1. Intra- and extracellular recordings were made from in vitro preparations of the lobster (Homarus gammarus) stomatogastric nervous system to study the nature and origin of pacemaker-like activity in a primary mechanoreceptor neurone, the anterior gastric receptor (AGR), whose two bilateral stretch-sensitive dendrites ramify in the tendon of powerstroke muscle GM1 of the gastric mill system. 2. Although the AGR is known to be autoactive, we report here that in 20% of our preparations, rather than autogenic tonic discharge, the receptor fired spontaneously in discrete bursts comprising three to ten action potentials and repeating at cycle frequencies of 0.5-2.5 Hz in the absence of mechanical stimulation. Intrasomatic recordings revealed that such rhythmic bursting was driven by slow oscillations in membrane potential, the frequency of which was voltage sensitive and dependent upon the level of stretch applied to the receptor terminals of the AGR. 3. Autoactive bursting of the AGR originated from an endogenous oscillatory mechanism in the sensory dendrites themselves, since (i) during both steady, repetitive firing and bursting, somatic and axonal impulses were always preceded 1:1 by dendritic action potentials, (ii) hyperpolarizing the AGR cell body to block triggering of axonal impulses revealed attenuated somatic spikes that continued to originate from the two peripheral dendrites...
1. Activation of gastric sensory afferents alters gastric motor and secretory function via the gastric vago-vagal reflex. In this report, we investigated in the rat the impact of gastric mechanoreceptor activation on the brain stem components of the reflex, which are located in the dorsal vagal complex (DVC), i.e. the nucleus of the solitary tract (NTS) and the subjacent dorsal motor nucleus (DMN). 2. In our extracellular recordings of single-cell activity in the DVC, we observed a relation between the response to antral distention and the location of the cell in the DVC. Specifically, cells that were excited by antral distention (ON cells) were located dorsal to those that were inhibited (OFF cells) by the same stimulus (mean depth = 536 +/- 15 and 627 +/- 14 microns for ON and OFF cells, respectively). 3. For a subset of DVC cells, the location was marked by ionophoretic ejection of Pontamine Blue from the recording barrel. Histological analysis indicated that ON cells were located in the NTS, and OFF cells were located in the ventral NTS or within the boundaries of the DMN. Together, these data led to the hypothesis that ON and OFF cells are functionally different groups of neurones, i.e. ON cells may be NTS neurones, and OFF cells may be DMN neurones. We tested this directly by employing both an intragastric balloon and a non-traumatic vagal stimulating electrode to determine whether inflation-related cells were NTS or DMN cells via orthodromic and antidromic activation...
Intraneural microstimulation (i.n.m.s.) was performed in awake human volunteers, using tungsten micro-electrodes inserted into median and ulnar nerve fascicles supplying the skin of the hand. The same electrodes were used alternatively to record impulse activity from single nerve fibres at the i.n.m.s. sites. Monitoring occasionally, with a proximal electrode, the impulse traffic evoked by i.n.m.s. distally in the same fascicle, established that the stimulation procedure could be made selective enough to activate single myelinated fibres in isolation, while also permitting multifibre recruitment. Monitoring propagated impulses also established that i.n.m.s. of a single myelinated fibre supplying a low-threshold mechanoreceptor in the hand might evoke an elementary sensation. Such sensations were fully endowed with cognitive attributes amenable to psychophysical estimation: quality, magnitude and localized projection. Psychophysical tests were made during i.n.m.s. at intraneural sites where single-unit activity was recorded from classified RA, PC, SA I or SA II mechanoreceptors. Changes in excitability of the nerve fibre of an identified unit, induced by further i.n.m.s., certified that the recorded unit had been stimulated during psychophysical tests. Comparing physical location of the receptive field of a recorded unit and localization of the projected field of the corresponding elementary sensation...
Electrophysiological and histological techniques were used to trace sensory pathways for stretch mechanoreceptor fibres from the distal colon to dorsal root ganglia. Extracellular and intracellular recording techniques revealed sensory pathways for mechanoreceptors to the prevertebral sympathetic ganglia but no further centrally. Histological studies involving the retrograde transport of horseradish peroxidase revealed sensory pathways from the distal colon to the spinal cord, mainly to the level of the second lumbar vertebra. Few (less than 2000) fibres were involved; their perikarya were small (ca. 25 micron). Sensory perikarya in spinal ganglia in the guinea-pig could be categorized into two populations, F and H cells, after a previously defined nomenclature for murine spinal ganglion cells. F and H cells were distinguished initially by their times to decay by 50% of the action potential. H cells took three times as long to repolarize. F and H cells were distinguished further by their electrical properties including membrane potential, input resistance and amplitude and duration of the after-potential following the action potential. Both F and H cells showed unusual time-dependent rectification following either depolarizing or hyperpolarizing current pulses. Threshold currents to show rectification were different for F and H cells. When taken in conjunction with conduction velocities...
1. Physical analysis of two visco-elastic models was performed, to afford a quantitative basis for examination of a theory of slip as applied to mechanoreceptor adaptation. In one model the coupling force between skin tissue and receptor was considered to be purely viscous; in another it was supposed to consist of parallel viscous and elastic forces, representing the properties of a gel.
Upper airway dilator muscles are phasically activated throughout breathing by respiratory pattern generator neurons. Studies have shown that non-physiological upper airway mechanoreceptive stimuli (e.g. rapidly imposed pulses of negative pressure) also activate these muscles. Such reflexes may become activated during conditions that alter airway resistance in order to stabilise airway patency.To determine the contribution of ongoing mechanoreceptive reflexes to phasic activity of airway dilators, we assessed genioglossal electromyogram (GG EMG: rectified with moving time average of 100 ms) during slow (physiological) oscillations in negative pressure generated spontaneously and passively (negative pressure ventilator).Nineteen healthy adults were studied while awake, during passive mechanical ventilation across normal physiological ranges of breathing rates (13–19 breaths min−1) and volumes (0.5–1.0 l) and during spontaneous breathing across the physiological range of end-tidal carbon dioxide (PET,CO2; 32–45 mmHg).Within-breath phasic changes in airway mechanoreceptor stimuli (negative pressure or flow) were highly correlated with within-breath phasic genioglossal activation, probably representing a robust mechanoreceptive reflex. These reflex relationships were largely unchanged by alterations in central drive to respiratory pump muscles or the rate of mechanical ventilation within the ranges studied. A multivariate model revealed that tonic GG EMG...
Previous work has suggested that end-stage renal disease (ESRD) patients may have an exaggerated sympathetic nervous system (SNS) response during exercise. We hypothesized that ESRD patients have an exaggerated blood pressure (BP) response during moderate static handgrip exercise (SHG 30%) and that the exaggerated BP response is mediated by SNS overactivation, characterized by augmented mechanoreceptor activation and blunted metaboreceptor control, as has been described in other chronic diseases. We measured hemodynamics and muscle sympathetic nerve activity (MSNA) in 13 ESRD and 16 controls during: 1) passive hand movement (PHM; mechanoreceptor isolation); 2) low-level rhythmic handgrip exercise (RHG 20%; central command and mechanoreceptor activation); 3) SHG 30%, followed by posthandgrip circulatory arrest (PHGCA; metaboreceptor activation); and 4) cold pressor test (CPT; nonexercise stimulus). ESRD patients had exaggerated increases in systolic BP during SHG 30%; however, the absolute and relative increase in MSNA was not augmented, excluding SNS overactivation as the cause of the exaggerated BP response. Increase in MSNA was not exaggerated during RHG 20% and PHM, demonstrating that mechanoreceptor activation is not heightened in ESRD. During PHGCA...
Special red cells were found on the adaxial surface of tertiary pulvini of Mimosa pudica and experiments performed to determine the origin and function of these cells. Using anatomical (light, scanning electron and transmission electron microscopy) and electrophysiological techniques, we have demonstrated that these red cells are real mechanoreceptor cells. They can generate receptor potential following mechanical stimuli and they are in connection with excitable motor cells (through plasmodesmata). We also provide evidence that these red cells are derived from stomatal subsidiary cells and not guard cells. As histochemical studies show red cells contain tannin, which is important in development of action potentials and movements of plants. These cells could be one of unidentified mechanoreceptors of mimosa.
Although the response of human cutaneous mechanoreceptors to controlled stimuli is well studied, it is not clear how these peripheral signals may be reflected in neuronal activity of the human CNS. We now test the hypothesis that individual neurons in the human thalamic principal somatic sensory nucleus [ventral caudal (Vc)] respond selectively to the optimal stimulus for one of the four mechanoreceptors. The optimal stimuli for particular mechanoreceptors were defined as follows: Pacinian corpuscles (PC), vibration at 128 Hz; rapidly adapting (RA), vibration at 32 or 64 Hz; slowly adapting type 1 (SA1), edge; slowly adapting type 2 (SA2), skin stretch. Nineteen neurons had a significant response to at least one optimal stimulus, and 17 had a significantly greater response to one stimulus than to the other three, including 7 PC-related, 7 RA-like, 3 SA1-like, and 2 SA2-like neurons. One of each of the SA1- and SA2-like thalamic neurons responded to vibration with firing rates that were lower than those to edge or stretch but not significantly. Except in the case of PC-related neurons, the receptive field (RF) sizes were larger for these thalamic neurons than for the corresponding mechanoreceptor. Von Frey thresholds were higher than those for the corresponding human RA and SA1 mechanoreceptors. These results suggest that there is a convergence of pathways transmitting input from multiple mechanoreceptors of one type on single thalamic neurons via the dorsal columns. They are also consistent with the presence of primate thalamic elements of modality and somatotopic isorepresentation.
It has been suggested that primary afferent C-fibres that respond to innocuous tactile stimuli are important in the sensation of pleasurable touch. Although it is known that C-tactile fibres terminate in the substantia gelatinosa (lamina II) of the spinal cord, virtually all of the neurons in this region are interneurons, and currently it is not known how impulses in C-mechanoreceptors are transmitted to higher centres. In the current study, I have tested the quantitative response properties of ‘wide dynamic range’ projection neurons in lamina I of the spinal cord to graded velocity brushing stimuli to identify whether low-threshold mechanoreceptor input to these neurons arises from myelinated or umyelinated nerve fibres. Graded velocity brushing stimuli (6.6–126 cm s−1) were used to characterize the mechanoreceptor inputs to ‘wide dynamic range’ neurons in lamina I of the dorsal horn that had axons that projected to the contralateral parabrachial nucleus. The most effective tactile stimuli for activation of ‘wide dynamic range’ lamina I spinoparabrachial neurons were low velocity brush strokes: peak discharge occurred at a mean velocity of 9.2 cm s−1 (range 6.6–20.4 cm s−1, s.d. 5.0 cm s−1), and declined exponentially as brush velocity increased. The data indicate that C-fibres...
The slowly-adapting type I mechanoreceptor (SA-I) exhibits variability in its steady-state firing rate both within an afferent upon repeated stimulation and between afferents. Additionally, inter-spike intervals of the SA-I are extremely variable during this steady-state firing. While variability of the SA-I response has been noted previously, the work presented herein provides a finer analysis of the impact of force and fiber on the SA-I response. Specifically, we test two hypotheses, that 1) fiber-to-fiber variation will significantly impact firing rate over the range of applied forces, and that 2) fiber-to-fiber variation will significantly impact the coefficient of variation (CV) of inter-spike intervals over the range of applied forces. Utilizing an ex vivo skin nerve preparation in the mouse, experiments were conducted with six SA-I fibers from five mice, and with compressive stimuli with force magnitudes up to 9.59 mN. We found fiber to significantly impact both firing rate and CV. These findings motivated the construction of a generalized input (force) – output (firing rate) model composed of a baseline response profile and a multiplicative fiber sensitivity factor. This work will inform future efforts to attribute variability to differences in skin...
The piloneural collar in mammalian hairy skin comprises an intricate pattern of circumferential and longitudinal sensory afferents that innervate primary and secondary pelage hairs. The longitudinal afferents tightly associate with terminal Schwann cell processes to form encapsulated lanceolate nerve endings of rapidly adapting mechanoreceptors. The molecular basis for piloneural development, maintenance and function is poorly understood. Here, we show that Nefh-expressing glutamatergic neurons represent a major population of longitudinal and circumferential sensory afferents innervating the piloneural collar. Our findings using a VGLUT2 conditional-null mouse model indicate that glutamate is essential for innervation, patterning and differentiation of NMDAR+ terminal Schwann cells during piloneural collar development. Similarly, treatment of adult mice with a selective NMDAR antagonist severely perturbed piloneural collar structure and reduced excitability of these mechanosensory neurons. Collectively, these results show that DRG-derived glutamate is essential for the proper development, maintenance and sensory function of the piloneural mechanoreceptor.
BACKGROUND & AIMS: Visceral mechanoreceptors are critical for perceived sensations and autonomic reflex control of gastrointestinal function. However, the molecular mechanisms underlying visceral mechanosensation remain poorly defined. Degenerin/epithelial Na+ channel (DEG/ENaC) family ion channels are candidate mechanosensory molecules, and we hypothesized that they influence visceral mechanosensation. We examined the influence of the DEG/ENaC channel ASIC1 on gastrointestinal mechanosensory function, on gastric emptying, and on fecal output. We also compared its role in gastrointestinal and somatic sensory function. METHODS: To assess the role of ASIC1 we studied wild-type and ASIC1-/- mice. Reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analysis determined expression of ASIC1 messenger RNA and protein in vagal and spinal sensory ganglia. Colonic, gastroesophageal, and cutaneous afferent fibers were characterized by functional subtype and their mechanical stimulus-response relationships were determined. Gastric emptying was determined by using a 13CO2 breath test. Behavioral tests assessed somatic mechanical and thermal sensitivity. RESULTS: ASIC1 was expressed in sensory ganglia and was lost after disruption of the ASIC1 gene. Loss of ASIC1 increased mechanosensitivity in all colonic and gastroesophageal mechanoreceptor subtypes. In addition...
Interactions between chondrocytes and their
extracellular matrix are partly mediated by ß1-integrin
receptors. Recent studies have shown that ß1-integrins
co-localize with a variety of cytoskeletal complexes,
signaling proteins and growth factor receptors. Since
mechanosensitive ion channels and integrins have been
proposed to participate in skeletal mechanotransduction,
in this study, we investigated the possible co-localization
of ß1-integrins with two ion channels and a P-type
ATPase in mouse limb-bud chondrocytes. The a
subunits of Na, K-ATPase, the epithelial sodium channel
(ENaC) and the voltage activated calcium channel
(VACC) were immunostained in organoid cultures
derived from limb-buds of 12-day-old mice using wellcharacterized
antibodies . Indirect immunofluorescence
revealed abundant expression of ß1-integrins and each of
the selected systems in limb-bud chondrocytes. Twofluorochrome
immunostaining demonstrated that ß1-
integrin, Na, K-ATPase, ENaC and VACC co-localize in
chondrocytes. Co-imunoprecipitation experiments
revealed co-localization and association of integrins with
ENaC, VACC and Na, K-ATPase. Cellular responses and
signaling cascades initiated by the influx of calcium or
sodium through putative mechanosensitive channels may
be regulated more effectively if such channels were
organized around integrins with receptors...
The mechanoreceptor innervation of fibular collateral ligaments from human knee joints is described. While a small number of 'non-Paciniform' endings were identified in 5 optimally-stained ligaments, 'Paciniform' endings were not identified. These 'non-Paciniform endings' were variable in shape, but each consisted of an encapsulated arborisation of neurites embedded in a granular matrix. The significance of these findings is discussed as they relate to (i) discrepancies of the extent to which certain periarticular tissues are innervated, and (ii) the role of periarticular mechanoreceptors in initiating protective muscular reflexes.
The posterior attachments of the dog knee joint lateral menisci have been studied to identify and characterize their mechanoreceptor innervation. Two basic types of mechanoreceptor were identified that appeared to be similar to the Type III and Type II endings described by Freeman & Wyke (1967) in cat knee periarticular tissues. Significantly, two distinct forms of Type II corpuscles were identified in this study, referred to as Types IIa and IIb, respectively. Endings were usually identified either at the point where the posterior meniscotibial ligament merged with the main body of the meniscus and the meniscofemoral ligament, or within the inner aspect of the meniscofemoral ligament where it joined the meniscal 'body'. The presence of encapsulated mechanoreceptors within the attachments of dog knee lateral menisci means that the central nervous system is being appraised of the mechanical state of these structures. A mechanism is suggested by which the tension of meniscal attachments could be varied according to knee joint position. A possible relationship between the morphology of the receptors identified in this study and the physiological responses of similar cat knee joint receptors is discussed.
Our previous finding that increasing myocardial contractility caused reflex systemic hypotension, the left ventricular (LV) mechanoreceptor reflex, suggested that the classical Bezold reflex (systemic hypotension and bradycardia after intracoronary administration of veratrum alkaloids) may be initiated by these same LV mechanoreceptors. In our working LV preparation with the coronary and systemic circulations isolated and perfused separately, intracoronary injection of veratrum alkaloids, like that of catecholamines or ouabain, had a positive inotropic effect which produced the hypotensive response typical of the LV mechanoreceptor reflex. To test directly if veratridine's positive inotropic effect initiates the Bezold reflex, verapamil, which blocks the slow Ca2+ channels of myocardial cells but leaves intracardiac nerves unaffected, was injected by the intracoronary route to prevent the increased contractility from intracoronary injection of veratridine which also abolished the reflex hypotension, demonstrating conclusively that increasing myocardial contractility and thereby activating LV mechanoreceptors but not chemoreceptors initiates the Bezold reflex. Contrariwise, decreasing contractility or cardiac asystole by administration of tetrodotoxin...
Naturalistic signals were created from vibrations made by locusts walking on a Sansevieria plant. Both naturalistic and Gaussian noise signals were used to mechanically stimulate VS-3 slit-sense mechanoreceptor neurons of the spider, Cupiennius salei, with stimulus amplitudes adjusted to give similar firing rates for either stimulus. Intracellular microelectrodes recorded action potentials, receptor potential, and receptor current, using current clamp and voltage clamp. Frequency response analysis showed that naturalistic stimulation contained relatively more power at low frequencies, and caused increased neuronal sensitivity to higher frequencies. In contrast, varying the amplitude of Gaussian stimulation did not change neuronal dynamics. Naturalistic stimulation contained less entropy than Gaussian, but signal entropy was higher than stimulus in the resultant receptor current, indicating addition of uncorrelated noise during transduction. The presence of added noise was supported by measuring linear information capacity in the receptor current. Total entropy and information capacity in action potentials produced by either stimulus were much lower than in earlier stages, and limited to the maximum entropy of binary signals. We conclude that the dynamics of action potential encoding in VS-3 neurons are sensitive to the form of stimulation...
1. The activity of neurones in the mesencephalic nucleus of the fifth nerve that respond to forces applied to the teeth were recorded using extracellular microelectrodes; the properties of these neurones have been studied. 2. Electrophysiological evidence consistent with the view that primary afferent intraoral mechanoreceptor fibres have their cell bodies in the trigeminal mesencephalic nucleus is presented. 3. Two groups of intraoral mechanoreceptor neurones were found. The first group, the periodontal mechanoreceptor neurones, which have been described by previous workers, responded to electrical stimulation of the ipsilateral superior or inferior dental nerves and to forces applied to single teeth in the ipsilateral maxilla or mandible respectively. The response characteristics of the mesencephalic periodontal mechanoreceptor neurones differed in two respects from those observed in peripheral nerve studies by previous workers: (a) there were no spontaneously active neurones, and (b) there were no neurones that responded for over 10 sec to a sustained application of a suprathreshold mechanical stimulus to the teeth. The second group, not described before, responded to electrical stimulation of the ipsilateral palatine nerve, and responded to forces applied to all the teeth in the maxillary arch...