A5016251231- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Sleep and Wakefulness Research
- Photoreceptor and optogenetics research
- Neuroscience of respiration and sleep
- Receptor Mechanisms and Signaling
- Neuroscience and Neural Engineering
- Obstructive Sleep Apnea Research
- Drug Transport and Resistance Mechanisms
- Circadian rhythm and melatonin
- Adenosine and Purinergic Signaling
- stochastic dynamics and bifurcation
- DNA Repair Mechanisms
- Ion channel regulation and function
- Cancer-related Molecular Pathways
- Immune cells in cancer
- Tryptophan and brain disorders
- Connexins and lens biology
- Inflammatory mediators and NSAID effects
- Artificial Intelligence in Healthcare and Education
- Clinical Reasoning and Diagnostic Skills
- Legume Nitrogen Fixing Symbiosis
- Cancer therapeutics and mechanisms
- Renal and related cancers
- Nonlinear Dynamics and Pattern Formation
Swansea University
2025
PsiOxus Therapeutics (United Kingdom)
2023
Vertex Pharmaceuticals (United Kingdom)
2015-2021
Eli Lilly (United Kingdom)
2012-2014
Vertex Pharmaceuticals (United States)
2014
Cardiff University
1999-2012
Eli Lilly (United States)
2009
RELX Group (United Kingdom)
2007
Singer (United States)
2007
University of California, Los Angeles
2005
Several aspects of perception, particularly those pertaining to vision, are closely linked the occipital alpha (α) rhythm. However, how α rhythm relates activity neurons that convey primary visual information is unknown. Here we show in behaving cats, thalamocortical lateral geniculate nucleus (LGN) operate a conventional relay-mode form two groups where cumulative firing subject cyclic suppression centered on negative peak one group and positive other. This leads an effective temporal...
Tonic GABA A receptor-mediated inhibition is typically generated byδ subunit-containing extrasynaptic receptors. Because the δ subunit highly expressed in thalamus, we tested whether thalamocortical (TC) neurons of dorsal lateral geniculate nucleus (dLGN) and ventrobasal complex exhibit tonic inhibition. Focal application gabazine (GBZ) (50 μ m ) revealed presence a 20 pA current 75 63% TC from both nuclei, respectively. No was observed GABAergic reticularis thalami (NRT). Bath 1μ increased...
The mechanism underlying a novel form of input signal amplification and bistability was investigated by intracellular recording in rat cat thalamocortical (TC) neurones maintained slices computer simulation with biophysical model these neurones. In narrow membrane potential range centred around −60 mV, TC challenged small (10–50 pA), short (50–200 ms) current steps produced stereotyped, large amplitude hyperpolarization (> 20 mV) terminated the burst firing action potentials, leading to...
Inhibition of pharyngeal motoneurons accompanies REM sleep and is a cause hypoventilation obstructive apnea in humans. One explanation posits that the neurotransmitters glycine γ-aminobutyric acid are responsible for motor inhibition. However, blockade mechanism at cranial nuclei increases activity all sleep-wake states, least sleep, arguing against it as major inhibition.To identify inhibition hypoglossal pool.Genioglossus diaphragm activities were recorded 34 rats across states....
Although EEG α (8–13 Hz) rhythms are traditionally thought to reflect an “idling” brain state, they also linked several important aspects of cognition, perception, and memory. Here we show that reactivating cholinergic input, a key component in normal cognition memory operations, slices the cat primary visual somatosensory thalamus, produces robust rhythms. These rely on activation muscarinic receptors primarily coordinated by activity recently discovered, gap junction-coupled subnetwork...
During deep sleep and anesthesia, the EEG of humans animals exhibits a distinctive slow (<1 Hz) rhythm. In inhibitory neurons nucleus reticularis thalami (NRT), this rhythm is reflected as oscillation membrane potential comprising stereotypical, recurring "up" "down" states. Here we show that reducing leak current through activation group I metabotropic glutamate receptors (mGluRs) with either trans-ACPD [(+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid] (50-100 microM) or DHPG...
An increasing number of EEG and resting state fMRI studies in both humans animals indicate that spontaneous low frequency fluctuations cerebral activity at <0.1 Hz (infra-slow oscillations, ISOs) represent a fundamental component brain functioning, being known to correlate with faster neuronal ensemble regulate behavioural performance influence seizure susceptibility. Although these oscillations have been commonly indicated involve the thalamus their basic cellular mechanisms remain poorly...
Although EEG alpha () (8-13 Hz) rhythms are often considered to reflect an 'idling' brain state, numerous studies indicate that they also related many aspects of perception. Recently, we outlined a potential cellular substrate by which such perception might be linked basic rhythm mechanisms. This scheme relies on specialized subset rhythmically bursting thalamocortical (TC) neurons (high-threshold cells) in the lateral geniculate nucleus (LGN) interconnected gap junctions (GJs). By...
1. The existence of a non-negligible steady-state ('window') component the low threshold, T-type Ca2+current (IT) and an appropriately large ratio IT to ILeak conductance (i.e. gT/gLeak) have been shown underlie novel form intrinsic bistability that is present in about 15 % thalamocortical (TC) neurones. 2. In experiments, dynamic clamp technique was used introduce into mammalian TC neurones vitro either artificial, i.e. computer-generated, order enhance endogenous IT, or artificial inward...
Obstructive sleep apnea (OSA) is a significant public health problem caused by repeated episodes of upper airway closure that occur only during sleep. Attempts to treat OSA pharmacologically have been unsuccessful because there has not identification target operating at cranial motor nuclei, blockade which can reactivate pharyngeal muscle activity throughout Increasing potassium conductance common mechanism state-dependent neuromodulators reduce motoneuron excitability. Therefore, we aimed...
During sleep and anesthesia, neocortical neurons exhibit rhythmic UP/DOWN membrane potential states. Although UP states are maintained by synaptic activity, the mechanisms that underlie initiation robust rhythmicity of unknown. Using a physiologically validated model state generation in mouse slices whereby cholinergic tone present vivo is reinstated, we show regular driven an electrophysiologically distinct subset morphologically identified layer 5 neurons, which intrinsic low-frequency...