Periglomerular afferent innervation of the mouse renal cortex.

Recent studies using a novel method for targeted ablation of afferent renal nerves have demonstrated their importance in the development and maintenance of some animal models of hypertension. However, relatively little is known about the anatomy of renal afferent nerves distal to the renal pelvis. Here, we investigated the anatomical relationship between renal glomeruli and afferent axons identified based on transient receptor potential vanilloid 1 channel (TRPV1) lineage or calcitonin gene related peptide (CGRP) immunolabeling. Analysis of over 6,000 (10,000 was accurate prior to the removal of the TH data during the review process) glomeruli from wildtype C57BL/6J mice and transgenic mice expressing tdTomato in TRPV1 lineage cells indicated that approximately half of all glomeruli sampled were closely apposed to tdTomato+ or CGRP+ afferent axons. Glomeruli were categorized as superficial, midcortical, or juxtamedullary based on their depth within the cortex. Juxtamedullary glomeruli were more likely to be closely apposed by afferent axon subtypes than more superficial glomeruli. High-resolution imaging of thick, cleared renal slices and subsequent distance transformations revealed that CGRP+ axons closely apposed to glomeruli were often found within 2 microns of nephrin+ labeling of glomerular podocytes. Furthermore, imaging of thick slices suggested that CGRP+ axon bundles can closely appose multiple glomeruli that share the same interlobular artery. Based on their expression of CGRP or tdTomato, prevalence near glomeruli, proximity to glomerular structures, and close apposition to multiple glomeruli within a module, we hypothesize that periglomerular afferent axons may function as mechanoreceptors monitoring glomerular pressure. These anatomical findings highlight the importance of further studies investigating the physiological role of periglomerular afferent axons in neural control of renal function in health and disease.

Interoception and Mental Health: A Roadmap.

Interoception refers to the process by which the nervous system senses, interprets, and integrates signals originating from within the body, providing a moment-by-moment mapping of the body's internal landscape across conscious and unconscious levels. Interoceptive signaling has been considered a component process of reflexes, urges, feelings, drives, adaptive responses, and cognitive and emotional experiences, highlighting its contributions to the maintenance of homeostatic functioning, body regulation, and survival. Dysfunction of interoception is increasingly recognized as an important component of different mental health conditions, including anxiety disorders, mood disorders, eating disorders, addictive disorders, and somatic symptom disorders. However, a number of conceptual and methodological challenges have made it difficult for interoceptive constructs to be broadly applied in mental health research and treatment settings. In November 2016, the Laureate Institute for Brain Research organized the first Interoception Summit, a gathering of interoception experts from around the world, with the goal of accelerating progress in understanding the role of interoception in mental health. The discussions at the meeting were organized around four themes: interoceptive assessment, interoceptive integration, interoceptive psychopathology, and the generation of a roadmap that could serve as a guide for future endeavors. This review article presents an overview of the emerging consensus generated by the meeting.

Identification of beta-2 as a key cell adhesion molecule in PCa cell neurotropic behavior: a novel ex vivo and biophysical approach.

Prostate cancer (PCa) is believed to metastasize through the blood/lymphatics systems; however, PCa may utilize the extensive innervation of the prostate for glandular egress. The interaction of PCa and its nerve fibers is observed in 80% of PCa and is termed perineural invasion (PNI). PCa cells have been observed traveling through the endoneurium of nerves, although the underlying mechanisms have not been elucidated. Voltage sensitive sodium channels (VSSC) are multimeric transmembrane protein complexes comprised of a pore-forming α subunit and one or two auxiliary beta (ß) subunits with inherent cell adhesion molecule (CAM) functions. The beta-2 isoform (gene SCN2B) interacts with several neural CAMs, while interacting putatively with other prominent neural CAMs. Furthermore, beta-2 exhibits elevated mRNA and protein levels in highly metastatic and castrate-resistant PCa. When overexpressed in weakly aggressive LNCaP cells (2BECFP), beta-2 alters LNCaP cell morphology and enhances LNCaP cell metastasis associated behavior in vitro. We hypothesize that PCa cells use beta-2 as a CAM during PNI and subsequent PCa metastasis. The objective of this study was to determine the effect of beta-2 expression on PCa cell neurotropic metastasis associated behavior. We overexpressed beta-2 as a fusion protein with enhanced cyan fluorescence protein (ECFP) in weakly aggressive LNCaP cells and observed neurotropic effects utilizing our novel ex vivo organotypic spinal cord co-culture model, and performed functional assays with neural matrices and atomic force microscopy. With increased beta-2 expression, PCa cells display a trend of enhanced association with nerve axons. On laminin, a neural CAM, overexpression of beta-2 enhances PCa cell migration, invasion, and growth. 2BECFP cells exhibit marked binding affinity to laminin relative to LNECFP controls, and recombinant beta-2 ectodomain elicits more binding events to laminin than BSA control. Functional overexpression of VSSC beta subunits in PCa may mediate PCa metastatic behavior through association with neural matrices.

Use of a virtual reality physical ride-on sailing simulator as a rehabilitation tool for recreational sports and community reintegration: a pilot study.

Participation in sailing by people with disabilities, particularly in small sailboats, is widely regarded as having positive outcomes on self-esteem and general health for the participants. However, a major hurdle for people with no previous experience of sailing, even by those without disabilities, is the perception that sailing is elitist, expensive, and dangerous. Real-time "ride-on" sailing simulators have the potential to bridge the gap between dry-land and on-the-water sailing. These provide a realistic, safe, and easily supervised medium in which nonsailors can easily and systematically learn the required skills before venturing out on the water. The authors report a 12-wk pilot therapeutic sailing program using the VSail-Access sailing simulation system followed by on-water experience. After completion of the training, all subjects demonstrated the ability to navigate a simple course around marker buoys (triangular configuration) on the computer screen, the ability to sail independently in winds of moderate strength (up to 14 knots) on water, and measurable improvements in their psychologic health. In addition, the subjects were able to participate in a sports activity with their respective family members and experienced a sense of optimism about their future.

Sialidase, chondroitinase ABC, and combination therapy after spinal cord contusion injury.

Axon regeneration in the central nervous system is severely hampered, limiting functional recovery. This is in part because of endogenous axon regeneration inhibitors that accumulate at the injury site. Therapeutic targeting of these inhibitors and their receptors may facilitate axon outgrowth and enhance recovery. A rat model of spinal cord contusion injury was used to test the effects of two bacterial enzyme therapies that target independent axon regeneration inhibitors, sialidase (Vibrio cholerae) and chondroitinase ABC (ChABC, Proteus vulgaris). The two enzymes, individually and in combination, were infused for 2 weeks via implanted osmotic pumps to the site of a moderate thoracic spinal cord contusion injury. Sialidase was completely stable, whereas ChABC retained>30% of its activity in vivo over the 2 week infusion period. Immunohistochemistry revealed that infused sialidase acted robustly throughout the spinal cord gray and white matter, whereas ChABC activity was more intense superficially. Sialidase treatment alone resulted in improved behavioral and anatomical outcomes. Rats treated exclusively with sialidase showed significantly increased hindlimb motor function, evidenced by higher Basso Beattie and Bresnahan (BBB) and BBB subscores, and fewer stepping errors on a horizontal ladder. Sialidase-treated rats also had increased serotonergic axons caudal to the injury. ChABC treatment, in contrast, did not enhance functional recovery or alter axon numbers after moderate spinal cord contusion injury, and dampened the response of sialidase in the dual enzyme treatment group. We conclude that sialidase infusion enhanced recovery from spinal cord contusion injury, and that combining sialidase with ChABC failed to improve outcomes.

Identification of the spinal pathways involved in the recovery of baroreflex control after spinal lesion in the rat using pseudorabies virus.

Neurons in the rostroventrolateral medulla (RVLM) mediate baroreflex regulation (BR) of spinal sympathetic preganglionic neurons. Previously, our laboratory has shown that recovery of BR occurs in the rat after spinal hemisection. (Zahner MR, Kulikowicz E, and Schramm LP. Am J Physiol Regul Integr Comp Physiol 301: R1584-R1590, 2011). The goal of these experiments was to determine whether the observed recovery of BR is mediated by the reorganization of ipsilateral pathways or by compensation by spared contralateral pathways. To determine this, we infected the left kidney in rats with the retrograde transynaptic tracer, pseudorabies virus (PRV), either 1 or 8 wk after left spinal hemisection at either T(3) or T(8), or after a sham lesion. In sham-lesioned rats, PRV infection of RVLM neurons was bilateral. In all rats with a left hemisection, regardless of the location of the lesion (T(3) or T(8)) or postlesion recovery time (1 or 8 wk), PRV infection of left RVLM neurons was significantly reduced compared with sham-lesioned rats (P < 0.05). In a separate group of rats, we performed BR tests by measuring responses of left renal sympathetic nerve activity to pharmacologically induced decreases and increases in arterial pressure. In rats with T(8) left hemisection and 8-wk recovery, BR was robust, and acute right upper thoracic hemisection abolished all BR of left renal sympathetic nerve activity. Collectively, these data suggest that the recovery of BR is not mediated by reorganization of ipsilateral bulbospinal connections, but instead by improved efficacy of existing contralateral pathways.

The lateral thoracic nerve and the cutaneous maximus muscle--a novel in vivo model system for nerve degeneration and regeneration studies.

We report a novel in vivo mouse model system to study regeneration of injured motor nerve and spatiotemporal pattern of denervation in experimental nerve diseases. The lateral thoracic nerve (LTN), as a pure motor nerve, innervates the cutaneous maximus muscle (CMM) by some of the shortest and the longest motor nerve fibers in the mouse body. Its branches and nerve terminals can be imaged in whole mount preparations. Here we describe the branching pattern of the LTN and its innervation of the CMM, and characterize degeneration and regeneration over time after a LTN crush by morphological and electrophysiological analyses. We demonstrate the utility of this model in a well-established neurotoxicity paradigm and in a genetic disease model of the peripheral neuropathy. Furthermore, this system enables punch biopsies that allow repeated and multi-location examinations for LTN regeneration and CMM reinnervation over time. The presence of the LTN and the CMM in a variety of species and its easy accessibility suggests that this in vivo model system offers considerable promise for future nerve degeneration and regeneration research.

Recovery of baroreflex control of renal sympathetic nerve activity after spinal lesions in the rat.

Spinal cord injury (SCI) has serious long-term consequences on sympathetic cardiovascular regulation. Orthostatic intolerance results from insufficient baroreflex regulation (BR) of sympathetic outflow to maintain proper blood pressure upon postural changes. Autonomic dysreflexia occurs due to insufficient inhibition of spinal sources of sympathetic activity. Both of these conditions result from the inability to control sympathetic activity caudal to SCI. It is well established that limited motor ability recovers after incomplete SCI. Therefore, the goal of this study was to determine whether recovery of BR occurs after chronic, left thoracic spinal cord hemisection at either T(3) or T(8). Baroreflex tests were performed in rats by measuring the reflex response of left (ipsilateral) renal sympathetic nerve activity to decreases and increases in arterial pressure produced by ramped infusions of sodium nitroprusside and phenylephrine, respectively. One week after a T(3) left hemisection, BR function was modestly impaired. However, 8 wk after a T(3) left hemisection, BR function was normal. One week after a T(8) left hemisection, BR function was significantly impaired, and 8 wk after a T(8) left hemisection, BR function was significantly improved. These results indicate that BR of renal sympathetic nerve activity in rats may partially recover after spinal cord hemisections, becoming normal by 8 wk after a T(3) lesion, but not after a T(8) lesion. The nature of the spinal cord and/or brain stem reorganization that mediates this recovery remains to be determined.

Spinal regions involved in baroreflex control of renal sympathetic nerve activity in the rat.

Spinal cord injury causes debilitating cardiovascular disturbances. The etiology of these disturbances remains obscure, partly because the locations of spinal cord pathways important for sympathetic control of cardiovascular function have not been thoroughly studied. To elucidate these pathways, we examined regions of the thoracic spinal cord important for reflex sympathetic control of arterial pressure (AP). In anesthetized rats, baroreceptor relationships between pharmacologically induced changes in AP and changes in left renal sympathetic nerve activity (RSNA) were generated in spinally intact rats and after acute surgical hemisection of either the dorsal, left, or right T8 spinal cord. None of these individual spinal lesions prevented the baroreceptor-mediated increases in RSNA caused by decreases in AP. Thus, baroreceptor-mediated increases in RSNA in rats are mediated by relatively diffuse, bilateral, descending, excitatory projections. The ability to reduce RSNA at increased AP was impaired after both dorsal and left hemisections, and baroreceptor gain was significantly decreased. Baroreceptor-induced maximum decreases in RSNA were not affected by right hemisections. However, baroreflex gain was impaired. Because both dorsal and left hemisections, but not right hemisections, attenuated the decrease in RSNA at elevated AP, we conclude that pathways involved in the tonic inhibition of spinal sources of sympathetic activity descend ipsilaterally in the dorsal spinal cord. Our results show that many lesions that do not fully transect the spinal cord spare portions of both descending excitatory pathways that may prevent orthostatic hypotension and descending inhibitory pathways that reduce the incidence of autonomic dysreflexia.

Sialidase enhances recovery from spinal cord contusion injury.

Axons fail to regenerate in the injured spinal cord, limiting motor and autonomic recovery and contributing to long-term morbidity. Endogenous inhibitors, including those on residual myelin, contribute to regeneration failure. One inhibitor, myelin-associated glycoprotein (MAG), binds to sialoglycans and other receptors on axons. MAG inhibition of axon outgrowth in some neurons is reversed by treatment with sialidase, an enzyme that hydrolyzes sialic acids and eliminates MAG-sialoglycan binding. We delivered recombinant sialidase intrathecally to rats following a spinal cord contusive injury. Sialidase (or saline solution) was infused to the injury site continuously for 2 wk and then motor behavior, autonomic physiology, and anatomic outcomes were determined 3 wk later. Sialidase treatment significantly enhanced hindlimb motor function, improved bulbospinally mediated autonomic reflexes, and increased axon sprouting. These findings validate sialoglycans as therapeutic targets and sialidase as a candidate therapy for spinal cord injury.

Effects of corticospinal tract stimulation on renal sympathetic nerve activity in rats with intact and chronically lesioned spinal cords.

Sympathetic preganglionic neurons and interneurons are closely apposed (presumably synapsed upon) by corticospinal tract (CST) axons. Sprouting of the thoracic CST rostral to lumbar spinal cord injuries (SCI) substantially increases the incidence of these appositions. To test our hypothesis that these additional synapses would increase CST control of sympathetic activity after SCI, we measured the effects of electrical stimulation of the CST on renal sympathetic nerve activity (RSNA) and arterial pressure (AP) in alpha-chloralose-anesthetized rats with either chronically intact or chronically lesioned spinal cords. Stimuli were delivered to the CST at intensities between 25-150 muA and frequencies between 25 and 75 Hz. Stimulation of the CST at the midcervical level decreased RSNA and AP. These decreases were not mediated by direct projections of the CST to the thoracic spinal cord because we could still elicit them by midcervical stimulation after acute lesions of the CST at caudal cervical levels. In contrast, caudal thoracic CST stimulation increased RSNA and AP. Neither the responses to cervical nor thoracic stimulation were affected by chronic lumbar SCI. These data show that the CST mediates decreases in RSNA via a cervical spinal system but excites spinal sympathetic neurons at caudal thoracic levels. Because chronic lumber spinal cord injury affected responses evoked from neither the cervical nor thoracic CST, we conclude that lesion-induced or regeneration-induced formation of new synapses between the CST and sympathetic neurons may not affect cardiovascular regulation.

Homer Wheelon, M.D., physiologist, artist, and poet: origins of the tailpieces in journals of the American Physiological Society.

Since 1953, illustrations have been inserted as "tailpieces" at the ends of articles in The American Journal of Physiology and The Journal of Applied Physiology. The drawings were made by Homer Wheelon, a member of the American Physiological Society from 1919 until his death in 1960. Forty-five years after his death, Wheelon is unknown, but he contributed 32 publications to the medical literature and trained J. Earl Thomas, an important 20th century gastrointestinal physiologist. Wheelon was born into poverty in 1883 to itinerant Methodist preachers, circumstances that guided his education and career choices. Throughout his life, Wheelon exhibited a fondness and talent for art and photography and an unusual breadth of intellectual interests and knowledge. Wheelon received a bachelor's degree from the University of Washington, then studied at the University of Oregon, Northwestern University, and St. Louis University. Earning his M.D. from St. Louis University and assuming a faculty position there, Wheelon and his graduate student, Thomas, conducted widely recognized gastrointestinal research. Returning to Seattle in 1921, Wheelon became a highly respected physician and hospital administrator, but he also found time to indulge his interest in visual art and poetry. In 1933, inspired by observing a rabbit being used in a pregnancy test, Wheelon began to write and illustrate an epic, 322-page poem, Rabbit No. 202, illustrations from which became the journals' tailpieces. The present study traces Wheelon's personal life and scientific career in an attempt to understand this complex man and the origins of his unusual poem and its drawings.

Sialidase enhances spinal axon outgrowth in vivo.

The adult CNS is an inhibitory environment for axon outgrowth, severely limiting recovery from traumatic injury. This limitation is due, in part, to endogenous axon regeneration inhibitors (ARIs) that accumulate at CNS injury sites. ARIs include myelin-associated glycoprotein, Nogo, oligodendrocyte-myelin glycoprotein, and chondroitin sulfate proteoglycans (CSPGs). Some ARIs bind to specific receptors on the axon growth cone to halt outgrowth. Reversing or blocking the actions of ARIs may promote recovery after CNS injury. We report that treatment with sialidase, an enzyme that cleaves one class of axonal receptors for myelin-associated glycoprotein, enhances spinal axon outgrowth into implanted peripheral nerve grafts in a rat model of brachial plexus avulsion, a traumatic injury in which nerve roots are torn from the spinal cord. Repair using peripheral nerve grafts is a promising restorative surgical treatment in humans, although functional improvement remains limited. To model brachial plexus avulsion in the rat, C8 nerve roots were cut flush to the spinal cord and a peroneal nerve graft was inserted into the lateral spinal cord at the lesion site. Infusion of Clostridium perfringens sialidase to the injury site markedly increased the number of spinal axons that grew into the graft (2.6-fold). Chondroitinase ABC, an enzyme that cleaves a different ARI (CSPGs), also enhanced axon outgrowth in this model. In contrast, phosphatidylinositol-specific phospholipase C, which cleaves oligodendrocyte-myelin glycoprotein and Nogo receptors, was without benefit. Molecular therapies targeting sialoglycoconjugates and CSPGs may aid functional recovery after brachial plexus avulsion or other nervous system injuries and diseases.

Spinal sympathetic interneurons: their identification and roles after spinal cord injury.

Primary afferent neurons rarely, if ever, synapse on the sympathetic preganglionic neurons that regulate the cardiovascular system, nor do sympathetic preganglionic neurons normally exhibit spontaneous activity in the absence of excitatory inputs. Therefore, after serious spinal cord injury "spinal sympathetic interneurons" provide the sole excitatory and inhibitory inputs to sympathetic preganglionic neurons. Few studies have addressed the anatomy and physiology of spinal sympathetic interneurons, to a great extent because they are difficult to identify. Therefore, this chapter begins with descriptions of both neurophysiological and neuroanatomical criteria for identifying spinal sympathetic interneurons, and it discusses the advantages and disadvantages of each. Spinal sympathetic interneurons also have been little studied because their importance in intact animals has been unknown, whereas the roles of direct projections from the brain to sympathetic preganglionic neurons are better known. This chapter presents evidence that spinal sympathetic interneurons play only a minor role in sympathetic regulation when the spinal cord is intact. However, they play an important role after spinal cord injury, both in generating ongoing activity in sympathetic nerves and in mediating segmental and intersegmental sympathetic reflexes. The spinal sympathetic interneurons that most directly influence the activity of sympathetic preganglionic neurons after spinal cord injury are located close to their associated sympathetic preganglionic neurons, and the inputs from distant segments that mediate multisegmental reflexes are relayed to sympathetic preganglionic neurons multisynaptically via spinal sympathetic interneurons. Finally, spinal sympathetic interneurons are more likely to be excited and less likely to be inhibited by both noxious and innocuous somatic stimuli after chronic spinal transection. The onset of this hyperexcitability corresponds to morphological changes in both sympathetic preganglionic neurons and primary afferents, and it may reflect the pathophysiological processes that lead to autonomic dysreflexia and the hypertensive crises that may occur with it in people after chronic spinal injury.

Increased close appositions between corticospinal tract axons and spinal sympathetic neurons after spinal cord injury in rats.

Treatments for spinal cord injury may promote new spinal cord synapses. However, the potential for new synapses between descending somatomotor and spinal sympathetic neurons has not been investigated. We studied rats with intact spinal cords and rats after a chronic, bilateral, dorsal spinal hemisection. We identified sympathetically related spinal neurons by transynaptic, retrograde transport of renally injected pseudorabies virus. We counted retrogradely labeled sympathetic preganglionic neurons (SPN) and putative sympathetic interneurons (IN) that, under light microscopy, appeared closely apposed by anterogradely labeled axons of the corticospinal tract (CST) and by axons descending from the well-established sympathetic regulatory region in the rostral ventrolateral medulla (RVLM). Spinal sympathetic neurons that were closely apposed by CST axons were significantly more numerous in lesioned rats than in unlesioned rats. CST axons closely apposed 5.4% of SPN and 10.3% of IN in rats with intact spinal cords, and 38.0% of SPN and 37.3% of IN in rats with chronically lesioned spinal cords. Further, CST appositions in SCI rats consisted of many more varicosities than those in uninjured rats. SPN and IN closely apposed by axons from the RVLM were not more numerous in lesioned rats. However, RVLM axons apposed many more SPN than IN in both control and lesioned rats. Therefore, RVLM sympathoexcitation may be mediated largely by direct synapses on SPN. Although we have not determined the functional significance of close appositions between the CST and spinal sympathetic neurons, we suggest that future studies of spinal cord repair and regeneration include an evaluation of potential, new, somatic-autonomic interactions.

Spinal interneurons infected by renal injection of pseudorabies virus in the rat.

The potency of spinal sympathetic reflexes is increased after spinal injury, and these reflexes may result in life-threatening hypertensive crises in humans. Few, if any, primary afferents project directly to sympathetic preganglionic neurons (SPN). Therefore, spinal sympathetic interneurons (IN) must play a major role in generating dysfunctional sympathetic activity after spinal cord injury. Furthermore, these IN are potentially aberrant targets, either for ascending and descending axons that may sprout after spinal cord injury or for axons that regenerate after spinal cord injury. We identified IN via the transsynaptic retrograde transport of pseudorabies virus (PRV) injected into the kidneys of rats. The proportion of infected IN ranged from approximately 1/3 to approximately 2/3 of the number of infected SPN. IN were heavily concentrated among the SPN in spinal lamina VII. However, IN were located in all lamina of the dorsal horn. The longitudinal distribution of infected IN was closely correlated with the longitudinal distribution of infected SPN. Few infected IN were found rostral or caudal to the longitudinal range of infected SPN. Infected IN were heterogeneous in both their sizes and the extent of their dendritic trees. The strong correlation between longitudinal distributions of infected IN and SPN supports physiological data demonstrating a segmental organization of spinal sympathetic reflexes. The paucity of infected IN in segments distant from SPN suggests that multisegmental sympathetic reflexes are mediated by projections onto IN rather than onto SPN themselves. The morphological heterogeneity of IN probably manifests the variety of systems that affect spinal sympathetic regulation.

Sympathetic activity and the underlying action potentials in sympathetic nerves: a simulation.

Understanding the relationship between activity recorded in sympathetic nerves and the action potentials of the axons that contribute to that activity is important for understanding the processing of sympathetic activity by the central nervous system. Because this relationship cannot be determined experimentally and is difficult to predict analytically, we simulated the summed action potentials of 300 axons. This simulation closely resembled actual sympathetic activity and permitted us to know how many action potentials contributed to each burst of simulated sympathetic activity and the durations and amplitudes of each burst. We used these simulated data to examine a statistical method (cluster analysis) that has been used to identify and quantify bursts of sympathetic activity. Simulation indicated that the integrals of bursts, whether determined directly from the simulation or by integrating bursts detected by cluster analysis, were linearly correlated to the number of action potentials contributing to bursts. The variances of samples of the simulated signal were also linearly correlated to the number of action potentials. The amplitudes of bursts of sympathetic activity were less well correlated to the number of underlying action potentials. A linear relationship existed between the average number of action potentials contributing to simulated bursts and the integral of the amplitude spectra obtained by Fourier transform of the simulated activity. Finally, simulated experiments indicated that relatively brief recordings might be sufficient to detect statistically significant changes in sympathetic activity.

Locations and morphologies of sympathetically correlated neurons in the T(10) spinal segment of the rat.

We precisely localized and morphologically characterized sympathetically correlated neurons in the acutely transected spinal cord of the rat. We have shown that these neurons are likely members of the spinal networks that generate sympathetic activity after spinal cord transection. In humans with injured spinal cords, these networks are responsible for hypertensive crises that occur in response to ordinarily innocuous stimuli. We recorded from neurons in the dorsal horn of the T(10) spinal segment of anesthetized rats after acute spinal cord transection at C(2). Neurons with activities closely correlated to renal sympathetic nerve activity (RSNA) were considered to be putative components of spinal sympathetic systems. These neurons had receptive fields on the left flank and abdomen. After characterizing their ongoing activities, receptive fields, and degrees of correlation with RSNA, we juxtacellularly labeled neurons with biotinamide and subsequently reconstructed their somas and dendrites histologically. Confirming our earlier studies, sympathetically correlated neurons were found in dorsal horn laminae III, IV, and V. For the first time, we also identified sympathetically correlated neurons in laminae I and II. The dendrites of all sympathetically correlated neurons projected to multiple lamina. By virtue of the positions of their somas and the broad projections of their dendrites, we concluded that sympathetically correlated neurons may receive direct input both from supraspinal systems and from nociceptive and non-nociceptive primary afferents.

Sensitivity of sympathetically correlated spinal interneurons, renal sympathetic nerve activity, and arterial pressure to somatic and visceral stimuli after chronic spinal injury.

In the chronic stage of spinal cord injury in humans, both innocuous and noxious somatic and visceral stimuli can elicit severe autonomic dysreflexia characterized by potentially dangerous, sympathetically mediated, increases in arterial pressure. We hypothesized that a similar sympathetic hyperexcitability would be manifested in spinal sympathetic networks of chronically spinally transected rats. To test this hypothesis, we compared the responses of sympathetically correlated spinal interneurons and arterial pressure to both innocuous and noxious stimuli in acutely and chronically spinally transected rats. Experiments were conducted in anesthetized female rats, either within hours of T(3) spinal transection (rats with acute spinal transection) or one month after T(3) spinal transection (rats with chronic spinal transection). Sympathetically correlated spinal interneurons were identified by cross correlating their ongoing activity with simultaneously recorded renal sympathetic nerve activity. Cutaneous stimuli (either light brushing or noxious pinch) were delivered to a wide area of the ipsilateral side of the rat. Colorectal distension was used as a noxious visceral stimulus. The activity of sympathetically correlated interneurons was increased by stimulation of more of the body surface and decreased by stimulation of less of the body surface in rats with chronic spinal transection than in rats with acute spinal transection. Colorectal distension elicited greater increases in arterial pressure in chronically than acutely spinally-transected rats without exciting significantly more interneurons in those rats. These results suggest that spinal circuits undergo significant plastic changes in the chronic stage of spinal cord injury, and they provide a mechanism for the observation, in some human patients, that many stimuli, both noxious and non-noxious, applied caudal to the site of spinal injury increase sympathetic activity and arterial pressure.