massive particles (WIMPs) as part of a larger electroweak sector particle search. The XENON100 detector has recently improved upon their world-best upper limits on WIMP-nucleon scattering cross sections from 2011 with new results presented in 2012, which have further ruled out much of the predicted regions for dark matter. In the low mass regime, the results shown so far have been conservative in addressing the claims of a WIMP detection by CoGeNT, DAMA and CRESSTII.

This thesis discusses a different approach to analyzing the XENON100 data with a profile likelihood statistical method using the ionization channel to improve both energy reconstruction and energy resolution and probe the low WIMP mass region. A Monte Carlo simulation using a combination of detector geometry and underlying statistical features of signal production has been developed to determine the ionization yield, which has only a few direct measurements, and to model WIMP interactions as input to the statistical technique. The resulting profile likelihood analysis, which includes systematic uncertainties in the energy scales and background and signal models, has been able to improve the current upper limits by a factor of 10 in the low mass region (6-10 GeV/c²) and about a factor of 2 up to 50 GeV/c². The discovery potential of the dataset is also studied, which has produced a 2.3σ significance for a 7.5 GeV/c² particle at a cross section of σ_χ-N=1.8×10^-43 cm² with a 95% confidence interval of [1.74×10^-44,7.76×10^-43] cm².

We propose an attention-based theory for how humans extract semantic information from objects located in our peripheral visual field. We build upon the scale invariance for extraction of semantic information from objects in center gaze. Our theory for peripheral vision hypothesizes that a vision attention vector runs parallel to the brain's main visual pathway. Information from this vision attention vector is able to combine with our brain's representation of our visual field, such that a peripheral target is able to be remapped and represented at center, in a downstream stage of the brain's visual processing. We connect our theory to previous observations of peripheral vision impairments and documented cases of specific types of letter confusions. We simulate these past findings by modeling peripheral vision object identification failures as an off-target vision attention vector. Our own crowding experiments show support for an active, attention-based mechanism for extraction of peripheral semantic information. We show that a fully crowded visual environment degrades peripheral vision abilities by over twice that of a locally peripherally crowded visual environment ($P = 2.02 \times 10^{-10}$). Additionally, we find instances where a letter on the outside of a peripheral cluster yields a smaller threshold letter height, as compared to a letter on the inside of that same peripheral cluster ($P = 1.20 \times 10^{-2}$). Such combination of simulation and experiment results offer support for our vision attention vector theory, which is, insofar as we are aware, the first comprehensive theory for how humans can extract a single semantic representation for objects anywhere in the visual field.

Additionally, we review our physics for life sciences (IPLS) laboratory revisions that have positively impacted over 4,850 undergraduate students at UCLA. To achieve learning outcomes of improved critical thinking and problem-solving persistence, we used a combination of ``flipped" pre-laboratory assignments, inquiry-based in-lab activities, and peer-based learning with undergraduate learning assistants. As a result of our revisions, an increased number of students reports pursuing their own scientific questions during physics experiments. On average, students show a pre/post quarter attitude shift of 0.50 Likert Levels ($P = 4.1 \times 10^{-12}$), as shown by E-CLASS assessment analysis. We additionally show that, after a second round of revisions, a decreased number of students reports immediately asking an expert like the instructor for help when facing a challenge during an experiment. (pre/post quarter attitude shift of -0.23 Likert Levels ($P = 1.0 \times 10^{-4}$)). Therefore, our evidence-based revisions of undergraduate physics labs show an increased development of important physics skills in our next generation of healthcare professionals. Our revisions may serve as an example to support other institutions in nation-wide efforts to optimize undergraduate physics education.

The integration of multimodal sensory information into a common neural code is a critical function of all complex nervous systems. This process is required for adaptive responding to incoming stimuli as well as the formation of a cognitive map of the external sensory environment. The underlying neural mechanisms of multimodal integration are poorly understood due, in part, to the technical difficulties of manipulating multimodal sensory information in combination with simultaneous in-vivo electrophysiological recording in awake behaving animals. We therefore developed a non-invasive multimodal virtual reality system that is conducive to wired electrophysiological recording techniques. This system allows for the dynamic presentation of highly immersive audiovisual virtual environments to rats maintained in a body fixed position on top of a quiet spherical treadmill. Notably, this allows the rats to remain at the same spatial location in the real world without the need for head fixation. This method opens the door for a wide array of future studies aimed at elucidating the underlying neural mechanisms of multimodal integration.

The hippocampal cognitive map is thought to be driven primarily by distal visual cues and self-motion cues, although other sensory cues have also been demonstrated to influence place cells. Performing controlled experiments exploring the precise role played by different sensory modalities in determining spatial representation in the hippocampus is challenging due to need to control non-specific stimuli such as scent cues and acoustic reflections.

To overcome these challenges we have developed an immersive virtual reality system for rats, in which any spatial information in these non-specific sensory cues are eliminated. The system combines full field of view visual stimuli with spatially accurate auditory stimuli to enable a variety of complex spatial tasks. To eliminate much of the subjectivity in identifiying single units in extracellular recording, an improved automated spike sorting method was developed based on existing gaussian mixture approaches.

These tools were then applied to determine whether visual cues alone are sufficient for standard place cell activity in the CA1 region of the hippocampus. Single unit activity was recorded both in virtual reality, where only visual cues and non-vestibular self-motion cues provided spatial information, and in the real world using a linear track experimental paradigm.

iiPlace cells displayed robust spatial selectivity in virtual reality, but only 20% of putative pyramidal cells were active in virtual reality, compared with 45% in the real world task. Distal visual and nonvestibular self-motion cues are thus sufficient to provide spatial selectivity, but vestibular and other sensory cues present int he real world are necessary to fully activate the place cell population. While bidirectional cells preferentially encode absolute position in the real world, they exhibited a distance coding scheme in virtual reality, suggesting that other sensory cues such as scent marks are necessary for a robust bidirectional position code.

The frequency of hippocampal theta oscillations was reduced in virtual reality, and its speed dependence abolished. Despite this, phase precession of place fields was essentially identical in the two environments. These results constrain mechanisms governing both hip- pocampal theta oscillations and the temporal code. Taken together, these results reveal cooperative and competitive interactions between sensory modalities for control over hip- pocampal spatiotemporal selectivity and theta rhythm.