Spinoreticular Tract Neurons Research Articles

The spino-bulbar-cerebellar pathway: organization and neurochemical properties of spinal cells that project to the lateral reticular nucleus in the rat.

In addition to classical spinocerebellar pathways, the cerebellum receives information from the spinal cord indirectly via spino-bulbar-cerebellar systems. One of the structures in this pathway is the lateral reticular nucleus (LRt). We performed series of experiments to investigate the organization and neurotransmitter content of spinoreticular tract (SRT) neurons in the lumbar spinal cord that project to the LRt. Three rats received injections of the b subunit of Cholera toxin (CTb) or Fluorogold (FG) within the left and right LRt. The majority of SRT cells (56–61%) were found within the contralateral medial intermediate gray matter where small numbers (7–10%) of double-labeled cells were also present on both sides of the cord. Six rats received unilateral spinal injections of CTb to label spinal projections to the LRt. Injections of FG were made also into the anterior lobe of the cerebellum to label LRt pre-cerebellar neurons. Terminals were found mainly ipsilateral to spinal injection sites within the central and ventrolateral regions of the LRt. Immunocytochemical analysis of SRT terminals revealed that the majority (75%) were contained vesicular glutamate transporter 2 but a minority (20%) contained the vesicular GABA transporter. The inhibitory subpopulation was found to be GABAergic, glycinergic, or contained both transmitters. Inhibitory and excitatory terminals were present within overlapping regions of the nucleus. Most CTb terminals contacting LRt pre-cerebellar neurons were excitatory (80%) whereas a minority were inhibitory and most cells (88%) received contacts from both inhibitory and excitatory terminals. This study shows that SRT axons in the LRt have the capacity to exert direct excitatory and inhibitory actions on LRt pre-cerebellar neurons. Thus spinal cord input has the capacity to facilitate or depress the activity of individual LRt cells which in turn adjust activity in the cerebellum to produce coordinated motor behaviors.

State-Dependent Changes in Glutamate, Glycine, GABA, and Dopamine Levels in Cat Lumbar Spinal Cord

Recent studies have indicated that the glycine receptor antagonist strychnine and the gamma-aminobutyric acid type A (GABA A) receptor antagonist bicuculline reduced the rapid-eye-movement (REM) sleep-specific inhibition of sensory inflow via the dorsal spinocerebellar tract (DSCT). These findings imply that the spinal release of glycine and GABA may be due directly to the REM sleep-specific activation of reticulospinal neurons and/or glutamate-activated last-order spinal interneurons. This study used in vivo microdialysis and high-performance liquid chromatography analysis techniques to provide evidence for these possibilities. Microdialysis probes were stereotaxically positioned in the L3 spinal cord gray matter corresponding to sites where maximal cerebellar-evoked field potentials or individual DSCT and nearby spinoreticular tract (SRT) neurons could be recorded. Glutamate, glycine, and GABA levels significantly increased during REM sleep by approximately 48, 48, and 14%, respectively, compared with the control state of wakefulness. In contrast, dopamine levels significantly decreased by about 28% during REM sleep compared with wakefulness. During the state of wakefulness, electrical stimulation of the nucleus reticularis gigantocellularis (NRGc) at intensities sufficient to inhibit DSCT neuron activity, also significantly increased glutamate and glycine levels by about 69 and 45%, respectively, but not GABA or dopamine levels. We suggest that the reciprocal changes in the release of glutamate, glycine, and GABA versus dopamine during REM sleep contribute to the reduction of sensory inflow to higher brain centers via the DSCT and nearby SRT during this behavioral state. The neural pathways involved in this process likely include reticulo- and diencephalospinal and spinal interneurons.

Transmission through the dorsal spinocerebellar and spinoreticular tracts: wakefulness versus thiopental anesthesia.

Most of what is known regarding the actions of injectable barbiturate anesthetics on the activity of lumbar sensory neurons arises from experiments performed in acute animal preparations that are exposed to invasive surgery and neural depression caused by coadministered inhalational anesthetics. Other parameters such as cortical synchronization and motor ouflow are typically not monitored, and, therefore, anesthetic actions on multiple cellular systems have not been quantitatively compared. The activities of antidromically identified dorsal spinocerebellar and spinoreticular tract neurons, neck motoneurons, and cortical neurons were monitored extracellularly before, during, and following recovery from the anesthetic state induced by thiopental in intact, chronically instrumented animal preparations. Intravenous administration of 15 mg/kg, but not 5 mg/kg, of thiopental to awake cats induced general anesthesia that was characterized by 5-10 min of cortical synchronization, reflected as large-amplitude slow-wave events and neck muscle atonia. However, even though the animal behaviorally began to reemerge from the anesthetic state after this 5-10-min period, neck muscle (neck motoneuron) activity recovered more slowly and remained significantly suppressed for up to 23 min after thiopental administration. The spontaneous activity of both dorsal spinocerebellar and spinoreticular tract neurons was maximally suppressed 5 min after administration but remained significantly attenuated for up to 17 min after injection. Peripheral nerve and glutamate-evoked responses of dorsal spinocerebellar and spinoreticular tract neurons were particularly sensitive to thiopental administration and remained suppressed for up to 20 min after injection. These results demonstrate that thiopental administration is associated with a prolonged blockade of motoneuron output and sensory transmission through the dorsal spinocerebellar and spinoreticular tracts that exceeds the duration of general anesthesia. Further, the blockade of glutamate-evoked neuronal responses indicates that these effects are due, in part, to a local action of the drug in the spinal cord. The authors suggest that this combination of lumbar sensory and motoneuron inhibition underlies the prolonged impairment of reflex coordination observed when thiopental is used clinically.

On the reduction of spontaneous and glutamate-driven spinocerebellar and spinoreticular tract neuronal activity during active sleep.

The present study was performed to provide evidence that dynamic neural processes underlie the reduction in dorsal spinocerebellar tract and spinoreticular tract neuron activity that occurs during active sleep. To ascertain the effect of local inhibition on the spontaneous and glutamate-evoked spike discharge of sensory tract neurons, preliminary control tests were performed during the state of quiet wakefulness, where GABA or glycine was co-administered in a sustained fashion during pulsatile release of glutamate to dorsal spinocerebellar tract (n=3) or spinoreticular tract (n=2) neurons. Co-administration of GABA or glycine also resulted in a significant marked suppression of spontaneous spike activity and glutamate-evoked responses of these cells. Extracellular recording experiments combined with juxtacellular application of glutamate were then performed on 20 antidromically identified dorsal spinocerebellar tract and spinoreticular tract neurons in the chronic intact cat as a function of sleep and wakefulness. The glutamate-evoked activity of a group of 10 sensory tract neurons (seven dorsal spinocerebellar tract, three spinoreticular tract), which exhibited a significant decrease in their spontaneous spike activity during active sleep, was examined. Glutamate-evoked activity in these cells was significantly attenuated during active sleep compared with wakefulness. In contrast, the glutamate-evoked activity of a second group of eight sensory tract neurons (four dorsal spinocerebellar tract, four spinoreticular tract), which exhibited a significant increase in their spontaneous spike activity during active sleep, was not significantly altered in a state-dependent manner. These data indicate that, during natural active sleep, a dynamic neural process is engaged onto certain dorsal spinocerebellar tract and spinoreticular tract neurons, which in turn dampens sensory throughput to higher brain centers.

Responses of spinoreticular cells to graded increases in renal venous pressure

Previous work established that occlusion of the renal vein excites spinoreticular tract (SRT) neurons of the cat. The present study was designed to determine the relationship between renal vein pressure level and SRT cell activity. Experiments were performed on 40 cats that were anesthetized with alpha-chloralose. Sixty SRT neurons in the T12-L2 segments were tested for responses to a renal vein pressure (RVP) of 60 mmHg. Twenty-three cells responded with an increase in activity. Stimulus response relationship for these cells were determined over the RVP range of 10-80 mmHg. RVP thresholds averaged 25 +/- 3 mmHg. Above this level greater increases in RVP were associated with greater increases in neuronal activity. At RVP of 80 mmHg cell activity increased from 4 +/- 2 to 21 +/- 5 spikes/s. Cells with both A delta- and C-fiber renal afferent inputs had significantly greater responses and lower thresholds than cells with only A delta input. Renal vein occlusion evoked increases in blood pressure. At a renal vein pressure of 80 mmHg, pressor responses averaged 16 +/- 5 mmHg. No significant changes in heart rate were observed. The results demonstrate that SRT cells are capable of encoding the level of RVP. Such responses may be important for grading of reflexes of renal origin that require supraspinal circuitry.

Intracellular records of the effects of primary afferent input in lumbar spinoreticular tract neurons in the cat

1. The afferent-evoked synaptic input to lumbar spinal cord (L5-S1) neurons that were activated antidromically from the medial pontomedullary reticular formation (nucleus reticularis gigantocelluaris and vicinity) was investigated with the use of intracellular recordings in pentobarbital sodium-anesthetized cats. 2. Spinoreticular tract (SRT) neurons (n = 33) were categorized into three types ("deep-inhibited," "deep-complex," and "intermediate") on the basis of their locations and of their responses to natural and electrical stimulation. 3. The deep-inhibited-type neurons, located in the medial part of the deeper laminae (approximately VI-VIII), comprised a large component of the sample (20/33). They had no demonstrable excitatory receptive field (RF). However, electrical stimulation of low-threshold cutaneous afferents of hindlimb nerves evoked inhibitory postsynaptic potentials (IPSPs) via an oligosynaptic linkage. High-threshold cutaneous and muscle afferents also evoked IPSPs. 4. In the deep-complex-type neurons (8/33), electrical stimulation of low-threshold cutaneous afferents evoked complex IPSP-excitatory postsynaptic potential (EPSP) sequences. With intense stimuli, long-latency C-fiber-like EPSPs were evoked. Two of these eight neurons were characterized as wide-dynamic-range (WDR) neurons with large, excitatory and inhibitory cutaneous RFs. 5. Intermediate-type neurons (5/33) were concentrated in the lateral spinal gray and relatively superficially (approximately lamina V). These neurons had convergent low- and high-threshold cutaneous inputs (WDR neurons). Electrical stimulation of low-threshold cutaneous afferent fibers from within the excitatory RF evoked mono- or disynaptic EPSPs followed by IPSPs. High-threshold muscle and cutaneous afferents also evoked EPSPs. 6. These results show that SRT neurons have a variety of response characteristics resulting from various degrees of spatial and temporal summation of primary afferent input. Neurons with widespread inhibitory responses but no excitatory drive from the periphery comprise a surprisingly large component of the SRT: the function of these cells is unknown. It is apparent that the spinoreticular projection has considerable functional heterogeneity.

Cocaine: effect on spinal projection neurons in the rat

In the anesthetized rat, systemic cocaine at an analgesic dose (25 mg/kg, IP) had no general influence on spontaneous activity in nociceptive spinoreticular tract neurons or in rostrally projecting low-threshold mechanoreceptive neurons of the spinal dorsal horn. Peripherally evoked activity was moderately (mean: 30%) reduced in 43% ( 6 14 ) of the spinoreticular tract neurons, whereas in 50% of them there was no marked change in evoked activity by cocaine. Evoked activity was slightly reduced in 25% ( 2 8 ) of the low-threshold mechanoreceptive neurons and not changed in 75% of them. The suppressive effect of a distant conditioning noxious stimulus on responses to spinoreticular tract neurons was enhanced by cocaine in 3 6 of the spinoreticular tract neurons. Primary afferent terminal excitability of A-fibers was slightly increased following cocaine as indicated by the increased amplitude (mean: 24%) of the antidromically evoked compound action potential recorded from the sural nerve. It is concluded that the previously shown marked enhancement of spontaneous activity in the bulborecticular formation is generated supraspinally. Thus, while cocaine-induced analgesia appears to be due primarily to supraspinal mechanisms, the present results suggest that spinal mechanisms are also involved possibly presynaptically.

Urinary bladder and hindlimb stimuli inhibit T1-T6 spinal and spinoreticular cells

Upper thoracic spinal neurons are primarily excited by cardiopulmonary spinal afferent input but are excited and inhibited by splanchnic afferent input. These data suggest that the greater the number of segments between a spinal neuron and spinal afferent input the greater the probability that the afferent input will inhibit the spinal neuron. Based on this idea we hypothesized that visceral (urinary bladder) and somatic (hindlimb) afferent input would inhibit upper thoracic spinal neurons. To test this hypothesis the activities of 69 spinal and 27 spinoreticular tract neurons in 45 alpha-chloralose-anesthetized cats were studied. Only neurons excited by both visceral and somatic thoracic afferent input were studied. Urinary bladder distension (UBD) inhibited 48 (50%), excited 6 (6%), and did not affect 41 (43%) of these neurons. Also, UBD inhibited the excitatory responses of these cells to noxious visceral and somatic stimuli. Hindlimb pinch also inhibited greater than 50% of the neurons. These data indicate that visceral and somatic afferent input to the lumbosacral spinal cord inhibits the activity of upper thoracic neurons. This inhibitory effect may play a role in localization of sensory and motor responses to noxious stimuli.

Effects of intracardiac bradykinin and capsaicin on spinal and spinoreticular neurons.

The responses of thoracic spinal and spinoreticular tract (SRT) neurons to activation of cardiac spinal afferents by injections of bradykinin (BK) and capsaicin (CAP) into the left atrium or pericardial sac were determined in vagotomized cats anesthetized with alpha-chloralose. Activities of spinal and SRT neurons in the T1-T5 spinal cord were recorded extracellularly. All neurons received excitatory somatic and cardiopulmonary sympathetic afferent input. Application of BK and CAP to the heart excited most SRT neurons and many spinal neurons but also inhibited some spinal neurons. The two drugs often affected spinal but not SRT neurons differently. Capsaicin excited high threshold and high threshold inhibitory neurons but not wide-dynamic range spinal neurons. In contrast, BK excited all three categories of spinal and SRT neurons. The differential responses of spinal neurons to intracardiac BK and CAP suggested that these compounds can stimulate functionally different populations of cardiac sympathetic afferents.

Spinoreticular cell responses to intrarenal injections of bradykinin.

Thirty cats were anesthetized with alpha-chloralose, paralyzed, and artificially ventilated. Extracellular unit activity was recorded from 63 spinoreticular tract (SRT) neurons in the T12-L2 segments. All cells were excited by renal nerve stimulation and had somatic receptive fields. Intrarenal injection of bradykinin (4 micrograms/kg) increased activity of 36 cells from 7 +/- 1 to 23 +/- 5 spikes/s. Latency to onset of responses averaged 11 +/- 2 s and latencies to peak were 26 +/- 5 s. Intrarenal injection of isotonic saline vehicle or intravenous injection of the same dose of bradykinin failed to alter activity. Responses increased as dosage increased from 2 to 12 micrograms/kg. Seventeen cells exhibited tachyphylaxis to repeated injections. Cells most likely to respond to bradykinin received both A delta- and C-fiber renal inputs and/or were located in lamina V of the spinal gray matter. Mechanical pressure applied to the renal capsule excited eight of the cells that responded to bradykinin. These results show that activation of renal afferent fibers with bradykinin leads to activation of T12-L2 SRT neurons. These cells may participate in the ascending limb of supraspinal reflexes initiated by renal receptors.

Immunocytochemical identification of long ascending peptidergic neurons contributing to the spinoreticular tract in the rat

In the present study, we examined the peptidergic content of lumbar spinoreticular tract neurons in the colchicine-treated rat. This was accomplished by combining the retrograde transport of the fluorescent dye True Blue with the immunocytochemical labeling of neurons containing cholecystokinin-8, dynorphin Al-8, somatostatin, substance P or vasoactive intestinal polypeptide. After True Blue injections into the caudal bulbar reticular formation, separate populations of retrogradely labeled cells were identified as containing cholecystokinin-like, dynorphin-like, substance P-like or vasoactive intestinal polypeptide-like immunoreactivity. Retrogradely labeled somatostatin-like neurons were not identified in any of the animals examined. Each population of double-labeled cells showed a different distribution in the lumbar spinal cord. The highest yield of double-labeling occurred for cholecystokinin, with 16% of all intrinsic cholecystokinin-like neurons containing True Blue. These double labeled neurons were found predominately at the border between lamina VII and the central canal region. About 11% of intrinsic vasoctive intestinal polypeptide-like neurons in the lumbar spinal cord were retrogradely labeled from the bulbar reticular formation. These neurons were found mostly in the lateral spinal nucleus, with only a few double-labeled cells located deep in the gray matter. Dynorphin-like double-labeled neurons were localized predominately near the central canal; a smaller population was also seen in the lateral spinal nucleus. It was found that double-labeled dynorphin-like neurons made up 8% of all' intrinsic dynorphin-like neurons. Retrogradely-labeled substance P-like neurons were rare; the few double-labeled neurons were found in the lateral spinal nucleus and lateral lamina V. These findings suggest a significant role for spinal cord peptides in long ascending systems beyond their involvement in local circuit physiology.

Funicular location of the ascending axons of neurons adjacent to the spinal cord central canal in the rat

Neurons adjacent to the central canal in the rat spinal cord were retrogradely labeled bilaterally after injection of horseradish peroxidase into the bulbar reticular formation. Lesions restricted to parts of the ventral lateral funiculus in thoracic or high lumbar segments on the side ipsilateral to the injections produced significant bilateral reductions in labeling. Lesions that included the entire ipsilateral ventral lateral funiculus greatly reduced the number of labeled neurons surrounding the central canal caudal to the lesion. Lesions of either the dorsal lateral funiculus, or midline lesions encompassing both the dorsal and ventral columns had no significant effect labeling. Spinoreticular tract neurons on both sides of the central canal issue axons that ascend in the ventral lateral funiculus of the side ipsilateral to their termination.

Raphe magnus inhibition of feline T1-T4 spinoreticular tract cell responses to visceral and somatic inputs

Background activity of spinoreticular tract neurons in the T1-T4 segments was on average inhibited 80% by electrical stimulation of nucleus raphe magnus. Nucleus raphe magnus stimulation inhibited responses of spinoreticular tract neurons to somatic input produced by touching the skin and hair (innocuous stimulus) or pinching the skin and muscle (noxious stimulus). Inhibition of responses to noxious and innocuous somatic inputs was not significantly different. Inhibition produced during nucleus raphe magnus stimulation was less effective when the activity of spinoreticular tract cells increased. This relationship was consistent for both background activity and responses to somatic noxious or innocuous input. Nucleus raphe magnus stimulation inhibited responses of spinoreticular tract neurons to visceral input produced by electrical stimulation of cardiopulmonary sympathetic afferent fibers. Responses to C-fiber sympathetic afferent fibers were more effectively inhibited than were responses to A-delta sympathetic afferent fibers. In conclusion, stimulation of the nucleus raphe magnus inhibits T1-T4 spinoreticular tract neuronal responses to visceral and somatic inputs. Since spinoreticular neurons project to the medullary reticular formation, activation of the nucleus raphe magnus could modulate affective-motivational behavior and cardiovascular adjustments that often occur during angina pectoris.

Location and properties of dorsal horn neurons at origin of spinoreticular tract in lumbar enlargement of the rat.

1. Spinoreticular tract neurons at the rat lumbar cord level were identified by antidromic activation following stimulation at mainly pontine and mesencephalic levels. These units, which were found in the dorsal half of the cord, could be separated into two groups according to their spinal location, electrophysiological properties, and their central projections. 2. Units in the dorsolateral funiculus nucleus projected mainly to the cuneiformis area and adjacent structures with frequent bilateral projections. They had the slowest conduction velocities, sometimes in the unmyelinated range. Generally, they were driven only by stimulation of subcutaneous and/or deep structures. 3. Neurons located in the dorsal horn mainly projected contralaterally to pontine and mesencephalic levels. their conduction velocities and the electrophysiological properties were identical to those observed for the rat spinothalamic tract (22). Almost all (86%) had clear cutaneous sensitivity and generally large receptive fields: 40% responded to nonnoxious and noxious mechanical cutaneous stimuli and frequently to noxious radiant heat, 26% were exclusively excited by light tactile stimuli, and 20% required noxious cutaneous mechanical stimulation for activation. There was a good correlation between responses to natural and transcutaneous electrical stimulation: units driven by noxious mechanical stimuli received A-delta- and/or C-fiber inputs. The remaining units (14%) had more complex receptive fields associated with both excitatory and inhibitory inputs originating from a single peripheral area. 4. The functional heterogeneity of the rat spinoreticular tract is reminiscent of that demonstrated for the rat and monkey spinothalamic tracts. Similarly, the rat spinoreticular neurons are under the influence of descending inhibitory controls originating from the nucleus raphe magnus and bulbar reticular formation. 5. Responses of the rat spinoreticular tract neurons are consistent with the involvement of this pathway in the transmission of messages of both innocuous and noxious origins.