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In our everyday lives, we receive information from our environment and respond to this received information by performing motor actions. A transformation between sensory information and motor action that is not a mere reflex, occurs inside our brain. Most of our goal-directed behavior involves this transformation, which may become impaired in different neurological and psychiatric disorders such as Parkinson’s disease. Therefore, it becomes important to know where and how this transformation happens in the brain. I trained mice in a whisker-based selective detection task to discover mechanisms of the sensory-motor transformation. In this type of behavior, mice learned to selectively respond to a brief whisker stimulation by licking a waterspout. Using widefield calcium imaging during task performance, my colleagues revealed regions in the cortex that became active during sensory and motor behavior. I performed whisker imaging to give insights about the mouse behavior as well as verifying the temporal limitations of widefield calcium imaging using recordings of local field potentials (Chapter 2). Among active regions in frontal cortex, I localized the site of transformation to the whisker motor cortex using single unit recording and advanced data analysis (Chapter 3). Importantly, I discovered a subcortical site of sensory-motor transformation in the dorsolateral striatum, residing down-stream of the whisker motor cortex (Chapter 4). Thus, my research describes a network composed of cortical and subcortical regions involved in sensory-motor transformation. Our findings may contribute towards developing therapeutics that target the motor cortex and dorsolateral striatum in health conditions that impair these regions and sensory and motor behavior in general.

The cerebral cortex is responsible for neural functions ranging from basic sensory processing to complex decision making. However, the underlying neural processes and the precise function of some cortical areas are not well understood. For humans the cortex is invaluable, providing us with our most powerful cognitive traits. For some species, the cortex can be removed leaving only minor deficits. Stark contrasts like these blur the overall function and importance of cortex. Recent advancements in recording and analysis technology present us with a unique opportunity to search for neural processes previously impossible to find. Recent work has found cortical regions in mice that do more than their functional name implies, in contrast to the specialized cortical regions in higher order species. In this study we explore the hidden functions of mouse motor cortex and elaborate on its role in the whisker system. The mouse whisker system is traditionally divided into sensory regions and motor regions, with sensory cortex (vS1) and motor cortex (vM1) sitting on the border. The functional divisions between sensory and motor cortex have recently blurred, both regions able to drive movements and encode sensory information. Whisker motor cortex, specifically, exhibits disparate functions, making it an ideal place to study multirole cortex. Here we take advantage of advanced neural recording and analysis techniques and uncover a motor cortex that acts as a sensory and possibly a higher order cortical region as well.In chapter 1, I provide an overview of how cortical regions were defined and then summarize how modern research is blurring the lines between functionally defined cortical areas. I then introduce sensory processing in the mouse whisker system with a focus on motor cortex, a cortical region where its function is increasingly blurring, and then describe how my research explored non-motor functionality in a motor region. In chapter 2, I present my first first-author publication where we determined if somatosensory cortex integrates sensory information over short or long timescales in order to estimate “mean” variables. In this work I first use neural decoding to quantify how well each neuron represents pieces of sensory information and find that some neurons correlate with choice. Chapter 3 is work that I collaborated on, we determined how multiple sensors contribute to the receptive field of individual neurons and the broader population. We discovered a map of sensory space distributed across somatosensory cortex and determined the map was dependent on neurons integrating information from multiple sensors in parallel. Chapter 4, we explore whether somatosensory cortex is necessary for a whisker dependent discrimination task and further determine what arrangement of sensors are required for task completion. Finally, in Chapter 5 I present my main project investigating vibrissae motor cortex. Here I study the sensory responses present in motor cortex, quantifying vM1 sensory tuning for the first time, and ultimately determining that vS1 does not drive the activity as previously thought. Incredibly, vM1 is not required for whisker movements in general but is required during demanding whisker dependent contexts, such as a whisker discrimination task, affecting both choice, whisker movements, and onset of lick response. Finally, in Chapter 6, I summarize what this tells us about sensory processing, propose some ideas for future research, and discuss how modern tools can enable us to find hidden functionality.

Understanding how cortical circuits process sensory information and support perception is a fundamental problem in neuroscience. Rodents, being tactile experts, actively use their whiskers to sense complex tactile features like surface texture, object shape and location. In this dissertation I address how cortical neurons integrate sensory information from individual whiskers to support accurate and precise representations of complex tactile features.Natural whisking during tactile exploration generates complex spatiotemporal sequences of whisker stimulation. Objects with different textures and shapes result in different patterns of whisker stimulation, sequentially stimulating different combinations of whiskers across time. I thus hypothesized that individual neurons in primary whisker somatosensory cortex (S1) are sensitive to specific features of tactile sequences. Chapter 2 describes the timescales at which S1 neurons integrated sensory input while rats discriminated between whisker impulse sequences that varied in single-impulse kinematics. While discrimination performance was consistent with integration at a relatively slow timescale (approximately 150ms), most S1 neurons integrated whisker input at a fast timescale (60ms) did not accurately represent the stimulus but were instead related to the rat’s behavioral choice. These findings show that S1 neurons encode whisker input at a fast timescale and suggest that areas downstream of S1 temporally integrate this information to guide perceptual discrimination. Given the precise representations of tactile sequences in S1, Chapter 3 explores the elementary computations underlying tactile stimulus integration by S1 neurons. Tactile sequences vary in spatial identity of stimulated whiskers and inter-whisker-deflection-intervals (Δt). Dense stimulation of local whisker pairs over a physiological range of Δt revealed a somatopically organized rate code for whisker combinations that was precise in space and coarser in time. Sublinear suppression for suboptimal combinations sharpened tuning relative to that expected from linear integration alone; analogous to the computation of motion direction selectivity in many visual circuits, thus suggesting a common computation for spatiotemporal feature extraction. Taken together, this dissertation shows that S1 neurons integrate sensory input in space and time to generate robust tuning for spatiotemporal features of tactile scenes.

Metal whiskers (MWs) represent hair-like protrusions on surfaces of manytechnologically important materials, such as Sn, Zn, Cd, Ag, and others. When grown across leads of electrical components, whiskers cause short circuits resulting in catastrophic device failures. Despite cumulative loss to industry, mostly through reliability issues, exceeding billions of dollars, MWs related research over the past 70 years, brought more questions than answers. Moreover, the absence of reliable accelerated life testing procedures makes it especially difficult to evaluate whisker propensity with tests limited in time.A recently developed theory about electric fields being the cause of MW growth holds a promise of shedding light on their fundamental nature. Its main statement is that nucleation and growth of MWs happen in response to local electric fields acting on metal films. We adopted an approach of generating electric fields through charged defects created in insulating glass substrates supporting Sn metal films. These defects are produced under ionizing radiation of gamma-rays. Use of ionizing radiation for generation of electric fields may be preferable to a simpler capacitor-type setup, which requires a second electrode, often leading to shorts due to whisker growth through the capacitor air gap.We observed accelerated MW growth upon exposure of Sn metal film samples deposited on glass to Ir-192 gamma-ray source. The source, having its highest photon energy below 1MeV, is not able to produce structural changes in the material, making the substrate charging the only effect responsible for stimulation of MW growth. Qualitatively, we observed that after applying up to 20 kGy radiation dose to Sn thin film coated glass over a course of approximately 60 days, both the whisker densities and lengths increased significantly compared to control samples. Using a parameter of acceleration ratio, characterizing whisker growth rate in radiation exposed vs. control sample, we are able to offer a quantitative assessment of whisker growth enhancement.Our observations offer insights into whisker physics and a possibility of development of non-destructive accelerated test desperately needed in multiple industrial applications.

CHAPTER 1: Somatosensory maps in rodents & primates—a reviewThis chapter reviews basic principles and recent findings in primate, human, and rodent somatosensory maps. Topographic maps of the body surface are a major feature of somatosensory cortex. In primates, parietal cortex contains four somatosensory areas, each with its own map, with the primary cutaneous map in area 3b. Rodents have at least three somatosensory areas, and the whisker map in rodent primary somatosensory cortex is a canonical system for studying cortical microcircuits, sensory coding, and map plasticity.Maps are not isomorphic to the body surface, but magnify behaviorally important skin regions, which include the hands and face in primates, and the whiskers in rodents. Within each map, intracortical circuits process tactile information, mediate spatial integration, and support active sensation. Functional representations are more overlapping than suggested by textbook depictions of map topography. Maps may also contain fine-scale representations of touch sub-modalities, or direction of tactile motion. In addition, somatosensory maps are plastic throughout life in response to altered use or injury.CHAPTER 2: Somatotopic precision of whisker tuning in layer 2/3 of rat barrel cortexAlthough cortical maps of the sensory periphery are topographically organized at a large scale, the fine-scale precision of the map at the level of neighboring cells varies between species, sensory modalities, and cortical layers. In rodent somatosensory cortex, where each whisker is mapped to a dedicated cortical column, cells in layer 4 of each column are predominantly tuned to the appropriate whisker (columnar whisker; CW). However, in mice, cells in the upper cortical layers display locally heterogeneous "salt-and-pepper" tuning. It remains unclear whether the same heterogeneity is found in the upper layers of the rat whisker map. To address this question, we examined whisker tuning in regular-spiking (RS) and fast-spiking (FS) units recorded from layer 2/3 whisker columns in anesthetized rats. Among RS units, we observe a narrow majority (59%) best tuned to the CW; a clear majority (88%) with the CW among a statistically comparable group of "equal best" whiskers; and a small number (12%) of units best driven by one or more surround whiskers and poorly responsive to the CW. CW-tuned units display sharper tuning and faster responses to their best whisker than non-CW-tuned units, but are distributed evenly along vertical and horizontal dimensions of the column. These results demonstrate tuning in rat L2/3 that is more homogeneous than in mouse layer 2, but less so than in rat or mouse layer 4. FS units are tuned to the CW more frequently (78%) than RS units, consistent with broadly sampled input from local excitatory cells most responsive, as a group, to the columnar whisker.

Seal whiskers have been found to produce unique wake flow structures that minimize self-induced vibration and reduce drag. The cause of these wake features are due to the peculiar three-dimensional morphology of the whisker surface. The whisker morphology can be described as an elliptical cross section with variation of diameter in the major and minor axis along the length and, angle of incidence, rotation of the elliptical plane with respect to the whisker axis, α at the peak and β at the trough. This research provided a more complete morphology characterization accomplished through CT scanning and analysis of 27 harbor and elephant seal whisker samples. The results of this study confirmed previously reported values and added a characterization of the angle of incidence finding that the majority of angles observed fall within ±5° and exhibit a random variation in magnitude and direction along the whisker length.While the wake effects of several parameters of the whisker morphology have been studied, the effect of the angle of incidence has not been well understood. This research examined the influence of the angle of incidence on the wake flow structure through series of water channel studies. Four models of whisker-like geometries based on the morphology study were tested which isolate the angle of incidence as the only variation between models. The model variations in angle of incidence selected provided a baseline case (α = β = 0°), captured the range of angles observed in nature (α = β = -5°, and α = β = -15°), and investigated the influence of direction of angle of incidence (α = -5°, β = -5°). The wake structure for each seal whisker model was measured through particle image velocimetry (PIV). Angle of incidence was found to influence the wake structure through reorganization of velocity field patterns, reduction of recovery length and modification of magnitude of Tu. The results of this research helped provide a more complete understanding of the seal whisker morphology relationship to wake structure and can provide insight into design practices for application of whisker-like geometry to various engineering problems.

Active sensing, which incorporates closed-loop behavioral selection of information during sensory acquisition, is an important feature of many sensory modalities. We used the rodent whisker tactile system as a platform for studying the role cortical sensory areas play in coordinating active sensing motions. We examined head and whisker motions of freely moving mice performing a tactile search for a randomly located reward, and found that mice select from a diverse range of available active sensing strategies. In particular, mice selectively employed a strategy we term contact maintenance, where whisking is modulated to counteract head motion and sustain repeated contacts, but only when doing so is likely to be useful for obtaining reward. The context dependent selection of sensing strategies, along with the observation of whisker repositioning prior to head motion, suggests the possibility of higher level control, beyond simple reflexive mechanisms. In order to further investigate a possible role for primary somatosensory cortex (SI) in coordinating whisk-by-whisk motion, we delivered closed-loop optogenetic feedback to SI, time locked to whisker motions estimated through facial electromyography. We found that stimulation regularized whisking (increasing overall periodicity), and shifted whisking frequency, changes that emulate behaviors of rodents actively contacting objects. Importantly, we observed changes to whisk timing only for stimulation locked to whisker protractions, possibly encoding that natural contacts are more likely during forward motion of the whiskers. Simultaneous neural recordings from SI show cyclic changes in excitability, specifically that responses to excitatory stimulation locked to whisker retractions appeared suppressed in contrast to stimulation during protractions that resulted in changes to whisk timing. Both effects are evident within single whisks. These findings support a role for sensory cortex in guiding whisk-by-whisk motor outputs, but suggest a coupling that depends on behavioral context, occurring on multiple timescales. Elucidating a role for sensory cortex in motor outputs is important to understanding active sensing, and may further provide novel insights to guide the design of sensory neuroprostheses that exploit active sensing context.

Salt crystal whiskers were grown from salt solution saturated nanoporous silica coatings. Coated substrates were partially immersed into an aqueous potassium chloride solution and then kept in a controlled relative humidity chamber for whisker growth. The salt solution was first wicked into the coating by capillary action, and then evaporation ensued and a supersaturated condition was reached. Crystals grew from the surface by a base growth mechanism in which salt ions were added to the surface of the crystal that was in contact with the nanoporous coating. Optical microscopy and SEM results demonstrated this mechanism. Crystals with whisker morphologies, typically 2 - 50 µm in lateral dimension and up to ~1 cm in length, emerged from the coating surface at a position above the original liquid level. Sheet-like crystals also formed from whiskers that had fallen flat onto the porous coating surface. Inspired by the sheet formation mechanism and liquid transportation phenomenon, a seeding technique was developed to reduce whisker width. Attritor ground salt particles were placed on the nanoporous coating surface to initiate simultaneous whiskers growth and salt nano-whiskers with lateral dimension as small as 50 nm were obtained on the surface of the coating. This crystal growth method can be applied to different materials, namely water soluble materials, and creates whisker crystals with controllable size and location on the nanoporous coating. Open celled foam is a three dimensional structure. In some applications, other materials are coated on internal surface of the foam to provide desired final product functionality. Because of their complicated 3D structures, coating onto foam is challenging. A new coating process that combines dip coating and spin coating was developed. Dip coating step was used to load the solution into the foam and a spin treatment step was added to remove the trapped liquid and redistribute the liquid to obtain uniform coating. The dip and spin process was also used to create -alumina and zeolite coatings, which are of interest for catalysis applications.

Thalamocortical neurons innervating the barrel cortex in neonatal rodents transiently store serotonin (5-HT) in synaptic vesicles by expressing the plasma membrane serotonin transporter (5-HTT) and the vesicular monoamine transporter (VMAT2). 5-HTT knock-out (ko) mice reveal a nearly complete absence of 5-HT in the cerebral cortex by immunohistochemistry, and of barrels, both at P7 and adulthood. Quantitative electron microscopy reveals that 5-HTT ko affects neither the density of synapses nor the length of synaptic contacts in layer IV. VMAT2 ko mice, completely lacking activity-dependent vesicular release of monoamines including 5-HT, also show a complete lack of 5-HT in the cortex but display largely normal barrel fields, despite sometimes markedly reduced postnatal growth. Transient 5-HTT expression is thus required for barrel pattern formation, whereas activity-dependent vesicular 5-HT release is not.