Injections of a retrograde tracer (Fluorogold) were made into the thalamus, gracile nucleus or lateral parabrachial nucleus to identify spinothalamic, post-synaptic dorsal column or spinoparabrachial projection neurons respectively (n=4 in each group). Fluorogold and Fos-like immunoreactivity was not colocalized in any dorsal horn neurons projecting to the thalamus or gracile nucleus. 
Here we investigate whether the input to this "claw area" arises from dorsal thalamic neurons that, in turn, receive their somatosensory input from the gracile nucleus. After injections of biotinylated dextran amine into the gracile nucleus and cholera toxin B chain into the claw area, terminations from the former and retrogradely labeled neurons from the latter overlapped substantially in the thalamic nucleus dorsalis intermedius ventralis anterior.
The number of p-p38 MAPK-immunoreactive (IR) cells was significantly increased in the L5 dorsal horn and the gracile nucleus ipsilateral to the injury at days 3-21 after SNL. Increased immunofluorescence labeling for OX-42 indicated that microglial cells were activated by SNL in the L5 dorsal horn and the gracile nucleus ipsilateral to the injury. These results demonstrate that SNL activates p38 MAPK pathway in microglia in the gracile nucleus as well as in the spinal cord dorsal horn.
Further, we have characterized the distribution of PKCgamma within gracile nucleus in terms of colocalization with various neurotransmitter receptors or enzymes and calcium binding proteins, and compared this with PKCgamma colocalization in cells of laminae I-III of the spinal cord. We show that approximately 90% of the PKCgamma cells in the gracile nucleus and 60% in the dorsal horn were immuno-positive for the AMPA receptor subunit glutamate 2/3 (GluR2/3). In the spinal cord, a quarter of PKCgamma cells expressed calbindin, but very few cells did so in the gracile nucleus. Electrical stimulation at c-fiber strength of the normal or injured sciatic nerve was used to induce c-fos as a marker of postsynaptic activation in the spinal cord and gracile nucleus.
In the present study, the gracile nucleus was targeted as one of the likely sources of low-threshold information from the penis to MRF. Histological reconstruction of the electrode tracks showed that the majority of neurons responding to penile stimulation were located ventrally within the medial one-third of the gracile nucleus surrounding obex. These results indicate that neurons in the gracile nucleus are likely part of the pathway that provides low-threshold penile inputs to MRF, a region known to play an important role in mating processes..
Increased swelling was found in gracile tract, gracile nucleus and dorsal roots but not in lateral columns, olfactory bulb, motor cortex, ventral roots or peripheral nerve.
Here, we tested in adult rats whether NT-3 infusion at the site of a moderate T9 spinal cord contusion would rescue sensory connections to the gracile nucleus in the medulla. Seven days after the contusion plus intrathecal (subarachnoid) vehicle infusion as a control, the CTB-positive innervation of the gracile nucleus was reduced to approximately 25% of sham-operated rats. These results are likely because TrkC is not present in axons of the dorsal columns or gracile nucleus, or in other dorsal column cell types, even after the contusion.
To test this hypothesis, we looked for neuropeptides in Abeta primary afferent terminals in the ipsilateral gracile nucleus and spinal dorsal horn in three nerve injury models: sciatic nerve transection (SNT), spinal nerve ligation (SNL), and chronic constriction injury (CCI). Although substance P was not detected in terminals of injured afferents in the gracile nucleus, CGRP was expressed in between 32 and 68% of these terminals, with a significantly higher proportion in the SNL and CCI models, compared with SNT.
NPR-A-immunoreactive perikarya were found in the red nucleus and the oculomotor nucleus in the midbrain, the parabrachial nucleus and the locus coeruleus in the pons, and the dorsal motor nucleus of the vagus, the hypoglossal nucleus, the cuneate nucleus, the gracile nucleus, the nucleus ambiguus, the lateral reticular nucleus, the reticular formation, and the inferior olivary nucleus in the medulla oblongata.
In order to reveal the somatotopic organization of the gracile nucleus of the dorsal column-trigeminal complex, neuroanatomical tracers were injected subcutaneously into various parts of the hindlimb and tail of prosimian galagos, New World monkeys, and Old World monkeys. In all taxa, terminations labeled by the injections were distributed in a patchy fashion along the rostrocaudal length of the ipsilateral gracile nucleus. Across taxa, afferents from the tail, foot, lower leg, and upper leg terminated in a mediolateral sequence within the gracile nucleus.
Spheroids were frequently seen (n = 91), and 10 horses each had more than 10 spheroids in the cuneate or gracile nucleus.
No terminal labelling was ever found in the inferior olive, but labelled terminals were consistently found in a well-localized site in the dorso-medial medulla, ventral to the gracile nucleus, termed the matrix region.
To clarify the functional role of the dorsal column nucleus (DCN) in nociception in rats with advancing age, single neuronal activity and substance P-like immunoreactivity (SP-LI) of the gracile nucleus (GN) were studied in aged rats (29 to 34 mo old) and adult rats (9 to 12 mo old).
The neurons with strong positive immuno-reaction signals were detected in cerebral cortex, cerebellar Purkinje cells, cerebellar nuclei, pyramidal neurons of hippocampus, caudate nucleus, lentiform nucleus, claustrum, nuclei in diencephalons, substantia nigra, cranial nerve nuclei, reticular formation in brain stem, pontine nuclei, red nucleus, superior and inferior olivary nucleus, gracile nucleus, cuneate nucleus, also the ventral horn, lateral horn, dorsal horn and the central gray matter in spinal cord.
Following nerve injury, phosphorylation of extracellular signal-regulated protein kinase (ERK), an important member of this family, is sequentially increased in neurons, microglia and astrocytes of the dorsal horn and gracile nucleus, and in injured large DRG neurons.
Cholera toxin B (CTB) labeling from the sciatic nerve of naive rats revealed effective labeling of the terminal fibers in the gracile nucleus at 3 days post-injection and a subpopulation of rapidly transporting fibers after 1 day. A preconditioning injury of the sciatic nerve reportedly can enhance growth of sensory axons but did not affect the terminal fiber area in the gracile nucleus.
Recent studies have reported that l-arginine-derived nitric oxide (NO) in the gracile nucleus modifies the hypotensive responses to electroacupuncture (EA) stimulation of Zusanli (ST 36). Unilateral EA stimulation of ST 36 in rats caused increases in nNOS immunostained cells in the rostral region of the ipsilateral gracile nucleus, but was not altered in the contralateral gracile nucleus compared with sham-treated rats (P < 0.05, n = 6-7). NADPH-diaphorase-positive cells were also increased in the ipsilateral gracile nucleus of rats with EA stimulation. nNOS immunostaining and NADPH-diaphorase reactivity was neither altered in the gracile nucleus and mNTS of non-acupoint stimulated rats nor other brainstem nuclei in rats with EA ST 36. These results show that nNOS immunoreactivity and NADPH-diaphorase reactivity are consistently increased in the gracile nucleus and the mNTS by EA ST 36. We conclude that EA ST 36 induces nNOS expression in the gracile nucleus and mNTS, and enhanced nNOS-NO in the nuclei may modify central cardiovascular regulation, which contribute to hypotensive effects of acupuncture..
Both gracile nucleus (P < 0.001) and cervical gracile fascicle (P = 0.001) contained significantly fewer spheroids in gad/Wld(S) mice, and secondary signs of axon pathology such as myelin loss were also reduced.
gamma-Synuclein immunoreactivity in the spheroids appeared in the gracile nucleus at 3 weeks of age and was maintained until 32 weeks.
Recent evidence shows that nitric oxide plays an important role in mediating the cardiovascular responses to EA stimulation through the gracile nucleus-thalamic pathway.
Immunoreactivity of pERK in gracile nucleus neurons was also dramatically increased after 0.1 mA stimulation to the injured nerve. These data suggest that the rats with peripheral nerve injury had an increased responsiveness to the low- or high-threshold peripheral stimuli in I-II, III-IV and gracile nucleus neurons. Furthermore, SNI rats that received neonatal capsaicin treatment showed a decreased number of pERK neurons after 0.1 mA stimulation in the dorsal horn and gracile nucleus neurons compared to the control rats.
Responses of neurons in the gracile nucleus (NG) of female rats to tactile and visceral stimulation change across the estrous cycle [ J.
RCP-immunoreactive (IR) perikarya are widely and selectively distributed in the cerebral cortex, septal nuclei, hippocampus, various hypothalamic nuclei, amygdala, nucleus colliculus, periaqueductal gray, parabrachial nuclei, locus coeruleus, cochlear nuclei, dorsal raphe nuclei, the solitary tractus nucleus and gracile nucleus, cerebellar cortex, various brainstem motor nuclei, the spinal dorsal and ventral horns.
Rats were perfused at 1, 2, 3, 5, and 7 days after incision, and COX-1 immunohistochemistry was performed on L3 to S2 spinal cord and gracile nucleus sections. COX-1 immunoreactivity increased in glia in the ipsilateral L4-L6 spinal dorsal horn and ipsilateral gracile nucleus after incision.
After 2 days IHH, %TUN in non-NR1 neurons was increased in the lateral reticular nucleus (LRt, P=0.05), nucleus of the solitary tract (NTS, P=0.004) and gracile nucleus (P=0.05).
In the gracile nucleus, virtually all puncta labeled for CTB appeared immunopositive for NR1. At the electron microscopic level, most immunopositive terminals in spinal cord and gracile nucleus displayed morphological characteristics of endings of myelinated primary afferents. Estimates for the gracile nucleus were higher (80%).
The expression of c-fos, a marker of neuronal activation, was examined in the gracile nucleus (GN) and nucleus of the solitary tract (NTS) after social interactions, including mating, between male and female prairie voles.
The purpose of these studies was to determine the role of gracile nucleus and the effects of l-arginine-derived nitric oxide (NO) synthesis in the nucleus on the cardiovascular responses to electroacupuncture (EA) stimulation of "Zusanli" (ST36). Arterial blood pressure and heart rate were monitored during EA stimulation of ST36 following microinjections of agents into gracile nucleus. The cardiovascular responses to EA ST36 were blocked by bilateral microinjection of lidocaine into gracile nucleus. Microinjection of L-arginine into gracile nucleus facilitated the hypotensive and bradycardiac responses to EA ST36. The cardiovascular responses to EA ST36 were attenuated by bilateral microinjection of neuronal NO synthase (nNOS) antisense oligos into gracile nucleus. Microinjection of nNOS sense oligos into gracile nucleus did not alter the cardiovascular response to EA ST36. The results demonstrate that a blockade of neuronal conduction in the gracile nucleus inhibits the cardiovascular responses to EA ST36. The hypotensive and bradycardiac responses to EA ST36 are modified by influences of L-arginine-derived NO synthesis in the gracile nucleus. We conclude that NO plays an important role in mediating the cardiovascular responses to EA ST36 through gracile nucleus..
Unilateral EA stimulation of BL 64 and BL 65 in rats caused increases in nNOS immunostaining cells in the ipsilateral and contralateral gracile nucleus compared with sham-treated rats (P<0.05, n=6). NADPH-diaphorase positive cells were also increased in the gracile nucleus of the rats with EA stimulation. These results show that nNOS immunoreactivity and NADPH-diaphorase reactivity are consistently increased in the gracile nucleus by low-frequency EA applied to BL 64 and BL 65. We conclude that EA stimulation of the cutaneous hindlimb acupoints induces nNOS expression in the gracile nucleus, and enhanced nNOS-NO in the area may mediate somatosympathetic reflex activities, which contribute to therapeutic effects of acupuncture..
In addition to the nuclei mentioned above, the highest densities of such immunoreactive fibers were located in the spinal trigeminal nucleus, the lateral reticular nucleus, the nucleus of the solitary tract, the superior colliculus, the substantia nigra, the nucleus ambiguus, the gracile nucleus, the cuneate nucleus, the motor hypoglossal nucleus, the medial and superior vestibular nuclei, the nucleus prepositus hypoglossi and the interpeduncular nucleus.
Following nerve section, VIP immunoreactivity was increased in laminae I-II of the spinal cord while NPY immunoreactivity was increased in laminae III-IV of the spinal cord and in the gracile nucleus. On the contralateral side, CTb labelling was detected in laminae I and III-V of the dorsal horn of the L4 and L5 spinal segments, as well as in the gracile nucleus.
Using nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry and nitric oxide synthase (NOS) immunocytochemistry combined with radioassay of calcium-dependent NOS activity, we examined the occurrence of NADPHd staining and NOS immunoreactivity (NOS-IR) in the dorsal root ganglia (DRG) neurons, dorsal root afferents, and axons projecting via gracile fascicle to gracile nucleus 14 days after unilateral sciatic nerve transection in the rabbit. A noticeable increase in the number of thick myelinated NADPHd-exhibiting and NOS-IR axons was noted in the ipsilateral gracile fascicle, terminating in dense, punctate NADPHd staining in the neuropil of the gracile nucleus.
The purpose of these studies was to determine the role of gracile nucleus (Gr) and the effects of L-arginine-derived nitric oxide (NO) synthesis in the nucleus on the cardiovascular responses to somatosympathetic reflexes (SSR).
The activation of glial cells in the spinal dorsal horn and the gracile nucleus by inflammation and nerve injury has been suggested to be involved in neuronal plasticity and central sensitization, hence contributing to tactile allodynia. At 3 weeks post-lesion, PSNL markedly increased glia fibrillary acidic protein (GFAP) immunoreactive (IR) astrocytes in both the L4-5 spinal dorsal horn and the gracile nucleus. In summary, our data indicate that PSNL activates ERK/MAP and JNK/MAP kinase pathways in astrocytes in the dorsal horn and the gracile nucleus, these events possibly being involved in the pathogenesis of neuropathic pain..
In our results, NOS positive neurones and processes were seen in the spinal trigeminal nucleus, gracile nucleus, nucleus of the solitary tract, nucleus ambiguus, reticular nuclei and lateral to the pyramidal tract of the medulla.
Histopathological examination showed swelling of preterminal axons in gracile nucleus and degeneration of myelin in peripheral nerves.
In order to clarify the functional role of glutamate receptors of the gracile nucleus neurons in rats with nerve injury-induced hyperalgesia, pharmacological, electrophysiological and in situ hybridization techniques were used in rats with chronic constriction nerve injury (CCI) of the sciatic nerve. A total of 54 wide dynamic range neurons were recorded from the gracile nucleus in the rats with CCI. The expression of ionotropic glutamate receptor subunit mRNAs in the gracile nucleus was studied using the in situ hybridization technique. The signals for NMDA subunits, NR2A, -2B and -2C, in the gracile nucleus neurons were not prominent, suggesting a low level expression of functional NMDA receptor complex. AMPA receptor subunits GluR1, -R2, -R3 and -R4 mRNAs were expressed in a large number of gracile nucleus neurons. the AMPA and NMDA receptors, are differentially involved in modulation of the wide dynamic range neuronal activity in the gracile nucleus following peripheral nerve injury..
Excellent labeling was obtained with BDA, which visualized fibers with fine terminal boutons in the L5 and T13 spinal cord segments, Clarke's nucleus and the gracile nucleus. Rarely observed crossed projections to the gracile nucleus and L5 ventral horn of the contralateral side could also be distinguished.
We extended our study to primary afferents to the gracile nucleus; immunostaining for GluR5/6/7 in weakly fixed sections was in puncta of variable size.
Inflammation was produced by injection of complete Freund's adjuvant into one hindpaw in rats, and neurons in the gracile nucleus were recorded 2-8 days later.
Staining was also observed in the gracile nucleus, the mesencephalic trigeminal nucleus, and the central pontine gray.
Neither routine histological nor immunohistochemical methods demonstrated comparable changes in the contralateral gracile nucleus. In a 77-year-old man who underwent leg amputation, the gracile nucleus on the amputated side was gliotic and showed several NPY and ubiquitin-immunoreactive spheroids, which were not seen in the contralateral non-transected side.
Multi- and single-unit recording was performed in the gracile nucleus in urethane-anesthetized rats to examine estrous variations in responses of its neurons to brushing the hindquarters and mechanical stimulation of the uterus, vaginal canal, cervix, and colon. These variations in both magnitude of response to tactile stimulation and characteristics of response to stimulation of reproductive organs, but not the colon, correlate with changes in mating behaviors of the female rat, suggesting that the gracile nucleus is a component of neural systems that control reproductive behaviors..
Although diabetes has been reported to increase the frequency of NAD in the central processes of sensory neurons in the gracile fasciculus of genetically diabetic BB rats, we have found that 8-10 months of streptozotocin-induced diabetes results in fewer dystrophic axons in the gracile nucleus than in age-matched controls.
Ten, 17 and 24 days after unilateral sciatic nerve section, the distribution of the neuropeptide Y Y1 receptor was seen in lamina II in the ipsilateral and contralateral side of the lumbar spinal cord and gracile nucleus, whereas neuropeptide Y immunoreactivity located strongly in laminae I-II and moderately in laminae III-IV in the ipsilateral side. This is particularly apparent in the gracile nucleus which shows clear neuropeptide Y staining following sciatic nerve section and no expression of the neuropeptide Y Y1 receptor..
Using combined fluorescent dye tracing and NPY immunostaining, we found in middle-aged rats that 46% injured DRG neurons projected to the gracile nucleus and 45% of injured neurons were also NPY-IR, whereas 42% spared DRG neurons projected to the gracile nucleus and 18% of spared neurons were also NPY-IR. Thus PSNL induces NPY up-regulation in spared as well as injured DRG neurons, both contribute to the increased NPY immunoreactivity in the gracile nucleus in the middle-aged rats.
Swelling of preterminal axons in the gracile nucleus increased in a dose-dependent manner. 1-Bromopropane induced weakness in the muscle strength of rat limbs and deterioration of MCV and DL in a dose-dependent manner, with morphological changes in peripheral nerve and preterminal axon in the gracile nucleus.
A total of 68 neurons were recorded from the ventro-postero-lateral nucleus of thalamus (VPL) in rats with a unilateral chronic constriction injury (CCI) of the sciatic nerve (n=20), sham operation (n=24) and naive rats (n=24), and effects of the lesion of dorsal column (DC) pathway [ DC lesion or DC+gracile nucleus lesions] on VPL nucleus neuronal activities were studied. Responses of LTM and WDR neurons to innocuous mechanical stimulation of the receptive fields were significantly decreased after DC and DC+gracile nucleus lesions in all animals. However, the responses of WDR neurons to noxious stimuli were selectively reduced only in rats with CCI by DC and DC+gracile nucleus lesions (P<0.05). The decrease in noxious stimulus-evoked responses of WDR neurons in the VPL nucleus contralateral to the CCI side after DC and DC+gracile nucleus lesions was greater than that in the VPL nucleus contralateral to the sham operated side and naive animals. These results indicated that DC and DC+gracile nucleus lesions produced selective and stronger effect on noxious responses of VPL nucleus WDR neurons receiving input from the site of nerve injury. The findings suggest that the gracile nucleus-thalamic pathway conveys, or modulates, nociceptive information to the VPL nucleus following peripheral nerve injury, resulting in an increase in VPL nucleus response to noxious stimuli that contributes to the development of mechanical hyperalgesia..
Neuronal nitric oxide synthase (nNOS) is induced in dorsal root ganglion neurons following axotomy in young rats, and is also increased in the gracile nucleus neurons of intact aged rats. The present study examined the influence of sciatic nerve axotomy on nNOS expression in the gracile nucleus in young compared to aged rats. In young rats, unilateral axotomy produced increased NADPHd containing neurons in the rostral region and the caudal region of the ipsilateral gracile nucleus compared to the side with intact sciatic nerve. In old rats, the NADPHd containing neurons in the ipsilateral gracile nucleus were moderately increased by axotomy over the age changes seen in the contralateral side. The results suggest that unilateral sciatic axotomy causes an increase in nNOS expression in the ipsilateral gracile nucleus of young rats, which is still seen in old rats as an increase over normal aging changes..
The ultrastructural localization of immunoreactivity for immunoglobulin G (IgG), F(ab')2 and complement C9 was examined with preembedding immunoelectron microscopy in the hypoglossal nucleus and gracile nucleus as well as in the L4 spinal cord dorsal horn 1 week following hypoglossal or sciatic nerve transection, respectively.
Centrally, injection of SBA in the sciatic nerve resulted in labelled terminals in somatotopically appropriate regions of laminae I-II of the dorsal horn, and in the gracile nucleus. The results show that SBA can be used as a transganglionic tracer to label fine calibre primary afferents that project to laminae I-II of the spinal cord and the gracile nucleus.
The projections from the midthoracic or lumbosacral level of the medial spinal cord are found: 1) ascending ipsilaterally in the dorsal column near the dorsal intermediate septum or the midline of the gracile fasciculus, respectively; 2) terminating primarily in the dorsal, lateral rim of the gracile nucleus and the medial rim of the cuneate nucleus or the dorsomedial rim of the gracile nucleus, respectively; and 3) ascending bilaterally with slight contralateral predominance in the ventrolateral quadrant of the spinal cord and terminating in the ventral and medial medullary reticular formation.
No CTB-labelled terminals were observed in the gracile nucleus, indicating that the lesion successfully severed all ascending dorsal column axons. No evidence of terminal staining in the gracile nucleus was apparent following any treatment.
Fos-like immunoreactive (Fos-LI) neurons are expressed in spinal cord laminae III-IV and the gracile nucleus by electrically stimulating the injured nerves at Abeta strength after sciatic nerve transection in rats. In this study, we investigated which receptors are involved in the regulation of the increased excitability in spinal and gracile nucleus neurons. Two hours after the stimulation, Fos-LI expression was increased in the spinal cord dorsal horn and the gracile nucleus in control rats. Baclofen inhibited the Fos-LI expression both in the spinal cord and the gracile nucleus. Morphine inhibited only the Fos-LI expression in the posterior cutaneous (PC) nerve territory of laminae I-II, but not in the sciatic nerve (SC) territory, laminae III-IV nor the gracile nucleus. MK-801 had an inhibitory but complicated effect in laminae I-II and the gracile nucleus.
We asked whether sympathetic sprouting is directed to injured or spared DRG neurons and whether these neurons project to the gracile nucleus. Seventy-nine percent projected to the gracile nucleus. Sympathetic sprouting induced by PSNT is not directed preferentially to injured or spared DRG neurons, but does show a preference for DRG neurons projecting to the gracile nucleus..
Following axotomy, BDNF-immunoreactive terminals appeared in the central axonal projections of large-diameter cells, including the deep dorsal horn and gracile nucleus.
Following a unilateral chronic constriction injury of the sciatic nerve, calcitonin gene-related peptide (CGRP)-immunoreactive (IR) fiber density increases in the ipsilateral gracile nucleus, and this is more pronounced in aged (16-month) rats where the fibers are dystrophic. In this study we show that a second type of partial sciatic nerve injury, a half-transection, also induces CGRP-IR fibers in the gracile nucleus, but this effect is strongly age-dependent, being much more pronounced in 8- to 10-month-old rats than in 2- to 3-month-old rats. Using double-labeling with fluorescent dye tracing for 8- to 10-month-old rats, we showed that neuron profiles in the dorsal root ganglion (DRG) with peripheral axons spared by the partial sciatic nerve injury were 10 times more likely to be CGRP mRNA-positive than profiles with injured peripheral axons, suggesting that spared neurons are more likely to contribute to the increase in CGRP-IR fibers in the gracile nucleus. Using combined fluorescent dye tracing with in situ hybridization for CGRP mRNA or CGRP immunostaining, we further showed that CGRP-expressing DRG neuron profiles with central projections to the gracile nucleus had peripheral axons spared by the partial nerve injury. We conclude that the increased CGRP immunoreactivity in the gracile nucleus following partial sciatic nerve injury originates from primary sensory neurons with axons spared by the injury. These neurons may still transmit cutaneous sensory information and thus the increased CGRP immunoreactive fibers in the gracile nucleus may be involved in the mechanical allodynia characteristic of neuropathic pain syndromes following partial nerve injury..
After injection of horseradish peroxidase (HRP) into the pelvic nerve of the rat, a small number of HRP-labeled axon terminals were found in the gracile nucleus. Double labeling experiments were also performed: Fluoro-Gold (FG) was injected into the pelvic nerve, while cholera toxin B subunit (CTb) was injected into the gracile nucleus or dorsal faciculus at the fifth and sixth cervical cord segments ipsilateral to the FG injection. The results suggest that some primary afferent information from pelvic visceral organs may be directly conveyed to gracile nucleus by the primary afferent neurons..
Neuropeptide plasticity in the gracile nucleus is thought to play a role in the development of neuropathic pain following nerve injury. Two weeks after chronic constriction injury of adult rat sciatic nerve, galanin, neuropeptide Y and calcitonin gene-related peptide immunoreactivities were increased in fibers and cells in the gracile nucleus ipsilateral to injury. These results show that partial nerve injury to the sciatic nerve induces increases in the content of galanin, neuropeptide Y and calcitonin gene-related peptide immunoreactivities in synaptic terminals within the gracile nucleus, which suggests that there may be increased release of these neuropeptides following sensory or spontaneous stimulation of large-diameter primary afferents following partial nerve injury, perhaps one mechanism involved in neuropathic pain. We also show an apparent transfer of these neuropeptides to the cells of the gracile nucleus, both neurons and glial cells, an intriguing phenomenon of unknown functional significance..
Blockade of transmission of visceral nociceptive signals through the rat sacral cord by microdialysis administration of morphine or 6-cyano-7-nitroquinoxaline-2,3-dione shows that postsynaptic DC neurons in the sacral cord transmit visceral nociceptive signals to the gracile nucleus. Retrograde tracing studies in rats demonstrate a concentration of postsynaptic DC neurons in the central gray matter of the L6-S1 spinal segments, and anterograde tracing studies show that labeled axons ascend from this region to the gracile nucleus.
A qualitative and quantitative increase of OX-42-IR microglial cells were observed in the medial portion of the dorsal horn and in the gracile nucleus of the brainstem on the side ipsilateral to the formalin injection, starting on days 1-3 and peaking on day 7 postinjection.
Neurons belonging to the dorsal column nuclei (main cuneate nucleus and gracile nucleus), or to the ventral posterolateral nucleus, were sampled for their response to stimulation of the peripheral cutaneous fields, as well as the antidromic response to stimulation of the contralateral medial lemniscus and ipsilateral somatosensory cortex, respectively.
The results showed that BDNF-immunoreactivity (-ir) in the gracile nucleus was significantly increased after the nerve injury. Neutralization of endogenous BDNF with its antiserum had no effects on NPY-ir in either the gracile nucleus or DRG.
A marked increase in CTB-positive fibers was also seen in the gracile nucleus.
Increased galanin immunoreactivity (IR) in the dorsal horn, in gracile nucleus, and in sensory neurons following chronic constriction injury (CCI) compared to complete sciatic transection suggested a facilitatory role in thermal and mechanical hypersensitivity (allodynia).
The distribution of the retrogradely-transganglionically transported lectin soybean agglutinin (SBA) and of SBA conjugated to horseradish peroxidase (SBA-HRP) has been examined in the L4-5 dorsal root ganglia, lumbar spinal cord and gracile nucleus at 2, 6 and 14 weeks after sciatic nerve transection and ligation. In the gracile nucleus, at all survival times, an increased distribution and amount of labelling was seen which may reflect sprouting of C and A-delta fibres.
We have examined the mechanisms underlying Abeta-evoked c-fos expression in the dorsal horn and gracile nucleus following either sciatic nerve section or crush injury. In contrast, however, Abeta-evoked c-fos expression in the gracile nucleus may be under some other control since its expression appears independent of peripheral nerve regeneration..
Single-neuronal activities were recorded from the gracile nucleus (GN) in rats at 10-14 days after application of four loose ligatures around the sciatic nerve (chronic constriction nerve injury; CCI).
In contrast to the increases which we saw in the gracile nucleus, after both types of injury there was a decrease in CGRP-IR in all laminae of the dorsal horn. We interpret our results in terms of local sprouting in the gracile nucleus and suggest that the increased response following CCI is due to the involvement of fibers from DRG neurons spared by the partial nerve injury. Increased CGRP release from spared afferents in the gracile nucleus might be important in neuropathic pain..
Lumbar dorsal rhizotomy did not induce endogenous immunoglobulin G (IgG) deposition or complement expression in the spinal cord dorsal horn, dorsal funiculus, or gracile nucleus.
Using in situ hybridization and the retrograde tracer, FluoroGold, we detected an increased number of medium- to large-sized rat dorsal root ganglion neurons projecting to the gracile nucleus that expressed alpha-calcitonin gene-related peptide messenger RNA following spinal nerve transection. Immunohistochemistry revealed a significant increase in calcitonin gene-related peptide immunoreactivity in the gracile nucleus and in laminae III-IV of the spinal dorsal horn. These results indicate that a subpopulation of dorsal root ganglion neurons express alpha-calcitonin gene-related peptide messenger RNA in response to peripheral nerve injury, and transport this peptide to the gracile nucleus and to laminae III-IV of the spinal dorsal horn.
Retrograde tracer injections in the medial ventroposterolateral thalamic nucleus labeled numerous cells in the contralateral Cu, with a smaller number in the gracile nucleus.
In the brainstem, neurons containing NAIP-LI were observed in cranial nerve nuclei (trigeminal, facial, vestibular, cochlear, vagus, and hypoglossal nerves) and in relay nuclei (pontine, olivary, lateral reticular, cuneate, gracile nucleus, and locus coeruleus).
A few double-labeled neurons were also seen in the caudomedial part of the gracile nucleus ipsilateral to the injections.
Likewise, increased PK11195 binding is seen in the gracile nucleus after anterograde neuronal injury following sciatic nerve transection.
The principal and unexpected finding in this study was that NADPH-diaphorase reactivity, which is considered a marker of neuronal nitric oxide synthase activity, was decidedly increased in the neuronal bodies of the gracile nucleus but decreased in the axons and axon terminals in old compared with young rats. In situ hybridization also revealed that nitric oxide synthase gene expression was enhanced predominantly in the gracile nucleus neurons of aged rats. The differences between the young and old rats were most dramatically evident in the gracile nucleus, but not evident in other brainstem nuclei.
These bodies were thought to be compatible with one type of axonal dystrophy in the gracile nucleus (termed 'old' spheroid by Jellinger), and are here referred to as the HDB-type spheroid based on their ultrastructure.
At the age of 5-10 months a massive accumulation of GlcNAc-Asn was detected along with lysosomal vacuolization, axonal swelling in the gracile nucleus and impaired neuromotor coordination.
High concentrations of binding sites were detected in the presubiculum, parafascicular thalamic nucleus, gracile nucleus, spinal trigeminal tract nucleus, and a number of brainstem nuclei, with virtually no labelling in the cerebellum.
When they were adults, the rats were given injections of Fluoro-Gold (FG) into the gracile nucleus to identify DRG neurons projecting to this structure.
An insulin-like immunoreactivity (ILIR) was localized in the neuronal somata, dendrites and myelinated axons in the gracile nucleus of the male Wistar rat. It is hypothesized that insulin-like substance(s) may be modulating nuclear activities as well as neurotransmission at the synapse in the gracile nucleus..
Sciatic nerve axotomy induces the transganglionic expression of the growth associated protein GAP-43 and neuropeptide Y (NPY) in lumbar DRG projections to the gracile nucleus.
Local application of neurotrophin-3 (NT-3) using implanted silicone chambers applied to the proximal transected sciatic nerve stump significantly diminished the transganglionic NPY response in the gracile nucleus and spinal cord but did not affect the CGRP transganglionic response.
Using in situ hybridization and the retrograde tracer, Fluorogold, we examined the expression of preprotachykinin (PPT) mRNA in the rat dorsal root ganglion neurons projecting to the gracile nucleus. Seven days after unilateral sciatic nerve transection, some medium- to large-sized neurons in the rat dorsal root ganglia projecting to the gracile nucleus express PPT mRNA, whereas very few gracile nucleus-projecting neurons on the contralateral side express PPT mRNA. Immunohistochemistry revealed an increase in substance P (SP) immunoreactivity in the gracile nucleus and large myelinated fibers in the dorsal root 2 weeks after unilateral sciatic nerve transection. The results suggest that medium to large DRG cells that project to the gracile nucleus express PPT mRNA de novo in response to peripheral nerve injury, and increased SP is transported to the gracile nucleus through large myelinated fibers. To determine whether the increased SP might affect the excitability of the gracile nucleus neurons postsynaptically, Fos expression after electrical stimulation of the injured sciatic nerve was examined. Multiple injections of the NK-1 receptor antagonist, CP-96,345, suppressed stimulus-induced Fos expression in gracile nucleus neurons including thalamic relay neurons.
The APP-IR in both axons and glial cells was already accentuated to a higher level as early as 4 weeks of age in the gracile nucleus of GAD mouse. The cells showing immunoreactivity for amyloid beta-protein became positive in axons and glial cells in the gracile nucleus by approximately the 9th week, and followed by an increase of A beta P-IR in order of the cervical, thoracic and lumbar spinal cords.
The results were as follows: Many ubiquitin-positive dot-like structures (DS) were first observed in the gracile nucleus affected primarily with axonal degeneration.
A total of 309 neurons were identified antidromically by stimulation of the dorsal column nuclei (229 from the nuneate nucleus and 80 from the gracile nucleus).
We provide evidence for activation of the complement cascade in the dorsal horn of the spinal cord and in the gracile nucleus in the brainstem following sciatic nerve transection in the adult rat.
A narrow degenerated gracile fascicle was found in all thoracic and cervical segments terminating in the gracile nucleus.
Our results showed the presence of HRP/ChAT double-labelled neurons in (1) the midline medulla: the periventricular gray beneath the 4th ventricle, C3 adrenergic area, raphe obscurus nucleus and medial longitudinal fasciculus, (2) the reticular formation: the medullary, lateral, intermediate, gigantocellular, lateral paragigantocellular and dorsal paragigantocellular reticular nuclei and gigantocellular reticular nucleus ventralis, and (3) sensory nuclei: the gracile nucleus, cuneate nucleus, external cuneate nucleus, spinal trigeminal nucleus interpolaris, prepositus hypoglossal nucleus and medial vestibular nucleus.
In order to disrupt the central pathways for somatosensory information, lesions were made in (i) the right gracile nucleus (GN) (n = 18), (ii) bilateral GN (n = 7), (iii) the right GN and the left VPL (n = 6), and (iv) bilateral VPL (n = 8), and (v) sham-operated animals (n = 5).
Both in normal and reeler mice, collaterals arising from these CS fibers projected to the ipsilateral red nucleus, basal pontine gray matter, inferior olivary complex, and the contralateral gracile nucleus.
Primary afferents of the interosseous nerve projected directly to the gracile nucleus in the brainstem and distributed all along its rostrocaudal extent.
A set of 11 cutaneous stimuli defined previously to differentiate among different types of cutaneous sensory receptors in the rat hindpaw was also effective in differentially activating second-order sensory neurons in the dorsal horn and the gracile nucleus of rats.
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..
To examine the structural plasticity of central dorsal root ganglia (DRG)-derived axons in the gracile nucleus, we evaluated the response of the lumbar DRG and their central projections to sciatic nerve injury in young and old rats. Dystrophic axons in the gracile nucleus of non-lesioned aged animals were not NPY-immunoreactive; however, after sciatic nerve transection, NPY immunoreactivity developed in both delicate axons and markedly swollen dystrophic elements, a finding confirmed by ultrastructural immunolocalization.
Increased immunostaining in the spinal gray matter, dorsal columns and gracile nucleus on the side of the lesion became evident after 3 days and was more pronounced with longer survival times up to 3 weeks (the longest survival tested).
Combined demonstration in the spinal cord of Fos protein-like immunoreactive neurons and neurons labeled retrogradely with Fluoro-Gold from the gracile nucleus showed that some of the Fos protein-like immunoreactive neurons in Rexed's laminae III and IV contributed to the postsynaptic dorsal column pathway.
Cutaneous primary afferent fibers projecting from the hindlimb to the medulla oblongata were distributed mainly in the ipsilateral gracile nucleus. Terminal labeling in the gracile nucleus was seen at all rostrocaudal levels of the nucleus, occasionally including the nuclear part straddling the midline (the median or accessory nucleus). The labeled axon terminals in the gracile nucleus were more densely distributed in the middle and caudal parts of the nucleus than in the rostral part. Although the fields of termination of the hindlimb cutaneous nerves overlapped in the gracile nucleus, the foci of the terminal labeling of the nerves innervating the distal parts of the hindlimb were located more medially or dorsomedially than those of the nerves innervating the proximal parts.
In the medulla, nitric oxide synthase-positive neurons and processes were observed in the gracile nucleus, spinal trigeminal nucleus, nucleus of the solitary tract, dorsal motor nucleus of the vagus, nucleus ambiguus, medial longitudinal fasciculus, reticular nuclei and lateral to the pyramidal tract.
No NPY receptor mRNA-positive cells were found in the normal rat gracile nucleus, or in this nucleus after axotomy.
On the other hand, the hypoinnervation displayed by a few regenerating serotonergic fibers was observed in the periventricular part of the prosencephalon, the ventromedial part of the hypothalamus, the dorsal hippocampus, the neocortex, the superior and inferior colliculi, the cerebellum, the dorsal tegmental nucleus of Gudden, the vestibular nuclei, the gracile nucleus and the cuneate nucleus.
A study was made on the development of cortical synapses in the gracile nucleus of rats using degeneration methods. Identification of axonal terminals in the gracile nucleus was also achieved by tracing the cortical fibres of 1 adult rat using horseradish peroxidase-wheat germ agglutinin (HRP-WGA). Light or electron microscopic changes were not seen, and in particular, the gracile nucleus was not smaller than in the control adult animals which survived 30 days or in neonates which survived 8-30 days, consistent with the small component of cortifugal fibres believed to terminate in secondary sensory nuclei. In neonates that survived a shorter period, terminal degeneration was only seen in cases operated at 4 days and later, indicating that cortical axons do not synapse in the gracile nucleus until postnatal day 4.
Using immunohistochemistry and in situ hybridization, we studied changes in expression of some neuropeptides in large and medium-sized neurons in lumbar 4 and 5 rat dorsal root ganglia projecting to the gracile nucleus, in response to peripheral axotomy. A dense network of neuropeptide Y-immunoreactive, large nerve fibres and terminals was seen in the ipsilateral gracile nucleus. None of these neuropeptide immunoreactivities could be detected in nerve fibres and terminals in the control or contralateral gracile nucleus.
Ageing axonal dystrophy was studied electron microscopically in the gracile nucleus of a very old Japanese monkey (28 years of age) from the standpoint of comparative neuropathology.
Immunocytochemical observation for substance P (SP) revealed that SP-positive cells increased in the lesioned sites, primarily in the gracile nucleus of the medulla and subsequently in the gracile fasciculus of the spinal cord. Using an electron microscope, in addition to SP-positive axonal terminals in the gracile nucleus, most SP-positive cells in the gracile tract were identified as reactive astrocytes whose processes surrounded myelinated and nonmyelinated axons, and extended their foot processes to the blood vessels.
LSB were prominent in the posterior column, gracile nucleus, cuneate nucleus, and the tegmentum of the midbrain and the pons associated with neuronal loss and gliosis.
Bilateral application of HRP to the sciatic nerves demonstrated that axons that innervate only the gracile nucleus on the intact side of the brainstem were present in the cuneate nucleus on the deafferented side.
Thereafter, labelled cells were first found in a few other nuclei: the gracile nucleus on E19.5 and the paraventricular nucleus on E20.5.
A dense network of serotonin-immunoreactive fibers was present in the reticular regions of DCN in cats, and in the pars triangularis of the cuneate nucleus and the peripheral and caudal regions of the gracile nucleus in owl monkeys.
The number of c-fos protein-like immunoreactive (Fos-LI) cells in the gracile nucleus was determined after electrical stimulation at A alpha/A beta-fiber strength of the normal and of the previously injured sciatic nerve in adult rats. However, stimulation 21 days after sciatic nerve transection resulted in numerous Fos-LI cells in the ipsilateral gracile nucleus. Combined Fos immunocytochemistry and retrograde labeling from the thalamus showed that the majority (76%; range = 70-80%) of the cells in the gracile nucleus that expressed Fos-LI after nerve injury projected to the thalamus.
The regions examined included the gracile nucleus, the column of Clarke and the spinal cord dorsal horn (superficial and deep laminae separately) after unilateral sciatic nerve transection, and the spinal trigeminal nucleus following unilateral infraorbital nerve transection.
Light and electron microscopic studies were carried out on the axonal dystrophy (AD) appearing in the gracile nucleus of normally aging and vitamin E (VE) deficient rats aged 18, 33, and 48 weeks.
Responses to innocuous and noxious mechanical and thermal stimuli were recorded from 90 neurons in the gracile nucleus of anesthetized cats. Many were recorded in the range of the cluster region of the gracile nucleus. Latencies of antidromic activation were shorter at more caudal locations in the gracile nucleus, indicating higher conduction velocities to the thalamus. The results indicate a greater proportion and more widespread distribution of cells with nociceptive input in the cat gracile nucleus than has been previously recognized.
No labeled cells were seen in the gracile nucleus. Stimulation at A alpha/beta fiber intensity 21 days after injury resulted in increases in the numbers of labeled cells in ipsilateral laminae II, III and IV and in the gracile nucleus.
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.
All these DRGs projected throughout the rostrocaudal extent of the gracile nucleus (Gr).
The projection of primary afferent fibers to the gracile nucleus was studied during development. At embryonic day E21 the caudal-most pole of the gracile nucleus still is not penetrated by labelled fibers. From postnatal day 1 onwards labelled fibers are found throughout the entire rostrocaudal extent of the gracile nucleus. These results suggest that primary afferent fibers from the hindlimb first grow to the rostral pole of the gracile nucleus and penetrate the rostral pole immediately upon their arrival. During further development more caudal parts of the gracile nucleus are gradually penetrated in a rostrocaudal fashion by primary afferent fibers of the hindlimb..
In the gracile nucleus, the organization of cutaneous afferent projections from hindlimb digits was more variable and complex than that found in the CN..
The caudal medial accessory subdivision of the inferior olive (cMAO) receives information from the hindlimb from both the gracile nucleus and the lumbosacral spinal cord. The dendritic spines in cMAO that receive input from the gracile nucleus often receive additional input from the lumbosacral spinal cord.
This study reports ultrastructural changes in the gracile nucleus of male Wistar rats after streptozotocin-induced diabetes. These degenerating profiles were absent in the gracile nucleus of the 3 and 7 days insulin-treated post-streptozotocin rats. During the late phase (9-12 months) a second wave of degeneration occurred in the gracile nucleus, similar to the acute phase. It is concluded that the ultrastructural changes observed in the gracile nucleus in the present study were the result of streptozotocin-induced diabetes rather than a toxic effect of streptozotocin, even in the acute phase..
The frequency of NAD failed to increase in the SMG of the same vitamin-E deficient animals in which a marked increase in severity of NAD was found in the gracile nucleus.
The present study describes the structural changes in the gracile nucleus of the spontaneously diabetic BB rat. It is concluded that degenerative changes occur in the gracile nucleus of the spontaneously diabetic BB rat..
Ultrastructural changes in the gracile nucleus of the rat have been examined after peripheral nerve injury. The sciatic nerve of adult rats was transected at mid-thigh level, and after survival times ranging from 1 day to 32 weeks sections from the gracile nucleus were prepared for electron microscopic examination. The results clearly show that various types of degenerative changes occur in the gracile nucleus after peripheral nerve injury.
The mean volume of the GABA-stained neurones in the gracile nucleus was 2319, and internal cuneate 3065 microns3, while the corresponding volume of unlabelled neurones in the gracile, internal and external cuneate nuclei was 3745, 8147 and 13318 microns3, respectively.
Severe loss of neurons was observed in the thalamus, globus pallidus, lateral geniculate body, gracile nucleus, Purkinje and retinal ganglion cells.
Comparison of these results with data on the other major source of somatosensory information for DAO, the gracile nucleus (examined previously with the same methods), suggests that the sensitivity of neurons in DAO to light cutaneous stimuli is mediated primarily by neurons in the dorsal horn. The sensitivity of neurons in DAO to tap, rub, or pressure, on the other hand, might be mediated by neurons in either the dorsal horn, the gracile nucleus, or both..
By contrast, there was marked depletion of synaptophysin immunoreactivity in the posterior column nuclei, with the gracile nucleus showing greater loss of positive puncta than the cuneate nucleus..
The upper limit of the hemorrhage was in the left gracile nucleus of the medulla oblongata, and the lower limit was in the left posterior horn of the spinal cord at L4.
Both control groups have a consistent dense projection in topographically adjacent regions of the dorsal funiculus and gracile nucleus. Transganglionic labeling after C-HRP sciatic nerve injections (N = 4) and retrograde labeling of L4, L5 dorsal root ganglion neurons after fast blue injections of the gracile nucleus (N = 6) both suggest that all dorsal column axons project to the gracile nucleus in the newborn rat. DRG neurons that project to the gracile nucleus were prelabeled by injecting fast blue into this nucleus at birth two days prior to the cervical overhemisection spinal injury.
Projections to the gracile nucleus, the vestibular nuclear complex, including nucleus X, and to trigeminal sensory nuclei were seen from all DRGs investigated..
Only few spheroids are observed in the gracile nucleus of the medulla in normal mice throughout the period examined, while they are first noted in GAD mice as early as 40 days after birth. The incidence of spheroids shifts from the gracile nucleus to the gracile fasciculus of the spinal cord with the progress of disease, suggesting that the degenerating axonal terminals of the dorsal ganglion cells back from the distal presynaptic parts in the gracile nucleus, along the tract of the gracile fasciculus, toward the cell bodies in the dorsal root ganglion. In addition to the gracile nucleus and the gracile fasciculus, which is one of the main ascending tracts of primary sensory neurons, it was noted that the other primary sensory neurons joined with some of the second-order neurons at the dorsal horn and neurons at all levels of the dorsal nucleus (Clarke's column) are also severely affected in this mutant.
Although 200 micrograms/kg clonidine directly suppressed regional cerebral metabolic rates for glucose in many regions (significant main effect of clonidine), it attenuated the naloxone-precipitated morphine withdrawal effect specifically in the lateral septal nucleus, medial habenula, subiculum and gracile nucleus (significant interactions between clonidine and morphine withdrawal).
Little or no staining is present in the deep dorsal horn, but GAP-43 does appear in the ipsilateral gracile nucleus 22 days after sciatic injury.
The present study reports ultrastructural changes in the gracile nucleus of male Wistar rats after alloxan-induced diabetes. During the late phase (9-12 months), a second wave of degeneration occurred in the gracile nucleus, similar to the acute phase..
In the gracile nucleus of clioquinol-treated rats, the presynaptic inhibition was remarkably diminished, and the excitatory synaptic transmission was less intensely inhibited by a conditioning sural nerve volley.
Substance P-like immunoreactivity (SPI) was observed in many axonal profiles within the gracile nucleus and fasciculus of 13-month-old mice. No SPI, however, was detected in the gracile nucleus and fasciculus in 3- and 6-month-old mice. The results suggest that the accumulation of SPI elements in axons of the gracile nucleus and fasciculus is one of the age-related changes in the central nervous system..
Spheroids from phenytoin-intoxicated epileptics showed significantly higher proportions of the tubulomembranous (TM) and layered membrane loop (LML) types in the gracile nucleus, appearance of the same types in the cuneate nucleus, and a significant decrease of the neurofilamentous (NF) type in both nuclei. The incidences of the complex body (CB) and granular material types and of the homogeneous dense-body (HDB) type, which appeared only in the gracile nucleus, showed no difference between the intoxicated patients and the controls.
Associated morphological changes were preterminal accumulation of axonal neurofilaments without synaptic disruption in the gracile nucleus.
Microinjection of DL-homocysteic acid into the contralateral gracile nucleus increased the discharge rate of APTN neurones. Microinjection of gamma-aminobutyric acid into the contralateral gracile nucleus blocked the gracile fasciculus evoked excitation of APTN neurones. On thirteen occasions cells in the gracile nucleus were driven antidromically by electrical stimulation of the APTN.
Injections into the lumbar enlargement labeled fibers and varicosities throughout most of the gracile nucleus. Injections in sacral cord labeled fibers in the most medial part of the gracile nucleus.
The gracile nucleus of the medulla oblongata and the gracile fascicules of the spinal cord were investigated for pathology at 130 days of age, and alpha-tocopherol was also assayed in the serum, liver, brain and spinal cord at that time. There were no pathological differences in the gracile nucleus and fascicules between the GAD mice fed the control and vitamin E-supplemented diet.
Light microscopic studies demonstrated the presence of GABA-positive cells in the gracile nucleus, the internal cuneate nucleus and the lateral cervical nucleus but not in the external cuneate nucleus.
The most intensive labeling of the gracile nucleus was found in the dorsal border of the nucleus and the lateral part of the caudal division.
Calcitonin gene-related peptide-like immunoreactivity was first detected in the fibers of the nucleus of spinal tract trigeminal nerve on gestational day 18, and thereafter appeared gradually in various brain stem areas such as in the fibers of the solitary tract, gracile nucleus, cuneate nucleus, inferior colliculus, superior colliculus, medial geniculate nucleus and in the neurons of the hypoglossal nucleus, facial nucleus, superior olive, parabrachial area, superior colliculus and peripeduncular nucleus.
Termination fields were consistently observed ipsilaterally in: lamina I from the L4 through S3 segments, being most dense in L6 and S1; lateral lamina V in L6 and S1-3; medial laminae VI-VII from L5 through S3; medial Clarke's column from L1 through L4; the ventral aspect of the gracile nucleus; and, nucleus Z.
NGFRI staining was seen in a variety of sensory pathways and related structures, such as olfactory tract and glomerular layer of olfactory bulb; retina, optic nerve and tract, lateral geniculate nucleus, medial terminal nucleus of the accessory optic tract, and olivary pretectal nucleus; ventral cochlear nucleus and to a lesser degree in dorsal cochlear nucleus, superior olive, and nucleus of lateral lemniscus; solitary tract; cuneate nucleus, gracile nucleus, and ventroposterior thalamic nucleus.
The micropunch region containing the gracile nucleus, the area postrema and the choroid plexus of the fourth ventricle contained the highest ChAT activity, but exhibited little [ 3H]QNB binding to muscarinic receptors.
Low densities were found in the area postrema, principle nucleus of the inferior olive, gracile nucleus, cuneate nucleus and the tractus of the NTS.
Pathological examination revealed neuroaxonal dystrophy and degeneration in the gracile nucleus of the medulla oblongata and the gracile fascicules of the spinal cord, which could be the main cause of the clinical signs.
Following injections in the first cervical segments and in the cervical enlargement labelled neurons were observed in the somatic motor and somatic sensory cortices, the paraventricular and the dorsomedial hypothalamic nucleus, the lateral hypothalamic area, the nuclei of field H of Forel, the red nucleus, the mesencephalic reticular formation, the deep layers of the superior colliculus, the Edinger-Westphal nucleus, the periaqueductal grey, the mesencephalic trigeminal nucleus, the loci coeruleus and subcoeruleus, the nuclei raphe dorsalis, centralis superior, raphe magnus, raphe pallidus, and raphe obscurus, the rhombencephalic reticular formation, the lateral, medial and caudal vestibular nuclei, the nucleus ambiguus, the nucleus of the solitary tract and the gracile nucleus.
The present study has shown that primary afferents from the sciatic nerve project predominantly to the ipsilateral gracile nucleus.
Comparisons of the anterograde labeling following injections involving both the gracile nucleus and the cuneate nucleus with that after injection restricted to the gracile nucleus alone suggested a somatotopic termination pattern in Inc, the superior colliculus, and the pretectal nuclei.
No c-fos induction was seen in the dorsal root ganglia, gracile nucleus or ventral horn.
The external cortex is the only collicular subdivision where an injection labels cells in the contralateral cuneate nucleus, gracile nucleus, and spinal trigeminal nucleus.
An investigation was carried out of the time of ingrowth of primary sensory fibres in the medulla and of their penetration into the gracile nucleus, and of the effect of an early loss of these fibres upon the development of the nucleus in rats. After injection of the conjugate horseradish peroxidase-wheat germ agglutinin in the hind limbs of fetuses, a bundle of labelled fibres was seen in close proximity of the gracile nucleus at embryonic day 17. Synaptic contacts within the gracile nucleus were found at all stages of the observation; the presynaptic processes consisted of an electron-lucent matrix which contained round vesicles. After transection of the primary sensory afferents at embryonic day 18 and 19, no degeneration was seen within the gracile nucleus; degenerated boutons were occasionally seen after deafferentation at embryonic day 20 and became more numerous thereafter; nerve cells in various stages of degeneration could also be seen. Removal of primary afferents to the gracile nucleus at the time they reach the nucleus or soon after was followed by a severe loss of nerve cells and a reduced increment in size of the remaining ones. Moreover, the results of the present investigation show that penetration of primary sensory fibres into the gracile nucleus takes place approximately 2 days after they have been seen in the medulla and are in keeping with observations made in other pathways of the nervous system of the rat as well as in other animals.
In addition to the previously reported enkephalinergic cells, we found many methionine-enkephalin-Arg6-Gly7-Leu8 containing neurons; the rostral and caudal linear nucleus of raphe, the median raphe nucleus, entire length of the raphe magnus nucleus, the medial longitudinal fasciculus, the cuneate nucleus, the external cuneate nucleus, the gracile nucleus, and the area postrema.
Three kinds of afferent sources of the PTA--the cerebral motor cortex, the anterior interpositus nucleus of the cerebellum, and the gracile nucleus--were subjected to electrolysis, suction, or injection of kainic acid or HRP for identification of axon terminals of each system.
Neurons containing preproenkephalin mRNA were found in the piriform cortex, ventral tenia tecta, several regions of the neocortex, nucleus accumbens, olfactory tubercle, caudate-putamen, lateral septum, bed nucleus of the stria terminalis, diagonal band of Broca, preoptic area, amygdala (especially central nucleus, with fewer labeled neurons in all other nuclei), hippocampal formation, anterior hypothalamic nucleus, perifornical region, lateral hypothalamus, paraventricular nucleus, dorsomedial and ventromedial hypothalamic nuclei, arcuate nucleus, dorsal and ventral premamillary nuclei, medial mamillary nucleus, lateral geniculate nucleus, zona incerta, periaqueductal gray, midbrain reticular formation, ventral tegmental area of Tsai, inferior colliculus, dorsal and ventral tegmental nuclei of Gudden, dorsal and ventral parabrachial nuclei, pontine and medullary reticular formation, several portions of the raphe nuclei, nucleus of the solitary tract, nucleus of the spinal trigeminal tract (especially substantia gelatinosa), ventral and dorsal cochlear nuclei, medial and spinal vestibular nuclei, cuneate and external cuneate nuclei, gracile nucleus, superior olive, nucleus of the trapezoid body, some deep cerebellar nuclei, Golgi neurons in the cerebellum, and most laminae of the spinal cord.
(3) N29, a stationary, synapse-dependent negative potential, localizes to the rostral cervical spine and is attributed to activation of the gracile nucleus relay cells.
Hindlimb RNm projects to only the lateral reticular nucleus, gracile nucleus, and lower spinal segments.
Axon terminals of the pudendal nerve were distributed, bilaterally with an ipsilateral predominance, to the gracile nucleus, as well as to the dorsal horn and dorsal commissural gray from L4 to S2.
This study evaluated the functional properties of neurons in the gracile nucleus that project to the dorsal accessory portion of the inferior olive (DAO) and compared these with properties of other efferents from the dorsal column nuclei (DCN).
This study examined the termination pattern within the dorsal accessory subdivision of the cat inferior olive of axons arising from the gracile nucleus. Only one terminal per thicket was labeled by injections in the gracile nucleus.
These axonal inclusions were distributed exclusively in the dorsolateral part of the caudal VPL, and their arrangement may be associated with fibres originating from the gracile nucleus.
A similar reorganization occurred in the gracile nucleus where, in intact and adult-lesioned cats, the cortical terminals also predominated in the side contralateral to the injection.
A morphological and quantitative study was carried out of the prenatal and early postnatal development of the gracile nucleus in the mutant rat 'mutilated foot' (mf), which is affected by a sensory neuropathy inherited by autosomal recessive transmission. These results suggest that the abnormalities observed in the gracile nucleus of mf rats are secondary to the decreased number of afferent fibres originating from the dorsal root ganglia and represent a form of 'anterograde transneuronal degeneration'.
The areas of degeneration argyrophilia were mainly located in the medial part of the ipsilateral L2-L6 dorsal horn laminae I-IV, the tract of Lissauer, the dorsal funiculus and the gracile nucleus. A few degenerating fibers could also be observed in the ipsilateral dorsal horn laminae V and VI, and in the ipsilateral ventral horn as well as in the contralateral dorsal horn and the gracile nucleus.
If, however, a small injection of the radioactive tracer was centered in the gracile nucleus and compared with an injection of WGA-HRP placed in the lumbar enlargement of the cord, the rostral and dorsal portions of the lateral VB were labeled from both sources.
Other centers less systematically or more sparsely labeled were the lateral hypothalamic area, ventrobasal complex, lateral geniculate nucleus pars ventralis, medial geniculate nucleus, interstitial nucleus of Cajal, Darkschewitsch nucleus, perirubral fields, cuneiform, tegmental pedunculopontine, and deep mesencephalic reticular nuclei, pontine reticular nucleus pars oralis, lateral and interpositus cerebellar nuclei, and gracile nucleus.
In the caudal medulla the representation of the leg within the gracile nucleus was medial to and separate from that of the wing within the cuneate nucleus (Cu).
Projection systems from the gracile nucleus and the cuneate nuclear complex to their terminal sites in the mesencephalon, diencephalon, and cerebellum were examined by means of anterograde autoradiography and retrograde horseradish peroxidase methods.
In the histopathological examination, axonal and myelin degeneration was disclosed in the gracile nucleus and in the gracile fasciculus of the cords as well as in the sciatic nerves.
Splanchnic afferent projections to the spinal cord and gracile nucleus were labeled following the application of HRP to the central cut end of the major splanchnic nerve. The dorsal column pathway terminated in the ventral gracile nucleus in four or five clusters, each occupying a region ranging in size from 0.01-0.1 mm3 and separated in the rostrocaudal axis by distances of 400-800 microns.
Following injections of tritiated amino acids into the L6 and S1 DRG, labeling was observed on the initial and halfway developed dystrophic terminals in the ipsilateral gracile nucleus.
The aim of this study was to investigate the functional role of the cortical projections to gracile nucleus.
Injections restricted to either the gracile nucleus or the cuneate nucleus revealed a somatotopic termination pattern in the intercollicular nucleus, superior colliculus and pretectal nuclei.
Unitary spike potentials were recorded from the gracile nucleus in vitro following stimulation of the ipsilateral dorsal column.
The field potentials which follow the compound tract action potential recorded from the rat gracile nucleus in vitro were studied.
The preparation and maintenance of a novel slice of the rat gracile nucleus is described. Extracellular recording revealed that a compound tract action potential (CAP) could be recorded from the gracile nucleus following stimulation of the ipsilateral dorsal column.
The cells in the gracile nucleus that project to the dorsal accessory olive were identified in cats with retrograde tracing techniques. In the gracile nucleus these cells are found almost exclusively in the transitional zone, just caudal to the obex and rostral to the clusters.
Injections of HRP confined to the gracile nucleus (GN) labeled more than 200 neurons within a narrow band extending across the ipsilateral dorsal horn subjacent to substantia gelatinosa of L4-6.
Most of the quadriceps afferents course to the gracile nucleus.
Transganglionically labeled dorsal root fibers were found to terminate ipsilaterally in the lamina I of the dorsal horn at levels of lower lumbar, sacral, and higher coccygeal cord segments and the gracile nucleus, and bilaterally with an ipsilateral predominance in the dorsal commissural gray and laminae III, IV, V, and VI of the dorsal horn at levels of lower lumbar, sacral, and higher coccygeal cord segments.
There also appeared to be quantitative differences in the projections from various levels of the gracile nucleus, with more midbrain projecting fibers originating in the rostral than in the middle and caudal parts of the nucleus..
Unilateral spinal cord lesions made between C7 and T1 vertebrae resulted in medullary degeneration in NC contralaterally, ipsilaterally in CU and lateral cuneate nucleus, and bilaterally in gracile nucleus, inferior olivary complex, and reticular formation.
Most responses in the gracile nucleus were to stimulation of skin and hairs of the tail, hind foot and leg, and trunk, in that order going from dorsal to ventral in the nucleus.
It was investigated the incidence of damaged nerve fibres in the gracile nucleus and the cuneate nucleus of the dog following an intermittent ligation of the abdominal aorta and 3-day survival. the caudal part of the gracile nucleus, the cell-nest region of the gracile nucleus and the region just before the beginning of the central canal. When comparing the region just before the beginning of the gracile nucleus with the caudal part of the gracile nucleus it was stated, that the higher density of decomposed fibres was in the region just below the obex. In common there were fewer disintegrated fibres in the cuneate than in the gracile nucleus..
VIP concentrations are moderately high (0.8-1 ng/mg protein) in gracile nucleus, area postrema, nucleus of the solitary tract, motor nucleus of the XIIth, locus ceruleus and dorsal tegmental nucleus.
The dorsal column nuclei were particularly studied; terminations in these nuclei following dorsolateral lesions followed a clear-cut pattern, with fibres arising from segments below T6 terminating in the gracile nucleus and those with more rostral origin solely in the cuneate nucleus.
The somatotropic representation of the hindlimb in the gracile nucleus was studied in two cats who had a congenital defect of one hindfoot. Electrophysiological single and multi-neurone recordings revealed an altered somatotopic representation in the gracile nucleus on the defective side. It is concluded that the remaining parts of the leg project onto the gracile nucleus in an ordered fashion, sharing the entire nucleus according to their present afferent fibres..
In 656 patients aged from one to 39 years, the incidence of axonal dystrophy in the gracile nucleus (ADG) is correlated with underlying diseases. The incidence drops to 8, 16, 31, and 60% when more than five spheroids in each gracile nucleus are taken into account.
An initial series comprising 22 animals with survival periods varying between 2 h and 4 days showed maximal labeling in the gracile nucleus after 24-48 h. In a second series of five cats, which were killed 24 h after injection, serial sections from the gracile nucleus were embedded in Epon following peroxidase processing, and cut at 2 micrometer. The total number of nerve cells in a single gracile nucleus was calculated to be about 50,000, out of which about 15,000 were retrogradely labeled. The results of this study support the idea of a heterogeneous organization of the gracile nucleus. However, a much larger proportion of the gracilo-diencephalic relay cells is situated in the rostral part of the gracile nucleus than has previously been thought.
In 63 patients with malabsorption syndromes, 16 with congenital biliary atresia (BA) and 47 with cystic fibrosis (CF), axonal dystrophy in the gracile nucleus (ADG) was studied.
Localized injections covering the entire cerebellar cortex and nuclei show that the gracile nucleus has a weak projection only to the cortex of the anterior lobe, but that there is a conspicuous projection from the main cuneate nucleus to the cerebellum.
The dorsal column nuclei project topographically upon the contralateral accessory nuclei with the gracile nucleus sending fibers primarily to the lateral half of the DAO and the cuneate nucleus projecting to rostral cell groups of the MAO.
The gracile nucleus and conus medullaris, the sites of predilection for spheroids and Lafora-like bodies, were examined light and electron microscopically in 91 dogs ranging from 1 month to 19 years of age.
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