Proportion and location of spinal neurons receiving ventral root afferent inputs in the cat

Spinal neurons receiving ventral root afferent inputs were investigated in anesthetized and paralyzed cats. We were concerned with the afferent fibers in the ventral root that travel distally and then enter the spinal cord through the dorsal root. The questions to be answered included the proportion and distribution of spinal neurons receiving ventral root afferent inputs and their peripheral input characteristics. The 1.7 ventral root was cut near the spinal cord and the distal stump was stimulated while making a systematic search for neurons in the entire gray matter of the ipsilateral spinal cord that responded to the stimulation. The following conclusions were made: (i) the afferent fibers in the cat ventral root enter the spinal cord through the dorsal root and evoke a variety of responses (excitation, inhibition, or mixed) in a large proportion of spinal neurons (about 20%): (ii) these responses seem to be mediated largely by spinal mechanisms: (iii) spinal neurons receiving ventral root afferent inputs are situated in a wide region of the ventral spinal cord: (iv) ventral root fibers in a single root enter the spinal cord and exert their responses over a large region of the spinal cord (at least two spinal segments rostrally and caudally): (v) some of the spinal neurons that responded to ventral root stimulation were found to be ascending tract cells, suggesting that ventral root afferent inputs can reach supraspinal structures: (vi) ventral root afferent fibers converge onto spinal neurons that have a variety of peripheral receptive field characteristics: and (vii) with some exceptions, most neurons receiving ventral root inputs were excited best by mechanical and/or thermal noxious stimuli applied to the periphery.     

Ventral root potentials of the cat's sacrococcygeal segments evoked by stimulation of intact and transected dorsal roots

The latency and amplitude of reflex-evoked potentials in the sacrococcygeal ventral roots of acute spinalized cats were investigated. The characteristics of the potentials were examined in response to electrical stimulation of intact and acutely transected dorsal roots. We found that: the last sacral and caudal (coccygeal) segments of the cat's spinal cord are endowed with electrophysiologic characteristics that distinguish them from other spinal segments (e.g., L7-S1); afferent stimulation of the corresponding intact dorsal roots evokes in the ventral root of segment S2 a small monosynaptic response, whereas no monosynaptic response is seen in segment Ca6; acute transection of the dorsal roots provokes an increment of the monosynaptic response in all segments studied except for Ca6; rhizotomy provokes in Ca5 the appearance of polysynaptic responses to electrical stimulation of the corresponding dorsal root; and transection of the cutaneous afferent fibers of the coccygeal motoneurons resulted in an increment of monosynaptic and polysynaptic responses, indicating the removal of inhibitory effects.     

The projection of the medial and posterior articular nerves of the cat's knee to the spinal cord

We studied the spinal projections of the medial and posterior articular nerves (MAN and PAN) of the knee joint in the cat with the aid of the transganglionic transport of horseradish peroxidase. The afferent fibers of the MAN entered the spinal cord via the lumbar dorsal roots L5 and L6 and those of the PAN entered via the dorsal roots L6 and L7. Within the dorsal root ganglia, most labeled neurons had small to medium diameters. A relatively higher number of medium-size cell bodies were labeled from the PAN than from the MAN. In the spinal cord labeled MAN afferent fibers and terminations were most dense in the L5 and L6 segments, and those of the PAN were most dense in L6 and L7, that is, in the respective segments of entry. Labeled afferent fibers from both nerves projected rostrally at least as far as L1 and caudally as far as S2. Labeled fibers were found in Lissauer's tract as well as in the dorsal column immediately adjacent to the dorsal horn. In the spinal gray matter, both nerves had two main projection fields, one in the cap of the dorsal horn in lamina I, the other in the deep dorsal horn in laminae V-VI and the dorsal part of lamina VII. Both nerves, but particularly the PAN, projected to the medial portion of Clarke's column. No projection was found to laminae II, III, and IV of the dorsal horn or to the ventral horn. Since these findings parallel observations on hindlimb muscle afferent fibers, the present data support the existence of a common pattern for the central distribution of deep somatic afferent fibers.     

Characterization of forms of immunoreactive somatostatin in sensory neuron and normal and deafferented spinal cord

In order to determine the contribution made by primary sensory afferents and supraspinal projections to the immunoreactive somatostatin (IRS) content of the spinal cord, measurements were made of the concentration of IRS in the dorsal and ventral halves of the cord in cats subjected to unilateral lumbosacral dorsal rhizotomy (L1-S3) alone or combined with spinal cord transection. The molecular forms of IRS (characterized by gel chromatography) in L7 lumbar spinal cord, L6-S1 dorsal roots, ventral roots and dorsal root ganglia, and sciatic nerve were also determined. S14 was the predominant form in all tissues examined, but two additional molecular forms corresponding to S28 and S11.5 kdalton were present in dorsal root ganglia and spinal cord; S28 but not S11.5 kdalton was detected in both dorsal roots and sciatic nerves. These results indicate that S14 and S28 and S28 are transported along the central and peripheral processes of dorsal root ganglia, but that spinal cord S11.5 kdalton originates in the central nervous system. IRS in the dorsal horn was reduced by ca. 40% following dorsal root section. Neither disruption of descending pathways by spinal transection nor surgical isolation of the lumbar segements lowered cord somatostatin content below that produced by dorsal root section, indicating that most of the somatostatin within the cord arises from the dorsal root and from neurons in local spinal segments. Although the total content of IRS in the dorsal horn was reduced by ca. 40% following dorsal rhizotomy, the pattern of molecular forms was not changed accordingly. Since S14 and S28 but not S11.5 kdalton are transported via the dorsal root, the dorsal root section would be predicted to produce a relatively greater decrease in S14 and S28 than in S11.5 kdalton. Therefore, failure to find a selective loss of S14 and S28 suggests that dorsal rhizotomy affects dorsal horn IRS content not only by removing afferent input but possibly also by modifyinh the processing of IRS by the remaining somatostatinergic neurons.     

Hindlimb movement in the cat induced by amplitude-modulated stimulation using extra-spinal electrodes

Hindlimb movement in the cat induced by electrical stimulation with an amplitude-modulated waveform of the dorsal surface of the L5-S1 spinal cord or the L5-S1 dorsal/ventral roots was investigated before and after acute spinal cord transection at the T13-L1 level. Stimulation of the spinal cord or dorsal/ventral root at the same spinal segment induced similar movements including coordinated multi-joint flexion or extension. The induced movements changed from flexion to extension when the stimulation was moved from rostral (L5) to caudal (S1) spinal segments. Stimulation of a dorsal or ventral root on one side induced only ipsilateral hindlimb movement. However, stimulation on the dorsal surface of the spinal cord along the midline or across the spinal cord induced bilateral movements. The extension induced by stimulation of L7 dorsal root produced the largest ground reaction force that was strong enough to support body weight. Dorsal root stimulation induced a larger ground reaction force than ventral root stimulation and produced a more graded recruitment curve. Stepping at different speeds could be generated by combined stimulation of the rostral (L5) and the caudal (L6/L7) spinal segments with an appropriate timing between the different stimulation channels. Acute transection of the spinal cord did not change the responses indicating that the induced movements did not require the involvement of the supraspinal locomotor centers. The methods and the stimulation strategy developed in this study might be utilized to restore locomotor function after spinal cord injury.     

Carbonic anhydrase activity in the normal and injured peripheral nervous system of the rat

The carbonic anhydrase reactivity of primary neurons and axons of the L4 and L5 lumbar levels was studied in rats before and after various surgical procedures including transection of the spinal cord, removal of dorsal root ganglia, and transection of ventral or dorsal roots or spinal nerves. In normal animals, carbonic anhydrase reactivity was confined to large and medium size neurons of the dorsal root ganglia, and was also present in a sizeable percentage of cells scattered throughout the thoracolumbar sympathetic chain and in the celiac ganglion. At root level, enzymatic staining could be detected in 48.7% of the dorsal root myelinated axons of most sizes, whereas in ventral roots, it was restricted to small myelinated axons, in a proportion much higher at the L4 than in the L5 level. Spinal motoneurons remained unlabeled, despite procedures aimed at increasing the somal concentration of carbonic anhydrase, such as ventral root ligation and blocking of the fast or slow axoplasmic transport using colchicine or iminodiproprionitrile. However, it is likely that reactive ventral root axons originate from neurons situated segmentally in the spinal cord, and do not constitute aberrant sensory fibers, as carbonic anhydrase activity remained unchanged in the L4 and L5 ventral roots after removal of the corresponding spinal ganglia, whereas it disappeared after damage to the spinal cord at the lumbar level, or at a site distal to a ventral root section. Enzymatic staining of neurons of the dorsal root ganglia was not modified by a dorsal rhizotomy, but showed a marked decrease after transection of the spinal nerve.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anatomical evidence for two spinal 'afferent-interneuron-efferent' reflex pathways involved in micturition in the rat: a 'pelvic nerve' reflex pathway and a 'sacrolumbar intersegmental' reflex pathway

We labeled interneurons in the L1-L2 and L6-S1 spinal cord segments of the rat that are involved in bladder innervation using transneuronal retrograde transport of pseudorabies virus (PRV) in normal animals and in animals with selected nerve transections. Preganglionic neurons were identified using antisera against choline acetyltransferase (ChAT). In some experiments we labelled parasympathetic preganglionic neurons (PPNs) in the L6-S1 spinal cord by retrograde transport of Fluorogold from the major pelvic ganglion. We identified bladder afferent terminals using the transganglionic transport of the anterograde tracer cholera toxin subunit b. We present anatomical evidence for two spinal pathways involved in innervation of the bladder. First, in the intact rat, afferent information from the bladder connects, via interneurons in L6-S1, to the PPNs that provide the efferent innervation of the bladder. The afferent terminals were located mainly in close apposition to interneurons located dorsal to the retrogradely labeled PPNs. Second, using L6-S1 ganglionectomies or L6-S1 ventral root rhizotomies we limited viral transport to the sympathetic pathways innervating the bladder. This procedure also labelled interneurons (but not PPNs) with PRV in the L6-S1 spinal cord in a location very similar to those described in the intact rat. These interneurons also receive bladder afferent terminals but we propose that they project to sympathetic preganglionic neurons, most of which are in the L1-L2 spinal segments. Based on this anatomical evidence, we propose the existence of two spinal reflex pathways involved in micturition: a pathway limited to a reflex arc in the pelvic nerve (presumably excitatory to the detrusor muscle); and a pathway involving the pelvic nerve and sympathetic nerve fibers, some of which may travel in the hypogastric (presumably inhibitory to the detrusor muscle).     

Immunohistochemical demonstration of some putative neurotransmitters in the lamprey spinal cord and spinal ganglia: 5-hydroxytryptamine-, tachykinin-, and neuropeptide-Y-immunoreactive neurons and fibers

The distribution of some putative neurotransmitters was investigated in the spinal cord and spinal ganglia of the lamprey, a primitive vertebrate, by using immunohistochemical methods. In the spinal cord a midline row of 5-hydroxytryptamine (5-HT)-immunoreactive neurons was present immediately ventral to the central canal over the entire length of the spinal cord. The ventral processes of these neurons formed a dense ventromedial plexus of varicosities. In the dorsal, lateral, and ventral spinal axon columns, several longitudinal 5-HT fibers were present. After chronic spinal transections the distribution of 5-HT fibers was unchanged; it is therefore concluded that there was no substantial descending 5-HT contribution and that the spinal 5-HT neurons supplied the regional 5-HT innervation. The spinal 5-HT cells sent fibers into the dorsal and ventral roots; 5-HT cell bodies and fibers were also present in the spinal dorsal root ganglia, in their dorsal, ventral, and lateral nerve branches, and in the dorsal and ventral branches of the ventral roots. Neurons and fibers containing peptides of the tachykinin (TK) family (to which, amongst others, substance P belongs) were found in the spinal cord. TK neurons in the spinal cord supplied the local TK innervation, as well as TK fibers in the dorsal and ventral roots. Fibers have been found containing either TK, or 5-HT, or both compounds. Neurons containing neuropeptide-Y (NPY)-immunoreactive material were present in a medial column just dorsal to the central canal. The NPY neurons have longitudinal, mainly descending, fibers that provide the local NPY innervation of the lamprey spinal cord. The present results provide evidence for local spinal systems containing 5-HT, TK, 5-HT and TK, or NPY, but in contrast to mammals, these compounds do not seem to arise from supraspinal neurons.     

Projection of nodose ganglion cells to the upper cervical spinal cord in the rat

Afferent fibers mediating pain from myocardial ischemia classically are believed to travel in sympathetic nerves to enter the thoracic spinal cord. After sympathectomies, angina pectoris still may radiate to the neck and inferior jaw. Sensory fibers from those regions are thought to enter the central nervous system through upper spinal cord segments. We postulated that axons from nodose ganglion cells might project to cervical cord segments. The purpose of this study was to determine the density and pathway of vagal afferent innervation to the upper cervical spinal cord. Following an injection of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the upper cervical spinal cord, approximately 5.8% of cells in the nodose ganglion contained reaction product. Cervical vagotomy did not diminish the density of WGA-HRP labeled cells in the nodose ganglion. However, a spinal cord hemisection cranial to the injection site eliminated labeling of nodose cells. These data indicate that a portion of vagal afferent neurons project from the nodose ganglion to the upper cervical spinal cord. In addition, vagal afferent fibers reach the spinal cord via a central route rather than through dorsal root ganglia.     

A light and electron microscopic analysis of the sacral parasympathetic nucleus after labelling primary afferent and efferent elements with HRP

Primary afferent input to the cat sacral parasympathetic nucleus (SPN) has been examined by injury filling sacral dorsal roots, ventral roots, or both with horseradish peroxidase (HRP). Appropriate spinal segments were processed for the demonstration of HRP with diaminobenzidine and prepared for sequential light (LM) and electron (EM) microscopy. At the LM level, a large fascicle of primary afferent fibers was observed passing ventrally along the lateral edge of the dorsal horn into the region of the SPN. Varicosities were seen throughout the course of the axons but were particularly abundant within the SPN. Injury filling of the ventral roots with HRP resulted in a Golgi-like labelling of preganglionic neurons and their dendritic arbors, as well as ventral root afferent fibers. Swellings on both dorsal and ventral root afferent axons were observed in close apposition to labelled preganglionic neurons and their dendrites. At the ultrastructural level, afferent terminals were found to contain clear spherical vesicles; 66% of these terminals also contained at least one dense-cored vesicle. Of particular interest was the presence of labelled dorsal and ventral root afferent terminals synapsing on labelled preganglionic neurons. Preganglionic neurons were also postsynaptic to unlabelled terminals containing clear spherical (79.7%) or pleomorphic vesicles (20.3%). These data indicate that preganglionic neurons receive direct input from several sources, and provide the first demonstration of direct input to these cells from sensory fibers in the dorsal and ventral roots. The connections described in the present study provide interesting and, as yet, unexplored possibilities for sensory and autonomic reflex integration.     

Evidence for invasion of regenerated ventral root afferents into the spinal cord of the rat subjected to sciatic neurectomy during the neonatal period

Sectioning the sciatic nerve of experimental animals at the neonatal stage triggers growth of afferent fibers in the ventral root. The present study examined the possibility that the regenerating fiber terminals grow into the spinal cord. The sciatic nerve on one side was cut in neonatal rats. After the rats were fully grown, either an electrophysiological or a histochemical study was performed. The results of electrophysiological experiments showed that stimulation of certain loci in the L5 spinal cord evoked antidromic potentials in the L5 ventral root with a long latency. Various evidence suggests that the long latency potentials are due to activation of C fibers. These C-fiber potentials were on average bigger and were elicited from more numerous loci on the side ipsilateral to the sciatic nerve lesion than on the contralateral side. Furthermore, stimulation of the spinal cord of unoperated normal rats rarely evoked such potentials. For the histochemical study, horseradish peroxidase (HRP) was injected into the L5 spinal cord after cutting the L4-L6 dorsal roots. A lot more cells in the L5 dorsal root ganglion (DRG) on the side ipsilateral to the sciatic nerve lesion were labeled with HRP transported retrogradely through the L5 ventral root than on the contralateral side. Control experiments showed that few DRG cells are labeled with HRP in normal unoperated rats. The combined results of the electrophysiological and histochemical studies suggest invasion of ventral root afferents into the spinal cord, given enough postoperative time. It is not known whether or not these terminals make functional synaptic contacts in the spinal cord.     

Distribution of NADPH-d and nNOS-IR in the thoracolumbar and sacrococcygeal spinal cord of the guinea pig

The distribution of NADPH-d staining and neuronal nitric oxide synthase (nNOS)-immunoreactivity in the spinal cord of the guinea pig was studied to evaluate the potential role of nitric oxide in lumbosacral afferent and spinal autonomic pathways and to compare the distribution of these two markers to that observed in other species. NADPH-d staining and nNOS-immunoreactivity were present in neurons and fibers in the superficial dorsal horn, dorsal commissure and in neurons around the central canal in all levels of the spinal cord examined. Sympathetic preganglionic neurons in the thoracic and rostral lumbar segments identified by choline acetyl transferase (ChAT) immunoreactivity exhibited prominent NADPH-d staining and nNOS-immunoreactivity; whereas the ChAT-immunoreactive parasympathetic preganglionic neurons in the sacral segments were not stained. The most prominent NADPH-d staining in the sacral segments occurred in fibers extending from Lissauer's tract through laminae I along the lateral edge of the dorsal horn to the region of the sacral parasympathetic nucleus (lateral collateral pathway of Lissauer). These fibers were prominent in the S1-S3 segments but not in adjacent (L5-L7 and Cx1) or thoracolumbar segments. These NADPH-d fibers were, for the most part, not nNOS-immunoreactive, but did overlap with a prominent fiber bundle containing vasoactive intestinal polypeptide immunoreactivity in the sacral spinal cord. These results indicate that nitric oxide may function as a transmitter in thoracolumbar sympathetic preganglionic neurons, but not in sacral parasympathetic preganglionic neurons. Although the functional significance of the NADPH-d positive, nNOS-negative fiber bundle on the lateral edge of the sacral dorsal horn remains to be determined, this fiber tract may represent, in part, visceral afferent projections to the sacral parasympathetic nucleus.     

Dermatomes and the central organization of dermatomes and body surface regions in the spinal cord dorsal horn in rats

Dermatomes and the associated central projection fields were studied with the application of fluorescent neurotracer, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), to 21 reference points on rat trunk and hindlimb skin. Segmental distribution and rostrocaudal central level of dorsal root ganglion (DRG) neurons innervating reference points were examined and DiI-induced fluorescent areas were mapped in the horizontal plane through lamina II of the dorsal horn. Segmental levels of DRG neurons innervating reference points were generally identical to the level determined using dye-extravasation methods. However, innervation of the first digit was situated in the L4 dermatome, not the L3 reported previously using those methods. Generally, afferents from a reference point projected to a single field in the ipsilateral dorsal horn. Reference points on ventral and dorsal median lines of the trunk were represented bilaterally. Afferents from reference points located on the ventral median line of the hindlimb projected to two separate fields: one on the medial margin of spinal cord segments L2-L5 and the other on the medial half of spinal cord segment L5. From the distribution of central projection fields of reference points, central projection fields of dermatomes were revealed as even in shape and located within corresponding spinal cord segments. The arrangement of peripheral and central fields of dermatomes and body surface regions suggests that peripheral and central projection fields of cutaneous afferent fibers are reshaped from the common prototypical pattern that exhibits an orderly and evenly sequenced arrangement.     

Spinal nerve root distribution of the myelinated and unmyelinated nerve fibers of a cat cutaneous nerve]

The distribution of myelinated and nomyelinated nerve fibres from n. saphenus in the dorsal and ventral roots of the cat spinal cord was investigated, using methods improving the signal-to-noise ratio in the neurogram of the nerve evoked response. Nerve fibres from n. saphneus enter the spinal cord through roots of segments L4-6. In the dorsal roots of these segments the nerve fibres have conduction velocities from 80 to 0.38 m/s. In the ventral roots four groups of the nerve fibres with conduction velocities 80--60, 40--30, 12.0--3.0 and 1.1--0.51 m/s are found that are likely to be afferents. The conditions for low amplitude potentials detection in the spinal cord roots as well as the possible functional significance of the nerve fibres in the ventral roots are discussed.     

Spinal neurons activated with the urethrogenital reflex in the male rat

The urethrogenital (UG) reflex is a spinal ejaculatory-like reflex. The location of spinal neurons activated by the UG reflex was examined in the male rat using the immediate early gene, c-fos. In addition, co localization of neurons containing galanin and choline acetyl transferase (ChAT) and serotonin fibers with fos-immunoreactive (fos-I) nuclei was examined. Activation of the UG reflex resulted in a significant increase in fos positive nuclei in segments T13-S1, compared to controls in which the UG reflex was not activated. Spinal circuits involved in the UG reflex include neurons relaying afferent information from the pudendal sensory nerve, in the dorsal horn and medial cord of L5-S1. Interneurons specifically activated with the UG reflex were identified in the medial, intermediate and lateral gray. A small proportion of parasympathetic and sympathetic preganglionic neurons in the intermediolateral cell column (IML) of L5-S1 and IML and medial gray of T13-L2, respectively, was activated with the UG reflex. A significant increase in the number of galanin containing neurons expressing c-fos in the medial gray of L3-L4 was also observed with the UG reflex. Serotonin fibers and varicosities were found throughout the spinal cord and were especially dense in the ventral horn, IML and medial gray. Fos activated neurons were found in close apposition to serotonin fibers in the IML and medial gray. These studies demonstrate the multisegmental intraspinal circuitry responsible for ejaculatory-like responses and demonstrate the potential involvement of galanin, acetylcholine and serotonin in mediation of the UG reflex.     

Central projections and connections of lumbar primary afferent fibers in adult rats: effectively revealed using Texas red-dextran amine tracing

Signals from lumbar primary afferent fibers are important for modulating locomotion of the hind-limbs.However,silver impregnation techniques,autoradiography,wheat germ agglutinin-horseradish peroxidase and cholera toxin B subunit-horseradish peroxidase cannot image the central projections and connections of the dorsal root in detail.Thus,we injected 3-k Da Texas red-dextran amine into the proximal trunks of L4 dorsal roots in adult rats.Confocal microscopy results revealed that numerous labeled arborizations and varicosities extended to the dorsal horn from T12–S4,to Clarke's column from T10–L2,and to the ventral horn from L1–5.The labeled varicosities at the L4 cord level were very dense,particularly in laminae I–Ⅲ,and the density decreased gradually in more rostral and caudal segments.In addition,they were predominately distributed in laminae I–IV,moderately in laminae V–VⅡ and sparsely in laminae VⅢ–X.Furthermore,direct contacts of lumbar afferent fibers with propriospinal neurons were widespread in gray matter.In conclusion,the projection and connection patterns of L4 afferents were illustrated in detail by Texas red-dextran amine-dorsal root tracing.     

Central generation of locomotion in the spinal dogfish.

After a transection of the spinal cord a dogfish performs continuous swimming movements with a phase lag between adjacent segments. It is shown that the intersegmental coordination remains after an extensive dorsal root transection as well as after curarization. In the former case the motor activity was recorded electromyographically in several segments along the body, in the latter case the intersegmental coordination was evaluated by recording the efferent activity in different ventral roots along the body. It was concluded that a spinal central network can account for the phase lag observed between successive segments during swimming. It was also shown that the efferent activity from parts of the spinal cord with no dorsal roots intact could be influenced by peripheral stimuli such as pressure on the pelvic fins; this result suggests that some afferent fibres reach the spinal cord via the ventral roots.     

Propriospinal neurons in the C1-C2 spinal segments project to the L5-S1 segments of the rat spinal cord

Physiological studies indicate that neurons in the upper cervical spinal cord have descending projections to the lumbosacral spinal cord and mediate inhibition of dorsal horn neurons activated from afferent input. In the present study, retrograde tracing techniques were used to examine the distribution of propriospinal neurons in C1-C2 spinal segments that project to lumbosacral spinal segments. Fluorogold or horseradish peroxidase were injected unilaterally or bilaterally into the L5-S1 spinal segments. After 2–4 days, rats were perfused with fixative and C1-C2 spinal segments were processed for retrograde labeling. Numerous neurons were found in the C1-C2 segments. In unilaterally and bilaterally injected rats, retrogradely labeled neurons were located on both the ipsilateral and contralateral sides. Retrogradely labeled neurons were located in the following locations: lateral cervical and spinal nuclei, nucleus proprius, ventral horn and the central gray region (area X). These studies demonstrate a descending projection from C1-C2 segments to the lower lumbar and sacral spinal cord. We hypothesize that many of these C1-C2 propriospinal neurons are important in modulating responses of spinal neurons at lower segmental levels to various peripheral stimuli.