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PubMed2004

Hypothalamic cocaine- and amphetamine-regulated transcript neurons project to areas expressing gonadotropin releasing hormone immunoreactivity and to the anteroventral periventricular nucleus in male and female rats.

Cocaine- and amphetamine-regulated transcript (CART) and CART-derived peptides are widely expressed in the hypothalamus. CART is involved in food intake control and is regulated by circulating leptin, a hormone implicated in a variety of endocrine functions. Lack of leptin (ob/ob mice) is associated with obesity, hypogonadism and infertility. In the arcuate nucleus, dorsomedial nucleus of the hypothalamus, and ventral premammillary nucleus, CART neurons also express leptin receptor long-form splice-variant. Recent studies have suggested that the facilitatory effect of leptin on gonadotropin-releasing hormone (GnRH) secretion is mediated by CART. In the present study, using dual- and triple-label immunohistochemistry, we identified CART fibers in close apposition with GnRH neurons expressing Fos in the afternoon of the proestrous day, as well as with GnRH neurons in male rats. In order to investigate the origin of these fibers, we injected the retrograde tracer Fluorogold into areas containing GnRH cell bodies. In male and female rats, the tracer was injected around the vascular organ of lamina terminalis, median preoptic nucleus and medial preoptic nucleus, as well as in the anteroventral periventricular nucleus. We observed retrogradely labeled neurons in various hypothalamic nuclei, including the arcuate, dorsomedial and ventral premammillary. In these areas, dual-label immunohistochemistry/in situ hybridization revealed that part of the retrogradely labeled neurons also express CART mRNA. As a control, we injected the anterograde tracer biotinylated dextran amine into the ventral premammillary nucleus of both males and females. Most projections targeted brain areas related to reproductive behavior and few fibers were closely associated with GnRH neurons. Our findings indicate that ventral premammillary nucleus CART neurons intermingle with brain circuitry involved in reproduction. Therefore, these neurons are well positioned to mediate leptin effect on reproductive control.

Animals↗
PubMed2004

Damage to the amygdalo-hippocampal projection in temporal lobe epilepsy: a tract-tracing study in chronic epileptic rats.

Both the amygdala and hippocampus are damaged in drug-resistant temporal lobe epilepsy (TLE), suggesting that amygdalo-hippocampal interconnectivity is compromised in TLE. Therefore, we examined one of the major projections from the amygdala to the hippocampus, the projection from the amygdala to the CA1 subfield of the hippocampus/subiculum border region, and assessed whether it is preserved in rats with spontaneous seizures. Male Wistar rats were injected with kainic acid (9 mg/kg, i.p.) to induce chronic epilepsy. The occurrence of spontaneous seizures was monitored 5 or 15 weeks later by video-recording the rats for up to 5 days. Saline-injected animals served as controls. Thereafter, the retrograde tracer Fluoro-gold was injected into the border region of the temporal CA1/subiculum. Rats were perfused for histology 1-2 weeks later and sections were immunohistochemically processed to detect Fluoro-gold-positive cells. Comparison of the labeling in control and epileptic tissue indicated that a large cluster of retrogradely labeled cells in the parvicellular division of the basal nucleus was well preserved in epilepsy, even when the neuronal damage in the amygdala was substantial. Another large cluster of retrogradely labeled cells in the lateral division of the amygdalo-hippocampal area, the posterior cortical nucleus (part of the vomeronasal amygdala), and the periamygdaloid cortex (part of the olfactory amygdala), however, had disappeared in epileptic brain in parallel to severe neuronal loss in these nuclei. These data demonstrate that a projection from the parvicellular division of the basal nucleus to the temporal CA1/subiculum region is resistant to status epilepticus-induced neuronal damage and provides a candidate pathway by which seizure activity can spread and propagate from the amygdala to the hippocampal formation.

Amygdala↗
PubMed2004

Identification of neural pathways involved in genital reflexes in the female: a combined anterograde and retrograde tracing study.

The medial preoptic area (MPOA) is important for reproductive behavior in females. However, the descending pathways mediating these responses to the spinal motor output are unknown. The MPOA does not directly innervate the spinal cord. Therefore, pathways mediating MPOA-induced changes in sexual behavior must relay in the brain. The nucleus paragigantocellularis (nPGi) projects heavily to spinal circuits involved in female sexual reflexes and is involved in the tonic inhibition of genital reflexes. However, the periaqueductal gray (PAG) is also important for female sexual behavior. The present study examined the hypothesis that the MPOA output relays through PAG and the nPGi before descending to the spinal cord. We used anterograde and retrograde tracing techniques to examine the descending pathways and relay sites from the MPOA to the spinal cord and the nPGi in the female rat. Injection of biotinylated dextran amine into the MPOA produced dense labeling in specific regions of the PAG and Barrington's nucleus; anterogradely labeled fibers terminated close to neurons retrogradely labeled from the spinal cord in the PAG, Barrington's nucleus, nPGi, lateral hypothalamus and paraventricular nucleus (PVN). Anterogradely labeled fibers and varicosities were also found close to neurons retrogradely labeled from the nPGi in the PAG, lateral hypothalamus and PVN. These results suggest that the major MPOA output relays in the PAG and nPGi before descending to innervate spinal circuits regulating female genital reflexes and that the MPOA plays a multifaceted role in female reproductive behavior through its modulation of PAG output systems.

Afferent Pathways↗
PubMed2004

Isolectin B4 binding neurons are not present in the rat knee joint.

Small-diameter sensory neurons are key contributors in joint pain and have been implicated in the pathogenesis of rheumatoid arthritis (RA). Small-diameter sensory neurons can be separated into at least two distinct populations, which include isolectin B4 (IB4)-binding and tyrosine receptor kinase (trk) A-expressing. While trkA-expressing neurons have been identified in the rat knee joint there are no data, we are aware of, to suggest that IB4-binding neurons are also present. We aimed to determine whether or not there exists a population of IB4-binding neurons in the rat knee joint. Retrograde nerve tracing with fluoro-gold (FG) was used to identify the complete population of knee joint afferents in the lumbar dorsal root ganglia (DRG) L3 and L4 of female Wistar rats. IB4 conjugated to fluorescein isothiocyanate (FITC) was used to identify the cell bodies of IB4-binding neurons in the DRG. Of 1096 FG-labeled cell bodies in the DRG of knee joint injected animals (n=4), none were double labeled with FITC. Injection of FG into skin over the medial aspect of the rat knee (n=3) showed 48% of these cutaneous afferents in L3 and L4 DRG were double-labeled with FG and FITC. A complete absence of IB4-binding neurons in the rat knee joint makes it unlikely that this predominantly cutaneous, IB4-binding population of afferent neurons could have any significant influence in chronic inflammatory joint disease. This suggests that trkA-expressing neurons are the sole population of small-diameter sensory neurons in the knee joint and implies a significant role for these afferents in the progression of RA.

Animals↗
PubMed2004

Rat trigeminal lamina I neurons that project to thalamic or parabrachial nuclei contain the mu-opioid receptor.

Ligands of the mu-opioid receptor are known to inhibit nociceptive transmission in the dorsal horn, yet the cellular site(s) of action for this inhibition remain to be fully elucidated. Neurons located in lamina I of the dorsal horn are involved in distinct aspects of nociceptive transmission. Neurons projecting to the thalamus are thought to be involved in sensory-discriminative aspects of pain perception, while neurons projecting to the parabrachial nucleus are thought to be important for emotional and/or autonomic responses to noxious stimuli. The present study examined these two populations of lamina I projection neurons in the trigeminal dorsal horn to determine if the mu-opioid receptor protein (MOR1) is differentially located in these populations of neurons. Lamina I projection neurons were identified using the retrograde tracer FluoroGold (FGold). FGold was injected into either the contralateral thalamus (ventral posterolateral (VPM)/ventral posterolateral (VPL) thalamic region) or into the ipsilateral parabrachial nuclei. The distribution of MOR1 in these neurons was determined using immunocytochemistry. The distribution of MOR1-ir within these two populations of lamina I projection neurons was examined by both confocal and electron microscopy. We found that both populations of projection neurons contained MOR1. Immunogold analyses revealed the presence of MOR1-ir at membrane sites and within the cytoplasm of these neurons. Cytoplasmic receptor labeling may represent sites of synthesis, recycling or reserve populations of receptors. MOR1 was primarily found in the somata and proximal dendrites of projection neurons. In addition, these neurons rarely received synaptic input from MOR1-containing axon terminals. These results indicate that lamina I neurons in trigeminal dorsal horn that project to the thalamic and parabrachial nuclei contain MOR1 and are likely sites of action for MOR ligands that modulate sensory and/or autonomic aspects of pain transmission in the trigeminal dorsal horn.

Animals↗
PubMed2005

Evidence that projections from the bed nucleus of the stria terminalis and from the lateral and medial regions of the preoptic area provide input to gonadotropin releasing hormone (GNRH) neurons in the female sheep brain.

The arcuate nucleus/ventromedial hypothalamic nucleus (ARC/VMH) region is thought to relay estrogen feedback signals to gonadotropin-releasing hormone (GnRH) cells in the sheep brain. This region sends major projections to the lateral preoptic area (lPOA), ventral bed nucleus of the stria terminals (vBnST) and the ventro-caudal division of the median preoptic nucleus (vcMePON) with little direct input to GnRH cell bodies, suggesting interneuronal relay to GnRH neurons. The brain stem also provides input to the POA. The present study aimed to identify possible relay circuits in the POA and BnST to GnRH neurons. Biotinylated dextran amine (BDA) was injected into lPOA (n=6), vBnST (n=2), vcMePON (n=3) and periventricular nucleus (PeriV; n=1) of ewes for anterograde tracing. GnRH immunoreactive (IR) perikarya appearing to receive input from BDA-containing varicosities were identified by fluorescence microscopy, with further analysis by confocal microscopy. When BDA was injected into rostral and caudal regions of lPOA (n=3), no tracer-filled varicose fibers were found in contact with GnRH-IR perikarya. Injections into the center of the lPOA (n=3) indicated direct projections to GnRH-IR cells. Injections into the vBnST, vcMePON and PeriV indicated that cells of these regions also provide input to GnRH cells. BDA-containing varicosities found in the MPOA were immunoreactive for NPY or were GABAergic or glutamatergic when the tracer was injected into vBnST and lPOA, but not when injections were placed in the vcMePON. With injection into the PeriV, tracer-filled varicosities in the MPOA were not immunoreactive for somatostatin or enkephalin. Injection of FluoroGold into ventral POA retrogradely labeled cells in the above mentioned areas, but few were also immunoreactive for estrogen receptor-alpha. Thus, cells of the vBnST, lPOA, vcMePON and PeriV project to GnRH neurons. These cells may provide an interneuronal route to GnRH neurons from the ARC/VMH, the brain stem and other regions of the brain.

Afferent Pathways↗
PubMed2005

Neurotrophin-3 is a target-derived neurotrophic factor for penile erection-inducing neurons.

The aim of this study was to determine whether the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin (NT)-3 could act as endogenous target-derived trophic factors for erection-inducing, i.e. penis-projecting major pelvic ganglion (MPG) neurons, and/or penile sensory neurons in adult rat. This was accomplished by studying the expression of NT mRNAs in the penis and their cognate receptors in the MPG and dorsal root ganglia (DRGs), and the retrograde axonal transport of radioiodinated NTs injected into the corpora cavernosa. Northern hybridization showed that NGF, BDNF, and NT-3 mRNAs are expressed in the shaft of the penis. In situ hybridization combined with usage of the retrograde tracer Fluoro-Gold showed that TrkC and p75 receptors are expressed in penis-projecting neurons of the MPG whereas the mRNAs for TrkA and TrkB receptors were undetectable. However, all the NT receptor mRNAs were expressed in penile sensory neurons of sacral level 1 (S1) DRG. (125)I-NT-3 injected into the shaft of the penis was retrogradely transported into the MPG and S1 DRG, whereas radioiodinated NGF and BDNF were transported specifically into the S1 DRG, thus confirming the existence of functional NT receptors in these penile neurons. In conclusion, these data suggest that NT-3 may act as a target-derived neurotrophic factor for both erection-inducing and penile sensory neurons, whereas NGF and BDNF may be more important for the sensory innervation of the penis.

Animals↗
PubMed2005

Reversal of the circadian expression of tyrosine-hydroxylase but not nitric oxide synthase levels in the spinal cord of dopamine D3 receptor knockout mice.

Circadian rhythms have been described for numerous transmitter synthesizing enzymes in the brain but rarely in spinal cord. We measured spinal tyrosine-hydroxylase (TH) and nitric oxide synthase (NOS) levels in the thoracic intermediolateral nucleus, the location of sympathetic preganglionic neurons, in male wild type (WT) and dopamine D(3) receptor knockout mice (D(3)KO). TH and NOS levels both displayed circadian patterns in WT and D(3)KO animals with overall reduced TH and increased NOS expression in the D(3)KO mice. The circadian pattern of NOS expression was similar in WT and D(3)KO mice. In contrast, TH expression was inverted in D(3)KO mice, with TH levels consistently lower than in WT throughout the day, but strongly increased temporarily 1 h prior to daylight. TH is the rate-limiting enzyme for the production of dopamine. Spinal dopamine dysfunction is implicated in a sleep disorder called restless legs syndrome (RLS). RLS follows a circadian rhythm and is relieved clinically by dopamine D(3) receptor agonists. Our observations of an altered circadian pattern in spinal dopamine synthesis in D(3)KO animals may provide insight into putative dopaminergic mechanisms contributing to RLS.

Animals↗
PubMed2005

Serotonergic systems associated with arousal and vigilance behaviors following administration of anxiogenic drugs.

Serotonergic systems play important roles in modulating behavioral arousal, including behavioral arousal and vigilance associated with anxiety states. To further our understanding of the neural systems associated with increases in anxiety states, we investigated the effects of multiple anxiogenic drugs on topographically organized subpopulations of serotonergic neurons using double immunohistochemical staining for c-Fos and tryptophan hydroxylase combined with topographical analysis of the rat dorsal raphe nucleus (DR). Anxiogenic drugs with diverse pharmacological properties including the adenosine receptor antagonist caffeine, the serotonin 5-HT2A/2C receptor agonist m-chlorophenyl piperazine (mCPP), the alpha2-adrenoreceptor antagonist yohimbine, and the benzodiazepine receptor partial inverse agonist N-methyl-beta-carboline-3-carboxamide (FG-7142) induced increases in behavioral arousal and vigilance behaviors consistent with an increase in anxiety state. In addition, these anxiogenic drugs, excluding yohimbine, had convergent actions on an anatomically-defined subset of serotonergic neurons within the middle and caudal, dorsal subdivision of the DR. High resolution topographical analysis revealed that at the mid-rostrocaudal level, caffeine and FG-7142 had convergent effects on c-Fos expression in serotonergic neurons that were restricted to a previously undefined region, which we have named the shell region of the dorsal part of the dorsal raphe nucleus (DRDSh), that overlaps the anatomical border between the dorsal part of the dorsal raphe nucleus, the ventral part of the dorsal raphe nucleus (DRV), and the ventrolateral part of the dorsal raphe nucleus (DRVL). Retrograde tracing methods revealed that DRDSh contains large numbers of neurons projecting to the basolateral amygdaloid nucleus, a forebrain structure important for emotional appraisal and modulation of anxiety-related physiological and behavioral responses. Together these findings support the hypothesis that there is a functional topographical organization in the DR and are consistent with the hypothesis that anxiogenic drugs have selective actions on a subpopulation of serotonergic neurons projecting to a distributed central autonomic and emotional motor control system regulating anxiety states and anxiety-related physiological and behavioral responses.

Adrenergic alpha-Antagonists↗
PubMed2005

Early and transient increase in spontaneous synaptic inputs to the rat facial motoneurons after axotomy in isolated brainstem slices of rats.

Section of motor nerve fibers (axotomy) elicits a variety of morphofunctional responses in the motoneurons in the motor nuclei. Later than the fifth post-operational day after section of the facial nerve, synapse elimination occurs in the facial motoneuron pool, leading to gradual abolishment of synaptic input-driven activities of the axotomized motoneurons. However, it remains unknown how the amount of synaptic input changes during this period between the axotomy and the synaptic elimination. Here we examined a hypothesis that axotomy of the motoneurons itself modifies the synaptic inputs to the motoneurons. One day after axotomy, the postsynaptic currents, mostly mediated by non-N-methyl-D-aspartic acid (non-NMDA) receptors, recorded from the axotomized facial motoneurons in the acute slice preparations of the rats were of higher frequency and larger amplitude than those in the intact motoneurons. This difference was not observed after the third post-operational day and appeared earlier than the changes in the electrophysiological properties and increase in the number of dead neurons in the axotomized motor nucleus. The larger postsynaptic current frequency of the axotomized motoneurons was observed both in the absence and in the presence of tetrodotoxin citrate, suggesting that increased excitability and facilitated release underlie the postsynaptic current frequency increase. These results suggest that synaptic re-organization occurs in the synapses of motoneurons at an early stage following axotomy.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2005

Prefrontal D1 and ventral hippocampal N-methyl-D-aspartate regulation of startle gating in rats.

BACKGROUND: Sensorimotor gating, as measured by prepulse inhibition of the startle reflex, is deficient in schizophrenia patients, and in rats after specific manipulations of limbic cortico-striato-pallido-thalamic circuitry. For example, prepulse inhibition in rats is disrupted after D1 blockade in the medial prefrontal cortex, and after N-methyl-D-aspartate infusion into the ventral hippocampus. In the present study, we examined whether these two substrates form part of an integrated circuit regulating sensorimotor gating, which might contribute to the loss of prepulse inhibition in patient populations. METHODS: Prepulse inhibition was assessed in male Sprague-Dawley rats after systemic or intra-medial prefrontal cortex administration of the D1 antagonist, SCH 23390. Separate rats received intra-medial prefrontal cortex infusion of the retrograde transported label Fluoro-Gold. In rats with sham or electrolytic lesions of the medial prefrontal cortex, prepulse inhibition was tested after infusion of N-methyl-D-aspartate or vehicle into ventral hippocampus regions that were determined to send projections to the medial prefrontal cortex. RESULTS: Prepulse inhibition was disrupted after systemic SCH 23390 treatment and after infusion of SCH 23390 into medial prefrontal cortex sites within the prelimbic and cingulate cortices. Fluoro-Gold infusion into these medial prefrontal cortex sites labeled cells in the ventral hippocampus complex, including regions CA1 and entorhinal cortex. N-methyl-D-aspartate infusions into these ventral hippocampus regions disrupted prepulse inhibition in rats after sham but not electrolytic lesions of the medial prefrontal cortex. CONCLUSIONS: Prepulse inhibition appears to be regulated by interacting substrates within the ventral hippocampus and MPFC. Specifically, NMDA activation of the ventral hippocampus appears to disrupt prepulse inhibition in a manner that is dependent on the integrity of infralimbic or cingulate cortical regions that also support a D1-mediated regulation of prepulse inhibition. Conceivably, dysfunction within these hippocampal-frontal circuits may contribute to sensorimotor gating deficits in schizophrenia.

Acoustic Stimulation↗
PubMed2005

The reciprocal connections of endomorphin 1- and endomorphin 2-containing neurons between the hypothalamus and nucleus tractus solitarii in the rat.

In the CNS, endomorphin 1- and endomorphin 2-immunoreactive neuronal cell bodies have been principally found both in the hypothalamus and nucleus tractus solitarii. Functionally, the hypothalamus and nucleus tractus solitarii are closely related in many aspects, especially in visceral functions. On the other hand, there are also many endomorphin-immunoreactive fibers and terminals in the two regions. In the present study, to investigate whether endomorphin 1-immunoreactive and endomorphin 2-immunoreactive neurons in the hypothalamus and nucleus tractus solitarii project reciprocally between these two regions, fluorescent retrograde labeling combined with immunofluorescence histochemical staining for endomorphin 1 and endomorphin 2 was used. After injection of Fluoro-Gold into the nucleus tractus solitarii of rats, endomorphin 1/Fluoro-Gold or endomorphin 2/Fluoro-Gold double-labeled neuronal cell bodies were predominantly observed in the arcuate nucleus of the hypothalamus, a few of which were also observed in the posterior hypothalamic area and periventricular hypothalamic nucleus. After injection of Fluoro-Gold into the medial zone of hypothalamic tuberal region and the lateral hypothalamic area, respectively, endomorphin 1/Fluoro-Gold or endomorphin 2/Fluoro-Gold double-labeled neuronal cell bodies were found chiefly in the medial, commissural, lateral and gelatinous parts of the nucleus tractus solitarii. These results provide morphological evidence that there exist reciprocal endomorphinergic connections between the hypothalamus and nucleus tractus solitarii.

Animals↗
PubMed2006

Distribution of hypothalamic, hippocampal and other limbic peptidergic neuronal cell bodies giving rise to retinopetal fibers: anterograde and retrograde tracing and neuropeptide immunohistochemical studies.

In our present work utilizing the retrograde or anterograde transport of tracers (biotinylated dextran amine and Fluorogold, respectively) we have provided direct evidence for the cells of origin of the limboretinal pathway in rats and their termination in the retina using light microscopic approach. Administration of biotinylated dextran amine into the vitreous body resulted in nerve cell body labeling in several structures: the supraoptic and paraventricular nuclei, the hippocampus (CA1, CA3), the dentate gyrus, the indusium griseum, the olfactory tubercle, and the medial habenula, all of them belong to the limbic system. We estimated that the total number of retrogradely labeled cells is 1495+/-516. We have seen fiber labeling in the retinorecipient suprachiasmatic nucleus and in the primary visual center, the lateral geniculate body, but labeled nerve cell bodies in these structures were never seen. Iontophoretic application of Fluorogold into the hippocampal formation, where the major part of the biotinylated dextran amine-labeled cell bodies was observed, resulted in labeled fibers in the optic nerve and in the retina indicating that the retrogradely labeled cells in the hippocampus and the dentate gyrus among others are the cells of origin of the centrifugal visual fibers. Sections showing biotinylated dextran amine labeling were stained for vasoactive intestinal polypeptide, pituitary adenylate cyclase activating polypeptide or luteinizing hormone-releasing hormone immunoreactivity using immunohistochemistry. Some biotinylated dextran amine-labeled cells also showed vasoactive intestinal polypeptide, pituitary adenylate cyclase activating polypeptide or luteinizing hormone-releasing hormone immunoreactivity. We conclude that the limboretinal pathway exists and that the cells of origin are partially vasoactive intestinal polypeptide, pituitary adenylate cyclase activating polypeptide or luteinizing hormone-releasing hormone immunoreactive.

Animals↗
PubMed2006

Lipopolysaccharide induces preproenkephalin transcription in hypophysiotropic neurons of the rat paraventricular hypothalamic nucleus suggesting a neuroendocrine role for enkephalins during immune stress.

Opioids have impact on stress responses and possess immune modulatory functions. We have previously shown that immune stress elevates the levels of preproenkephalin transcript in a variety of autonomic structures in the rat brain, including the paraventricular hypothalamic nucleus. By using in situ hybridization with an intronic probe recognizing the preproenkephalin heteronuclear RNA combined with retrograde tract tracing, we examined the efferent target of the enkephalinergic neurons in the paraventricular hypothalamic nucleus that display induced transcriptional activity during immune challenge. Rats were first given i.p. injections of the tracer substance Fluoro-Gold, which following this route of administration is taken up only by nerve terminals residing outside the blood-brain barrier, and were then given an i.v. injection of lipopolysaccharide. Neuronal cell bodies retrogradely labeled with Fluoro-Gold were detected by immunohistochemistry, and-using a dual-labeling approach-the same cells were then examined for their expression of preproenkephalin heteronuclear RNA. We found that over 90% of the neurons that expressed preproenkephalin heteronuclear RNA also contained Fluoro-Gold. In addition, approximately 40% of the neurons expressing preproenkephalin heteronuclear RNA co-expressed mRNA for corticotropin-releasing hormone, the main adrenocorticotropic hormone secretagogue. These data show that the paraventricular hypothalamic neurons that display induced preproenkephalin transcription following immune challenge are almost exclusively hypophysiotropic neurons, indicating a role for enkephalin in the hypothalamic control of hormone release during infectious and inflammatory conditions.

Animals↗
PubMed2006

Inter-enlargement pathways in the ventrolateral funiculus of the adult rat spinal cord.

The ventrolateral funiculus (VLF) in the spinal cord contains important ascending and descending pathways related to locomotion and interlimb coordination. The primary purpose of this descriptive study was to investigate the distribution of inter-enlargement pathways in the adult rat spinal cord with an emphasis on the VLF. We made discrete unilateral injections of Fluoro-Gold (FG) into the right VLF at thoracic segment (T) 9, and either unilateral or bilateral injections of Fluoro-Ruby (FR) into the intermediate gray matter at the cervical (C) 5-6, C7-8, or lumbar (L) 2 segmental levels. Inter-enlargement neurons with ascending axons in the right VLF were found bilaterally in laminae VII and VIII throughout the rostral lumbar spinal cord (L1-L3) and predominantly contralaterally in the caudal lumbosacral (L4-S1) spinal cord. Following left unilateral FR injections at C5-6 or C7-8 and right unilateral VLF injections of FG at T9, very few double-labeled neurons could be found anywhere in the lumbar spinal cord. Similar injections of FR at L2 revealed an almost symmetrical bilateral distribution of double-labeled neurons throughout the cervical spinal cord (C1-8). These results describe ascending and descending pathways within the spinal cord that interconnect the two enlargements and involve both commissural and ipsilateral interneurons. The majority of inter-enlargement neurons had axons within the VLF at T9. These observations support the hypothesis that the VLF contains long ascending and descending axons with propriospinal inter-enlargement, commissural and ipsilateral connections that are anatomically well-suited to mediate interlimb coordination.

Animals↗
PubMed2006

Glutamatergic innervation of the hypothalamic median eminence and posterior pituitary of the rat.

Recent studies have localized the glutamatergic cell marker type-2 vesicular glutamate transporter (VGLUT2) to distinct peptidergic neurosecretory systems that regulate hypophysial functions in rats. The present studies were aimed to map the neuronal sources of VGLUT2 in the median eminence and the posterior pituitary, the main terminal fields of hypothalamic neurosecretory neurons. Neurons innervating these regions were identified by the uptake of the retrograde tract-tracer Fluoro-Gold (FG) from the systemic circulation, whereas glutamatergic perikarya of the hypothalamus were visualized via the radioisotopic in situ hybridization detection of VGLUT2 mRNA. The results of dual-labeling studies established that the majority of neurons accumulating FG and also expressing VGLUT2 mRNA were located within the paraventricular, periventricular and supraoptic nuclei and around the organum vasculosum of the lamina terminalis and the preoptic area. In contrast, only few FG-accumulating cells exhibited VGLUT2 mRNA signal in the arcuate nucleus. Dual-label immunofluorescent studies of the median eminence and posterior pituitary to determine the subcellular location of VGLUT2, revealed the association of VGLUT2 immunoreactivity with SV2 protein, a marker for small clear vesicles in neurosecretory endings. Electron microscopic studies using pre-embedding colloidal gold labeling confirmed the localization of VGLUT2 in small clear synaptic vesicles. These data suggest that neurosecretory neurons located mainly within the paraventricular, anterior periventricular and supraoptic nuclei and around the organum vasculosum of the lamina terminalis and the preoptic area secrete glutamate into the fenestrated vessels of the median eminence and posterior pituitary. The functional aspects of the putative neuropeptide/glutamate co-release from neuroendocrine terminals remain to be elucidated.

Animals↗
PubMed2005

Changes in P2X3 receptor expression in the trigeminal ganglion following monoarthritis of the temporomandibular joint in rats.

The pathophysiological mechanisms of orofacial deep-tissue pain is still unclear. Previously, P2X receptors (P2XR) in sensory neurons have been shown to play a role in the signal transduction of cutaneous pain. We investigated the functional significance of P2X3R in relation to orofacial deep-tissue pain caused by monoarthritis of the temporomandibular joint (TMJ). Monoarthritis was induced by the injection of complete Freund's adjuvant (CFA) into the unilateral TMJ of the rat. The pain associated with monoarthritis was assessed by the pressure pain threshold (PPT), which was defined as the amount of pressure required to induce vocalization. Fifteen days after CFA-treatment, changes in PPT were examined after injection of P2XR agonists or antagonists into the TMJ. The number of cells expressing P2X3R in trigeminal ganglia (TG) was investigated by immunohistochemistry. Inflamed TMJ showed a continuous decline in PPT during the experimental period (P<0.001). Injection of alpha,beta-meATP, an agonist of P2X1,3,2/3R, dramatically reduced the bilateral PPTs of both inflamed and non-inflamed TMJs (P<0.01) although beta,gamma-me-l-ATP, a selective agonist of P2X1R, did not. The decreased PPTs of inflamed TMJ were reversed either by PPADS, an antagonist of P2X1,2,3,5,1/5,4/5R, or by TNP-ATP, an antagonist of P2X1,3,2/3,1/5R. Immunohistochemically, the number of P2X3R-positive cells increased in the small cell group in TG (P<0.01), whereas there was no change in medium or large cell groups after the CFA-injection. Retrograde tracing confirmed that TMJ neurons in the TG exhibited P2X3R immunoreactivity. Our results suggested that P2X3R plays an important role in orofacial pressure pain caused by monoarthritis of TMJ.

Adenosine Triphosphate↗
PubMed2006

Enhanced excitability of nociceptive trigeminal ganglion neurons by satellite glial cytokine following peripheral inflammation.

Peripheral nerve injury activates satellite cells to produce interleukin 1beta (IL-1beta) which mediates inflammation and hyperalgesia. This study investigated the hypothesis that activation of satellite glial cells modulates the excitability of trigeminal ganglion (TRG) neurons via IL-1beta following inflammation. Inflammation was induced by injection of complete Freund's adjuvant (CFA) into the whisker pad area. The threshold for escape from mechanical stimulation applied to the whisker pad in inflamed rats was significantly lower than that in control. Two days post-CFA injection, the mean percentage of TRG neurons encircled by glial fibrillary acidic protein (GFAP)-/IL-1beta-immunoreactive cells was significantly increased compared to controls. GFAP and IL-1beta immunoreactivities were coexpressed in the same cells. Fluorogold (FG) labeling identified the site of inflammation. The number of FG-labeled IL-receptor type I (IL-1RI) TRG neurons in inflamed rats was significantly greater than in controls. In FG-labeled small TRG neurons, the size of IL-1beta (1 nM) induced-depolarization in inflamed rats was larger than in controls. IL-1beta application significantly increased firing rates evoked by depolarizing pulses in the neurons of inflamed rats, compared to controls. The response to IL-1beta was abolished by treatment with the IL-1RI antagonist. These results suggest that activation of satellite glial cells modulates the excitability of small-diameter TRG neurons via IL-1beta following inflammation, and that the upregulation of IL-1RI in the soma may contribute to the mechanism underlying inflammatory hyperalgesia. Therefore IL-1beta blockers are potential therapeutic agents for prevention of trigeminal hyperalgesia.

Animals↗