Types Of Afferents Research Articles

Developmental Learning in a Pain-Related System: Evidence for a Cross-Modality Mechanism

The nociceptive spinal reflex system performs highly precise sensorimotor transformations that require functionally specified synaptic strengths. The specification is gradually attained during early development and appears to be learning dependent. Here we determine the time course of this specification for heat-nociceptive tail withdrawal reflexes and analyze which types of primary afferents are important for the learning by applying various forms of noninvasive sensory deprivations. The percentage of erroneous heat-nociceptive tail withdrawal reflexes (i.e., movements directed toward the stimulation) decreased gradually from 64.1 +/- 2.5% (mean +/- SEM) to <10% during postnatal days 10-21. This improvement was completely blocked by anesthetizing the tail during the adaptation period, confirming that an experience-dependent mechanism is involved in the specification of synaptic strengths. However, the results show that the adaptation occurs to a significant extent despite local analgesia and protection of the tail from noxious input, provided that tactile sensitivity is preserved. Therefore, it appears that a nociceptive input is not necessary for the adaptation, and that input from tactile receptors can be used to guide the nociceptive synaptic organization during development. Sensory deprivation in the adult rat failed to affect the heat-nociceptive withdrawal reflex system, indicating that the adaptation has a "critical period" during early development. These findings provide a key to the puzzle of how pain-related systems can be functionally adapted through experience despite the rare occurrence of noxious input during early life.

Functional morphology and physiological properties of bronchopulmonary C-fiber afferents.

Nonmyelinated (C-) fibers represent the majority of vagal afferents innervating the airways and lung, and play an important role in regulating the respiratory and cardiovascular functions under both normal and abnormal physiologic conditions. Studies of the relationship between the conduction velocities of the vagal afferents and their sensitivities to capsaicin and other chemical irritants reveal that C-fibers are the primary type of chemosensitive afferents in the rat lung. Furthermore, a distinct sensitivity to capsaicin and a weak response to lung inflation are the defining characteristics of these afferents. In cultured rat nodose and jugular ganglion neurons, capsaicin-sensitive cells were identified by measurement of the capsaicin-evoked calcium transients using the Fura-2-based ratiometric imaging technique. The percentage of capsaicin-sensitive neurons gradually decreases as the cell diameter increases. However, the capsaicin-sensitive neurons cannot be precisely identified solely on the basis of the cell size. Anandamide, an endogenous cannabinoid released from leukocytes and epithelial cells, consistently evokes a stimulatory effect on pulmonary C-fiber endings by activating vanilloid receptor type 1 (VR1). The discharge pattern of pulmonary C-fibers evoked by anandamide closely resembles that produced by a much lower ( approximately 1/600) dose of capsaicin in the same fibers. Whether anandamide acts as a potential endogenous ligand to VR1 at the C-fiber terminals is unclear, and the physiological role of VR1 in modulating the transduction properties of these afferents also remains to be determined.

Fimbrial control of bidirectional synaptic plasticity of medial perforant path-dentate transmission.

Lesions of the fimbria-fornix (FF) tract cause profound impairments of cognitive ability in animals. Our previous study showed that spatial performance correlates with long-term potentiation (LTP) of the dentate gyrus (DG), but not of the CA1 region, in rats with bilateral FF lesions, suggesting that FF lesions selectively inhibited LTP in the DG. The cortical input to the DG is anatomically and physiologically divided into two types of afferents, i.e., the medial perforant path (MPP) and the lateral perforant path (LPP), which show distinct synaptic properties. To elucidate the difference in the FF modulation of these two inputs, field responses were recorded from MPP- or LPP-DG synapses in anesthetized rats. MPP-DG synapses of rats with FF lesions displayed neither LTP in response to theta-burst stimulation nor long-term depression (LTD) in response to low-frequency burst stimulation. In contrast to the MPP, LPP-DG synapses showed normal LTP in rats with FF lesions. The low-frequency burst stimulation could not induce LTD at LPP-DG synapses in either intact or FF-lesioned rats. These results suggest that the FF pathway selectively supports the mechanisms of bidirectional synaptic plasticity at MPP-DG synapses. This study provides new insights into external control of information processing in the hippocampus.

Vagal intraganglionic laminar endings and intramuscular arrays mature at different rates in pre-weanling rat stomach

To assess whether vagal afferents in the gastrointestinal (GI) tract mature postnatally and differentiate at different rates, potentially reflecting the changing functional requirements of weaning and independence, the vagal afferent innervation of the stomach was inventoried in pre-weanling and adult rats. Wheatgerm agglutinin–horseradish peroxidase was injected into the nodose ganglia of 9-day-old and adult rats, and after tracer transport, the animals were sacrificed. Their stomachs were prepared as wholemounts and processed with tetramethylbenzidine. Inventories were obtained with a counting grid that was systematically positioned throughout the wholemounts by the use of a sampling template that was adjusted for stomach size and shape. Densities in the gastric antrum, corpus, and forestomach were determined for (1) afferent bundles, (2) individual fibers separated from the bundles and presumably located near their targets, (3) differentiated intraganglionic laminar endings (IGLEs) associated with myenteric ganglia, and (4) differentiated intramuscular arrays (IMAs) situated within the smooth muscle layers. In pre-weanling rats, which were 10 days old at perfusion, the distributions of vagal bundles and fibers were similar to those of adults, suggesting that the basic vagal architecture develops early. Differentiated IGLEs were also distributed in a mature pattern in 10 day olds, whereas few IMAs had yet been distributed and differentiated in the forestomach of the pre-weanlings. The authors hypothesize that these different developmental patterns for the two types of vagal afferents are consistent with their putative functional roles as, respectively, mechanoreceptors (IGLEs) that coordinate rhythmic motor function needed early for the digestion of milk and stretch receptors (IMAs) needed later as the GI tract matures for the transition to solid food at weaning.

Separation and estimation of muscle spindle and tension receptor populations by vibration of the biceps muscle in the frog.

Frog spinal cord reflex behaviors have been used to test the idea of spinal primitives. We have suggested a significant role for proprioception in regulation of primitives. However the in vivo behavior of spindle and golgi tendon receptors in frogs in response to vibration are not well described and the proportions of these proprioceptors are not established. In this study, we examine the selectivity of muscle vibration in the spinal frog. The aim of the study was (1) to examine how hindlimb muscle spindles and GTO receptors are activated by muscle vibration and (2) to estimate the relative numbers of GTO receptors and spindle afferents in a selected muscle, for comparison with the mammal. Single muscle afferents from the biceps muscle were identified in the dorsal roots. These were tested in response to biceps vibration, intramuscular stimulation and biceps nerve stimulation. Biceps units were categorized into two types: First, spindle afferents which had a high conduction velocity (approximately 20-30 m/s), responded reliably (were entrained 1:1) to muscle vibration, and exhibited distinct pauses to shortening muscle contractions. Second, golgi tendon organ afferents, which had a lower conduction velocity (approximately 10-20 m/s), responded less reliably to muscle vibration at physiologic muscle lengths, but responded more reliably at extended lengths or with background muscle contraction, and exhibited distinct bursts to shortening muscle contractions. Vibration responses of these units were tested with and without muscle curarization. Ensemble (suction electrode) recordings from the dorsal roots were used to provide rough estimates of the proportions of the two muscle afferent types.

Musings on the wanderer: what's new in our understanding of vago-vagal reflexes? I. Morphology and topography of vagal afferents innervating the GI tract.

An understanding of the events initiating vago-vagal reflexes requires knowledge of mechanisms of transduction by vagal afferents. Such information presumes an understanding of receptor morphology and location. Anatomic studies have recently characterized two types of vagal afferents, both putative mechanoreceptors distributed in gastrointestinal (GI) smooth muscle. These two receptors are highly specialized in that they 1) are morphologically distinct, 2) have different smooth muscle targets, 3) form complexes with dissimilar accessory cells, and 4) vary in their regional distributions throughout the GI tract. By comparison, information on the architecture and regional distributions of other classes of vagal afferents, notably chemoreceptors, has only begun to accumulate. Progress on the study of the two mechanoreceptors, however, illustrates general principles and delineates experimental issues that may apply to other submodalities of vagal afferents. By extension from morphological and physiological observations on the two species of smooth muscle endings, it is reasonable to hypothesize that additional classes of vagal receptors are also differentiated morphologically and that they vary in structure, accessory cells, regional distributions, and other features. A full appreciation of vago-vagal reflexes will require thorough structural and regional analyses of each of the types of vagal receptors within the GI tract.

Summary: Peripheral Pharmacology of Cough

Hypersensitivity of the `cough receptors' is one of the primary causes of uncontrollable and nonproductive cough. These receptors are therefore the logical targets in developing antitussive therapeutics. The articles in this section focus primarily on the types of lung afferents mediating the cough reflexes and the mechanisms involved in regulating the activity and sensitivity of these afferents. Several major issues have been discussed in these presentations, including the pharmacologic, physiologic and neurochemical characteristics of the cough receptors; the effect of phenotypic switch of the rapidly adapting receptors (RARs) during chronic airway infection; the interaction between RARs and C-fiber afferents both at the receptor level and in the centrally mediated reflex pathway; and the cellular mechanisms and ion channel species involved in the hypersensitivity of the cough receptors. A number of important questions have emerged from these investigations. Answers to these questions should further advance our understanding of the peripheral mechanisms of cough reflexes.

Two N-methyl-D-aspartate receptors in rat dorsal root ganglia with different subunit composition and localization.

N-methyl-D-aspartate (NMDA) receptors in sensory afferents participate in chronic pain by mediating peripheral and central sensitization. We studied the presence of NMDA receptor subunits in different types of primary afferents. Western blots indicated that rat dorsal root ganglia (DRG) contain NR1, NR2B, NR2C, and NR2D but not NR2A. Real-time RT-PCR showed that NR2B and NR2D were expressed at higher levels than NR2A and NR2C in DRG. Immunofluorescence with an antibody that recognized NR1 and another that recognized NR2A and NR2B showed that NR1 and NR2B colocalized in 90% of DRG neurons, including most A-fibers (identified by the presence of neurofilament 200 kDa). In contrast, an antibody recognizing NR2C and NR2D labeled only neurofilament-negative DRG profiles. This antibody stained practically all DRG cells that contained calcitonin gene-related peptide and neurokinins and those that bound isolectin B4. The percentage of cells immunoreactive for NR1, NR2A/NR2B, and NR2C/NR2D were the same in the T9, T12, L4, and L6 DRG. The intracellular distribution of the NR2 subunits was strikingly different: Whereas NR2A/NR2B immunoreactivity was found in the Golgi apparatus and occasionally at the plasma membrane, NR2C/NR2D immunoreactivity was found in the cytoplasm but not in the Golgi. The NR1 subunit was present throughout the cytoplasm and was more intense in the Golgi. These findings indicate that DRG neurons have two different NMDA receptors, one containing the NR1, NR2D, and possibly the NR2C subunits, found only in C-fibers, and the diheteromer NR1/NR2B, present in the Golgi apparatus of both A- and C-fibers.

Neurotransmission of the cochlear inner hair cell synapse--implications for inner ear therapy.

The cochlear inner hair cells (IHCs) are connected to afferent type I auditory neurons and use probably L-glutamate as a neurotransmitter. This IHC synapse receives efferent input from the lateral part of the efferent olivocochlear system with neurons originating in the brainstem and terminating below IHCs synapsing with the afferent type I dendrites. A number of substances have been proposed to function as neurotransmitter or neuromodulator in the lateral efferent system: acetylcholine, gamma-aminobutyric acid (GABA), dopamine, enkephalin and dynorphin. With the aid of microiontophoretic techniques, we studied several transmitter candidates and characterized their receptor subtypes as well as their function on spontaneous or evoked activity of afferent dendrites. The results showed that the glutamatergic transmission of IHCs is facilitated by all types of glutamate receptors: ionotropic glutamate receptors of the N-methyl-D-aspartic acid (NMDA) and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type as well as group I and II metabotropic glutamate receptors. This excitatory glutamatergic transmission is under inhibitory control of GABA (mediated by GABA(A) receptors) and dopamine (mediated by D1 and D2 receptors). In contrast, acetylcholine was able to excite afferent dendrites via muscarinic receptors. These results demonstrate that the lateral efferent system has modulatory function on the glutamatergic neurotransmission of IHCs. Excitation of afferent dendrites by glutamate released from IHCs can thus be tuned in different physiological or pathophysiological conditions. This could have therapeutic implications as it is known that noise exposure is followed by an excitotoxic injury of the IHC synapse. During overexcitation of IHCs, a possible therapy based on the neurochemical data would be (a) glutamate antagonists, (b) dopamine agonists, (c) GABA agonists or a combination from a, b and a, c.

Encoding of Direction of Fingertip Forces by Human Tactile Afferents

In most manipulations, we use our fingertips to apply time-varying forces to the target object in controlled directions. Here we used microneurography to assess how single tactile afferents encode the direction of fingertip forces at magnitudes, rates, and directions comparable to those arising in everyday manipulations. Using a flat stimulus surface, we applied forces to a standard site on the fingertip while recording impulse activity in 196 tactile afferents with receptive fields distributed over the entire terminal phalanx. Forces were applied in one of five directions: normal force and forces at a 20 degrees angle from the normal in the radial, distal, ulnar, or proximal directions. Nearly all afferents responded, and the responses in most slowly adapting (SA)-I, SA-II, and fast adapting (FA)-I afferents were broadly tuned to a preferred direction of force. Among afferents of each type, the preferred directions were distributed in all angular directions with reference to the stimulation site, but not uniformly. The SA-I population was biased for tangential force components in the distal direction, the SA-II population was biased in the proximal direction, and the FA-I population was biased in the proximal and radial directions. Anisotropic mechanical properties of the fingertip and the spatial relationship between the receptive field center of the afferent and the stimulus site appeared to influence the preferred direction in a manner dependent on afferent type. We conclude that tactile afferents from the whole terminal phalanx potentially contribute to the encoding of direction of fingertip forces similar to those that occur when subjects manipulate objects under natural conditions.

Increasing the Number of Synapses Modifies Olfactory Perception inDrosophila

The Drosophila mutant gigas produces an enlargement of postmitotic cells caused by additional rounds of DNA replication. In neurons, the mutant cell establishes more synapses than normal. We have taken advantage of this feature to study the effect of synapse number on odorant perception. Mosaic adults were generated in which one antenna was homozygous for gigas, whereas the contralateral side served as an internal control. Morphological analysis indicates that the number and type of sensory afferents forming the mutant antenna, as well as their projection to the olfactory glomeruli, are normal. In contrast, the volume of identified glomeruli increases to a variable extent, and mutant sensory neurons branch profusely. The number of synapses, estimated in the ventral (V) glomerulus that receives ipsilateral afferents only, is increased twofold to threefold. Large-dense-core vesicle-containing terminals that probably modulate olfactory centers are identified in the V glomerulus. Their number and size are not modified by the mutant input. Sensory transduction, measured by electroantennograms, is normal in amplitude and kinetics. In odorant tests, however, the profile of the behavioral response to ethyl acetate shows attractive responses to concentrations to which sibling controls remain indifferent (10(-)8 and 10(-)7 v/v). In addition, the intensity of the response is augmented both at attractive and repulsive odorant concentrations with respect to that of controls. These results demonstrate that increased synapse number in the sensory neurons can modify the behavior of the organism, allowing a higher sensitivity of perception.

Sensitivity of vagal afferent endings to chemical irritants in the rat lung

This study was carried out to investigate the relationship between the conduction velocity of the vagal afferents arising from the rat lungs and their sensitivities to capsaicin, other chemical irritants, and lung inflation. We recorded single-unit activities of vagal pulmonary afferents ( n=205) in anesthetized, open-chest rats, and distinguished C fibers (conduction velocity<2 m/sec) from myelinated afferents; the latter group was further classified into rapidly adapting pulmonary receptors (RARs) and slowly adapting pulmonary stretch receptors (SARs) on the basis of their adaptation indexes to lung inflation. Right-atrial injection of capsaicin (1 μg/kg) evoked an abrupt and intense stimulatory effect in 88.9% (64/72) of the pulmonary C fibers tested, but only a mild stimulation in 6.3% (3/48) of the RARs and none of the SARs. Other inhaled and injected chemical stimulants (e.g., cigarette smoke, lactic acid) activated 68.9% (42/61) of the pulmonary C fibers. The same chemical irritants exerted a mild stimulatory effect in only 14.5% (8/55) of the RARs; this subgroup of RARs exhibited a low or no baseline activity, and half of them were located near the hilum. Chemical stimulants had little or no effect on SARs. The response of pulmonary C fibers to lung inflation (tracheal pressure=30 cm H 2O) was not only extremely weak, but also showed a longer onset latency and an irregular pattern. In a sharp contrast, lung inflation evoked rapid and vigorous discharges in both RARs and SARs. In conclusion, C fibers are the primary type of chemosensitive vagal pulmonary afferents in rat lungs.

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Bronchopulmonary C-fiber endings and rapidly adapting pulmonary receptors (RARs) are primarily responsible for eliciting the defense reflexes in protecting the lungs against inhaled irritants. In anesthetized animals, inhalation of cigarette smoke, one of the common inhaled irritants, into the lungs elicits pulmonary chemoreflexes that are mediated through the stimulation of pulmonary C fibers. When the C-fiber conduction is selectively blocked in the vagus nerves, the same smoke inhalation triggered only augmented breaths, a reflex effect of activating RARs, in the same animals. Indeed, electrophysiologic study shows that inhaled smoke exerts a direct stimulatory effect on both types of afferents. Increasing evidence indicates that the excitability of these afferents and therefore their reflex actions are enhanced by airway mucosal inflammation; one such example is the airway hyperresponsiveness induced by acute exposure to ozone. Although the mechanism underlying the inflammation-induced hypersensitivity of C-fiber endings is not fully understood, the possible involvement of local release of certain inflammatory mediators, such as histamine and prostaglandin E(2) (PGE(2), should be considered. It is believed that changes in the membrane properties mediated by the activation of certain specific receptor proteins located on the membrane of these nerve terminals are involved, as the sensitizing effects of PGE(2) can be also demonstrated in cultured pulmonary C neurons.

The Contactin-Related Protein FAR-2 Defines Purkinje Cell Clusters and Labels Subpopulations of Climbing Fibers in the Developing Cerebellum

FAR-2 is a novel neural member of the Ig superfamily, which is related to F11/F3/contactin and axonin-1/TAG-1. This protein is expressed by subpopulations of Purkinje cells in the chicken cerebellum and FAR-2-positive clusters of these neurons alternate with FAR-2-negative clusters in both tangential dimensions of the cerebellar cortex. Furthermore, FAR-2 is also expressed by one type of Purkinje cell afferents, namely, the climbing fibers, and different subpopulations of these axons show distinct levels of FAR-2 expression. Homology modeling using axonin-1 as a template reveals that the four aminoterminal Ig domains of FAR-2 form a compact U-shaped structure, which is likely to contain functionally important ligand-binding sites. FAR-2 is binding to the Ig superfamily protein NgCAM/L1, but not to the related receptor NrCAM, and it is also interacting with the modular ECM protein tenascin-R. These results suggest that FAR-2 may contribute to the formation of somatotopic maps of cerebellar afferents during the development of the nervous system.

Gastrointestinal projection maps of the vagus nerve are specified permanently in the perinatal period

The vagal innervation of the proximal gastrointestinal (GI) tract is lateralized. To determine whether this pattern is specified as early as the perinatal period, neonatal rat pups were given unilateral cervical vagotomies. Separate groups received (1) transections below the left nodose ganglion, (2) left cervical resections that included removal of the nodose ganglion, or (3) sham surgeries. At 4 months of age, each animal’s vagal afferent projections from the unoperated side were mapped by injecting the nodose with WGA-HRP, preparing the stomach as wholemounts, and processing the tissue with tetramethyl benzidine. The two types of vagal afferent endings in GI smooth muscle, namely intraganglionic laminar endings and intramuscular arrays, were surveyed separately, and their regional distributions were mapped. Changes in the nucleus of the solitary tract (NST) and dorsal motor nucleus of the vagus (DMNX) were assessed with cell counts and area measurements. Neonatal loss of the vagus innervating one side of the GI tract, with or without ganglionectomy, did not cause the unoperated vagus to sprout to the denervated side. In addition, removal of the projections to the one side of the target organ did not produce a reorganization of the projection maps of the unoperated vagus within its normal or ipsilateral wall of the GI tract. Although the regional patterns of the unoperated ipsilateral vagus were not affected, the packing densities of both types of afferents supplied by this trunk were moderately reduced. The DMNX of the vagotomized side displayed extensive (∼83%) neuronal loss; the DMNX on the unoperated side as well as the NST on both sides exhibited limited (∼20–25%) losses. The lack of a peripheral projection field reorganization — except for a moderate down-regulation — after complete unilateral denervation suggests that both the laterality and the afferent terminal phenotypes (or target tissues) of the vagus in the proximal GI tract are specified by postnatal day one in the rat. The present results, taken together with other observations, also suggest that three different combinations of signals orchestrate the commitments of vagal afferents respectively to (1) the side of the organ, (2) the region within the organ wall, and (3) the accessory and innervated tissues that complex with the fully differentiated ending.

Cochlear microphonic potentials: a new recording technique.

A new instrumentation and a particular method for detecting and recording cochlear microphonic potentials (CMPs) are described here. The CMPs were recorded in rats by means of pure tones (4,000, 2,000, 1,000, 500, and 250 Hz) and intraepidermic electrodes; the electrocochleography technique was avoided. An experimental design that included the use of a glutamatergic agonist (kainic acid [KA]) and an aminoglycoside antibiotic (kanamycin [KANA]) was carried out to demonstrate the origin of the recorded potential. Morphological studies showed that KA selectively eliminated the afferent type I dendrites of the spiral ganglion, while the administration of KANA resulted in the absence of outer hair cells. When CMPs were recorded after KA administration, no alterations were detected. In contrast, KANA administration resulted in the absence of any selective electrophysiological activity corresponding to CMPs. All these results were compared with the recording of the compound action potential of the eighth nerve obtained by electrocochleography. These findings and the great specificity of the reproduction of the sound stimulus confirm that the CMPs can be recorded by the new equipment.

Tactile functions of mechanoreceptive afferents innervating the hand.

Four types of mechanoreceptive afferents innervate the glabrous skin of the hand. Evidence from more than three decades of combined psychophysical and neurophysiological research supports the idea that each afferent type serves a distinctly different sensory function and that these functions explain most of tactual perceptual function. The available evidence supports the following hypotheses: (1) The slowly adapting type 1 system provides the information on which form and texture perception are based. (2) The cutaneous rapidly adapting system provides information about minute skin motion and, thereby, plays a critical role in grip control. (3) The Pacinian system is responsible for the detection and perception of distant events by vibrations transmitted through objects, probes, and tools held in the hand. (4) The slowly adapting type 2 system provides information for the perception of hand conformation and for the perception of forces acting on the hand. The authors review the evidence on which these hypotheses are based. They also review the role of proprioceptive afferents in the perception of hand conformation because they appear to play a significant role along with cutaneous afferents.

Prostaglandin E(2) enhances chemical and mechanical sensitivities of pulmonary C fibers in the rat.

It has been recently reported that pulmonary reflex responses to injection or inhalation challenge of capsaicin are enhanced by exogenous Prostaglandin E(2) (PGE(2)). The present study was carried out to determine whether PGE(2) enhances the stimulatory effects of chemical stimulants and lung inflation on vagal pulmonary C fibers, and if so, whether the excitabilities of other types of lung afferents are also augmented by PGE(2). In anesthetized, open-chest rats, administration of PGE(2) (1.5 microgram/kg/min for 2 min) did not significantly change the baseline activity of vagal pulmonary C fibers, but it markedly enhanced the stimulatory effects of both low (0.25 microgram/kg) and high doses (0.5 microgram/kg) of capsaicin on these fibers. Similarly, potentiating effects of PGE(2) were found on the pulmonary C-fiber responses to injections of lactic acid and adenosine, although considerable variability existed in the degrees of potentiation between the different stimulants. Furthermore, PGE(2) infusion also significantly enhanced the C-fiber response to constant-pressure lung inflation (tracheal pressure [Pt] = 30 cm H(2)O). In contrast, PGE(2) did not alter the responses of either slowly adapting pulmonary receptors or rapidly adapting pulmonary receptors to lung inflation. In summary, these results show that the sensitivity of pulmonary C-fiber afferents to both mechanical and chemical stimuli is enhanced by PGE(2), suggesting that endogenous release of this autocoid may play a part in the airway irritation and dyspneic sensation associated with airway inflammation.

Vestibular stimulation leads to distinct hemodynamic patterning.

Previous studies demonstrated that responses of a particular sympathetic nerve to vestibular stimulation depend on the type of tissue the nerve innervates as well as its anatomic location. In the present study, we sought to determine whether such precise patterning of vestibulosympathetic reflexes could lead to specific hemodynamic alterations in response to vestibular afferent activation. We simultaneously measured changes in systemic blood pressure and blood flow (with the use of Doppler flowmetry) to the hindlimb (femoral artery), forelimb (brachial artery), and kidney (renal artery) in chloralose-urethane-anesthetized, baroreceptor-denervated cats. Electrical vestibular stimulation led to depressor responses, 8 +/- 2 mmHg (mean +/- SE) in magnitude, that were accompanied by decreases in femoral vasoconstriction (23 +/- 4% decrease in vascular resistance or 36 +/- 7% increase in vascular conductance) and increases in brachial vascular tone (resistance increase of 10 +/- 6% and conductance decrease of 11 +/- 4%). Relatively small changes (<5%) in renal vascular tone were observed. In contrast, electrical stimulation of muscle and cutaneous afferents produced pressor responses (20 +/- 6 mmHg) that were accompanied by vasoconstriction in all three beds. These data suggest that vestibular inputs lead to a complex pattern of cardiovascular changes that is distinct from that which occurs in response to activation of other types of somatic afferents.

GABA B receptor-mediated effects on expression of c-Fos in rat trigeminal nucleus following high- and low-intensity afferent stimulation.

We examined the effects of systemic administration of a GABA(B) receptor agonist, baclofen, or antagonist, phaclofen, on the expression of c-Fos protein induced 3h after electrical stimulation of the trigeminal ganglion at low (0.1 mA) or high intensities (1.0 mA) in the urethane-anesthetized rat. In saline-treated rats, 10 min stimulation of the trigeminal ganglion induced c-Fos-immunopositive neurons throughout the full extent of the ipsilateral superficial layers of the trigeminal nucleus caudalis, and dorsal or dorsomedial part of the nuclei rostral to obex (trigeminal nucleus principalis, dorsomedial nucleus of trigeminal nucleus oralis and dorsomedial nucleus of trigeminal nucleus interpolaris). Animals stimulated at 1.0 mA induced a significantly higher number of labeled neurons in all the trigeminal sensory nuclei than animals stimulated at 0.1 mA. In rats treated with 20mg/kg i.p. baclofen and stimulated at 0.1 mA, the numbers of Fos-positive neurons in all the trigeminal sensory nuclei were significantly decreased compared to saline-treated controls. After stimulation at 1.0 mA in rats treated with baclofen, the numbers of Fos-positive neurons in all the trigeminal sensory nuclei were also significantly decreased. In rats treated with 2mg/kg i.p. phaclofen and stimulated at 1.0 mA, the numbers of Fos-positive neurons were significantly increased in all the trigeminal sensory nuclei. However, after stimulation at 0.1 mA in rats treated with phaclofen, the numbers of Fos-positive neurons were significantly decreased in the superficial layers and magnocellular zone of trigeminal nucleus caudalis and dorsomedial nucleus of trigeminal nucleus oralis. These results indicate that the expression of c-Fos in the trigeminal sensory nucleus is differentially regulated through GABAB receptors in a manner that is dependent on the nucleus and the type of primary afferents that are activated by different stimulus intensities. Systemic administration of baclofen could inhibit both nociceptive and non-nociceptive sensory activity in the trigeminal sensory nucleus. Systemic administration of phaclofen could enhance nociceptive sensory activity but not non-nociceptive activity.