Lumbosacral spinal cord epidural stimulation improves voiding function after human spinal cord injury.

Deficits in urologic function after spinal cord injury (SCI) manifest both as a failure to store and empty, greatly impacting daily life. While current management strategies are necessary for urological maintenance, they oftentimes are associated with life-long side effects. Our objective was to investigate the efficacy of spinal cord epidural stimulation (scES) as a promising therapy to improve bladder control after SCI. A bladder mapping study was undertaken for sixteen sessions over the course of four months in an individual with chronic, motor complete SCI. Varying combinations of stimulating cathode electrodes were initially tested during filling cystometry resulting in the identification of an effective configuration for reflexive bladder emptying at the caudal end of the electrode array. Subsequent systematic testing of different frequencies at a fixed stimulus intensity and pulse width yielded lowest post-void residual volumes at 30 Hz. These stimulation parameters were then tested in four additional research participants and found to also improve reflexive voiding efficiency. Taken together with SCI studies on step, stand, voluntary motor control and cardiovascular regulation, these findings further corroborate that scES has an all-encompassing potential to increase the central state of excitability, allowing for the control of multiple body functions, including the urological system.

Training-Induced Functional Gains following SCI.

We previously demonstrated that daily, hour-long training sessions significantly improved both locomotor (limb kinematics, gait, and hindlimb flexor-extensor bursting patterns) and nonlocomotor (bladder function and at-level mechanical allodynia) functions following a moderate contusive spinal cord injury. The amount of training needed to achieve this recovery is unknown. Furthermore, whether this recovery is induced primarily by neuronal activity below the lesion or other aspects related to general exercise is unclear. Therefore, the current study objectives were to (1) test the efficacy of 30 minutes of step training for recovery following a clinically relevant contusion injury in male Wistar rats and (2) test the efficacy of training without hindlimb engagement. The results indicate that as little as 30 minutes of step training six days per week enhances overground locomotion in male rats with contusive spinal cord injury but does not alter allodynia or bladder function. Thirty minutes of forelimb-only exercise did not alter locomotion, allodynia, or bladder function, and neither training protocol altered the amount of in-cage activity. Taken together, locomotor improvements were facilitated by hindlimb step training for 30 minutes, but longer durations of training are required to affect nonlocomotor systems.

Convergence and cross talk in urogenital neural circuitries.

Despite common comorbidity of sexual and urinary dysfunctions, the interrelationships between the neural control of these functions are poorly understood. The medullary reticular formation (MRF) contributes to both mating/arousal functions and micturition, making it a good site to test circuitry interactions. Urethane-anesthetized adult Wistar rats were used to examine the impact of electrically stimulating different nerve targets [dorsal nerve of the penis (DNP) or clitoris (DNC); L6/S1 trunk] on responses of individual extracellularly recorded MRF neurons. The effect of bladder filling on MRF neurons was also examined, as was stimulation of DNP on bladder reflexes via cystometry. In total, 236 MRF neurons responded to neurostimulation: 102 to DNP stimulation (12 males), 64 to DNC stimulation (12 females), and 70 to L6/S1 trunk stimulation (12 males). Amplitude thresholds were significantly different at DNP (15.0 ± 0.6 µA), DNC (10.5 ± 0.7 µA), and L6/S1 trunk (54.2 ± 4.6 µA), whereas similar frequency responses were found (max responses near 30-40 Hz). In five males, filling/voiding cycles were lengthened with DNP stimulation (11.0 ± 0.9 µA), with a maximal effective frequency plateau beginning at 30 Hz. Bladder effects lasted ≈ 2 min after DNP stimulus offset. Many MRF neurons receiving DNP/DNC input responded to bladder filling (35.0% and 68.3%, respectively), either just before (43%) or simultaneously with (57%) the voiding reflex. Taken together, MRF-evoked responses with neurostimulation of multiple nerve targets along with different responses to bladder infusion have implications for the role of MRF in multiple aspects of urogenital functions.

Select spinal lesions reveal multiple ascending pathways in the rat conveying input from the male genitalia.

The specific white matter location of all the spinal pathways conveying penile input to the rostral medulla is not known. Our previous studies using rats demonstrated the loss of low but not high threshold penile inputs to medullary reticular formation (MRF) neurons after acute and chronic dorsal column (DC) lesions of the T8 spinal cord and loss of all penile inputs after lesioning the dorsal three-fifths of the cord. In the present study, select T8 lesions were made and terminal electrophysiological recordings were performed 45-60 days later in a limited portion of the nucleus reticularis gigantocellularis (Gi) and Gi pars alpha. Lesions included subtotal dorsal hemisections that spared only the lateral half of the dorsal portion of the lateral funiculus on one side, dorsal and over-dorsal hemisections, and subtotal transections that spared predominantly just the ventromedial white matter. Electrophysiological data for 448 single unit recordings obtained from 32 urethane-anaesthetized rats, when analysed in groups based upon histological lesion reconstructions, revealed (1) ascending bilateral projections in the dorsal, dorsolateral and ventrolateral white matter of the spinal cord conveying information from the male external genitalia to MRF, and (2) ascending bilateral projections in the ventrolateral white matter conveying information from the pelvic visceral organs (bladder, descending colon, urethra) to MRF. Multiple spinal pathways from the penis to the MRF may correspond to different functions, including those processing affective/pleasure/motivational, nociception, and mating-specific (such as for erection and ejaculation) inputs.

A quantitative method for assessing stages of the rat estrous cycle.

The impact of gender and/or hormone variations on a wide variety of neural functions makes the choice between studying males or females (or both) of a given species difficult. Although female rats are widely used experimentally, few studies control for the stage of estrus. More detailed information about how to distinguish the various stages of the estrous cycle is needed. For the present study, vaginal smears were obtained once a day and stained using an adaptation of the Papanicolaou (PAP) procedure. Images are provided of unstained "wet" samples and the corresponding PAP stained smears illustrating the cellular profile for each stage of the cycle as well as post-ovariectomy. The different cell populations across the cycle were quantified and ratios determined to show trends between the predominant and other cell types in each stage of the estrous cycle. Both stained and unstained images and cell quantification data provide valuable guidelines for distinguishing the stages of the estrous cycle.

Co-expression of P2X receptor subunits on rat nodose neurons that bind the isolectin GS-I-B4.

Triple fluorescent histochemistry was used to describe the types of overlap in visceral sensory neurons (nodose ganglion) for the labeling of the isolectin B4 from Griffonia simplicifolia type one (GS-I-B4) and their immunoreactivity (IR) for two of the ATP receptor subunits (P2X1/3 or P2X2/3). The vast majority of nodose neurons expressed GS-I-B4-binding and most of these displayed P2X receptor IR. Most of the P2X-IR was co-expressed on these individual nodose neurons (P2X1/P2X3 or P2X2/P2X3). A very small subpopulation of neurons that were GS-I-B4 negative but P2X positive displayed a very high relative intensity of P2X3-IR. The functional role that these expression patterns play in visceral sensory processing is currently unclear.

Effects of acute and chronic midthoracic spinal cord injury on neural circuits for male sexual function. II. Descending pathways.

In normal animals, microstimulation of the medullary reticular formation (MRF) has two effects on efferent neurons in the motor branch of the pudendal nerve (PudM). MRF microstimulation depresses motoneuron reflex discharges (RD) elicited by dorsal nerve of the penis (DNP) stimulation and produces long latency sympathetic fiber responses (SFR). The midthoracic spinal location of these descending MRF-PudM projections was studied electrophysiologically using a variety of acute and chronic lesions. Chronic lesions, in 27 mature male rats, included dorsal (DHx) or lateral (LHx) hemisections or moderate/severe contusions (Cx) at spinal level T(8). Behavioral data (sexual reflex latency, bladder voiding) obtained throughout the recovery period revealed a significant impairment of urogenital function for the DHx and severe Cx groups of animals. Microstimulation-induced PudM-RDs and PudM-SFRs, obtained in terminal electrophysiological experiments 30 days postinjury in the same 27 rats (urethan-anesthetized), were tested for a combined total of 1,404 bilateral MRF sites. PudM-RD was obtained for LHx and moderate Cx groups of animals but not for DHx or severe Cx groups. PudM-SFRs were obtained for LHx, DHx (although significantly weakened) and moderate Cx groups but not for those having received either an over-DHx or a severe Cx injury. PudM responses also were tested for 6 MRF sites in six intact control rats both before and after various select acute spinal cord lesions. For MRF sites producing a robust PudM-RD and PudM-SFR, acute bilateral lesions confined to the dorsolateral quadrant (DLQ) eliminated the PudM-RD but failed to eliminate PudM-SFRs. A deeper lesion encompassing additional white matter located dorsally in the ventrolateral quadrant (VLQ) was necessary to eliminate PudM-SFRs. Overall, these electrophysiological results provide evidence for descending projections conveying information between MRF and the lower thoracic/lumbosacral male urogenital circuitry within the DLQ and the dorsal-most aspect of VLQ at the midthoracic level of spinal cord. The alterations of supraspinal projections observed after chronic injury are likely of important clinical significance for functional recovery in cases of clinically incomplete spinal cord injury at midthoracic spinal cord.

Brainstem microstimulation activates sympathetic fibers in pudendal nerve motor branch.

A bilateral spino-bulbo-spinal circuit conveys information from/to the male urogenital tract and perineal muscles. This is the first electrophysiological report of another descending pathway, one which conveys output from the medullary reticular formation (MRF) to activate postganglionic sympathetic fibers contained within the motor branch of the pudendal nerve (PudM). In anesthetized rats, long latency (> 150 ms) discharges were elicited in the PudM following ipsilateral or contralateral microstimulation of the MRF. These firing bursts were not observed in rats after sectioning the lower lumbar sympathetic trunk. The most robust activation was observed when neurons in or near the lateral paragigantocellular reticular nucleus were microstimulated bilaterally. Urogenital dysfunction that occurs following severe spinal cord injury probably results from disrupting these and other supraspinal circuits.

Effects of acute and chronic midthoracic spinal cord injury on neural circuits for male sexual function. I. Ascending pathways.

Normal male reproductive function, particularly ejaculation, requires the integrity of urogenital sensory input and its ascending spinal projections. After midthoracic chronic spinal cord injury, sexual dysfunction occurs in both rats and humans. Neurons in the medullary reticular formation (MRF) are involved in the processing of bilaterally convergent sensory inputs from multiple cutaneous, mucocutaneous, and visceral regions of the body, including the penis and male urogenital tract. A variety of acute and chronic lesions were used to determine the midthoracic location of ascending spinal pathways conveying sensory input from the penis and male urogenital tract to MRF. A total of 371 single neurons were recorded in the MRF of 34 urethan-anesthetized mature male rats. Twenty-seven rats received a chronic T8 dorsal (DHx) or lateral (LHx) hemisection or contusion (Cx) injury 30 days before the terminal electrophysiological experiments. In addition, nine dorsal nerve of the penis (DNP)-responsive MRF neurons in seven intact control animals were tested completely both before and after various select acute spinal cord lesions. The chronic lesion data indicate that low and high threshold input from the penis (mucocutaneous) and male urogenital tract (visceral) ascend bilaterally within the dorsal quadrant at T8 as opposed to high threshold input from the hindpaws (cutaneous), which ascends unilaterally in the ventrolateral quadrant (VLQ). The acute lesion data indicate that the low-threshold information conveyed from the penis and male urogenital tract ascends in the dorsal columns, as opposed to the high-threshold nociceptive inputs that ascend bilaterally in the dorsolateral quadrant (DLQ). These results, as well as previous data on ascending projections from female reproductive organs within the dorsal columns and DLQ to other caudal brain stem nuclei, provide evidence for ascending pathways conveying nociceptive information centrally via the DLQ. This spinal gray-DLQ pathway(s) conveying information from mucocutaneous/pelvic/visceral territories therefore differs from the traditionally recognized spinal gray-VLQ pathway(s), which is known to convey nociceptive information from cutaneous regions of the body.

Changes in neuronal receptive field characteristics in caudal brain stem following chronic spinal cord injury.

Chronic spinal cord injury pain is poorly understood and, thus, not effectively relieved by traditional treatments. In the present study, a variety of partial, severe and sham chronic spinal lesions were made in 31 male rats at spinal level T8. During routine care/handling and brief behavioral testing of the animals throughout the 30-day recovery period, the majority of those with severe contusion injuries (verified histologically) showed signs of mechanical hypersensitivity on the dorsolateral trunk just rostral to the level of injury (i.e., upper thoracic territory). Terminal electrophysiological experiments were performed on all rats (urethane anesthesia). Single unit recordings were made at two supraspinal locations within the caudal brainstem, the nucleus reticularis gigantocellularis and nucleus reticularis gigantocellularis pars alpha. Neurons in these areas normally receive bilateral nociceptive somatovisceral inputs from many parts of the body. Seventy-three percent of the animals with severe contusion injuries developed novel low-threshold neuronal responses to stimulation of the dorsolateral trunk (upper thoracic territory). This amount was significantly greater than for animals with more moderate spinal lesions (dorsal or lateral hemisection; 29% and 25%, respectively) or sham controls (0%). These data suggest (1) that the spinal contusion is a reliable model for studies of the neural mechanisms that underly central spinal cord injury-related pain and (2) that the caudal brainstem is one supraspinal location where neurons undergo significant changes in responsiveness following severe chronic spinal cord injury. The observed plasticity is likely part of the central reorganization producing the multitude of sensory disturbances that surface following spinal cord injury.

Anodally focused polarization of peripheral nerve allows discrimination of myelinated and unmyelinated fiber input to brainstem nuclei.

We investigated the ability of a novel direct current (DC) polarization technique to block selectively the conduction in peripheral myelinated nerve fibers and allowing propagation in only unmyelinated fibers. In anesthetized adult rats, distal branches of the sciatic nerve (caudal cutaneous sural and tibial nerves) were exposed for electrical stimulation of A- and C-fibers. Two specially fabricated trough electrodes of different size and surface area were placed onto the sciatic nerve. Through these proximal electrodes a controlled ramped DC was timed to coincide with the arrival of A- and C-fiber action potentials, evoked electrically at the distal nerves or naturally from the foot or ankle, with the intent of blocking propagation in A-fibers while allowing C-fiber throughput. Neuronal recordings were made both peripherally (proximal sciatic nerve fascicles or L5 dorsal roots) and centrally (single cells in the nucleus gracilis or nucleus reticularis gigantocellularis). The DC polarization was shown to block conduction in myelinated A-fibers effectively, while allowing conduction in the unmyelinated C-fibers, without activation of fibers via the DC polarization itself. This was dependent upon the following factors: electrode polarity, onset rate of polarization, peak amplitude of polarization, distance between polarizing electrodes, size difference between polarizing electrodes, and gross nerve size. These experiments demonstrate that anodally focused DC polarization, applied utilizing two trough electrodes of different sizes, is capable of effectively, reversibly, and reproducibly blocking conduction in myelinated A-fibers evoked either electrically or naturally, while still allowing conduction to occur in the unmyelinated C-fiber population. In the context of experimental usage, we have demonstrated blocking of low-threshold A-fiber, but not C-fiber, mediated inputs to the caudal brainstem. This technique should find wide application in studies involving the processing of information conveyed centrally by the unmyelinated C-fiber afferent population, including discriminating afferent responses to peripheral stimuli, the role of C-fiber input in reflex activity, and the plasticity following injury or other manipulations.

Brainstem microstimulation differentially inhibits pudendal motoneuron reflex inputs.

Sensory information from the genitourinary tract is transmitted to perineal muscle reflex circuits in the spinal cord and to the medullary reticular formation (MRF). This is the first report of a functional descending connection between neurons in the MRF and sensory inputs of the pudendal motoneuron reflex circuitry. In anesthetized rats, microstimulation of the MRF produced a decrease in amplitude and increase in latency of pudendal motoneuron reflex discharges (PMRD) elicited by stimulation of the dorsal nerve of the penis. No effects on pelvic nerve-elicited PMRD were found. The most robust reflex depression was observed when the lateral paragigantocellular reticular nucleus was microstimulated bilaterally. Reproductive abnormalities that occur following severe spinal cord injury probably result from disruption of these descending connections.

Responses of medullary reticular formation neurons to input from the male genitalia.

1. The medullary reticular formation (MRF) is known to be involved in the modulation of certain reproductive behaviors. Ejaculation in the male, disrupted after spinal transection, may depend on a spinal-bulbo-spinal connection. To determine whether single neurons in the MRF receive sensory input from the male genitalia, the present study was undertaken using electrophysiological techniques. 2. The MRF of 14 urethan-anesthetized mature male rats was searched for single neurons responsive to bilateral electrical stimulation of the dorsal nerve of the penis (DNP). In addition, each DNP-responsive neuron was tested for responsiveness to bilateral electrical stimulation of the pelvic nerve (PN) and to mechanical stimulation (gentle touch, pressure, pinch) of the external genitalia, anus, urethra, and skin over most regions of the body. 3. A total of 165 single neurons responsive to bilateral electrical stimulation of the DNP were isolated and characterized throughout the MRF. All neurons responded to both ipsilateral and contralateral DNP stimulation. The majority of responses were excitatory, and most neurons had no background activity. Some neurons required wind-up with bilateral electrical stimulation of the DNP to respond. 4. About half of the neurons were located in the nucleus reticularis gigantocellularis (Gi); the remainder were located in surrounding (dorsal, ventral, lateral) regions of the MRF. Variations in response properties were found among neurons located in different MRF regions. 5. Eighty-eight DNP-responsive neurons were additionally responsive to bilateral electrical stimulation of the PN. None of the responses to bilateral PN were stronger than those for bilateral DNP and many (48%) were weaker. 6. Of the 165 DNP-responsive neurons, all were responsive to pressure/pinching of the penis; 16% responded to gentle stroking of the glans. Most of these neurons were additionally responsive (bilaterally) to pinching more than one (often all) of the following areas: perineum, scrotum, anus, ears, and toes (forefoot and hindfoot). 7. In conclusion, neurons located in the MRF of male rats are involved in the processing of bilaterally convergent inputs from multiple cutaneous and visceral regions of the body, including the penis and male urogenital tract. These neurons likely exert their effects by directly and/or indirectly activating ascending pathways to rostral regions of the brain important for somatovisceral sensation and motor behavior, and descending pathways to the spinal cord for modulation of segmental sexual reflexes. Contributions are likely for a wide spectrum of sensations and reproductive behaviors.

Spinal and vagal influences on the responses of rat solitary nucleus neurons to stimulation of uterus, cervix and vagina.

Neurons in the rat solitary nucleus (NTS) respond to mechanical stimulation of the uterine horn, cervix and vagina. The present study examined how these responses were affected by bilateral vagotomy and/or T10-T12 spinal transection for 12 single NTS neurons recorded in 12 rats anesthetized with halothane/nitrous oxide. Spinal transections all responses. Vagotomies eliminated responses only to uterine horn stimulation and either reduced the excitatory or enhanced the inhibitory responses to cervix and vaginal stimuli. These results suggest that NTS neuronal responses to cervix and vaginal stimulation depend upon input from the spinal dorsal horn and are facilitated by vagal input, whereas responses to uterine horn stimulation may require both spinal and vagal input.

Are there separate central nervous system pathways for touch and pain?

Information about bodily events is conveyed by primary sensory fibres to higher brain centres through neurons in the dorsal column nuclei (DCN) and spinal dorsal horn. The DCN route is commonly considered a 'touch pathway', separate from the spinal pain pathway', in part because DCN neurons respond to gentle tactile stimulation of small skin areas. Here we report that DCN neurons can additionally respond to gentle and noxious stimulation of viscera and widespread skin regions. These and other experimental and clinical data suggest that the DCN and spinal routes cooperate, rather than operate separately, to produce the many perceptions of touch and pain, an ensemble view that encourages novel approaches to health care and research.

Responses of neurons in caudal solitary nucleus of female rats to stimulation of vagina, cervix, uterine horn and colon.

Neurons in the caudal part of the solitary nucleus (NTS) are known for their processing of information derived from many viscera, including cardiovascular, respiratory and alimentary tract organs. This study characterized responses of NTS neurons in female rats in estrus to mechanical stimulation of four pelvic visceral organs (i.e. the vaginal canal, cervix, uterine horn and colon) as well to gentle mechanical skin stimulation. Of the 90 neurons tested, 31% responded with excitation or inhibition to one (22%) or more (9%) visceral stimuli. Responses included 13% to vaginal distension, 12% to cervix stimulation, 10% to uterine distension and 4% to colon distension. None responded to gentle cutaneous stimuli. These results expand the domain of visceral functions of NTS neurons to include pelvic female reproductive organs. The failure of NTS neurons to respond to gentle cutaneous stimuli contrasts with convergent responses of neurons in the gracile nucleus to skin and pelvic visceral stimuli [13] indicating the two nuclei are involved in different aspects of visceral function.

Intraspinal modulation of neuronal responses to uterine and cervix stimulation in rat L1 and L6 dorsal horn.

This two-part study examined intraspinal processing of input from the uterus, cervix and skin within the caudal spinal cord of virgin rats in estrus. The first part examined the effects of removing either pelvic or hypogastric nerve input (by appropriate dorsal rhizotomies) on neuronal responses to stimulation of uterus, cervix and skin in either the L1 or L6 dorsal horn of decerebrate, spinalized unanesthetized rats. Bilateral section of the T13-L2 roots (through which most hypogastric afferents travel) eliminated almost all responses to uterine distension in L1 and L6. Such rhizotomies also decreased the inhibitory effects of cervix input on neurons in L6. Bilateral section of the L6-S2 roots (through which most pelvic afferents travel) had no effect on responses to uterus, but decreased the inhibitory effects of cervix input on neurons in L1. Sections of both sets of roots eliminated responses to cervix stimulation in L6. The second part examined neuronal responses in T13/L1 of urethane-anesthetized rats before and after a T10 spinal transection. Transection increased the probability of observing neurons excited by uterine stimulation. Transection also increased excitatory responses and decreased inhibitory responses to cervix stimulation. These results confirm previous findings that input from the uterus to the spinal cord is mainly by way of the hypogastric nerve, while that from the cervix is by way of both the pelvic and hypogastric nerves. The results also demonstrate that descending influences in the estrous rat mainly increase the ability of cervix stimulation to inhibit spinal neuronal activity and reduce the effectiveness of uterine stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuronal responses to stimulation of the cervix, uterus, colon, and skin in the rat spinal cord.

1. Previous studies in the rat have shown that the hypogastric nerve conveys input from the cervix and uterus mainly to the T13-L3 segments of the spinal cord, whereas the pelvic nerve conveys input from the cervix and vaginal canal mainly to the L6-S2 segments. 2. To study the effects of this input, the dorsal horns of the T13-L1, L6-S2, and L4-L5 segments in 13 decerebrate, T10-spinalized, unanesthetized, and paralyzed adult female rats in estrus were searched for neurons responsive to gentle mechanical stimulation of the cervix. The 87 neurons found were then further tested for their responses to gentle mechanical stimulation of the skin and to distension of both uterine horns, distension of the colon, and shearing stimulation of the colon and vaginal canal. 3. Neurons responsive to cervix stimulation, primarily by excitation, were readily found in the ventral part of the dorsal horn in T13-L1 and throughout the dorsal horn in L6-S2. Cervix-responsive neurons were less readily found throughout the dorsal horn in L4-L5, where 25% were inhibited by the stimulation. All but one neuron had cutaneous receptive fields. 4. The 30 cervix-responsive neurons in T13-L1 had large bilateral cutaneous receptive fields covering the perineum and hind-limbs. Most (76%) also responded, primarily by excitation, to uterine distension, as well as to colonic stimulation (59%). More than half were activated by both types of stimulation. 5. The 33 cervix-responsive neurons in L6-S2 had cutaneous receptive fields in the same regions as those in T13-L1, but generally smaller, particularly for neurons in the dorsal part of the dorsal horn, many of whose receptive fields were confined to the perineum. The L6-S2 neurons also exhibited less convergent input from other visceral structures, particularly the uterus. Fewer neurons (42%) responded to uterine distension, mostly by being inhibited, whereas about the same proportion (51%) responded with excitation to colonic stimulation. Only 24% responded to both uterus and colon. 6. All 24 cervix-responsive neurons in medial L4-L5 had small cutaneous receptive fields on the toes, and the neurons received less convergent input from other visceral structures (25% from the uterus, 33% from the colon, 13% from both). 7. These results indicate the presence of an extensive system of neurons throughout the caudal spinal cord of the rat, concentrated in separated thoracolumbar and lumbosacral segments, that is concerned with input from the reproductive tract.(ABSTRACT TRUNCATED AT 400 WORDS)

Glial cells: possible determinants of neuronal uptake of tritiated proline.

When tritiated proline is injected into various sensory and integrative areas of the brain, it fails to be incorporated into the proteins of neuronal soma located within the injection site. In contrast, such incorporation does occur when [3H]proline is injected into dorsal root ganglia. The basis for this difference is unclear because brain and dorsal root ganglion tissue differ in configurational factors (e.g. synapses, dendrites) as well as in the embryological origin of their respective neuronal and non-neuronal cell populations. To determine if configurational factors might account for [3H]proline's incorporation into somal neuronal proteins in dorsal root ganglia, [3H]proline was injected into autonomic (pelvic and superior cervical) and sensory (dorsal root and nodose) ganglia in the rat. These ganglia differ in synaptic and cellular configurations, but have the same neural origin (neural crest). Virtually all neuronal soma were labeled in autoradiograms of all of these injection sites, suggesting that configurational factors do not account for the labeling of dorsal root ganglion neurons by [3H]proline. To address the issue of embryological origin, cellular labeling patterns after [3H]proline injection into the hypoglossal nucleus, dorsal motor nucleus of the vagus and the ventral horn of spinal cord were compared with those after [3H]proline injections into the adjacent solitary nucleus, gracile nucleus and central cervical nucleus of the spinal cord. The neurons in the former three nuclei (i.e. motoneurons) originate from the neural tube, but their axons are associated primarily with Schwann cells which originate from the neural crest. Although neurons in the latter three regions also originate from the neural tube, their axons are myelinated entirely by neural tube-derived glia (i.e. oligodendrocytes).(ABSTRACT TRUNCATED AT 250 WORDS)