Jim Deuchars

• BSc, PhD
• Professor (Full) at University of Leeds

Transcutaneous auricular nerve stimulation (tANS) applied to specific parts of the external ear has positive health effects in both healthy volunteers and patient groups. However, due to differences between studies in ear stimulation sites and extent of effect on autonomic variables, it is challenging to determine what part of the external ear is t...

The action potential and its all-or-none nature is fundamental to neural communication. Canonically the action potential is initiated once voltage-activated Na⁺ channels are activated, and their rapid kinetics of activation and inactivation give rise to the action potential’s all-or-none nature. Here we show that cerebrospinal fluid contacting neur...

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...

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...

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...

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...

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...

The expression of long non-coding RNAs is highly enriched in the human nervous system. However, the function of neuronal lncRNAs in the cytoplasm and their potential translation remains poorly understood. Here we performed Poly-Ribo-Seq to understand the interaction of lncRNAs with the translation machinery and the functional consequences during ne...

Objectives: The dorsal vagal complex (DVC) senses insulin and controls glucose homeostasis, feeding behaviour and body weight. Three-days of high-fat diet (HFD) in rats are sufficient to induce insulin resistance in the DVC and impair its ability to regulate feeding behaviour. HFD-feeding is associated with increased dynamin-related protein 1 (Drp...

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...

LncRNAs are less conserved, yet more tissue and developmental-stage specific than mRNAs and are particularly enriched in the nervous system of Drosophila melanogaster , mouse and human. The function of cytoplasmic lncRNAs and their potential translation remains poorly understood. Here we performed Poly-Ribo-Seq to understand the interaction of lncR...

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...

The dorsal vagal complex (DVC) senses changes in insulin levels and controls glucose homeostasis, feeding behaviour and body weight. Three days of high-fat diet (HFD) in rats is sufficient to induce insulin resistance in the DVC and impair its ability to regulate feeding behaviour. HFD-feeding is associated with increased mitochondrial fission in t...

A significant unmet need exists for the delivery of biologic drugs such as polypeptides or nucleic acids, to the central nervous system (CNS) for the treatment and understanding of neurodegenerative diseases. Naturally occurring toxoids have been considered as tools to meet this need. However, due to the complexity of tethering macromolecular drugs...

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...

Background: There is no definitive method of accurately diagnosing appendicitis before surgery. We evaluated the feasibility of collecting breath samples in children with abdominal pain and gathered preliminary data on the accuracy of breath tests. Methods: We conducted a prospective pilot study at a large tertiary referral paediatric hospital i...

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...

Music has been associated with alterations in autonomic function. Tempo, the speed of music, is one of many musical parameters that may drive autonomic modulation. However, direct measures of sympathetic nervous system activity and control groups and/or control stimuli do not feature in prior work. This article therefore reports an investigation in...

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...

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...

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...

Background Despite positive outcomes of transcutaneous vagus nerve stimulation (tVNS) via the auricular branch of the vagus nerve (ABVN), the mechanisms underlying these outcomes remain unclear. Additionally, previous studies have not been controlled the possible placebo effects of tVNS. Objective To test the hypothesis that tVNS acutely improves...

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...

The integration of somatosensory information is generally assumed to be a function of the central nervous system (CNS). Here we describe fully functional GABAergic communication within rodent peripheral sensory ganglia and show that it can modulate transmission of pain-related signals from the peripheral sensory nerves to the CNS. We found that sen...

Background Despite positive outcomes across a variety of disease states, invasive vagus nerve stimulation (VNS) has been associated with adverse side‐effects. Given this, non‐invasive VNS (tVNS) via the auricular branch of the vagus nerve (ABVN) has been proposed as an alternative approach. However, the mechanisms underlying these positive outcomes...

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...

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...

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...

Increasing age can alter the autonomic balance towards elevated sympathetic nerve activity and reduced parasympathetic activity. This age‐associated autonomic dysfunction is linked with chronic conditions such as cardiovascular disease and impaired mental health. Vagus nerve stimulation (VNS), using a surgically‐implanted bipolar electrode in the n...

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...

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...

Neurogenesis occurs throughout life in the subgranular zone of the dentate gyrus, and postnatal-born granule cells migrate into the granule cell layer and extend axons to their target areas. The α7⁎nicotinic receptor has been implicated in neuronal maturation during development of the brain and is abundant in interneurons of the hippocampal formati...

Heart failure (HF) is a serious problem within the developed world. β-adrenergic receptors (βAR) undergo dramatic remodelling in HF characterised by a reduction in β1AR expression and decreased sympathetic responsiveness. Less is known about the consequences of HF for the β2AR, which is normally located predominantly within small invaginations of t...

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...

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...

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...

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...

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...

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...

New findings What is the topic for this review? Vagus nerve stimulation is now used as a treatment for refractory epilepsy and depression, despite an incomplete understanding of the mechanisms involved. What advances does it highlight? We review current and potential therapeutic applications of vagus nerve stimulation and some potential mechanisms...

Connexin (Cx) proteins localized to neuronal and glial syncytia provide the ultrastructural components for intercellular communication via gap junctions. In this study, a Cx45 reporter mouse model in which the Cx45 coding sequence is substituted for enhanced green fluorescent protein (eGFP) was used to characterize Cx45 expressing neurones within a...

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...

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...

As is known, hippocampal pyramidal neurons are highly sensitive to cerebral ischemia, while some other hippocampal neurons (particularly, interneurons) survive and keep their functional activity under these conditions for a longer time. We studied interneurons of the rat hippocampal organotypic culture after 30-min-long oxygen-glucose deprivation (...

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...

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...

Kv3 voltage-gated K(+) channels are important in shaping neuronal excitability and are abundant in the CNS, with each Kv3 gene exhibiting a unique expression pattern. Mice lacking the gene encoding for the Kv3.3 subunit exhibit motor deficits. Furthermore, mutations in this gene have been linked to the human disease spinocerebellar ataxia 13, assoc...

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...

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...

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...

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...

The level of electrotonic coupling in the inferior olive is extremely high, but its functional role in cerebellar motor control remains elusive. Here, we subjected mice that lack olivary coupling to paradigms that require learning-dependent timing. Cx36-deficient mice showed impaired timing of both locomotion and eye-blink responses that were condi...

Connexin36 (Cx36) is the main connexin isoform expressed in neurons of the central nervous system (CNS) and in pancreatic beta-cells, i.e. two types of excitable cells that share - in spite of their different origins - a number of common features. Previous studies on Cx36 deficient mice have documented that loss of Cx36 resulted in phenotypic abnor...

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...

Electrical synapses, particularly gap junctions composed of connexin (Cx) 36, have been suggested to synchronize neuronal network oscillations. Recently, we generated Cx30.2-deficient mice which express beta-galactosidase under control of Cx30.2 gene regulatory elements. In the central nervous system beta-galactosidase activity representing Cx30.2...

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...

Background: retraction of nerve terminals is a characteristic feature of development, injury and insult and may herald many neurodegenerative diseases. Although morphological events have been well characterized, we know relatively little about the nature of the underlying cellular machinery. Evidence suggests a strong local component in determining...

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...

Retraction of nerve terminals is a characteristic feature of development, injury and insult and may herald many neurodegenerative diseases. Although morphological events have been well characterized, we know relatively little about the nature of the underlying cellular machinery. Evidence suggests a strong local component in determining which neuro...

We previously identified an action of nitric oxide (NO) within the nucleus tractus solitarii (NTS) that attenuates the cardiac component of the baroreceptor reflex. In the present study we have tested the hypothesis that angiotensin II (AngII), acting on angiotensin type 1 receptors (AT1R), can release NO within the NTS and that its actions are med...

Hyperpolarization-activated cyclic nucleotide-gated (HCN) non-selective cation channels in neurons carry currents proposed to perform diverse functions, including the hyperpolarization activated Ih current. The 4 HCN subunits have unique but overlapping patterns of expression in the CNS. Here, we examined the distribution of HCN1 channel subunits i...

P2X receptors in the nervous system are involved in both neuronal and glial functions. Pharmacological tools to differentiate the seven P2X subunits are limited, hence localisation studies have examined their distribution. Such studies have provided conflicting data on the localisation of the P2X1 receptor subunit in the CNS. We therefore tested fo...

Differentiation of pluripotent embryonic stem (ES) cells through multipotent neural stem (NS) cells into differentiated neurons is accompanied by wholesale changes in transcriptional programs. One factor that is present at all three stages and a key to neuronal differentiation is the RE1-silencing transcription factor (REST/NRSF). Here, we have use...

Voltage gated K+ channels (Kv) are a diverse group of channels important in determining neuronal excitability. The Kv superfamily is divided into 12 subfamilies (Kv1-12) and members of the Kv3 subfamily are highly abundant in the CNS, with each Kv3 gene (Kv3.1-Kv3.4) exhibiting a unique expression pattern. Since the localisation of Kv subunits is i...

ENT1 is an equilibrative nucleoside transporter that enables trans-membrane bi-directional diffusion of biologically active purines such as adenosine. In spinal cord dorsal horn and in sensory afferent neurons, adenosine acts as a neuromodulator with complex pro- and anti-nociceptive actions. Although uptake and release mechanisms for adenosine are...

Extracellular adenosine is present at the mammalian neuromuscular junction (NMJ) by virtue of its release from activated nerve terminals and muscle fibers, and as a metabolite of adenosine tri-phosphate, which is coreleased with acetylcholine. Two activities for adenosine have been described: an inhibitory effect presumed to be modulated by the A1...

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...

Adenosine triphosphate is released into the synaptic cleft of the neuromuscular junction during normal synaptic transmission, and in much greater quantities following injury and ischaemia. There is much data to suggest roles for presynaptic P2 receptors but little to demonstrate which specific receptor subunits are present. Here we show P2X7 recept...

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...

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...

The central projections and neurochemistry of vagal afferent neurones supplying the heart in the rat were investigated by injecting cholera toxin B-subunit into the pericardium. Transganglionically transported cholera toxin B-subunit was visualized in the medulla oblongata in axons and varicosities that were predominantly aggregated in the dorsomed...

There is a wealth of information supporting the presence of nitric oxide synthase (NOS) isoforms in the nucleus tractus solitarii (NTS). This chapter summarizes the state-of-play regarding nitric oxide (NO) signalling and modulation of cardiovascular function within the NTS. We begin with a brief and general account of NO signalling within the cent...

Voltage-gated potassium (Kv) channels are critical to regulation of neurotransmitter release throughout the nervous system but the roles and identity of the subtypes involved remain unclear. Here we show that Kv3 channels regulate transmitter release at the mouse neuromuscular junction (NMJ). Light- and electron-microscopic immunohistochemistry rev...

P2X receptors are ligand gated ion channels activated by extracellular ATP. There are seven P2X subunits, P2X(1-7), and all are expressed in the CNS. The P2X(4) receptor subunit (P2X(4)R) is likely to be important in the CNS as it has been reported to be expressed throughout the brain and spinal cord. However, P2X(4)Rs have been identified as restr...

Dual intracellular recordings in the CA1 region of adult rat hippocampal slices and biocytin filling of synaptically connected cells were used to study the excitatory postsynaptic potentials (EPSPs) elicited in basket ( n = 7 ) and bistratified interneurones ( n = 7 ) by action potentials activated in simultaneously recorded pyramidal cells. Intern...

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...

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...

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...

Presynaptic P2X(7) receptors are thought to play a role in the modulation of transmitter release and have been localised to terminals with the location and morphology typical of excitatory boutons. To test the hypothesis that this receptor is preferentially associated with excitatory terminals we combined immunohistochemistry for the P2X(7) recepto...

Development of the nervous system is accompanied by expansion and differentiation of the neuronal progenitors within the embryonic neuroepithelium. Although the role of growth factors in this process is well documented, there is increasing evidence for a role of neurotransmitters. Acetylcholine is known to exert many actions on developing neural ce...

Development of the nervous system is accompanied by expansion and differentiation of the neuronal progenitors within the embryonic neuroepithelium. Although the role of growth factors in this process is well documented, there is increasing evidence for a role of neurotransmitters. Acetylcholine is known to exert many actions on developing neural ce...

ATP is involved in central respiratory control and may mediate changes in the activity of medullary respiratory neurones during hypercapnia, thus playing an important role in central chemoreception. The main objective of this study was to explore further the role of ATP-mediated signalling in respiratory control and central chemoreception by charac...

The angiotensin II type 1 receptor (AT1R) in the central nervous system (CNS) plays a pivotal role in determining blood pressure. However, the relationship of the receptor to neurones in the spinal cord which are the final CNS contribution to sympathetic outflow is unknown. Here we first use RT-PCR to show that AT1A, AT1B and AT2 receptors are expr...

GABA(B) receptor subunits are widely expressed on neurons throughout the CNS, at both pre- and postsynaptic sites, where they mediate the late, slow component of the inhibitory response to the major inhibitory neurotransmitter GABA. The existence of functional GABA(B) receptors on nonneuronal cells has been reported previously, although the molecul...