A5032933053- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Photoreceptor and optogenetics research
- Sleep and Wakefulness Research
- Ion channel regulation and function
- Lipid Membrane Structure and Behavior
- Retinal Development and Disorders
- Advanced Memory and Neural Computing
- Epilepsy research and treatment
- Neural Networks and Applications
- Single-cell and spatial transcriptomics
- EEG and Brain-Computer Interfaces
- Memory and Neural Mechanisms
- Electrochemical Analysis and Applications
- Visual perception and processing mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Adenosine and Purinergic Signaling
- Neuroscience and Neural Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience, Education and Cognitive Function
- Olfactory and Sensory Function Studies
- Axon Guidance and Neuronal Signaling
- Circadian rhythm and melatonin
- Genetics, Bioinformatics, and Biomedical Research
- Neuroscience of respiration and sleep
University of Oxford
2016-2025
Mansfield Community Hospital
2024
Institute of Pharmacology
2017
RELX Group (United Kingdom)
2007
Singer (United States)
2007
Cold Spring Harbor Laboratory
2003-2006
Abstract The brain processes information through multiple layers of neurons. This deep architecture is representationally powerful, but complicates learning because it difficult to identify the responsible neurons when a mistake made. In machine learning, backpropagation algorithm assigns blame by multiplying error signals with all synaptic weights on each neuron’s axon and further downstream. However, this involves precise, symmetric backward connectivity pattern, which thought be...
To determine how patterned visual activity regulates the development of axonal projections, we collected in vivo time-lapse images retinal axons from albino Xenopus tadpoles which binocular innervation optic tectum was induced. Axons added branch tips with nearly equal probability all territories, but eliminated them preferentially territory dominated by opposite eye. This selective elimination abolished blockade N-methyl-D-aspartate receptors. These results describe a correlation-based...
Neurotransmission during development regulates synaptic maturation in neural circuits, but the contribution of different neurotransmitter systems is unclear. We investigated role GABA A receptor-mediated Cl − conductances responses Xenopus visual system. Intracellular concentration ([Cl ] i ) was found to be high immature tectal neurons and then falls over a period several weeks. GABAergic synapses are present at early stages and, when activated by optic nerve stimulation or stimuli, induce...
Epileptic seizures are characterized by periods of hypersynchronous, hyperexcitability within brain networks. Most involve two stages: an initial tonic phase, followed a longer clonic phase that is rhythmic bouts synchronized network activity called afterdischarges (ADs). Here we investigate the cellular and mechanisms underlying hippocampal ADs in effort to understand how they maintain seizure activity. Using vitro slice models from rats mice, performed electrophysiological recordings CA3...
Reproducibility in molecular and cellular studies is fundamental to scientific discovery. To establish the reproducibility of a well-defined long-term neuronal differentiation protocol, we repeated comparison same two iPSC lines across five distinct laboratories. Despite uncovering acceptable variability within individual laboratories, detect poor cross-site differential gene expression signature between these lines. Factor analysis identifies laboratory as largest source variation along...
Induced pluripotent stem cell (iPSC)-derived cortical neurons potentially present a powerful new model to understand corticogenesis and neurological disease. Previous work has established that differentiation protocols can produce neurons, but little been done characterize these at cellular resolution. In particular, it is unclear what extent in vitro two-dimensional, relatively disordered culture conditions recapitulate the development of vivo layer identity. Single-cell multiplex reverse...
Benzodiazepine-resistant status epilepticus is an ongoing clinical challenge. Burman et al. show that longer seizure duration a useful indicator of benzodiazepine resistance, and resistance caused by changes in GABAA receptor-mediated synaptic transmission. The findings could help optimise current management protocols.
Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools for remote control of targeted cell populations using chemical actuators that bind to modified receptors. Despite the popularity DREADDs in neuroscience and sleep research, potential effects DREADD actuator clozapine-N-oxide (CNO) on have never been systematically tested. Here, we show intraperitoneal injections commonly used CNO doses (1, 5, 10 mg/kg) alter wild-type male laboratory mice. Using...
Seizure-induced release of the neuromodulator adenosine is a potent endogenous anticonvulsant mechanism, which limits extension seizures and mediates seizure arrest. For this reason several adenosine-based therapies for epilepsy are currently under development. However, it not known how modulates GABAergic transmission in context activity. This may be particularly relevant as strong activation inputs during epileptiform activity can switch GABA A receptor (GABA R) signaling from inhibitory...
Astrocytes influence neuronal maturation and function by providing trophic support, regulating the extracellular environment, modulating signaling at synapses. The emergence of induced pluripotent stem cell (iPSC) technology offers a human system with which to validate re-evaluate insights from animal studies. Here, we set out examine interactions between astrocytes neurons derived common cortical progenitor pool, thereby recapitulating aspects in vivo development. We show that iPSC-derived...
Fast synaptic inhibition in the brain is mediated by pre-synaptic release of neurotransmitter γ-Aminobutyric acid (GABA)and post-synaptic activation GABA-sensitive ionotropic receptors. As with excitatory synapses, it being increasinly appreciated that a variety plastic processes occur at inhibitory which operate over range timescales. Here we examine form activity-dependent plasticity somewhat unique to GABAergic transmission. This involves short-lasting changes ionic driving force for...
GABA B receptors are G-protein-coupled that mediate inhibitory synaptic actions through a series of downstream target proteins. It is increasingly appreciated the receptor forms part larger signaling complexes, which enable to multiple different effects within neurons. Here we report can physically associate with potassium-chloride cotransporter protein, KCC2, sets driving force for chloride-permeable ionotropic A in mature Using biochemical, molecular, and functional studies rodent...
Current anti-epileptic medications that boost synaptic inhibition are effective in reducing several types of epileptic seizure activity. Nevertheless, these drugs can generate significant side-effects and even paradoxical responses due to the broad nature their action. Recently developed chemogenetic techniques provide opportunity pharmacologically recruit endogenous inhibitory mechanisms a selective circuit-specific manner. Here we use chemogenetics assess potential supressing epileptiform...
Astrocytes can both sense and shape the evolution of neuronal network activity are known to possess unique ion regulatory mechanisms. Here we explore relationship between astrocytic intracellular pH dynamics synchronous that occurs during seizure-like activity. By combining confocal two-photon imaging genetically encoded reporters with simultaneous electrophysiological recordings, perform measurements in defined cell populations relate these ongoing This approach reveals marked differences...