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Convergence of cortico- and cuneopontine projections onto components of the pontocerebellar system in the rat: an anatomical and electrophysiological study.

Previous studies in the rat have demonstrated that corresponding peripheral tactile and somatosensory cortical inputs converge within the granule cell layer of various cerebellar lobules and further that descending corticopontine projections from the forelimb sensory cortex (FLSCx) partially overlap with the projection zones of ascending basilar pontine afferents from nucleus cuneatus (NC). The present study employed anatomical and electrophysiological procedures to determine whether cortical and dorsal column nuclear afferent projections converge on pontine neurons that, in turn, provide mossy fiber input to the granule cell layer of the paramedian lobule (PML), i.e., that portion of the rodent cerebellum shown to receive forelimb peripheral inputs. The combination of the orthograde and retrograde axonal transport of horseradish peroxidase (HRP) conjugated to wheat germ agglutinin (WGA) was used light microscopically to demonstrate that orthogradely labeled projections from injections of the FLSCx and NC converged with ponto-paramedian projection neurons that were retrogradely labeled from injections of the PML. These studies were also repeated in conjunction with ablations of either the FLSCx or NC which resulted in the ultrastructural identification of degenerating, as well as WGA-HRP labeled axonal boutons of these pontine afferent projections thus confirming that such projections actually formed synaptic contacts with the retrogradely labeled pontoparamedian projection neurons. Single unit recording analyses of neurons in the ventromedial region of the basilar pons following combined electrical stimulation of various regions of the sensorimotor cortex and the contralateral body surface indicated that approximately 40% of all cells recorded responded to electrical stimulation of corresponding regions of the cortex and periphery, particularly the FLSCx and the forepaw. Natural cutaneous stimuli applied to the forepaw that also elicited responses in these same groups of basilar pontine neurons and were associated with relatively small receptive fields. Taken together, these observations indicate that the previously observed convergence of peripheral and somatosensory cortical inputs within the granule cell layer of the cerebellar cortex may be at least partially organized at the level of the basilar pons.

Action Potentials↗

Convergence patterns and multiple species interactions in a designed plant mixture of five species.

It is known that convergence and divergence can occur in complex plant communities, but the relative importance of biotic and abiotic factors driving these processes is less clear. We addressed this issue in an experiment using a range of mixed stands of five species that are common in Swiss fens (Carex elata, C. flava, Lycopus europaeus, Lysimachia vulgaris and Mentha aquatica) and two levels of water and nutrients. One hundred and seventy-six experimental mixtures were maintained in large pots (75 l) for two consecutive growing seasons in an experimental garden. The stands varied systematically in the initial relative abundance of each of the five species and in overall initial stand abundance. The changes in biomass over 2 years were modelled as linear functions of treatments and the initial biomass of each species. The dynamics of the system were mainly driven by differences in the identity of species and by a negative feedback mechanism but also by different abiotic conditions. In all mixtures, C. elata became more dominant over time, which caused an overall convergence of community composition. In addition, the rate of change of each species' biomass was negatively related to its own initial abundance. Thus, a negative feedback further contributed to the convergence of communities. Species responded differently to water level and nutrient supply, causing community dynamics to differ among treatments. However, the different abiotic conditions only slightly modified the overall convergence pattern. Competitive interactions between more than two species were weaker than the negative feedback but still significantly influenced the species' final relative abundance. The negative feedback suggests that there is niche partitioning between the species, which permits their coexistence.

Biomass↗

Convergence of cervical and trigeminal sensory afferents.

Cranial nociceptive perception shows a distinct topographic distribution, with the trigeminal nerve receiving sensory information from the anterior portions of the head, the greater occipital nerve, and branches of the upper cervical roots in the posterior regions. However, this distribution is not respected during headache attacks, even if the etiology of the headache is specific for only one nerve. Nociceptive information from the trigeminal and cervical territories activates the neurons in the trigeminal nucleus caudalis that extend to the C2 spinal segment and lateral cervical nucleus in the dorsolateral cervical area. These neurons are classified as multimodal because they receive sensory information from more than one afferent type. Clinically, trigeminal activation produces symptoms in the trigeminal and cervical territory and cervical activation produces symptoms in the cervical and trigeminal territory. The overlap between the trigeminal nerve and cervical is known as a convergence mechanism. For some time, convergence mechanisms were thought to be secondary to clinical observations. However, animal studies and clinical evidence have expanded our knowledge of convergence mechanisms. In this paper, the role of convergence mechanisms in nociceptive physiology, physiopathology of the headaches, clinical diagnosis, and therapeutic conduct are reviewed.

Electrophysiology↗

Quantification of mitral regurgitation with the proximal flow convergence method: a clinical study.

Accurate quantitation of valvular incompetence remains an important goal in clinical cardiology. It has been shown previously that when color flow Doppler mapping is used, simple measurements of apparent jet size do not correlate closely with regurgitant flow rate and regurgitant fraction. Recently the proximal flow convergence method has been proposed to quantify valvular regurgitation by analysis of the converging flow field proximal to a regurgitant lesion. Flow rate Q can be calculated as Q = 2 pi r2v(a), where v(a) is the aliasing velocity at a distance r from the orifice. In 54 patients (43 with sinus rhythm and 11 with atrial fibrillation) who had at least mild mitral regurgitation according to semiquantitative assessment, regurgitant stroke volume, regurgitant flow rate, and regurgitant fraction were calculated with the proximal flow convergence method and compared with values that were obtained by the Doppler two-dimensional echocardiographic method. Regurgitant stroke volumes (Vr) as calculated by the proximal flow convergence method correlated very closely with values that were obtained by the Doppler two-dimensional method, with r = 0.93 (y = 0.95x + 0.55) and delta Vr = -0.3 +/- 4.0 cm3. Regurgitant flow rates (Q) as calculated by both methods showed a similar correlation: r = 0.93 (y = 0.95x + 54) and delta Q = -34 +/- 284 cm3/min. The correlation for regurgitant fraction (RF) as calculated by both techniques showed r = 0.89 (y = 0.98x + 0.006) and delta RF = -0.005 +/- 0.06. All correlations were slightly better for the group of patients with sinus rhythm than for the study group of patients with atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Diffuse noxious inhibitory controls (DNIC): evidence for post-synaptic inhibition of trigeminal nucleus caudalis convergent neurones.

Activity produced by direct microelectrophoretic application of glutamate onto 19 convergent neurones in trigeminal nucleus caudalis, was strongly depressed during and after the application of heterotopic noxious conditioning stimuli: noxious heat (52 degrees C) applied to the tail, noxious pinches applied to the tail or hindpaws and intraperitoneal injections of bradykinin produced mean reductions in activity of 80-90%. The same noxious conditioning stimuli had no effect on the activities of any of 5 noxious-only or 5-non-noxious-only neurones. These effects were similar to those previously reported to influence peripherally evoked activities of nucleus caudalis convergent neurones and which have been termed diffuse noxious inhibitory controls (DNIC). It is therefore proposed that DNIC act on nucleus caudalis convergent neurones by a final post-synaptic inhibitory mechanism involving hyperpolarization of the neuronal membrane. Consistent with this hypothesis, it was also found that the noxious conditioning stimuli could restore firing of convergent neurones which had been excessively depolarised by large doses of glutamate.

Animals↗

Single unit activity at ventromedial medulla level in the awake, freely moving rat: effects of noxious heat and light tactile stimuli onto convergent neurons.

In this study, we recorded single unit activity at the ventromedial medulla (VMM) level in the awake, freely moving rat. In agreement with previous work under the same conditions, we found a vast majority of neurons which possess heterosensory and heterosegmental inputs ('convergent'). These units are activated either by auditory or mechanical innocuous and noxious stimuli applied all over the body surface. The activation threshold of these neurons is very low since light stimulation such as air puff produce intense bursts. In addition to this highly represented neuronal class, we also find another consistent VMM group of neurons which fire in relation to precise or generalized body movements. The main result of the present work is that, in addition to auditory and mechanical inputs, a relatively high proportion of VMM convergent neurons are activated by noxious heat pulses between 43 and 51 degrees C. In this range, it was possible to obtain stimulus-response functions with 2 degrees C steps only when a skin twitch reflex produced by the heat was present, also encoding the temperature intensity. In comparison to the VMM activations produced by an intense noxious heat pulse such as 51 degrees C, either auditory or controlled light touch stimuli induced a more robust response in terms of maximum frequency of discharge. Differential properties of VMM neurons in relation to innocuous and noxious information were also found using repetitive stimulation: although a strong and fast habituation of the 51 degrees C responses was observed, this phenomenon was not present for light touch induced activations. We propose that these differential properties might reflect separate pathways reaching the VMM, the one carrying innocuous information possibly relayed through the dorsal column nuclei. Although obtaining stimulus-response functions might implicate the VMM convergent neurons in the sensory-discriminative aspect of pain, their massive heterosensory and heterosegmental inputs favor a role in more general processes such as alertness or stress. Also, due to massive convergent properties, the involvement of this neuronal class in specific bulbospinal descending control systems of nociceptive information is questionable, Finally, our results obtained in the awake, freely moving rat strongly differ from the anesthetized preparation in that we found neither nociceptive specific units nor neurons inhibited by noxious peripheral stimulations largely described in this approach.

Action Potentials↗

The ability of inhibitory controls to 'switch-off' activity in dorsal horn convergent neurones in the rat.

Unitary extracellular recordings were made from 51 convergent neurones in the dorsal horn of the lumbar spinal cords of urethane anaesthetized rats. All the cells tested responded to sustained noxious mechanical stimulation of their receptive fields on the ipsilateral hindpaw, but only 26/49 gave tonic responses lasting for more than 5 min. In all 26 cells, these tonic responses were depressed by diffuse noxious inhibitory controls (DNIC) triggered by applying noxious conditioning stimuli elsewhere on the body. In seven cells, the inhibitory effects could involve a complete abolition of activity and in five cells, when this occurred, activity did not return during 2.5-6-min periods of observation following removal of the conditioning stimuli. However, in those cases, activity could be restored to pre-conditioning levels by further manipulations of the receptive field-either removal and re-application of the original stimulus or brief application of an additional stimulus. These results show that inhibitory controls can 'switch-off' activity in at least a small proportion of dorsal horn convergent neurones. One possible explanation would be that in these neurones, responses to sustained noxious stimuli may depend on activity in a positive feedback circuit within the central nervous system, which when interrupted, may be restored only by additional afferent inputs. The existence of such a loop could also explain the finding of convergent convergent neurones which initially were not spontaneously active but which after stimulation of their receptive fields, developed on-going discharges which could be switched-off by DNIC.

Animals↗

Convergence insufficiency and failure of accommodation following midfacial trauma.

A prospective evaluation of patients who had sustained midfacial trauma was carried out in order to determine the prevalence of impaired convergence and accommodation and to establish the risk factors for such defects. Of 52 patients in this study, 11 suffered accommodation and/or convergence disturbances. They included 6 males (17% of the male population) and 5 females (29% of the female population). Nine of these 11 patients sustained their injuries due to alleged assaults (24.3% of all assaulted patients) and 2 following simple falls (25% of all fall victims). Five patients complained of double vision for near (5/11 = 45.5%) and another 4 had blurred vision and/or difficulty with reading (4/11 = 36.4%). The remaining two were asymptomatic. Six patients were randomly selected to receive orthoptic exercises/treatment while the other five were monitored for signs of spontaneous recovery. Within six months of injury/surgery, 83% of the treated patients (n = 5) and 80% of the non-treated patients (n = 4) recovered to within the normal values of accommodation and convergence. No significant statistical relationship was found between the incidence of accommodation and/or convergence failure, and the cause or the type of fracture sustained. It may, however, be related to the severity of both the impact and the associated closed head trauma.

Accidental Falls↗

Convergence insufficiency in a rural population.

Convergence insufficiency represents a significant problem in optometric practice. The percentage of cases in a rural area was compared with that in a previous sample from an urban area, with respect to the general incidence, and the effects of age and taking of medicines as an indicator of health. The percentage of convergence insufficiency in the rural area was about half that in the urban area, and the percentage taking medicines was about two-thirds. The incidence of convergence insufficiency increased with age in both populations. When both samples were taken together, the incidence of convergence insufficiency was three times greater in those taking medicines.

Adolescent↗

Cavity convergence angles for direct composite inlays.

Direct composite inlays may sometimes be difficult to remove from the cavity following primary polymerization. The aim of this work was to find the lowest cavity convergence angle (taper) which would allow reliable inlay removal. Cavity finish and cavity size were also taken into account. Standardized mesio-occlusal-distal cavities of 6 degrees taper were cut into 10 teeth of varying mesiodistal width and finished with either 12-bladed tungsten carbide or 25 microns diamond burs. After separating medium had been applied. Coltene Brilliant Dentin composite resin was packed into the cavity and light cured. The force required to remove the inlay was measured with an Instron Universal Testing Machine. The cavities were then refinished with the alternative finish and the experiment repeated. The same sequence was used for cavities of 12 degrees and finally 18 degrees convergence angle which were cut consecutively in the same 10 teeth. Force levels related to cavity convergence angle, cavity finish and tooth size were tested by ANOVA and regression analysis. The forces required to remove some of the inlays from the 6 degrees, and to a lesser extent 12 degrees angled cavities, proved unacceptably high, while an 18 degrees convergence angle resulted in statistically significant lower forces which were unlikely to damage tooth or inlay. Cavity finish and tooth size did not influence inlay withdrawal force.

Analysis of Variance↗

Convergence of sensory input from tooth pulp, optic chiasm and sciatic nerve onto locus coeruleus neurons in the rat.

Electrophysiological studies using rats were performed to determine whether or not neurons in the locus coeruleus (LC), subcoeruleus and parabrachial areas receive convergence of sensory input from tooth pulp (TP), optic chiasm (OC) and sciatic nerve (SN). Convergence of input from these nerves was observed in 23% and 33% of LC and subcoeruleus neurons, respectively, and from two nerves in 31% and 20% of LC and subcoeruleus neurons, respectively, while convergence was rarely detected in parabranchial neurons. These results suggest that there is a convergence of peripheral sensory input onto more than half the noradrenergic coerulear neurons.

Animals↗

Intrathecal N-methyl-D-aspartate induces hyperexcitability in rat dorsal horn convergent neurones.

We have investigated the effects of intrathecal (i.t.) N-methyl-D-aspartate (NMDA) and an NMDA antagonist D-2-amino-5-phosphonovalerate (APV) on spontaneous and evoked activity in rat dorsal horn convergent neurones. Extracellular recordings were made from 54 convergent neurones located in both the superficial and deep dorsal horn. NMDA induced a dose-dependent increase in the spontaneous firing rate of convergent neurones, with 1 microM and 1 mM NMDA producing firing rates significantly greater than i.t. saline. In addition, NMDA induced hyperexcitability to subsequent noxious mechanical stimuli at 1 microM and 1 mM, and to innocuous stimuli at 1 mM. The NMDA-induced spontaneous hyperexcitability was reversed by pretreatment with 1 microM APV i.t. Diffuse noxious inhibitory controls (DNIC) applied to areas of the body remote from the receptive field also inhibited the NMDA-induced effects. There was no difference between the responses of superficial and deep dorsal horn neurones, suggesting a uniform excitatory action of NMDA on convergent neurones. Our results support a role for the NMDA receptor in mediating a central component of hyperalgesia, at the level of the spinal cord dorsal horn.

2-Amino-5-phosphonovalerate↗

Estimates of the convergence of association projections from area 17 to rostral area 18 in the cat depend on injection site size.

To estimate the degree of convergence of corticocortical projections from area 17 to the rostral part of area 18 in the cat, we injected the retrograde tracer diamidino yellow either at single or multiple adjacent sites in area 18. We measured the diameters of the individual or larger composite injections and the diameters of the labelled regions in area 17; from these values we estimated convergence factors. Small injections led to underestimates of the overall convergence of this pathway. A maximal value for convergence (about 3 mm) was obtained with larger composite injections (above about 3 mm in diameter). These results indicate that some area 17-to-18 projections may arborize widely in area 18. Their detection may require that injected tracer covers a large portion of their arbors.

Amidines↗

Convergence of cutaneous, tooth pulp, visceral, neck and muscle afferents onto nociceptive and non-nociceptive neurones in trigeminal subnucleus caudalis (medullary dorsal horn) and its implications for referred pain.

Because of the likely involvement of central convergence of afferent inputs in mechanisms underlying referred pain, the activity of single neurones was recorded in the cat's trigeminal (V) subnucleus caudalis (medullary dorsal horn) to test for the presence and extent of convergent inputs to the neurones. In chloralose-anaesthetized or decerebrate unanaesthetized cats, electrical stimuli were applied to afferents supplying facial skin, oral mucosa, canine and premolar tooth pulp, laryngeal mucosa, cervical skin and muscle, and jaw and tongue muscles, and tactile and noxious mechanical and thermal stimuli were applied to skin and mucosa. Considerable proportions of caudalis neurones which could be functionally classified on the basis of their cutaneous receptive field properties as low-threshold mechanoreceptive (LTM), wide-dynamic-range (WDR), or nociceptive-specific (NS) neurones, could be excited by electrical stimulation of several of these afferent inputs. Extensive convergence of afferent inputs, including inputs from skin or mucosal areas outside the neuronal oral-facial receptive field delineated by natural stimuli, was a particular feature of the units classified as cutaneous nociceptive neurones (i.e., WDR and NS). On the basis of antidromic activation, 15% of these WDR and NS neurones were shown to have a direct projection to the contralateral thalamus. The findings question the use of terminology and classifications of somatosensory neurones based only on the cutaneous receptive field properties of the neurones since distinctions between the different neuronal populations become less obvious when properties other than those related to cutaneous afferent inputs are taken into account. Moreover, the observations of extensive convergence of different types of afferents, which was especially apparent in cutaneous nociceptive neurones, also suggest a role for these neurones in mediating deep pain and in spread and referral of pain.

Animals↗

Effects of tizanidine (DS 103-282) on dorsal horn convergent neurones in the rat.

The effects of tizanidine, a new muscle relaxant, 5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiazole (DS 103-282) were studied on the activity of lumbar dorsal horn convergent neurons in anaesthetized paralysed rats. Following i.v. administration of tizanidine both the A- and C-fibre evoked responses were depressed in a dose-dependent manner in the 0.125-1.0 mg/kg range. The smaller dose employed (0.125 mg/kg) induced a significant depression of the C-fibre evoked responses (39.6 +/- 13.4% of the control responses) and a total recovery was observed 10 min after the injection: when the doses were increased, stronger and longer-lasting depressant effects were obtained. Identical but less powerful effects were observed on A-fibre responses. None of the depressive effects was correlated with variations in blood pressure. Microelectrophoretically applied tizanidine was found to depress current-dependently, the discharges of convergent neurones evoked by microelectrophoretically applied DL-homocysteic acid. In contrast, tizanidine (0.5, 1 mg/kg; i.v.) was found to be ineffective against the activities of non-nociceptive neurones triggered by mechanical stimulation of their receptive fields. It is concluded that tizanidine depresses specifically the activities of dorsal horn convergent neurones, probably in part by a post-synaptic inhibitory action. Owing to the role of convergent neurones in pain processes, the present result could explain, at least partially, the analgesic action of this compound.

Action Potentials↗

Somatic and vagal afferent convergence on solitary tract neurons in cat: electrophysiological characteristics.

Electrophysiological characteristics are described for 67 neurones localized to subnuclei of the solitary tract or the area of the dorsal motor nucleus of the vagus in alpha-chloralose-anesthetized, paralysed cats which received vagal and hindlimb sural or peroneal nerve excitation. The peroneal and sural nerves were stimulated in an exposed hindlimb preparation; the ipsilateral vagus was stimulated at the cervical level. Compound action potentials were recorded from all three nerves. Neurons were recorded with extracellular microelectrodes from the brain stem solitary area contralateral to the stimulated somatic nerves. Ninety-one percent of the recorded neurons were spontaneously active. Eighteen percent and 5% of the neurons received only peroneal or sural excitation, respectively, while 59% of the neurons received convergent peroneal and sural excitation. Thirty-nine of the 67 neurons were also tested for vagal input of which 41% responded with excitation. All of the neurons tested for vagal input also received converging excitation from one or both of the somatic nerves. Thirty-one percent of the vagal-excited neurons received converging input from both the peroneal and sural nerves. The combined mean minimal conduction velocity for peroneal and sural input was 31 +/- 1 m/s (mean +/- 1 S.E., range 9-54 m/s). Thirty-six percent of the peroneal and 31% of the sural afferents were Group II fibers. Significant periods of inhibition of spontaneous neuronal spike activity followed peroneal and sural excitation in 43 and 39% of the neurons, respectively. In many neurons, both excitation and inhibition of spike activity could be elicited at stimulus intensities as low as 1.2 times threshold for the lowest threshold fibers in each nerve. Somatic nerve-induced inhibition of spontaneous neuron activity without prior excitation was also observed. These results suggest that neurons of the solitary tract nuclei receive Group II and Group III somatic afferents which converge on neurons also receiving excitatory vagal input. Consequently, somesthetic and kinesthetic as well as visceral receptor activation may directly modulate solitary tract neurons. A possible conclusion is that the nucleus tractus solitarius is the initial central site of mediation of somatosympathetic reflexes. Modulation of the nucleus tractus solitarius by somatic afferents may then adjust sympathetic tone, via modulation of other medullary centers, in visceral and somatic tissues to match somatic metabolic needs.

Action Potentials↗

Convergence of cortical and cerebellar projections on single basilar pontine neurons: a light and electron microscopic study in the rat.

A protocol that involved a combination of two orthogradely transported tracer substances, wheat agglutinin-horseradish peroxidase and Phaseolus vulgaris leucoagglutinin injected at separate locations in the same animal was utilized to investigate the possible congruence of axonal projection fields formed by the cerebral cortical and cerebellar afferents to the basilar pontine nuclei. When large placements of tracer material were made in the cerebellar nuclei to label the cerebellopontine projections and a second tracer was injected in one of several cerebral cortical areas to visualize certain corticopontine projections, it was noted that axon terminal zones of the cortical and cerebellar systems occupied greater or lesser amounts of the same basilar pontine territory depending on the location of the cerebral cortical injection. Cerebellopontine terminal fields exhibited their greatest congruency with projections from the motor cortex containing the representation for facial musculature and with projections from the forelimb sensorimotor cortex. A lesser degree of overlap was observed when cerebellar projection zones were visualized in combination with basilar pontine projections from sensory face cortex, hindlimb sensorimotor cortex, visual cortex and auditory cortex. In addition, it was apparent that portions of the cerebellopontine and corticopontine terminal fields did not overlap at all. A related series of electron microscopic experiments was undertaken to establish that within the zones of overlapping cerebellar and cortical projections, there was in fact a convergence of the two afferent systems on single basilar pontine neurons. Boutons of the corticopontine system were labeled by the orthograde transport of wheat germ agglutinin horseradish peroxidase injected into the sensorimotor cortex while cerebellopontine terminals were marked for electron microscopic identification in the same animal by transecting the brachium conjunctivum and allowing sufficient time for boutons in the pontine nuclei to exhibit degeneration. Although the number of definitive examples of convergence was small, nonetheless it was possible to observe single basilar pontine neuron dendrites receiving synaptic contacts from both the cortical and cerebellar afferents systems. Taken together these observations indicate that some basilar pontine neurons receive a dual or convergent input from the cerebral cortex and cerebellar nuclei. It is difficult to estimate the prevalence of such convergence since cortical and cerebellar inputs typically contact distal and proximal pontine neuron dendrites, respectively, thus limiting the chances that both types of boutons can be observed in contact with a single basilar pontine neuron dendrite.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Convergence patterns of afferent information from the temporomandibular joint and masseter muscle in the trigeminal subnucleus caudalis.

Convergence patterns of afferent information from the temporomandibular joint (TMJ) and the masseter muscle (Mm) in the trigeminal subnucleus caudalis in response to natural stimulation were examined in anesthetized rats for a better understanding of masticatory pain phenomena. All neurons tested (135) could be placed in one of the following three classes according to their responsiveness to natural stimulation in the TMJ and/or the Mm: Class I neurons, excited by only innocuous stimuli; Class II neurons, excited by only noxious stimuli; Class III neurons, excited by both. Afferent inputs from the TMJ and the Mm converged on 108 (80%) of the 135 neurons. Of these convergent neurons, 79% received nociceptive information from the TMJ and/or the Mm. The results suggest that convergent caudalis neurons that receive nociceptive information from the TMJ and/or the Mm may be important to referred pain associated with dysfunction of the masticatory system.

Action Potentials↗