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  • 1.
    Wang, Bei
    et al.
    Xidian Univ, Peoples R China; Uppsala Univ, Sweden.
    Prasad, Sonal
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Hellman, Oskar
    Uppsala Univ, Sweden.
    Li, Hao
    Uppsala Univ, Sweden.
    Fridberger, Anders
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Hjort, Klas
    Uppsala Univ, Sweden.
    Liquid Metal-Based High-Density Interconnect Technology for Stretchable Printed Circuits2023In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028Article in journal (Refereed)
    Abstract [en]

    High-density interconnect (HDI) technology for liquid metal (LM)-based stretchable printed circuit boards is crucial for expanding their applicability. HDI technology provides high-resolution multilayer circuits with a high density of components, as required for next generation of neuroprobes and ultrasonic and sensor arrays. This study presents a HDI technique utilizing laser engraved micro grooves in silicone with a protective lift-off mask of polyvinyl alcohol (PVA) and subsequent microscale LM particle spray deposition. This approach achieves high-resolution LM patterns and enables multilayer connectivity and high-density integration of components simultaneously, that is, realizing HDI technology. It is demonstrated using a stretchable 0201 LED display with a density of six leads per mm2 and a cochlear implant (CI) electrode array. The demonstrated manufacturing of the CI has the potential to enable fully automated printed circuit board manufacturing of such implants with increased precision and throughput. Implants in guinea pigs show that the CI is capable of activating the auditory neuron with electrical auditory brainstem response (eABR) and electrical compound action potential (eCAP) of high quality. Moreover, the U-shaped cross section of the LM interconnects provides a higher mechanical shock resistance of the circuit than that of normal rectangular cross sections. A liquid metal based high-density interconnect technology that is capable of fabricating high resolution circuits and integrating electronic high-density components in multilayer stretchable system, which are demonstrated by a stretchable high-density integrated LEDs display and an eight-electroe array of a cochlear implant.image

  • 2.
    Prasad, Sonal
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Vona, Barbara
    Department of Otorhinolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University Tübingen, Tübingen, Germany.
    Diñeiro, Marta
    Laboratorio de Medicina Molecular, Instituto de Medicina Oncologica y Molecular de Asturias, Oviedo, Spain.
    Costales, María
    Department of Otorhinolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain.
    González-Aguado, Rocío
    Department of Otorhinolaryngology, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
    Fontalba, Ana
    Department of Genetics, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
    Diego-Pérez, Clara
    Department of Otorhinolaryngology, Hospital Universitario de Salamanca, Salamanca, Spain.
    Subasioglu, Asli
    Department of Medical Genetics, Izmir Ataturk Education and Research Hospital, Izmir, Turkey.
    Bademci, Guney
    John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
    Tekin, Mustafa
    John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
    Cabanillas, Rubén
    Área de Medicina de Precisión, Instituto de Medicina Oncologica y Molecular de Asturias, Oviedo, Spain.
    Cadiñanos, Juan
    Laboratorio de Medicina Molecular, Instituto de Medicina Oncologica y Molecular de Asturias, Oviedo, Spain.
    Fridberger, Anders
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Radixin modulates the function of outer hair cell stereocilia2020In: Communications Biology, E-ISSN 2399-3642, Vol. 3, no 1, article id 792Article in journal (Refereed)
    Abstract [en]

    The stereocilia of the inner ear sensory cells contain the actin-binding protein radixin, encoded by RDX. Radixin is important for hearing but remains functionally obscure. To determine how radixin influences hearing sensitivity, we used a custom rapid imaging technique to visualize stereocilia motion while measuring electrical potential amplitudes during acoustic stimulation. Radixin inhibition decreased sound-evoked electrical potentials. Other functional measures, including electrically induced sensory cell motility and sound-evoked stereocilia deflections, showed a minor amplitude increase. These unique functional alterations demonstrate radixin as necessary for conversion of sound into electrical signals at acoustic rates. We identified patients with RDX variants with normal hearing at birth who showed rapidly deteriorating hearing during the first months of life. This may be overlooked by newborn hearing screening and explained by multiple disturbances in postnatal sensory cells. We conclude radixin is necessary for ensuring normal conversion of sound to electrical signals in the inner ear.

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  • 3.
    Gorinski, Nataliya
    et al.
    Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
    Bijata, Monika
    Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany / Cell Biophysics, Nencki Institute, Pasteur Str. 3, 02-093, Warsaw, Poland.
    Prasad, Sonal
    Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
    Wirth, Alexander
    Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
    Abdel Galil, Dalia
    Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
    Zeug, Andre
    Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, German.
    Bazovkina, Daria
    Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia.
    Kondaurova, Elena
    Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia.
    Kulikova, Elizabeth
    Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia.
    Ilchibaeva, Tatiana
    Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia.
    Zareba-Koziol, Monika
    Cell Biophysics, Nencki Institute, Pasteur Str. 3, 02-093, Warsaw, Poland.
    Papaleo, Francesco
    Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163, Genova, Italy.
    Scheggia, Diego
    Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163, Genova, Italy.
    Kochlamazashvili, Gaga
    Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163, Genova, Italy.
    Dityatev, Alexander
    Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163, Genova, Italy / Molecular Neuroplasticity, DZNE, Leipziger Str. 44, 39120, Magdeburg, Germany.
    Smyth, Ian
    Anatomy & Developmental Biology, Monash University, 3800, Melbourne, Australia.
    Krzystyniak, Adam
    Cell Biophysics, Nencki Institute, Pasteur Str. 3, 02-093, Warsaw, Poland.
    Wlodarczyk, Jakub
    Cell Biophysics, Nencki Institute, Pasteur Str. 3, 02-093, Warsaw, Poland.
    Richter, Diethelm W.
    Neuro and Sensory Physiology, University of Göttingen, 37073, Göttingen, Germany.
    Strekalova, Tatyana
    Sechenov First Moscow State Medical University, Moscow, Russia / Neuroscience, Maastricht University, 6229 ER, Maastricht, Netherlands / Laboratory of Psychiatric Neurobiology and Institute of General Pathology and Pathophysiology, Sechenov First Moscow State Medical University, Trubetskaya 8, 119315, Moscow, Russia.
    Sigrist, Stephan
    Institute of Biology, Free University Berlin, Takustr. 6, 14195, Berlin, Germany.
    Bang, Claudia
    Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
    Hobuß, Lisa
    Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
    Fiedler, Jan
    Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
    Thum, Thomas
    Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
    Naumenko, Vladimir S.
    Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia.
    Pandey, Ghanshyam
    Department of Psychiatry, University of Illinois, 1601 W. Taylor Street, Chicago, IL, 60612, USA.
    Ponimaskin, Evgeni
    Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
    Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors2019In: Nature Communications, E-ISSN 2041-1723, Vol. 10, no 1, p. 1-14, article id 3924Article in journal (Refereed)
    Abstract [en]

    The serotonergic system and in particular serotonin 1A receptor (5-HT1AR) are implicated in major depressive disorder (MDD). Here we demonstrated that 5-HT1AR is palmitoylated in human and rodent brains, and identified ZDHHC21 as a major palmitoyl acyltransferase, whose depletion reduced palmitoylation and consequently signaling functions of 5-HT1AR. Two rodent models for depression-like behavior show reduced brain ZDHHC21 expression and attenuated 5-HT1AR palmitoylation. Moreover, selective knock-down of ZDHHC21 in the murine forebrain induced depression-like behavior. We also identified the microRNA miR-30e as a negative regulator of Zdhhc21 expression. Through analysis of the post-mortem brain samples in individuals with MDD that died by suicide we find that miR-30e expression is increased, while ZDHHC21 expression, as well as palmitoylation of 5-HT1AR, are reduced within the prefrontal cortex. Our study suggests that downregulation of 5-HT1AR palmitoylation is a mechanism involved in depression, making the restoration of 5-HT1AR palmitoylation a promising clinical strategy for the treatment of MDD.

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    Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors
  • 4.
    Strimbu, Clark Elliott
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Columbia Univ, NY 10032 USA.
    Prasad, Sonal
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Hakizimana, Pierre
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Fridberger, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Control of hearing sensitivity by tectorial membrane calcium2019In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 116, no 12, p. 5756-5764Article in journal (Refereed)
    Abstract [en]

    When sound stimulates the stereocilia on the sensory cells in the hearing organ, Ca2+ ions flow through mechanically gated ion channels. This Ca2+ influx is thought to be important for ensuring that the mechanically gated channels operate within their most sensitive response region, setting the fraction of channels open at rest, and possibly for the continued maintenance of stereocilia. Since the extracellular Ca2+ concentration will affect the amount of Ca2+ entering during stimulation, it is important to determine the level of the ion close to the sensory cells. Using fluorescence imaging and fluorescence correlation spectroscopy, we measured the Ca2+ concentration near guinea pig stereocilia in situ. Surprisingly, we found that an acellular accessory structure close to the stereocilia, the tectorial membrane, had much higher Ca2+ than the surrounding fluid. Loud sounds depleted Ca2+ from the tectorial membrane, and Ca2+ manipulations had large effects on hair cell function. Hence, the tectorial membrane contributes to control of hearing sensitivity by influencing the ionic environment around the stereocilia.

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  • 5.
    Prasad, Sonal
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Hannover Med Sch, Germany.
    Ponimaskin, Evgeni
    Hannover Med Sch, Germany; Inst Cytol and Genet, Russia.
    Zeug, Andre
    Hannover Med Sch, Germany.
    Serotonin receptor oligomerization regulates cAMP-based signaling2019In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 132, no 16, article id UNSP jcs230334Article in journal (Refereed)
    Abstract [en]

    Protein-protein interaction is often investigated using quantitative molecular microscopy with Forster resonant energy transfer (FRET). Here, we combined linear unmixing FRET (lux-FRET) with the simultaneous application of a FRET-based biosensor for cAMP to investigate the oligomerization between the 5-HT7 receptor (5-HT7R, also known as HTR7) and the 5-HT1A receptor (5-HT1AR, also known as HTR1A) and its importance for cAMP signaling. We found that the 5-HT7R not only stimulates cAMP production, but also forms heterooligomers with 5-HT1AR, which blocks the inhibitory effect of the latter. 5-HT7R signaling, however, is not affected by this hetero-oligomerization. By modeling the kinetics of intracellular cAMP level changes in relation to the 5-HT7R:5-HT1AR stoichiometry, we were able to decipher the complex signaling characteristics of endogenous serotonin receptors in cultured hippocampal neurons. Our findings indicate that serotonergic signaling is not only modulated by the concentration of an individual receptor but also by its specific interaction with other receptors in endogenous systems. We conclude that the regulated ratio of serotonin receptors in immature and mature neurons may be critically involved in both the onset and response to treatments of psychiatric diseases, such as anxiety and depression.

  • 6.
    Prasad, Sonal
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Fridberger, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Investigating the Role of Radixin in Modulation of Stereocilia Length and Stiffness2018In: TO THE EAR AND BACK AGAIN - ADVANCES IN AUDITORY BIOPHYSICS, AMER INST PHYSICS , 2018, Vol. 1965, article id UNSP 060007Conference paper (Refereed)
    Abstract [en]

    Mammalian hearing depends on deflection of stereocilia on the sensory outer hair cells of the inner ear. Previous data indicate that the stiffness of outer hair cell stereocilia are actively regulated. The molecular mechanism that regulate the deflection of stereocilia are presently less known. The aim of the study is to investigate the mechanistic pathway that underlie the stiffness modulation of outer hair cell stereocilia. Our hypothesis is that the membrane-cytoskeleton linker protein radixin, which is present at high concentration in stereocilia, could contribute to stiffness regulation. To test this hypothesis, we use the radixin blocker DX-52-1 which binds strongly and specifically to radixin. Time-resolved confocal imaging was used to visualize the sound-evoked motion of stereocilia in a semi-intact preparation of the guinea pig temporal bone. Cochlear microphonic potentials were also measured, using electrodes positioned in scala media. We found that the DX-52-1 inhibitor leads to an increase in stereocilia movements and decline in the amplitude of the cochlear microphonic potential. However, DX-52-1 caused a paradoxical increase in electromotility. These results suggest that radixin has a functionally important regulatory role in the mature inner ear.

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