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  1. Article ; Online: The locus coeruleus directs sensory-motor reflex amplitude across environmental contexts.

    Witts, Emily C / Mathews, Miranda A / Murray, Andrew J

    Current biology : CB

    2023  Volume 33, Issue 21, Page(s) 4679–4688.e3

    Abstract: Purposeful movement across unpredictable environments requires quick, accurate, and contextually appropriate motor corrections in response to disruptions in balance and posture. ...

    Abstract Purposeful movement across unpredictable environments requires quick, accurate, and contextually appropriate motor corrections in response to disruptions in balance and posture.
    MeSH term(s) Humans ; Mice ; Animals ; Locus Coeruleus/physiology ; Reflex/physiology ; Spinal Cord/physiology ; Norepinephrine
    Chemical Substances Norepinephrine (X4W3ENH1CV)
    Language English
    Publishing date 2023-09-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2023.08.085
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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    Jg. 1995 - 2021: Lesesall (2.OG)
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  2. Article ; Online: Pitx2 cholinergic interneurons are the source of C bouton synapses on brainstem motor neurons.

    Rozani, Ismini / Tsapara, Georgia / Witts, Emily C / Deaville, S James / Miles, Gareth B / Zagoraiou, Laskaro

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 4936

    Abstract: Cholinergic neuromodulation has been described throughout the brain and has been implicated in various functions including attention, food intake and response to stress. Cholinergic modulation is also thought to be important for regulating motor systems, ...

    Abstract Cholinergic neuromodulation has been described throughout the brain and has been implicated in various functions including attention, food intake and response to stress. Cholinergic modulation is also thought to be important for regulating motor systems, as revealed by studies of large cholinergic synapses on spinal motor neurons, called C boutons, which seem to control motor neuron excitability in a task-dependent manner. C boutons on spinal motor neurons stem from spinal interneurons that express the transcription factor Pitx2. C boutons have also been identified on the motor neurons of specific cranial nuclei. However, the source and roles of cranial C boutons are less clear. Previous studies suggest that they originate from Pitx2+ and Pitx2- neurons, in contrast to spinal cord C boutons that originate solely from Pitx2 neurons. Here, we address this controversy using mouse genetics, and demonstrate that brainstem C boutons are Pitx2+ derived. We also identify new Pitx2 populations and map the cholinergic Pitx2 neurons of the mouse brain. Taken together, our data present important new information about the anatomical organization of cholinergic systems which impact motor systems of the brainstem. These findings will enable further analyses of the specific roles of cholinergic modulation in motor control.
    MeSH term(s) Animals ; Brain Stem/cytology ; Brain Stem/physiology ; Cholinergic Neurons/cytology ; Cholinergic Neurons/metabolism ; Female ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Interneurons/cytology ; Interneurons/metabolism ; Male ; Mice ; Mice, Transgenic ; Motor Neurons/cytology ; Motor Neurons/metabolism ; Presynaptic Terminals/physiology ; Spinal Cord/cytology ; Spinal Cord/physiology ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Homeobox Protein PITX2
    Chemical Substances Homeodomain Proteins ; Transcription Factors
    Language English
    Publishing date 2019-03-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-39996-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Adenosine-mediated modulation of ventral horn interneurons and spinal motoneurons in neonatal mice.

    Witts, Emily C / Nascimento, Filipe / Miles, Gareth B

    Journal of neurophysiology

    2015  Volume 114, Issue 4, Page(s) 2305–2315

    Abstract: Neuromodulation allows neural networks to adapt to varying environmental and biomechanical demands. Purinergic signaling is known to be an important modulatory system in many parts of the CNS, including motor control circuitry. We have recently shown ... ...

    Abstract Neuromodulation allows neural networks to adapt to varying environmental and biomechanical demands. Purinergic signaling is known to be an important modulatory system in many parts of the CNS, including motor control circuitry. We have recently shown that adenosine modulates the output of mammalian spinal locomotor control circuitry (Witts EC, Panetta KM, Miles GB. J Neurophysiol 107: 1925-1934, 2012). Here we investigated the cellular mechanisms underlying this adenosine-mediated modulation. Whole cell patch-clamp recordings were performed on ventral horn interneurons and motoneurons within in vitro mouse spinal cord slice preparations. We found that adenosine hyperpolarized interneurons and reduced the frequency and amplitude of synaptic inputs to interneurons. Both effects were blocked by the A1-type adenosine receptor antagonist DPCPX. Analysis of miniature postsynaptic currents recorded from interneurons revealed that adenosine reduced their frequency but not amplitude, suggesting that adenosine acts on presynaptic receptors to modulate synaptic transmission. In contrast to interneurons, recordings from motoneurons revealed an adenosine-mediated depolarization. The frequency and amplitude of synaptic inputs to motoneurons were again reduced by adenosine, but we saw no effect on miniature postsynaptic currents. Again these effects on motoneurons were blocked by DPCPX. Taken together, these results demonstrate differential effects of adenosine, acting via A1 receptors, in the mouse spinal cord. Adenosine has a general inhibitory action on ventral horn interneurons while potentially maintaining motoneuron excitability. This may allow for adaptation of the locomotor pattern generated by interneuronal networks while helping to ensure the maintenance of overall motor output.
    MeSH term(s) Adenosine/metabolism ; Adenosine A1 Receptor Antagonists/pharmacology ; Animals ; Interneurons/drug effects ; Interneurons/physiology ; Membrane Potentials/drug effects ; Membrane Potentials/physiology ; Mice, Inbred C57BL ; Motor Neurons/drug effects ; Motor Neurons/physiology ; Patch-Clamp Techniques ; Receptor, Adenosine A1/metabolism ; Spinal Cord/drug effects ; Spinal Cord/physiology ; Tissue Culture Techniques ; Xanthines/pharmacology
    Chemical Substances Adenosine A1 Receptor Antagonists ; Receptor, Adenosine A1 ; Xanthines ; 1,3-dipropyl-8-cyclopentylxanthine (9PTP4FOI9E) ; Adenosine (K72T3FS567)
    Language English
    Publishing date 2015-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80161-6
    ISSN 1522-1598 ; 0022-3077
    ISSN (online) 1522-1598
    ISSN 0022-3077
    DOI 10.1152/jn.00574.2014
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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.224: Show issues Location:
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  4. Article ; Online: Arrays of microscopic organic LEDs for high-resolution optogenetics.

    Steude, Anja / Witts, Emily C / Miles, Gareth B / Gather, Malte C

    Science advances

    2016  Volume 2, Issue 5, Page(s) e1600061

    Abstract: Optogenetics is a paradigm-changing new method to study and manipulate the behavior of cells with light. Following major advances of the used genetic constructs over the last decade, the light sources required for optogenetic control are now receiving ... ...

    Abstract Optogenetics is a paradigm-changing new method to study and manipulate the behavior of cells with light. Following major advances of the used genetic constructs over the last decade, the light sources required for optogenetic control are now receiving increased attention. We report a novel optogenetic illumination platform based on high-density arrays of microscopic organic light-emitting diodes (OLEDs). Because of the small dimensions of each array element (6 × 9 μm(2)) and the use of ultrathin device encapsulation, these arrays enable illumination of cells with unprecedented spatiotemporal resolution. We show that adherent eukaryotic cells readily proliferate on these arrays, and we demonstrate specific light-induced control of the ionic current across the membrane of individual live cells expressing different optogenetic constructs. Our work paves the way for the use of OLEDs for cell-specific optogenetic control in cultured neuronal networks and for acute brain slices, or as implants in vivo.
    MeSH term(s) Biomarkers ; Cell Adhesion/radiation effects ; Cell Survival/radiation effects ; Electronics/instrumentation ; Electronics/methods ; Gene Expression ; HEK293 Cells ; Humans ; Light ; Optical Phenomena ; Optogenetics/instrumentation ; Optogenetics/methods ; Photic Stimulation
    Chemical Substances Biomarkers
    Language English
    Publishing date 2016
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.1600061
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Anatomy and function of cholinergic C bouton inputs to motor neurons.

    Witts, Emily C / Zagoraiou, Laskaro / Miles, Gareth B

    Journal of anatomy

    2013  Volume 224, Issue 1, Page(s) 52–60

    Abstract: Motor control circuitry of the central nervous system must be flexible so that motor behaviours can be adapted to suit the varying demands of different states, developmental stages, and environments. Flexibility in motor control is largely provided by ... ...

    Abstract Motor control circuitry of the central nervous system must be flexible so that motor behaviours can be adapted to suit the varying demands of different states, developmental stages, and environments. Flexibility in motor control is largely provided by neuromodulatory systems which can adjust the output of motor circuits by modulating the properties and connectivity of neurons within them. The spinal circuitry which controls locomotion is subject to a range of neuromodulatory influences, including some which are intrinsic to the spinal cord. One such intrinsic neuromodulatory system, for which a wealth of anatomical information has recently been combined with new physiological data, is the C bouton system. C boutons are large, cholinergic inputs to motor neurons which were first described over 40 years ago but whose source and function have until recently remained a mystery. In this review we discuss how the convergence of anatomical, molecular genetic and physiological data has recently led to significant advances in our understanding of this unique neuromodulatory system. We also highlight evidence that C boutons are involved in spinal cord injury and disease, revealing their potential as targets for novel therapeutic strategies.
    MeSH term(s) Acetylcholine/metabolism ; Humans ; Motor Activity/physiology ; Motor Neurons/physiology ; Spinal Cord/cytology ; Spinal Cord/physiology ; Synapses/physiology
    Chemical Substances Acetylcholine (N9YNS0M02X)
    Language English
    Publishing date 2013-05-23
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2955-5
    ISSN 1469-7580 ; 0021-8782
    ISSN (online) 1469-7580
    ISSN 0021-8782
    DOI 10.1111/joa.12063
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    In stock of ZB MED Cologne/Königswinter

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  6. Article ; Online: Glial-derived adenosine modulates spinal motor networks in mice.

    Witts, Emily C / Panetta, Kara M / Miles, Gareth B

    Journal of neurophysiology

    2011  Volume 107, Issue 7, Page(s) 1925–1934

    Abstract: The activation of purinergic receptors modulates central pattern generators controlling rhythmic motor behaviors, including respiration in rodents and swimming in frog tadpoles. The present study aimed to determine whether purinergic signaling also ... ...

    Abstract The activation of purinergic receptors modulates central pattern generators controlling rhythmic motor behaviors, including respiration in rodents and swimming in frog tadpoles. The present study aimed to determine whether purinergic signaling also modulates the mammalian locomotor central pattern generator. This was investigated by using isolated spinal cord preparations obtained from neonatal mice in which locomotor-related activity can be induced pharmacologically. The application of either ATP or adenosine led to a reduction in the frequency of locomotor activity recorded from ventral roots. ATP had no effect when applied in the presence of both the adenosine receptor antagonist theophylline and the ectonucleotidase inhibitor ARL67156, demonstrating that the effects of ATP application result from the breakdown of ATP to adenosine and subsequent activation of adenosine receptors. The application of theophylline or the A(1)-specific antagonist cyclopentyl dipropylxanthine, but not the A(2A)-receptor antagonist SCH58261, caused an increase in locomotor burst frequency, demonstrating that endogenously derived adenosine activates A(1) receptors during locomotor network activity. Furthermore, theophylline had no effect in the presence of the ectonucleotidase inhibitor ARL67156 or the glial toxins methionine sulfoximine or ethyl fluoracetate, suggesting that endogenous adenosine is derived from ATP, which is released from glia. Finally, adenosine had no effect on slow rhythmic activity recorded upon blockade of all inhibitory transmission, suggesting that adenosine may act via the modulation of inhibitory transmission. Together, these data highlight endogenous purinergic gliotransmission, involving activation of A(1) receptors, as an important intrinsic modulatory system controlling the frequency of activity generated by spinal locomotor circuitry in mammals.
    MeSH term(s) Adenosine/pharmacology ; Adenosine Triphosphate/analogs & derivatives ; Adenosine Triphosphate/pharmacology ; Analgesics/pharmacology ; Animals ; Animals, Newborn ; Enzyme Inhibitors/pharmacology ; In Vitro Techniques ; Mice ; Mice, Inbred C57BL ; Motor Neurons/drug effects ; Nerve Net/drug effects ; Nerve Net/physiology ; Periodicity ; Purinergic Antagonists/pharmacology ; Spinal Cord/cytology
    Chemical Substances 6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP ; Analgesics ; Enzyme Inhibitors ; Purinergic Antagonists ; Adenosine Triphosphate (8L70Q75FXE) ; Adenosine (K72T3FS567)
    Language English
    Publishing date 2011-12-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80161-6
    ISSN 1522-1598 ; 0022-3077
    ISSN (online) 1522-1598
    ISSN 0022-3077
    DOI 10.1152/jn.00513.2011
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  7. Article ; Online: Fast targeted gene transfection and optogenetic modification of single neurons using femtosecond laser irradiation.

    Antkowiak, Maciej / Torres-Mapa, Maria Leilani / Witts, Emily C / Miles, Gareth B / Dholakia, Kishan / Gunn-Moore, Frank J

    Scientific reports

    2013  Volume 3, Page(s) 3281

    Abstract: A prevailing problem in neuroscience is the fast and targeted delivery of DNA into selected neurons. The development of an appropriate methodology would enable the transfection of multiple genes into the same cell or different genes into different ... ...

    Abstract A prevailing problem in neuroscience is the fast and targeted delivery of DNA into selected neurons. The development of an appropriate methodology would enable the transfection of multiple genes into the same cell or different genes into different neighboring cells as well as rapid cell selective functionalization of neurons. Here, we show that optimized femtosecond optical transfection fulfills these requirements. We also demonstrate successful optical transfection of channelrhodopsin-2 in single selected neurons. We extend the functionality of this technique for wider uptake by neuroscientists by using fast three-dimensional laser beam steering enabling an image-guided "point-and-transfect" user-friendly transfection of selected cells. A sub-second transfection timescale per cell makes this method more rapid by at least two orders of magnitude when compared to alternative single-cell transfection techniques. This novel technology provides the ability to carry out large-scale cell selective genetic studies on neuronal ensembles and perform rapid genetic programming of neural circuits.
    MeSH term(s) Animals ; Bacterial Proteins/genetics ; Cells, Cultured ; Channelrhodopsins ; Female ; Lasers ; Luminescent Proteins/genetics ; Neurons/cytology ; Neurons/metabolism ; Optogenetics ; Plasmids/genetics ; Plasmids/metabolism ; Rats ; Rats, Inbred F344 ; Time Factors ; Transfection ; Videotape Recording
    Chemical Substances Bacterial Proteins ; Channelrhodopsins ; Luminescent Proteins ; yellow fluorescent protein, Bacteria
    Language English
    Publishing date 2013-11-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep03281
    Database MEDical Literature Analysis and Retrieval System OnLINE

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