Single Nerve Fibers Research Articles

CHRONIC MENTAL STRESS IS A CAUSE OF ESSENTIAL HYPERTENSION: PRESENCE OF BIOLOGICAL MARKERS OF STRESS

1. In searching for biological evidence that essential hypertension is caused by chronic mental stress, a disputed proposition, parallels are noted with panic disorder, which provides an explicit clinical model of recurring stress responses. 2. There is clinical comorbidity; panic disorder prevalence is increased threefold in essential hypertension. Plasma cortisol is elevated in both. 3. In panic disorder and essential hypertension, but not in health, single sympathetic nerve fibres commonly fire repeatedly within an individual cardiac cycle; this appears to be a signature of stress exposure. For both conditions, adrenaline cotransmission is present in sympathetic nerves. 4. Tissue nerve growth factor is increased in both (nerve growth factor is a stress reactant). There is induction of the adrenaline synthesizing enzyme, phenylethanolamine-N-methyltransferase, in sympathetic nerves, an explicit indicator of mental stress exposure. 5. The question of whether chronic mental stress causes high blood pressure, still hotly debated, has been reviewed by an Australian Government body, the Specialist Medical Review Council. Despite the challenging medicolegal implications, the Council determined that stress is one proven cause of hypertension, this ruling being published in the 27 March 2002 Australian Government Gazette. This judgement was reached after consideration of the epidemiological evidence, but in particular after review of the specific elements of the neural pathophysiology of essential hypertension, described above.

The Single Nerve Fiber Action Potential and the Filter Bank—A Modeling Approach

Single fiber action potentials (SFAPs) from peripheral nerves, such as recorded with cuff electrodes, can be modelled as the convolution of a source current and a weight function that describes the recording electrodes and the surrounding medium. It is shown that for cuff electrodes, the weight function is linearly scaled with the action potential (AP) velocity and that it is, therefore, possible to implement a model of the recorded SFAPs based on a wavelet multiresolution technique (filterbank), where the wavelet scale is proportional to the AP velocity. The model resulted in single fiber action potentials matching the results from other models with a goodness of fit exceeding 0.99. This formulation of the SFAP may serve as a basis for model-based wavelet analysis and for advanced cuff design.

A computer model of medial efferent suppression in the mammalian auditory system

Stimulation of the olivocochlear bundle reduces basilar membrane displacement, driven auditory nerve activity, and compound action potential (CAP) response to acoustic stimulation. These effects were simulated using a computer model of the auditory periphery. The model simulates the medial efferent activity by attenuating the basilar membrane response. The model was evaluated against three animal studies reporting measurements at three levels of the auditory system; basilar membrane, single auditory nerve fibers and whole auditory nerve CAP. The CAP data included conditions where tones were masked by noise and "unmasked" by stimulation of the olivocochlear bundle. The model was able to simulate the data both qualitatively and quantitatively. As a consequence, it may be a suitable platform for studying the contribution of the efferent system to auditory processing of more complex auditory sounds in distracting backgrounds.

THE BRAIN ON ITSELF

The Nobel Prize in Physiology or Medicine has been given in recognition of work in the neurosciences a number of times. Laureates have been awarded for work on both fundamental and more complex nervous system functions. This review is restricted to contributions by 20th century laureates to the understanding of fundamental nervous system function on the cellular level. In 1906, Camillo Golgi and Ramón y Cajal were awarded for their work on the microscopic structure of the nervous system. Their achievement and those of others within this field, coupled with technological progress, gradually allowed more complex physiological studies. In 1932, the prize was awarded to Charles Sherrington and Edgar Adrian for their discoveries of how neurons function. They were followed in 1944 by Herbert Gasser and Joseph Erlanger who uncovered the highly differentiated functions of single nerve fibers. Alan Hodgkin and Andrew Huxley were awarded for the detection of the ionic mechanism of the action potential and its mathematical explanation in 1963. In 1991, Erwin Neher and Bernd Sakmann were awarded for their work on single ion channels. Although the scientists who proved the hypothesis (Fridjof Nansen, Wilhelm His, and August Forel) were never awarded by the Nobel Committee, their studies gave rise to one of the most fundamental questions in 20th century neuroscience: How is information carried from one neuron to another or to an effector cell? This was first solved in the vegetative nervous system, and, in 1936, Henry Dale and Otto Loewi received the prize for their discoveries relating to chemical transmission of nerve impulses. In 1963, John Eccles was awarded the prize for his work on the physiology of synapses. In 1970, Bernhard Katz received the Nobel Prize for the discovery of quantal release. Katz shared the prize with Julius Axelrod and Ulf von Euler, who were central in finding that transmitters are stored in presynaptic vesicles and that the effect in many synapses is terminated by reuptake. This review does not include 21st century laureates, although the prize has already been given to neuroscientists twice this century; Arvid Carlsson, Paul Greengard, and Eric Kandel received the award in 2000 for their discoveries related to signal transduction, and Richard Axel and Linda Buck received the award in 2004 for their work in the field of odorant receptors and the organization of the olfactory system.

Responses evoked in single sympathetic nerve fibres of the rat tail artery by systemic hypoxia are dependent on core temperature

No direct evidence exists of the changes evoked by systemic hypoxia in sympathetic nerves to the rat cutaneous circulation, and of the concomitant changes in cutaneous blood flow. Here we investigated responses evoked by two levels of systemic hypoxia (12% and 8% inspired O(2)) in single sympathetic units supplying tail caudal ventral artery (CVA) in spontaneously breathing anaesthetized rats, whilst simultaneously recording tail blood flow and vascular resistance (TVR) from the CVA, under conditions of modest hypothermia and hyperthermia. During modest hypothermia and normoxia, TVR was high and CVA unit activity was present, with marked respiratory modulation and a rhythmictiy (T-rhythm) that was often independent of respiration. Hypoxia evoked a graded fall in TVR indicating vasodilatation, but there were no consistent changes in CVA unit firing rate or T-rhythm frequency, although respiratory modulation increased. By contrast, during hyperthermia, TVR was low and CVA unit activity was absent. Systemic hypoxia evoked graded increases in TVR, indicating vasoconstriction, and in 8% O(2) there was recommencement of firing in some CVA units, at low discharge rate, with respiratory modulation but no T-rhythm. These results indicate that the changes evoked by systemic hypoxia in TVR and sympathetic nerve activity to CVA are dependent on core temperature. During modest hypothermia, hypoxia-induced cutaneous vasodilatation in the tail is independent of sympathetic activity, whereas during hyperthermia, when sympathetic activity is 'switched off', severe hypoxia initiates respiratory-related low level activity, causing cutaneous vasoconstriction.

Innervation of the triangular fibrocartilage complex of the human wrist: Quantitative immunohistochemical study

The distribution of neural elements in the triangular fibrocartilage complex (TFCC) of the human wrists was studied via immunohistochemical staining of protein gene product (PGP) 9.5 and calcitonin gene-related peptide (CGRP). Articular branches projecting to the TFCC arose from the dorsal branch of the ulnar nerve in all wrists examined. The TFCC is subdivided into the following six regions: the articular disc proper (ADP), meniscus homolog (MH), radio-ulnar ligament (RUL), loose part of ulnar collateral ligament (lUCL), dense part of ulnar collateral ligament (dUCL), and internal portion (IP). The IP consists of a mixture of dense and loose connective tissues enclosed by the ADP, MH, RUL, and UCL, and resides deep in the prestyloid recess, which is a pit in the MH. The densities of PGP 9.5-positive neural elements, including free nerve endings, single nerve fibers, nerve fascicles, and perivascular neural nets, were significantly higher in the IP than in other regions. Some of the neural elements except for the perivascular neural nets were positive for CGRP. The high density of neural elements in the IP suggests that sensory nerves projecting to the TFCC enter into the IP and from there distribute to adjacent regions such as the MH and RUL. Free nerve endings are responsible for pain transmission. The high density of free nerve endings in the IP suggests that the IP is a source of ulnar side wrist pain.

Impulse Activity in Corneal Sensory Nerve Fibers after Photorefractive Keratectomy

To evaluate the changes in spontaneous and stimulus-evoked nerve impulse activity of corneal polymodal and mechanonociceptor sensory fibers of the cornea after photorefractive keratectomy (PRK). A central corneal ablation 6 mm in diameter and 70 microm in depth was performed with an excimer laser in both eyes of three anesthetized cats, after removal of the corneal epithelium. Single nerve fiber activity was recorded in these animals 12 to 48 hours after surgery. Activity in corneal nerve fibers with receptive fields (RFs) within and/or close to the wound, as well as with RFs far from the lesioned area, was studied. Incidence and frequency of spontaneous discharges and nerve impulse firing responses to mechanical (Cochet-Bonet esthesiometer) and chemical (CO(2) gas pulses) stimuli were studied. The incidence of nociceptor fibers exhibiting ongoing activity (15/35 vs. 1/9) and the frequency of their spontaneous firing (0.25 +/- 0.09 impulses [imp]/s versus 0.08 +/- 0.08 imp/s) was higher in fibers with RFs within and/or bordering the wounded area than in those with RFs far away from the wound. Mechanical responsiveness of fibers with RFs within or nearby the ablated area was often reduced. In these fibers, CO(2) pulses evoked a lower-frequency impulse discharge (0.9 +/- 0.2 imp/s inside, 2.3 +/- 0.7 imp/s outside the wound). CO(2)-evoked discharges recorded from fibers innervating the intact wound border were similar to those recorded in corneal fibers of intact cats. The spontaneous impulse activity and the abnormal responsiveness shown by a part of the corneal nerve fibers innervating the injured cornea are presumably the neurophysiological substrate of the pain sensations experienced by human patients hours after PRK surgery.

Characteristics of mechanoreceptive units in the rat urinary bladder

Sensory information from the urinary bladder is carried out mainly by the pelvic nerve and the hypogastric nerve. However little is known about the response properties of mechanoreceptors innervated in the urinary bladder. Especially peripheral receptive field properties innervated by single pelvic nerve fiber and threshold of mechanoreceptors on the bladder surface are not yet quantitatively studied. Therefore, in this study, we systematically investigated characteristics of pelvic mechanoreceptors in rats.

AFM combines functional and morphological analysis of peripheral myelinated and demyelinated nerve fibers

Demyelination of the myelinated peripheral or central axon is a common pathophysiological step in the clinical manifestation of several human diseases of the peripheral and the central nervous system such as the majority of Charcot-Marie-Tooth syndromes and multiple sclerosis, respectively. The structural degradation of the axon insulating myelin sheath has profound consequences for ionic conduction and nerve function in general, but also affects the micromechanical properties of the nerve fiber. We have for the first time investigated mechanical properties of rehydrated, isolated peripheral nerve fibers from mouse using atomic force microscopy (AFM). We have generated quantitative maps of elastic modulus along myelinated and demyelinated axons, together with quantitative maps of axon topography. This study shows that AFM can combine functional and morphological analysis of neurological tissue at the level of single nerve fibers.

Cholinergic innervation of the pancreas in the sheep

Antibodies raised against vesicular acetylcholine transporter (VAChT) were applied to study the cholinergic innervation pattern of the pancreas of the sheep. To determine whether the cholinergic pancreatic neuronal elements contain tyrosine hydroxylase (TH), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP) or substance P (SP) double immunocytochemistry was used. A moderate number of VAChT-immunoreactive (IR) nerve terminals were distributed between the acini, whereas only single cholinergic nerve fibres innervated the interlobular connective tissue. VAChT-positive nerve fibres supplying the endocrine pancreas were found only occasionally. The pancreatic blood vessels and ducts system were devoid of VAChT-containing nerve endings. All intrapancreatic neurons studied showed immunoreactivity to VAChT, but intrapancreatic ganglia were not innervated with cholinergic nerve fibres. The colocalization of VAChT and TH or VAChT and SP was detected in distinct populations of nerve fibres localized amongst the acini, but not within the islet nor in the connective tissue. Single VAChT-IR nerve terminals co-expressing NPY were distributed around the acini, islets as well as in the connective tissue septa. A moderate number of VAChT-IR/VIP-IR nerve endings were located in the exocrine pancreas, whereas the islets and connective tissue were innervated with VAChT/VIP-containing nerve fibres only occasionally. In the vast majority of VAChT-positive intrapancreatic perikarya the presence of TH was additionally found. A moderate number of VAChT-IR intrapancreatic perikarya co-expressed NPY, SP or VIP. The results of the present study demonstrate species-dependent cholinergic innervation pattern of the pancreas of the sheep. The co-localization of VAChT with the neuropeptides suggests the existence of functional interactions influencing the ovine pancreas (mainly exocrine) activity.

Post‐spike excitability indicates changes in membrane potential of isolated C‐fibers

Recording of action potentials from single unmyelinated nerve fibers by microneurography is an important tool to investigate peripheral neural functions in human neuropathies. However, the interpretation of microneurography recordings can be difficult because axonal membrane potential is not revealed by this method. We tested the hypothesis that the recovery cycle of excitability after a single action potential is correlated with changes in the axonal membrane potential. To this end, we used the threshold tracking technique to study how different chemical mediators, with known effects on the membrane potential, influence the post-spike superexcitability of C-fiber compound action potentials in isolated rat sural and vagus nerves. We found that: (1) some chemical mediators (e.g., adenosine 5'-triphosphate) produce a reduction or loss of superexcitability together with increased axonal excitability, indicating membrane depolarization; (2) blockade of axonal hyperpolarization-activated (Ih) currents produces an enhancement of superexcitability together with a decreased excitability, indicating membrane hyperpolarization; and (3) application of calcium produces an increase in membrane threshold without an alteration in superexcitability, indicating a non-specific increase in surface charge and a change in the voltage-dependent activation of sodium channels. In addition, we demonstrated that membrane depolarization and hyperpolarization induce opposite post-spike latency shifts (changes in supernormality) in rat and human nerve segments. Thus, recordings of post-spike excitability and shifts in latency are sensitive techniques for detection of various types of neuromodulation, which are correlated with changes in membrane potential of unmyelinated peripheral axons and may help to understand observations obtained by microneurography in peripheral human neuropathies.

Estrogen Amplifies Pain Responses to Uterine Cervical Distension in Rats by Altering Transient Receptor Potential-1 Function

Estrogen sensitizes responses to painful stimuli, but its contribution to acute and chronic pain from the uterine cervix is unknown. Previous studies link the excitatory transient receptor potiential-1 channel (TRPV-1) to sensitization in viscera, and show that estrogen increases TRPV-1 expression in afferents from the uterine cervix. Here, we tested whether estrogen enhanced responses to uterine cervical distension in rats, and whether this involved TRPV-1 channels. Ovariectomized rats, with or without estrogen replacement, were anesthetized and hypogastric nerve and abdominal muscle contraction reflex responses to graded uterine cervical distension were recorded. Single unit hypogastric nerve fiber firing was measured before and after acute treatment with the TRPV-1 antagonist, capsaizepine, or vehicle. Abdominal muscle contraction reflex responses to uterine cervical distension were enhanced in estrogen-treated rats. Hypogastric afferent responses to cervical distension were reduced by capsaizepine in estrogen-treated animals, but were unaffected in ovariectomized animals without estrogen replacement. These data suggest that the TRPV-1 channel is unimportant for normal mechanosensation in the cervix in the absence of estrogen, since capsaizepine failed to reduce responses to uterine cervical distension in rats without estrogen replacement. In contrast, TRPV-1 function is important for estrogen-induced sensitization. These data raise the possibility that acute and chronic pain coming from the cervix, such as labor or cancer, may be enhanced by estrogen and might be reduced by antagonists of TRPV-1.

The 1932 and 1944 Nobel Prizes in Physiology or Medicine: Rewards for Ground-Breaking Studies in Neurophysiology

In 1932 Sherrington and Adrian were awarded the Nobel Prize in Physiology or Medicine “for their discoveries regarding the functions of neurons” and in 1944 Erlanger and Gasser were awarded the same prize “for their discoveries relating to the highly differentiated functions of single nerve fibres.” Sherrington made important discoveries on the reflex functions of the spinal cord, formulated the concept of the “synapse,” defined the principle of the “final common path,” studied “reciprocal innervation” and showed that central inhibition was an active phenomenon. He distinguished three types of receptors: extero-, intero-, and proprioceptive, studied the proprioceptive reflexes in the decerebrate animal and mapped their pathways in the spinal cord. Adrian made fundamental discoveries on the function of single nerve fibers, developed new techniques for the amplification of the weak signals and discovered that increased stimulation resulted in increased frequency of the impulses, the amplitude being unaffected. Erlanger and Gasser introduced the cathode-ray oscillograph and demonstrated the existence of three main groups of nerve fibers, A, B, and C, the conduction velocities of which were in approximately linear relationship with the fiber diameter, the A-fibers being the fastest and thickest and the C-fibers the slowest and having the finest diameter. Together the contributions by the four Laureates paved the way to modern neurophysiology.

Development of a regeneration-type neural interface: A microtube guide for axon growth of neuronal cells fabricated using focused-ion-beam chemical vapor deposition

The authors’ goal is to develop a neural interface system that enables connection of the human nervous system with external devices and allows transmission of information in both directions. One way to connect interface to neurons is a regenerative electrode, where the electrode is placed between the two cut ends of a nerve. The cut nerve fiber can regenerate through channels in a metallic electrode on a two-dimensional (2D) plane of the regenerative electrode. As this type of electrode enables both the recording of signals from a single nerve fiber and the stimulation of a single nerve fiber, attempts have been made to develop it using traditional 2D microfabrication techniques. However, it is difficult to process such electrodes with these 2D microfabrication techniques, particularly the high-density integrated structure of the electrical wiring. The authors previously designed a neural interface system—a type of regenerative electrode consisting of an electrode segment and many carbon microtubes for guiding the regenerating axons of the neuronal cells—that can be made through three-dimensional processing. In the current study, the authors have fabricated a prototype of the guiding segment of the electrode (which was previously reported) and evaluated the biocompatibility of diamondlike carbon (DLC) made by focused-ion-beam chemical vapor deposition (FIB-CVD) and carbon microtubes in vitro. The microtubes were fabricated using FIB-CVD. DLC was deposited with a scanning 30keV Ga+ ion beam in an atmosphere containing phenanthrene (C14H10). The scanning patterns were determined by a computer-aided-design system before the fabrication. The beam was scanned over a Au-coated glass capillary or polycarbonate membrane to deposit DLC and form the carbon microtubes. For observation of the axon growth through the microtubes, the authors fabricated bifurcated carbon microtubes with an inner diameter of 3–6μm on the glass capillary and straight microtubes on the polycarbonate membrane. The fabricated microtubes were immersed in a culture medium containing nerve growth factor and PC12 cells were cultured inside the capillary and on the membrane to evaluate whether they could extend axons through the microtubes. Here, the authors show that cultured rat phaeochromocytomas adhered to and survived for days on a DLC surface while preserving their morphology provided that the adhesion molecule poly-D-lysine was used as an organic substance to anchor the cells to the DLC surface. As a result, cells spread and neurites projected on the DLC area, suggesting that the DLC had little cytotoxic effect.

Otoferlin, Defective in a Human Deafness Form, Is Essential for Exocytosis at the Auditory Ribbon Synapse

The auditory inner hair cell (IHC) ribbon synapse operates with an exceptional temporal precision and maintains a high level of neurotransmitter release. However, the molecular mechanisms underlying IHC synaptic exocytosis are largely unknown. We studied otoferlin, a predicted C2-domain transmembrane protein, which is defective in a recessive form of human deafness. We show that otoferlin expression in the hair cells correlates with afferent synaptogenesis and find that otoferlin localizes to ribbon-associated synaptic vesicles. Otoferlin binds Ca(2+) and displays Ca(2+)-dependent interactions with the SNARE proteins syntaxin1 and SNAP25. Otoferlin deficient mice (Otof(-/-)) are profoundly deaf. Exocytosis in Otof(-/-) IHCs is almost completely abolished, despite normal ribbon synapse morphogenesis and Ca(2+) current. Thus, otoferlin is essential for a late step of synaptic vesicle exocytosis and may act as the major Ca(2+) sensor triggering membrane fusion at the IHC ribbon synapse.

Reflexes from the lungs and airways: historical perspective

Historical aspects of respiratory reflexes from the lungs and airways are reviewed, up until about 10 yr ago. For most of the 19th century, the possible reflex inputs into the "respiratory center," the position of which had been identified, were very speculative. There was little concept of reflex control of the pattern of breathing. Then, in 1868, Breuer published his paper on "The self-steering of respiration via the Nervus Vagus." For the first time this established the role of vagal inflation and deflation reflexes in determining the pattern of breathing. Head later extended Breuer's work, and Kratschmer laid a similar basis for reflexes from the nose and larynx. Then, 50-60 yr later, the development of the thermionic valve and the oscilloscope allowed recording action potentials from single nerve fibers in the vagus. In 1933, Adrian showed that slowly adapting pulmonary stretch receptors were responsible for the inflation reflex. Later, Knowlton and Larrabee described rapidly adapting receptors and showed that they mediated deep augmented breaths and the deflation reflex. Still later, it was established that rapidly adapting receptors were, at least in part, responsible for cough. In 1954, Paintal began his study of C-fiber receptors (J receptors), work greatly extended by the Coleridges. Since approximately 10 yr ago, when the field of this review stops, there has been an explosion of research on lung and airway receptors, many aspects of which are dealt with in other papers in this series.

Sensory‐motor function of human periodontal mechanoreceptors*

Natural teeth are equipped with periodontal mechanoreceptors that signal information about tooth loads. In the present review, the basic force-encoding properties of human periodontal receptors will be presented along with a discussion about their likely functional role in the control of human mastication. Microneurographic recordings from single nerve fibres reveal that human periodontal receptors adapt slowly to maintained tooth loads. Most receptors are broadly tuned to the direction of force application, and about half respond to forces applied to more than one tooth. Populations of periodontal receptors, nevertheless, reliably encode information about both the teeth stimulated, and the direction of forces applied to the individual teeth. Information about the magnitude of tooth loads is made available in the mean firing rate response of periodontal receptors. Most receptors exhibit a markedly curved relationship between discharge rate and force amplitude, featuring the highest sensitivity to changes in tooth load at very low force levels (below 1 N for anterior teeth and 4 N for posterior teeth). Thus, periodontal receptors efficiently encode tooth load when subjects contact and gently manipulate food using the teeth. It is demonstrated that signals from periodontal receptors are used in the fine motor control of the jaw and it is clear from studies of various patient groups (e.g. patients with dental implants) that important sensory-motor functions are lost or impaired when these receptors are removed during the extraction of teeth.

Cardiac nociceptors innervated by vagal afferents in rats

It is reported that cardiac afferent information is transmitted through at least three different pathways to the CNS: sympathetic, parasympathetic, and somatic; however, there are few studies concerning the role of afferent fibers of vagus nerves for eliciting cardiac sensation including pain. Especially, receptive field properties innervated by single vagal nerve fiber and mechanical threshold of nociceptors on the cardiac surface are not yet quantitatively studied. Therefore, in this study, we systematically investigated characteristics of vagal units innervating cardiac nociceptors in rats. Using anesthetized and artificially ventilated rats, 37 single unit recordings were made from fine nerve filaments of the left vagal nerve. For quantitative mechanical stimulation, the cardiac surface was stimulated by a von Frey type device. In addition, bradykinin was used for checking the chemical sensitivity of the nociceptor. Electrical stimulation was used to estimate the conduction velocity of the recorded nerve fiber. All units recorded from the vagal nerve were either Aδ- or C-polymodal nociceptors. About 70% of the afferents had conduction velocities in the C-fiber range. In 60% of the units, the peripheral receptive field covered spot-like areas, but we also found larger and continuous receptive fields. Our results show that a majority of nociceptors innervated by vagal afferents are the C-polymodal type with spot-like receptive fields. We consider it to relate to the ambiguous and dull pain of angina pectoris.

Ryanodine receptors and BK channels act as a presynaptic depressor of neurotransmission in cochlear inner hair cells

Ryanodine receptors (RyRs) are known to contribute to the regulation of free cytosolic calcium concentration. This family of intracellular calcium channels plays a significant role in calcium-induced-calcium-release (CICR), and have been implicated in calcium-dependent processes requiring exquisite spatio-temporal regulation. In order to characterize the importance of these intracellular calcium channels in cochlear physiology, we perfused the guinea pig cochlea with antagonistic concentrations of ryanodine. The distortion products of the cochlear microphonic and the compound action potential of the auditory nerve were reversibly inhibited by ryanodine (IC(50)=27.3 microm, Hill coefficient=1.9), indicating an action at the cochlear amplifier. Single auditory nerve fibre recordings showed that ryanodine slightly increased spontaneous firing rates by 22%, suggesting an excitatory effect of ryanodine. This paradoxical effect could be explained by an inhibitory action of ryanodine on presynaptic BK channels of inner hair cells (IHC). Indeed, perfusing iberiotoxin also increased the spontaneous firing activity of the auditory nerve fibres. Furthermore, whole-cell patch-clamp recordings demonstrated that ryanodine inhibits BK currents at the IHC level. Conversely, immunohistochemistry demonstrated a strong expression of RyR in IHCs and, more particularly, below the cuticular plate where membranous BK channels are highly expressed. Overall, the study demonstrated a key role for RyR and CICR in signal transduction at the IHCs. We therefore propose that coupled RyR--BK channels act to suppress the fast neurotransmission in IHCs.

Adaptive Optics Ophthalmoscopy: Results and Applications

The living human eye's optical aberrations set a limit to retinal imaging in the clinical setting. Progress in the field of adaptive optics has offered unique solutions to this problem. The purpose of this review is to summarize the most recent advances in adaptive optics ophthalmoscopy. Adaptive optics technology has been combined with flood illumination imaging, confocal scanning laser ophthalmoscopy, and optical coherence tomography for the high resolution imaging of the retina. The advent of adaptive optics technology has provided the technical platform for the compensation of the eye's aberration and made possible the observation of single cones, small capillaries, nerve fibers, and leukocyte dynamics as well as the ultrastructure of the optic nerve head lamina cribrosa in vivo. Detailed imaging of retinal infrastructure provides valuable information for the study of retinal physiology and pathology.