A5045463206- Zebrafish Biomedical Research Applications
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Neurogenesis and neuroplasticity mechanisms
- Muscle activation and electromyography studies
- Neurobiology and Insect Physiology Research
- Neural dynamics and brain function
- Spinal Cord Injury Research
- Neurological disorders and treatments
- Botulinum Toxin and Related Neurological Disorders
- Neuroscience of respiration and sleep
- Pluripotent Stem Cells Research
- Nerve injury and regeneration
- Parkinson's Disease Mechanisms and Treatments
- Pain Mechanisms and Treatments
- Developmental Biology and Gene Regulation
- Cellular Mechanics and Interactions
- Adipose Tissue and Metabolism
- Transcranial Magnetic Stimulation Studies
- Muscle Physiology and Disorders
- Primate Behavior and Ecology
- Congenital heart defects research
- Electromagnetic Fields and Biological Effects
- Robotic Locomotion and Control
University College London
2015-2024
National Hospital for Neurology and Neurosurgery
2018-2024
University College London Hospitals NHS Foundation Trust
2022
Dalhousie University
2008-2018
Sobell House
2015-2018
Alberta Bible College
2015
Cognitive Neuroimaging Lab
2015
Health Sciences Centre
2014
Neuroscience Institute
2010
Institute of Neurobiology
2005-2007
To effect movement, motoneurons must respond appropriately to motor commands. Their responsiveness these inputs, or excitability, is regulated by neuromodulators. Possible sources of modulation include the abundant cholinergic “C boutons” that surround motoneuron somata. In present study, recordings from in spinal cord slices demonstrated activation m 2 -type muscarinic receptors increases excitability reducing action potential afterhyperpolarization. Analyses isolated preparations which...
Abstract The human immunodeficiency virus type 1 (HIV‐1) protein Tat is known to be released from HIV‐1‐infected cells. We show that micromolar concentrations of depolarized young rat and adult neurons. In addition, Tat, at similar concentrations, was toxic fetal neurons in culture. Tat‐induced responses were insensitive the Na + channel blocker tetrodotoxin, suggesting a direct effect on depolarizations cytotoxicity blocked by excitatory amino acid antagonist kynurenate. N ‐methylv D...
1. We examined the ability of muscular and joint afferents from hip region to entrain fictive locomotion evoked by stimulation mesencephalic locomotor in decerebrate cat mechanically imposed, sinusoidal flexion extension movements. 2. A method is presented for qualitative quantitative analysis entrainment. 3. Hip capsular were shown denervation experiments be unnecessary mediating 4. As population was progressively decreased selective denervation, strength entrainment concomitantly...
Abstract The intrinsic properties of mammalian spinal motoneurons provide them with the capability to produce high rates sustained firing in response transient inputs (bistability). Even though it has been suggested that a persistent dendritic calcium current is responsible for depolarizing drive underlying this property, such not demonstrated these cells. In study, currents are recorded from functionally mature mouse using somatic whole‐cell patch‐clamp techniques. Under conditions...
The capacity of embryonic stem (ES) cells to form functional motoneurons (MNs) and appropriate connections with muscle was investigated in vitro . ES were obtained from a transgenic mouse line which the gene for enhanced green fluorescent protein (eGFP) is expressed under control promotor MN specific homeobox Hb9 exposed retinoic acid (RA) sonic hedgehog agonist (Hh-Ag1.3) stimulate differentiation into MNs marked by expression eGFP cholinergic transmitter synthetic enzyme choline...
Spike frequency adaptation (SFA) is a fundamental property of repetitive firing in motoneurones (MNs). Early SFA (occurring over several hundred milliseconds) thought to be important the initiation muscular contraction. To date mechanisms underlying spinal MNs remain unclear. In present study, we used both whole-cell patch-clamp recordings lumbar cord slices prepared from motor functionally mature mice and computer modelling investigate SFA. Pharmacological blocking agents applied during...
Motor behaviors result from the interplay between brain and spinal cord. Reticulospinal neurons, situated supraspinal structures that initiate motor movements cord executes them, play key integrative roles in these behaviors. However, molecular identities of mammalian reticular formation neurons mediate have not yet been determined, thus limiting their study health disease. In medullary mouse, we identified express transcription factors Lhx3 and/or Chx10, demonstrate form a significant...
Layering of neural circuits facilitates the separation neurons with high spatial sensitivity from those that play integrative temporal roles. Although anatomical layers are readily identifiable in brain, layering is not structurally obvious spinal cord. But computational studies motor behaviors have led to concept layered processing It has been postulated V3 interneurons (INs) multiple roles locomotion, leading us investigate whether they form microcircuits. Using patch-clamp recordings...
Deletion of SCN9A encoding the voltage-gated sodium channel NaV1.7 in humans leads to profound pain insensitivity and anosmia. Conditional deletion sensory neurons mice also abolishes pain, suggesting that locus analgesia is nociceptor. Here we demonstrate, using vivo calcium imaging extracellular recording, knockout have essentially normal nociceptor activity. However, synaptic transmission from central terminals spinal cord greatly reduced by an opioid-dependent mechanism. Analgesia...
Deep brain stimulation (DBS) is used increasingly worldwide for the treatment of Parkinson's disease, dystonia, tremor and pain. As with any implanted system, however, DBS introduces a new series problems related to its hardware. Infection, malfunction lead migration or fracture may increase patient morbidity should be considered when evaluating risk/benefit ratio this therapy. This work highlights several factors felt hardware complications.The authors undertook prospective analysis their...
Abstract Spinal neurons and networks that generate rhythmic locomotor activity remain incompletely defined, prompting the use of molecular biological strategies to label populations in postnatal mouse. During spinal cord development, expression Lhx3 absence Isl1 specifies a V2 interneuronal fate. In this study, V2‐derived interneurons were identified by yellow fluorescent protein (YFP) double‐transgenic offspring Cre/+ × thy1‐loxP‐stop‐loxP‐YFP mice. While some motoneurons labelled, several...
Motor neurons, which relay neural commands to drive skeletal muscle movements, encompass types ranging from "slow" "fast," whose biophysical properties govern the timing, gradation, and amplitude of force. Here we identify noncanonical Notch ligand Delta-like homolog 1 (Dlk1) as a determinant motor neuron functional diversification. Dlk1, expressed by ~30% is necessary sufficient promote fast signature in mouse chick. Dlk1 suppresses signaling activates expression K(+) channel subunit Kcng4...
The synaptic pathways of mesencephalic locomotor region (MLR)-evoked excitatory and inhibitory postsynaptic potentials (EPSPs IPSPs) recorded from lumbar motoneurons unanesthetized decerebrate cats during fictive locomotion were analyzed prior to, during, after cold block the medial reticular formation (MedRF) or low thoracic ventral funiculus (VF). As others have shown, electrical stimulation MLR typically evoked short-latency mixed excitatory/inhibitory PSPs in flexor extensor motoneurons....
Abstract Motoneurons integrate synaptic input and produce output in the form of trains action potentials such that appropriate muscle contraction occurs. Motoneuronal calcium currents play an important role production this repetitive firing. Because these change postnatal period, it is necessary to study them animals which motor system ‘functionally mature’, is, are able weight‐bear walk. In study, were recorded using whole‐cell patch‐clamp techniques from large (> 20 μm) ventral horn...