A Biologically Inspired Controllable Stiffness Multimodal Whisker Follicle

This thesis takes a soft robotics approach to understand the computational role of a soft whisker follicle with mechanisms to control the stiffness of the whisker. In particular, the thesis explores the role of the controllable stiffness whisker follicle to selectively favour low frequency geometric features of an object or the high frequency texture features of the object.Tactile sensing is one of the most essential and complex sensory systems for most living beings. To acquire tactile information and explore the environment, animals use various biological mechanisms and transducing techniques. Whiskers, or vibrissae are a form of mammalian hair, found on almost all mammals other than homo sapiens. For many mammals, and especially rodents, these whiskers are essential as a means of tactile sensing.The mammalian whisker follicle contains multiple sensory receptors strategically organised to capture tactile sensory stimuli of different frequencies via the vibrissal system. Nocturnal mammals such as rats heavily depend on whisker based tactile perception to find their way through burrows and identify objects. There is diversity in the whiskers in terms of the physical structure and nervous innervation. The robotics community has developed many different whisker sensors inspired by this biological basis. They take diverse mechanical, electronic, and computational approaches to use whiskers to identify the geometry, mechanical properties, and objects' texture. Some work addresses specific object identification features and others address multiple features such as texture and shape etc. Therefore, it is vital to have a comprehensive discussion of the literature and to understand the merits of bio-inspired and pure-engineered approaches to whisker-based tactile perception.The most important contribution is the design and use of a novel soft whisker follicle comprising two different frequency-dependent data capturing modules to derive more profound insights into the biological basis of tactile perception in the mammalian whisker follicle. The new insights into the biological basis of tactile perception using whiskers provide new design guidelines to develop efficient robotic whiskers

A stiffness controllable multimodal whisker sensor follicle for texture comparison

Mammals like rats, who live in dark burrows, heav-ily depend on tactile perception obtained through the vibrissalsystem to move through gaps and to discriminate textures. Theorganization of a mammalian whisker follicle contains multiplesensory receptors and glands strategically organized to capturetactile sensory stimuli of different frequencies. In this paper, weused a controllable stiffness soft robotic follicle to test the hy-pothesis that the multimodal sensory receptors together with thecontrollable stiffness tissues in the whisker follicle form a physicalstructure to maximize tactile information. In our design, the ringsinus and ringwulst of a biological follicle are represented by alinear actuator connected to a stiffness controllable mechanismin-between two different frequency-dependent data capturingmodules. In this paper, we show for the first time the effectof the interplay between the stiffness and the speed of whiskingon maximizing a difference metric for texture classification

Embodied active tactile perception

Tactile perception plays an important role in an agent safely interacting with the environment while acquiring information about it. Bio-inspired robotics opens up possibilities for a new paradigm leveraging the morphology of the body, which filters the tactile information in physical interactions and enables investigations of new designs for embodied active tactile perception. The subjects of morphology embodied active perception and motor embodied active perception is defined and discussed in this chapter. In the scope of morphology embodied active perception, sensor optimization and sensor adaptation are further defined to describe the change of sensor morphology in the design phase and the interacting phase, respectively. More specifically, the concept of online and offline sensor adjustment is presented. Sensor optimization is solely considered in the offline process for optimization and evolution design of the sensor structure and characteristics. Sensor adaptation and motor embodied active perception are considered in the online process to actively shape the sensing process with the morphology change of the sensors themselves and the action of the body where the sensors are placed, respectively. "Design as a whole" is proposed as an inverse problem to address the sensing tasks. The design of new tactile sensors should not focus on the sensor per se but should also include design parameters for sensor optimization, sensor adaptation, and motor actions

Visual Tactile Integration in Rats and Underlying Neuronal Mechanisms

Our experience of the world depends on integration of cues from multiple senses to form unified percepts. How the brain merges information across sensory modalities has been the object of debate. To measure how rats bring together information across sensory modalities, we devised an orientation categorization task that combines vision and touch. Rats encounter an object\u2013comprised of alternating black and white raised bars\u2013that looks and feels like a grating and can be explored by vision (V), touch (T), or both (VT). The grating is rotated to assume one orientation on each trial, spanning a range of 180 degrees. Rats learn to lick one spout for orientations of 0\ub145 degrees (\u201chorizontal\u201d) and the opposite spout for orientations of 90\ub145\ub0 (\u201cvertical\u201d). Though training was in VT condition, rats could recognize the object and apply the rules of the task on first exposure to V and to T conditions. This suggests that the multimodal percept corresponds to that of the single modalities. Quantifying their performance, we found that rats have good orientation acuity using their whiskers and snout (T condition); however under our default conditions, typically performance is superior by vision (V condition). Illumination could be adjusted to render V and T performance equivalent. Independently of whether V and T performance is made equivalent, performance is always highest in the VT condition, indicating multisensory enhancement. Is the enhancement optimal with respect to the best linear combination? To answer this, we computed the performance expected by optimal integration in the framework of Bayesian decision theory and found that most rats combine visual and tactile information better than predicted by the standard ideal\u2013observer model. To confirm these results, we interpreted the data in two additional frameworks: Summation of mutual information for each sensory channel and probabilities of independent events. All three analyses agree that rats combine vision and touch better than could be accounted for by a linear interaction. Electrophysiological recordings in the posterior parietal cortex (PPC) of behaving rats revealed that neuronal activity is modulated by decision of the rats as well as by categorical or graded modality-shared representations of the stimulus orientation. Because the population of PPC neurons expresses activity ranging from strongly stimulus-related (e.g. graded in relation to stimulus orientation) to strongly choice-related (e.g. modulated by stimulus category but not by orientation within a category) we suggest that this region is involved in the percept-to-choice transformation

MECHANOSENSORY FEEDBACK FOR FLIGHT CONTROL AND PREY CAPTURE IN THE ECHOLOCATING BAT

Throughout the animal kingdom, organisms have evolved neural systems that process biologically relevant stimuli to guide a wide range of species-specific behaviors. Bats, comprising 25% of mammalian species, rely on diverse sensory modalities to carry out tasks such as foraging, obstacle avoidance and social communication. While it is well known that many bat species use echolocation to find food and steer around obstacles, they also depend on other senses. For instance, some bats predominantly use vision to navigate, and others use olfaction to find food sources. In addition, bats rely on airflow sensors to stabilize their flight, primarily through signals carried by microscopic hairs embedded in their wings and tail membranes. Studies have shown that bats performing an obstacle avoidance task show changes in their flight behavior when dorsal wing hairs are removed. Additionally, electrophysiological studies have shown that wing hairs are involved in airflow sensing, but little is known about the contribution of sensory hairs on the ventral surfaces of the wing and tail membranes to their flight control and other complex behaviors, such as prey handling. Chapter 1 of my dissertation presents a general introduction to bat echolocation, flight kinematics, and airflow sensing for flight control. In Chapter 2, I review sensory hairs across the animal kingdom, from invertebrates to vertebrates. I discuss the role of sensory hairs for functions ranging from detection to locomotion and propose the use and benefit of mechanosensors in biologically-inspired technology. In Chapter 3, I devised an experiment to evaluate changes in capture success, as well changes in flight kinematics and adaptive sonar behavior, before and after depilation of sensory hairs in order to ascertain if these sensory hairs have a functional role in both airflow sensing for flight control and tactile sensing for prey handling. In Chapter 4, I designed an experiment aimed at determining if firing patterns of S1 neurons change with airflow speed and angle of attack and if wing hair depilation affects S1 responses to whole wing stimulation. To answer these questions, I record neural activity in S1 of sedated big brown bats while the entire contralateral wing is systematically exposed to naturalistic airflow in a wind tunnel. Finally, in Chapter 5, I address open questions that remain, present experiments aimed at filling these gaps, and consider key points important for future work

Not Black and White: BMP Signaling Drives Melanocyte Differentiation Down Stream of Stem Cell Activation

Tissue stem cells (SCs) maintain, regenerate, and repair the body over the course of an organism’s lifetime. To preserve their long-term function, SCs must exert precise control over their cell state dynamics as they move from quiescence to activation and commit to full differentiation. My graduate research has been centered on investigating the molecular mechanisms that fuel these transitions in melanocyte stem cells (McSCs), a unique neural crest-derived SC population located in the hair follicle (HF). Through periodic bouts synchronous with HF cycling, quiescent McSCs become activated to proliferate, giving rise to committed proliferative progeny (McCP) that differentiate into mature pigment-producing melanocytes. The signaling factors and gene expression programs that orchestrate these cellular changes are still incompletely understood. To elucidate new insights into this process, I developed fluorescence-activated cell sorting strategies to isolate quiescent, activated, and differentiating McSC lineage cells from the mouse skin at discrete stages of the hair cycle. I then performed single cell RNA-sequencing (scRNA-seq) to reveal the evolving transcriptional signatures of the lineage with high resolution. Comparative bioinformatic analyses suggested that BMP and WNT signaling increase concomitantly throughout differentiation. I then sought to understand the role of BMP signaling in McSC lineage progression and whether this pathway engages in crosstalk with WNT signaling. To do so, I performed conditional lineage-specific genetic ablation of Bmpr1a to extinguish BMP signaling, which resulted in gray hair. However, McSCs remained intact and functional in these mutant animals, indicating dysfunction in their differentiating progeny. ScRNA-seq and pseudotime analysis of Bmpr1a null cells indicated a block in the differentiation program just downstream of the early McCP stage, and I detected further signs of melanocyte immaturity using immunofluorescence and electron microscopy analyses. Seeking mechanistic understanding, I interrogated changes in transcription factor expression at this blockage point. I found reduced nuclear levels of the master regulator MITF and WNT mediator LEF1. Using WNT mutant mouse models, cell culture systems, and chromatin profiling, I provide evidence demonstrating cooperation of BMP and WNT signaling to trigger complete differentiation of McCP into melanocytes through MITF and LEF1 activity. Altogether, I have generated a thorough characterization of the transcriptional and chromatin landscape changes that temporally define McSC lineage commitment in vivo. My findings underscore a critical role for signaling through BMPR1a to achieve full melanocyte differentiation in the HF. These findings raise intriguing questions about the role of BMP in hair and coat color variation, age-related hair graying, and melanoma initiation and progression

All-optical interrogation of neural circuits during behaviour

This thesis explores the fundamental question of how patterns of neural activity encode information and guide behaviour. To address this, one needs three things: a way to record neural activity so that one can correlate neuronal responses with environmental variables; a flexible and specific way to influence neural activity so that one can modulate the variables that may underlie how information is encoded; a robust behavioural paradigm that allows one to assess how modulation of both environmental and neural variables modify behaviour. Techniques combining all three would be transformative for investigating which features of neural activity, and which neurons, most influence behavioural output. Previous electrical and optogenetic microstimulation studies have told us much about the impact of spatially or genetically defined groups of neurons, however they lack the flexibility to probe the contribution of specific, functionally defined subsets. In this thesis I leverage a combination of existing technologies to approach this goal. I combine two-photon calcium imaging with two-photon optogenetics and digital holography to generate an “all-optical” method for simultaneous reading and writing of neural activity in vivo with high spatio-temporal resolution. Calcium imaging allows for cellular resolution recordings from neural populations. Two-photon optogenetics allows for targeted activation of individual cells. Digital holography, using spatial light modulators (SLMs), allows for simultaneous photostimulation of tens to hundreds of neurons in arbitrary spatial locations. Taken together, I demonstrate that this method allows one to map the functional signature of neurons in superficial mouse barrel cortex and to target photostimulation to functionally-defined subsets of cells. I develop a suite of software that allows for quick, intuitive execution of such experiments and I combine this with a behavioural paradigm testing the effect of targeted perturbations on behaviour. In doing so, I demonstrate that animals are able to reliably detect the targeted activation of tens of neurons, with some sensitive to as few as five cortical cells. I demonstrate that such learning can be specific to targeted cells, and that the lower bound of perception shifts with training. The temporal structure of such perturbations had little impact on behaviour, however different groups of neurons drive behaviour to different extents. In order to probe which characteristics underly such variation, I tested whether the sensory response strength or correlation structure of targeted ensembles influenced their behavioural salience. Whilst these final experiments were inconclusive, they demonstrate their feasibility and provide us with some key actionable improvements that could further strengthen the all-optical approach. This thesis therefore represents a significant step forward towards the goal of combining high resolution readout and perturbation of neural activity with behaviour in order to investigate which features of the neural code are behaviourally relevant