Tactile information processing within a trigemino-cerebellar pathway

Throughout this study the maxillary vibrissae have been regarded as tactile organs in the sense that they convey detailed information relating to the contact or imminent contact between external objects and the face of the cat. The possible use of these hairs as a composite organ in orientation and searching behaviour, especially in the dark, is stressed.In this interpretation of the results of this study an attempt has been made to view the function of mechanoreceptive afferents in as wide a sense as possible, recognising the possibility of parallel processing of tactile information in separate functional pathways. The experimental work has been directed towards establish¬ ing the role of tactile information in the synthesis and control of motor activity by its influence on cells of the cerebellar cortex. This in itself would seem to pre-define the function of such an influence by the presumption of a purely motor operation of the cerebellum. However, in terms of the percept ion of the spatial and temporal relationships between the body and external objects the cerebellum may not act simply as a high order motor ganglion but as an integral part of a more broadly defined somatosensory system

Characterization of polarization sensitive neurons of the central complex in the brain of the desert locust (Schistocerca gregaria)

Charakterisierung von polarisationssensitiven Neuronen des Zentralkomplexes im Gehirn der Wüstenheuschrecke (Schistocerca gregaria)

Touching upon regulators of Piezo2 in mouse somatosensation

ABSTRACT Mechanosensation is an integral property of sensory systems like audition and somatosensation. The molecular determinants of mechanotransduction in mammals are only beginning to be understood. In 2010, Piezo2, a member of the Piezo family, was identified as the bona fide mechanotransducer in the somatosensory system of mice. Since then Piezo2 has been implicated in light touch, proprioception, mechanical allodynia and hyperalgesia. In order to understand more about the function of Piezo channels and their role in mechanosensation, an understanding of its regulators is vital. Protein-protein interactions are the bedrock of ion channel regulation and in the context of Piezo2, few such interactions (Stoml3 and Runx1) have been described. Recently it has also been found that the activity of Piezo2 is linked strongly to the properties of the cellular membrane. Depletion of cholesterol, mediated by Piezo2 interactor Stoml3, was shown to potentiate Piezo2 mediated currents. Furthermore, TRPV1 mediated modulation of Piezo2 was shown to involve membrane phospholipid PI(4,5)P2. In 2016, our lab reported the first systematic characterization of the Piezo2 interactors in somatosensory neurons of mice. Through a mass-spectrometry based interactomics approach, 36 proteins were identified as potential Piezo2 interactors. Within these proteins we found some known modulators of somatosensory mechanotransduction including Kv1.1 and CamKII. Besides these, there were some proteins which presented as highly unlikely interactors of Piezo2, such as Pericentrin (Pcnt). Other proteins identified in the screen were involved in cellular processes like protein localization, protein phosphorylation and vesicle mediated transport. In the current study, I describe the characterization of two of the Piezo2 interactors identified in the mass-spectrometry screen. The first part of the results describes Pericentrin (Pcnt) as a low probability interactor of Piezo2. The results show that Pcnt is expressed in close proximity with Piezo2 in both peripheral endings and cell bodies of DRG neurons. Additionally, Pcnt is shown to functionally modulate Piezo2 in DRG neurons. Loss of Pcnt in these neurons was found to potentiate Piezo2 currents and increase Piezo2 membrane expression. Though the mechanism of Piezo2-Pcnt interaction remains to be explored, the results do provide validation of the interactomics screen. The fact that the screen can successfully identify bona fide Piezo2 interactors makes it a useful resource for understanding Piezo2 function. The second part of the results aims to characterize the interaction between Piezo2 and Mtmr2. Mtmr2, is a member of the myotubularin phosphatase family which is involved in the phospholipid synthesis pathway. It was identified as a high probability interactor of Piezo2, and notably, two other members of the same family, Mtmr1 and Mtmr5 (Sbf2) were also identified in the screen. The results presented here suggest that Mtmr2 is involved in a bi-directional regulation of Piezo2 function in DRG neurons i.e. loss of Mtmr2 potentiates Piezo2 mediated currents and overexpression of Mtmr2 suppresses Piezo2 currents. Furthermore, the phosphatase activity of Mtmr2 was found to be indispensable for its regulation of Piezo2. Pharmacological modulations of the phospholipid pathway show that PI(3,5)P2 plays a crucial role in the regulation of Piezo2. Further evidence for phospholipid interaction with Piezo2 came with the identification of a peptide segment of Piezo2 that can bind to PI(3,5)P2. Additionally, modulation of Piezo2 by osmotic stress is shown to rely on PI(3,5)P2 levels and Mtmr2 activity. The results presented here provide additional evidence for regulation of Piezo2 by membrane lipids and how proteins regulating these lipids are relevant to Piezo2 physiology. In summary, since the identification of Piezo2, a quest to learn about its function and regulation has been underway. The results of this study combined with the interactomics screen published in 2016 have attempted to answer some fundamental questions about Piezo2 physiology. A characterization of the other proteins identified in our screen will help reveal more facets of Piezo2 regulation. Future studies will also add to structural information on Piezo2 which can further help elucidate its role as the bona fide mechanotransducer of the mammalian somatosensory system

Tactile Arrays for Virtual Textures

This thesis describes the development of three new tactile stimulators for active touch, i.e. devices to deliver virtual touch stimuli to the fingertip in response to exploratory movements by the user. All three stimulators are designed to provide spatiotemporal patterns of mechanical input to the skin via an array of contactors, each under individual computer control. Drive mechanisms are based on piezoelectric bimorphs in a cantilever geometry. The first of these is a 25-contactor array (5 × 5 contactors at 2 mm spacing). It is a rugged design with a compact drive system and is capable of producing strong stimuli when running from low voltage supplies. Combined with a PC mouse, it can be used for active exploration tasks. Pilot studies were performed which demonstrated that subjects could successfully use the device for discrimination of line orientation, simple shape identification and line following tasks. A 24-contactor stimulator (6 × 4 contactors at 2 mm spacing) with improved bandwidth was then developed. This features control electronics designed to transmit arbitrary waveforms to each channel (generated on-the-fly, in real time) and software for rapid development of experiments. It is built around a graphics tablet, giving high precision position capability over a large 2D workspace. Experiments using two-component stimuli (components at 40 Hz and 320 Hz) indicate that spectral balance within active stimuli is discriminable independent of overall intensity, and that the spatial variation (texture) within the target is easier to detect at 320 Hz that at 40 Hz. The third system developed (again 6 × 4 contactors at 2 mm spacing) was a lightweight modular stimulator developed for fingertip and thumb grasping tasks; furthermore it was integrated with force-feedback on each digit and a complex graphical display, forming a multi-modal Virtual Reality device for the display of virtual textiles. It is capable of broadband stimulation with real-time generated outputs derived from a physical model of the fabric surface. In an evaluation study, virtual textiles generated from physical measurements of real textiles were ranked in categories reflecting key mechanical and textural properties. The results were compared with a similar study performed on the real fabrics from which the virtual textiles had been derived. There was good agreement between the ratings of the virtual textiles and the real textiles, indicating that the virtual textiles are a good representation of the real textiles and that the system is delivering appropriate cues to the user

Symposium on Frontiers of Molecular Neurobiology

Membrane structure, synaptic transmission, and fibrous proteins of neurons - conferenc

The Functional Diversity of Mammalian Touch Receptors

Humans in the modern world can survive without the Aristotelian senses of vision, hearing, smell or taste, but no one is completely without the ability to sense touch. This sense is essential for everything from basic tasks like tool manipulation to the complex interactions that underlie social bonding, sexual reproduction and pleasure. Touch receptors are embedded in the skin, at the interface of our bodies and the world. A remarkable array of varied receptor types tile our skin to signal different features of the objects we touch and alert us to their shape and texture. An early investigator of the neurological basis of touch, Maximillian von Frey, proposed in 1895 that the morphological diversity of neural endings in the skin could represent functional specificity. It is indeed the evolution of diverse receptor structures that has endowed the sensory organ of our skin with remarkable somatosensory functions. Here I explore the evolution of mechanosensing, and discuss how diversity in form and organization of touch receptors, from the cellular to organismal level, can shape the function of touch reception

Discharge Patterns of Single Fibers in the Cat's Auditory Nerve

Discharge patterns of single fibers in cat auditory nerve in response to controlled acoustic stimul

ENCODING OF SALTATORY TACTILE VELOCITY IN THE ADULT OROFACIAL SOMATOSENSORY SYSTEM

Processing dynamic tactile inputs is a key function of somatosensory systems. Spatial velocity encoding mechanisms by the nervous system are important for skilled movement production and may play a role in recovery of motor function following neurological insult. Little is known about tactile velocity encoding in trigeminal networks associated with mechanosensory inputs to the face, or the consequences of movement. High resolution functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates of velocity encoding in the human orofacial somatosensory system during unilateral saltatory pneumotactile inputs to perioral hairy skin in 20 healthy adults. A custom multichannel, scalable pneumotactile array consisting of 7 TAC-Cells was used to present 5 stimulus conditions: 5 cm/s, 25 cm/s, 65 cm/s, ALL-ON synchronous activation, and ALL-OFF. The spatial organization of cerebral and cerebellar blood oxygen level-dependent (BOLD) response as a function of stimulus velocity was analyzed using general linear modeling (GLM) of pooled group fMRI signal data. The sequential saltatory inputs to the lower face produced localized, predominantly contralateral BOLD responses in primary somatosensory (SI), secondary somatosensory (SII), primary motor (MI), supplemental motor area (SMA), posterior parietal cortices (PPC), and insula, whose spatial organization and intensity were highly dependent on velocity. Additionally, ipsilateral sensorimotor, insular and cerebellar BOLD responses were prominent during the lowest velocity (5 cm/s). Advisor: Steven M. Barlo

ENCODING OF SALTATORY TACTILE VELOCITY IN THE ADULT OROFACIAL SOMATOSENSORY SYSTEM

Processing dynamic tactile inputs is a key function of somatosensory systems. Spatial velocity encoding mechanisms by the nervous system are important for skilled movement production and may play a role in recovery of motor function following neurological insult. Little is known about tactile velocity encoding in trigeminal networks associated with mechanosensory inputs to the face, or the consequences of movement. High resolution functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates of velocity encoding in the human orofacial somatosensory system during unilateral saltatory pneumotactile inputs to perioral hairy skin in 20 healthy adults. A custom multichannel, scalable pneumotactile array consisting of 7 TAC-Cells was used to present 5 stimulus conditions: 5 cm/s, 25 cm/s, 65 cm/s, ALL-ON synchronous activation, and ALL-OFF. The spatial organization of cerebral and cerebellar blood oxygen level-dependent (BOLD) response as a function of stimulus velocity was analyzed using general linear modeling (GLM) of pooled group fMRI signal data. The sequential saltatory inputs to the lower face produced localized, predominantly contralateral BOLD responses in primary somatosensory (SI), secondary somatosensory (SII), primary motor (MI), supplemental motor area (SMA), posterior parietal cortices (PPC), and insula, whose spatial organization and intensity were highly dependent on velocity. Additionally, ipsilateral sensorimotor, insular and cerebellar BOLD responses were prominent during the lowest velocity (5 cm/s). Advisor: Steven M. Barlo