Optogenetic Stimulation of Type I GAD65+ Cells in Taste Buds Activates Gustatory Neurons and Drives Appetitive Licking Behavior in Sodium-Depleted Mice

ABSTRACTIn the vestibular peripheral organs, type I and type II hair cells (HCs) transmit incoming signals via glutamatergic quantal transmission onto afferent nerve fibers. Additionally, type I HCs transmit via ‘non-quantal’ transmission to calyx afferent fibers, by accumulation of glutamate and potassium in the synaptic cleft. Vestibular efferent inputs originating in the brainstem contact type II HCs and vestibular afferents. Here, we aimed at characterizing the synaptic efferent inputs to type II HCs using electrical and optogenetic stimulation of efferent fibers combined with in vitro whole-cell patch clamp recording from type II HCs in the rodent vestibular crista. Properties of efferent synaptic currents in type II HCs were similar to those found in cochlear hair cells and mediated by activation of α9/α10 nicotinic acetylcholine receptors (AChRs) and SK potassium channels. While efferents showed a low probability of release at low frequencies of stimulation, repetitive stimulation resulted in facilitation and increased probability of release. Notably, the membrane potential of type II HCs measured during optogenetic stimulation of efferents showed a strong hyperpolarization even in response to single pulses and was further enhanced by repetitive stimulation. Such efferent-mediated inhibition of type II HCs can provide a mechanism to adjust the contribution of signals from type I and type II HCs to vestibular nerve fibers. As a result, the relative input of type I hair cells to vestibular afferents will be strengthened, emphasizing the phasic properties of the incoming signal that are transmitted via fast non-quantal transmission.New and NoteworthyType II vestibular hair cells (HCs) receive inputs from efferent fibers originating in the brainstem. We used in vitro optogenetic and electrical stimulation of efferent fibers to study their synaptic inputs to type II HCs. Efferent inputs inhibited type II HCs, similar to cochlear efferent effects. We propose that efferent inputs adjust the contribution of signals from type I and type II HCs that report different components of the incoming signal to vestibular nerve fibers.

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Faculty Opinions recommendation of Optogenetic stimulation of a hippocampal engram activates fear memory recall.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.14256961.15779281 ◽

2012 ◽

Author(s):

Ted Abel ◽

Robbert Havekes

Keyword(s):

Fear Memory ◽

Memory Recall ◽

Optogenetic Stimulation ◽

Stimulation Of

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Faculty Opinions recommendation of Exogenous Stimulation of Type I Interferon Protects Mice with Chronic Granulomatous Disease from Aspergillosis through Early Recruitment of Host-Protective Neutrophils into the Lung.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732916050.793544454 ◽

2018 ◽

Author(s):

Ashraf Ibrahim

Keyword(s):

Chronic Granulomatous Disease ◽

Type I Interferon ◽

Type I ◽

Granulomatous Disease ◽

Early Recruitment ◽

Stimulation Of

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Faculty Opinions recommendation of Wireless Optogenetic Stimulation of Oxytocin Neurons in a Semi-natural Setup Dynamically Elevates Both Pro-social and Agonistic Behaviors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738143860.793576394 ◽

2020 ◽

Author(s):

Gerd Kempermann

Keyword(s):

Optogenetic Stimulation ◽

Stimulation Of

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Incerto-thalamic modulation of fear via GABA and dopamine

Neuropsychopharmacology ◽

10.1038/s41386-021-01006-5 ◽

2021 ◽

Author(s):

Archana Venkataraman ◽

Sarah C. Hunter ◽

Maria Dhinojwala ◽

Diana Ghebrezadik ◽

JiDong Guo ◽

...

Keyword(s):

Brain Regions ◽

Zona Incerta ◽

Dependent Manner ◽

Post Traumatic Stress ◽

Functional Roles ◽

Functional Connections ◽

Optogenetic Stimulation ◽

Fear Generalization ◽

Stimulation Of

AbstractFear generalization and deficits in extinction learning are debilitating dimensions of Post-Traumatic Stress Disorder (PTSD). Most understanding of the neurobiology underlying these dimensions comes from studies of cortical and limbic brain regions. While thalamic and subthalamic regions have been implicated in modulating fear, the potential for incerto-thalamic pathways to suppress fear generalization and rescue deficits in extinction recall remains unexplored. We first used patch-clamp electrophysiology to examine functional connections between the subthalamic zona incerta and thalamic reuniens (RE). Optogenetic stimulation of GABAergic ZI → RE cell terminals in vitro induced inhibitory post-synaptic currents (IPSCs) in the RE. We then combined high-intensity discriminative auditory fear conditioning with cell-type-specific and projection-specific optogenetics in mice to assess functional roles of GABAergic ZI → RE cell projections in modulating fear generalization and extinction recall. In addition, we used a similar approach to test the possibility of fear generalization and extinction recall being modulated by a smaller subset of GABAergic ZI → RE cells, the A13 dopaminergic cell population. Optogenetic stimulation of GABAergic ZI → RE cell terminals attenuated fear generalization and enhanced extinction recall. In contrast, optogenetic stimulation of dopaminergic ZI → RE cell terminals had no effect on fear generalization but enhanced extinction recall in a dopamine receptor D1-dependent manner. Our findings shed new light on the neuroanatomy and neurochemistry of ZI-located cells that contribute to adaptive fear by increasing the precision and extinction of learned associations. In so doing, these data reveal novel neuroanatomical substrates that could be therapeutically targeted for treatment of PTSD.

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Involvement of MCH-oxytocin neural relay within the hypothalamus in murine nursing behavior

Scientific Reports ◽

10.1038/s41598-021-82773-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yoko Kato ◽

Harumi Katsumata ◽

Ayumu Inutsuka ◽

Akihiro Yamanaka ◽

Tatsushi Onaka ◽

...

Keyword(s):

Mammalian Species ◽

Virgin Female ◽

Essential Elements ◽

Hypothalamic Nucleus ◽

Male Mice ◽

Hypothalamic Area ◽

Functional Roles ◽

Genetic Ablation ◽

Optogenetic Stimulation ◽

Stimulation Of

AbstractMultiple sequential actions, performed during parental behaviors, are essential elements of reproduction in mammalian species. We showed that neurons expressing melanin concentrating hormone (MCH) in the lateral hypothalamic area (LHA) are more active in rodents of both sexes when exhibiting parental nursing behavior. Genetic ablation of the LHA-MCH neurons impaired maternal nursing. The post-birth survival rate was lower in pups born to female mice with congenitally ablated MCH neurons under control of tet-off system, exhibiting reduced crouching behavior. Virgin female and male mice with ablated MCH neurons were less interested in pups and maternal care. Chemogenetic and optogenetic stimulation of LHA-MCH neurons induced parental nursing in virgin female and male mice. LHA-MCH GABAergic neurons project fibres to the paraventricular hypothalamic nucleus (PVN) neurons. Optogenetic stimulation of PVN induces nursing crouching behavior along with increasing plasma oxytocin levels. The hypothalamic MCH neural relays play important functional roles in parental nursing behavior in female and male mice.

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Establishment of a New Device for Electrical Stimulation of Non-Degenerative Cartilage Cells In Vitro

International Journal of Molecular Sciences ◽

10.3390/ijms22010394 ◽

2021 ◽

Vol 22 (1) ◽

pp. 394

Author(s):

Simone Krueger ◽

Alexander Riess ◽

Anika Jonitz-Heincke ◽

Alina Weizel ◽

Anika Seyfarth ◽

...

Keyword(s):

Electrical Stimulation ◽

Electric Fields ◽

Cartilage Tissue ◽

Type I ◽

Dependent Manner ◽

New Device ◽

Alternating Electric Fields ◽

Cartilage Cells ◽

Stimulation Of

In cell-based therapies for cartilage lesions, the main problem is still the formation of fibrous cartilage, caused by underlying de-differentiation processes ex vivo. Biophysical stimulation is a promising approach to optimize cell-based procedures and to adapt them more closely to physiological conditions. The occurrence of mechano-electrical transduction phenomena within cartilage tissue is physiological and based on streaming and diffusion potentials. The application of exogenous electric fields can be used to mimic endogenous fields and, thus, support the differentiation of chondrocytes in vitro. For this purpose, we have developed a new device for electrical stimulation of chondrocytes, which operates on the basis of capacitive coupling of alternating electric fields. The reusable and sterilizable stimulation device allows the simultaneous use of 12 cavities with independently applicable fields using only one main supply. The first parameter settings for the stimulation of human non-degenerative chondrocytes, seeded on collagen type I elastin-based scaffolds, were derived from numerical electric field simulations. Our first results suggest that applied alternating electric fields induce chondrogenic re-differentiation at the gene and especially at the protein level of human de-differentiated chondrocytes in a frequency-dependent manner. In future studies, further parameter optimizations will be performed to improve the differentiation capacity of human cartilage cells.

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Tumor Necrosis Factor Alpha Inhibits Type I Collagen Synthesis through Repressive CCAAT/Enhancer-Binding Proteins

Molecular and Cellular Biology ◽

10.1128/mcb.20.3.912-918.2000 ◽

2000 ◽

Vol 20 (3) ◽

pp. 912-918 ◽

Cited By ~ 115

Author(s):

Patricia Greenwel ◽

Shizuko Tanaka ◽

Dmitri Penkov ◽

Wen Zhang ◽

Michelle Olive ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Type I Collagen ◽

Type I ◽

Necrosis Factor Alpha ◽

Gene Coding ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor ◽

Stimulation Of

ABSTRACT Extracellular matrix (ECM) formation and remodeling are critical processes for proper morphogenesis, organogenesis, and tissue repair. The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) inhibits ECM accumulation by stimulating the expression of matrix proteolytic enzymes and by downregulating the deposition of structural macromolecules such as type I collagen. Stimulation of ECM degradation has been linked to prolonged activation of jun gene expression by the cytokine. Here we demonstrate that TNF-α inhibits transcription of the gene coding for the α2 chain of type I collagen [α2(I) collagen] in cultured fibroblasts by stimulating the synthesis and binding of repressive CCAAT/enhancer proteins (C/EBPs) to a previously identified TNF-α-responsive element. This conclusion was based on the concomitant identification of C/EBPβ and C/EBPδ as TNF-α-induced factors by biochemical purification and expression library screening. It was further supported by the ability of the C/EBP-specific dominant-negative (DN) protein to block TNF-α inhibition of α2(I) collagen but not TNF-α stimulation of the MMP-13 protease. The DN protein also blocked TNF-α downregulation of the gene coding for the α1 chain of type I collagen. The study therefore implicates repressive C/EBPs in the TNF-α-induced signaling pathway that controls ECM formation and remodeling.

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