Susan Deuchars

Susan Deuchars
University of Leeds · School of Biomedical Sciences

BSc (Hons), PhD

About

81
Publications
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Publications

Publications (81)
Preprint
Manipulation of neural stem cell proliferation and differentiation in the postnatal CNS is receiving significant attention due to therapeutic potential. In the spinal cord, such manipulations may promote repair in conditions such as multiple sclerosis or spinal cord injury, but may also limit excessive cell proliferation contributing to tumours suc...
Article
Full-text available
Autonomic parasympathetic preganglionic neurons (PGN) drive contraction of the bladder during micturition but remain quiescent during bladder filling. This quiescence is postulated to be due to recurrent inhibition of PGN by fast-firing adjoining interneurons. Here, we defined four distinct neuronal types within lamina VII of the lumbosacral spinal...
Article
Objectives Failed back surgery syndrome (FBSS) is associated with impaired autonomic tone, characterized by sympathetic prevalence and vagal withdrawal. Although spinal cord stimulation (SCS) alleviates pain in FBSS, there is limited research investigating how SCS affects measures of autonomic function. This was a prospective, open-label, feasibili...
Preprint
Full-text available
Autonomic parasympathetic preganglionic neurons (PGN) drive contraction of the bladder during micturition but remain quiescent during bladder filling. This quiescence is postulated to be due to recurrent inhibition of PGN by fast-firing adjoining interneurons. Here, we defined four distinct neuronal types within lamina VII of the lumbosacral spinal...
Preprint
Full-text available
The action potential and its all-or-none nature is fundamental to neural communication. Canonically the action potential is initiated once voltage-gated Na ⁺ (NaV) channels are activated and their rapid kinetics of activation and inactivation give rise to the all-or-none nature. Here we show that cerebrospinal fluid contacting neurons (CSFcNs) surr...
Article
Full-text available
Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve s...
Article
Full-text available
Background Myocardial infarction (MI) reperfusion therapy causes paradoxical cardiac complications. Following restoration of blood flow to infarcted regions, a multitude of inflammatory cells are recruited to the site of injury for tissue repair. Continual progression of cardiac inflammatory responses does, however, lead to adverse cardiac remodeli...
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Tracing of neurons plays an essential role in elucidating neural networks in the brain and spinal cord. Cholera toxin B subunit (CTB) is already widely used as a tracer although its use is limited by the need for immunohistochemical detection. A new construct incorporating non-canonical azido amino acids (azido-CTB) offers a novel way to expand the...
Article
Full-text available
Ageing is associated with attenuated autonomic function. Transcutaneous vagal nerve stimulation (tVNS) improved autonomic function in healthy young participants. We therefore investigated the effects of a single session of tVNS (studies 1 and 2) and tVNS administered daily for two weeks (study 3) in volunteers aged ≥ 55 years. tVNS was performed us...
Article
Background: Electrical stimulation on select areas of the external auricular dermatome influences the autonomic nervous system. It has been postulated that activation of the Auricular Branch of the Vagus Nerve (ABVN) mediates such autonomic changes. However, the underlying neural pathways mediating these effects are unknown and, further, our under...
Article
The modern science of physiology began in Europe. Deciding on exactly who the first physiologist was is not easy but excellent candidates include Claude Bernard and Carl Ludwig. The Nobel Prize in Physiology or Medicine was inaugurated in 1901 with the first award mentioning the word “physiology” being made to Ivan Pavlov (Russia) in 1904.
Article
New findings: What is the topic of this review? This review briefly considers what modulates sympathetic nerve activity and how it may change as we age or in pathological conditions. It then focuses on transcutaneous vagus nerve stimulation, a method of neuromodulation in autonomic cardiovascular control. What advances does it highlight? The revie...
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Full-text available
Chronically elevated sympathetic nervous activity underlies many cardiovascular diseases. Elucidating the mechanisms contributing to sympathetic nervous system output may reveal new avenues of treatment. The contribution of the gap junctional protein connexin 36 (Cx36) to the regulation of sympathetic activity and thus blood pressure and heart rate...
Conference Paper
Non-invasive trigeminal nerve stimulation (TNS) is under investigation as an adjunctive neuromodulation therapy for treatment-resistant epilepsy and treatment-resistant major depressive disorder. The mechanism of action of TNS is unclear but the nucleus tractus solitarius (NTS), a key brainstem region associated with cardiovascular autonomic contro...
Article
Lamina X of the spinal cord is a functionally diverse area with roles in locomotion, autonomic control and processing of mechano and nociceptive information. It is also a neurochemically diverse region. However the different populations of cells in lamina X remain to be fully characterised. To determine the co-localisation of the enzymes responsibl...
Article
The human ear seems an unlikely candidate for therapies aimed at improving cardiac function, but the ear and the heart share a common connection: the vagus nerve. In recent years there has been increasing interest in the auricular branch of the vagus nerve (ABVN), a unique cutaneous subdivision of the vagus distributed to the external ear. Non-inva...
Conference Paper
Ageing is associated with autonomic dysfunction and increased risk of chronic cardiovascular disease. The aim of the present study is to assess the effects of a non-invasive method of vagus nerve stimulation, transcutaneous vagus nerve stimulation (tVNS) on autonomic activity in older healthy human subjects aged >60 years. tVNS was applied to the t...
Article
Full-text available
The region surrounding the central canal (CC) of the spinal cord is a highly plastic area, defined as a postnatal neurogenic niche. Within this region are ependymal cells which can proliferate and differentiate to form new astrocytes and oligodendrocytes following injury and cerebrospinal fluid contacting cells (CSFcCs). The specific environmental...
Article
Full-text available
GABAergic and cholinergic systems play an important part in autonomic pathways. To determine the distribution of the enzymes responsible for the production of GABA and acetylcholine in areas involved in autonomic control in the mouse brainstem, we used a transgenic mouse expressing green fluorescent protein (GFP) in glutamate decarboxylase 67 (GAD6...
Article
The sympathetic nervous system comprises one half of the autonomic nervous system and participates in maintaining homeostasis and enabling organisms to respond in an appropriate manner to perturbations in their environment, either internal or external. The sympathetic preganglionic neurons (SPNs) lie within the spinal cord and their axons traverse...
Article
Sympathetic control of end organs relies on the activity of sympathetic preganglionic neurones (SPNs) within the spinal cord. These SPNs exhibit heterogeneity with respect to function, neurochemistry, location, descending inputs and patterns of activity. Part of this heterogeneity is bestowed by local spinal circuitry. Our understanding of the role...
Article
Full-text available
Background Vagus nerve stimulation (VNS) is currently used to treat refractory epilepsy and is being investigated as a potential therapy for a range of conditions, including heart failure, tinnitus, obesity and Alzheimer's disease. However, the invasive nature and expense limits the use of VNS in patient populations and hinders the exploration of t...
Article
Full-text available
Sensory information arising from the upper neck is important in the reflex control of posture and eye position. It has also been linked to the autonomic control of the cardiovascular and respiratory systems. Whiplash associated disorders (WAD) and cervical dystonia, which involve disturbance to the neck region, can often present with abnormalities...
Article
Full-text available
The area surrounding the central canal of the postnatal mammalian spinal cord is a highly plastic region that exhibits many similarities to other postnatal neurogenic niches, such as the subventricular zone. Within this region, ependymal cells have been identified as neural stem cells however very little is known about their properties and how the...
Article
Full-text available
The Na(+)/K(+) ATPase (NKA) is an essential membrane protein underlying the membrane potential in excitable cells. Transmembrane ion transport is performed by the catalytic α subunits (α1-4). The predominant subunits in neurons are α1 and α3, which have different affinities for Na(+) and K(+), impacting on transport kinetics. The exchange rate of N...
Article
Pericytes play important roles in vascular control and may form an important part of the blood brain barrier. Here we introduce a simple method for fluorescently labelling pericytes to enable further studies in live or fixed tissue of rats and mice. Following intraperitoneal injection, the fluorescent tracer Fluorogold was rapidly taken up into vas...
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Full-text available
Background Mefloquine is an anti-malarial drug that can have neurological side effects. This study examines how mefloquine (MF) influences central nervous control of autonomic and respiratory systems using the arterially perfused working heart brainstem preparation (WHBP) of the rat. Recordings of nerve activity were made from the thoracic sympathe...
Article
Vagus is Latin for Wandering and the vagus nerve fully deserves this name due to its extensive distribution through the body. Indeed, one of the lines of the song that accompanied the 2012 GL Brown Lecture exaggerates this diversity, "My function's almost anythin', and Vagus is my name" Altering vagal activity was first investigated in the 1880s as...
Conference Paper
Transcranial direct current stimulation (tDCS) of the primary motor cortex is a possible therapy to enhance motor rehabilitation after stroke. The aim of this study is to determine any potential autonomic effects of the tDCS electrode montage conventionally used in stroke therapy. The study was approved by the University of Leeds Ethics Committee a...
Chapter
The varied and complex roles of interneurons in the control of spinal cord function have provoked widespread interest in understanding how these neurons operate to enable appropriate and synchronised output from the spinal cord. This chapter focuses on the role of spinal interneurons in autonomic control and examines their properties, morphology, i...
Article
Sudden death accounts for 30–50% of total mortality in chronic heart failure (CHF) patients. The occurrence of sudden death in CHF exhibits a circadian periodicity and may be exacerbated by a morning peak in cardiac sympathetic activity. As amiodarone has been found to protect against cardiac events in CHF patients (Amiodarone trials meta-analysis...
Article
Full-text available
Modulatory influences on sympathetic nervous system activity are diverse and far reaching, acting at select points in the complex pathways controlling sympathetic outflow to enable subtle changes or more global effects. Changes in the degree of sympathetic neuromodulation can have serious consequences on homeostatic variables such as heart rate, bl...
Article
Full-text available
Neuronal networks generating rhythmic activity as an emergent property are common throughout the nervous system. Some are responsible for rhythmic behaviours, as is the case for the spinal cord locomotor networks; however, for others the function is more subtle and usually involves information processing and/or transfer. An example of the latter is...
Article
Neuronal gap junctions are receiving increasing attention as a physiological means of intercellular communication, yet our understanding of them is poorly developed when compared to synaptic communication. Using microfluorimetry, we demonstrate that differentiation of SN56 cells (hybridoma cells derived from murine septal neurones) leads to the spo...
Article
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Development of the patch clamp technique by the Nobel Prize winners Bert Sakmann and Erwin Neher led to huge advances in ion channel research. Their work laid the foundations and revolutionized electrophysiological studies of cells and ion channels. These ion channels underlie many basic cellular physiological processes and, therefore, are key ther...
Article
The intermedius nucleus of the medulla (InM) is a small perihypoglossal brainstem nucleus, which receives afferent information from the neck musculature and also descending inputs from the vestibular nuclei, the gustatory portion of the nucleus of the solitary tract (NTS) and cortical areas involved in movements of the tongue. The InM sends monosyn...
Article
The application of antibodies to living cells has the potential to modulate the function of specific proteins by virtue of their high specificity. This specificity has proven effective in determining the involvement of many proteins in neuronal function where specific agonists and antagonists do not exist, e.g. ion channel subunits. We discuss a wa...
Article
Full-text available
The sympathetic tone is primarily defined by the level of activity of the sympathetic preganglionic neurons. We report a novel inhibitory influence on sympathetic activity, that of tonic GABAergic inhibition which could have a profound global effect on sympathetic outflow. Recording from identified SPNs in the intermediolateral cell column (IML) of...
Article
We sought to determine whether histamine has effects on single neurons in the dorsal vagal complex of the brainstem since previous studies have suggested a role for histamine receptors in this region. Using whole-cell patch clamp recordings from neurons within the nucleus of the tractus solitarius (NTS) and the dorsal vagal nucleus (DVN), histamine...
Article
Voltage-gated potassium (Kv) channels are essential components of neuronal excitability. The Kv3.4 channel protein is widely distributed throughout the central nervous system (CNS), where it can form heteromeric or homomeric Kv3 channels. Electrophysiological studies reported here highlight a functional role for this channel protein within neurons...
Article
Full-text available
Microinjection of opioid receptor agonists into the nucleus tractus solitarius (NTS) has differential effects on cardiovascular, respiratory, and gastrointestinal responses. This can be achieved either by presynaptic modulation of inputs onto neurons or by postsynaptic activation of receptors on neurons in specific regions. Therefore we sought to d...
Article
Full-text available
Sensory afferent signals from neck muscles have been postulated to influence central cardiorespiratory control as components of postural reflexes, but neuronal pathways for this action have not been identified. The intermedius nucleus of the medulla (InM) is a target of neck muscle spindle afferents and is ideally located to influence such reflexes...
Article
Full-text available
The role of interneurones in the control of sympathetic activity has been somewhat of a mystery since, for many years, it was difficult to target these cells for study. Recently scientists have started to unravel the action potential properties of these neurones, where they receive their inputs from and where they project to. This review looks at t...
Article
The application of antibodies to living neurones has the potential to modulate function of specific proteins by virtue of their high specificity. This specificity has proven effective in determining the involvement of many proteins in neuronal function where specific agonists and antagonists do not exist, e.g. ion channel subunits. We discuss studi...
Article
Full-text available
Homeostatic maintenance of widespread functions is critically dependent on the activity of the sympathetic nervous system. This activity is generated by the CNS acting on the sole output cells in the spinal cord, sympathetic preganglionic neurons (SPNs). SPNs are subject to control from both supraspinal and spinal inputs that exert effects through...
Article
Full-text available
The voltage-gated potassium channel subunit Kv3.1 confers fast firing characteristics to neurones. Kv3.1b subunit immunoreactivity (Kv3.1b-IR) was widespread throughout the medulla oblongata, with labelled neurones in the gracile, cuneate and spinal trigeminal nuclei. In the nucleus of the solitary tract (NTS), Kv3.1b-IR neurones were predominantly...
Article
Full-text available
Fast inhibition in the nervous system is commonly mediated by GABA(A) receptors comprised of 2alpha/2beta/1gamma subunits. In contrast, GABA(C) receptors containing only rho subunits (rho1-rho3) have been predominantly detected in the retina. However, here using reverse transcription-PCR and in situ hybridization we show that mRNA encoding the rho1...
Article
Full-text available
Activation of adenosine A2A receptors (A2ARs) in the CNS produces a variety of neuromodulatory actions dependent on the region and preparation examined. In autonomic regions of the spinal cord, A1R activation decreases excitatory synaptic transmission, but the effects of A2AR stimulation are unknown. We sought to determine the location and function...
Article
Voltage-gated K+ channels (Kv) are divided into eight subfamilies (Kv1-8) and play a major role in determining the excitability of neurones. Members of the Kv3 subfamily are highly abundant in the CNS, with each Kv3 gene (Kv3.1-Kv3.4) exhibiting a unique pattern of expression, although single neurones can express more than one subtype. Of the Kv3 s...
Article
Interneurones in the spinal cord are likely to play an important role in the generation of activity in sympathetic preganglionic neurones (SPNs) and, therefore, sympathetic outflow. Although the properties of these interneurones have rarely been studied directly, here we show that neurones antecedent to SPNs contain the voltage-gated potassium chan...
Article
G-protein-coupled receptors (GPCRs) are considered the most diverse and ubiquitous family of integral membrane proteins and play a pivotal role in many cellular signalling pathways. In any single neuron, GPCRs can be located both pre- and postsynaptically or exclusively in either domain. Generally, activation of the same receptor at its different l...