Celiac and superior mesenteric ganglia removal improves glucose tolerance and reduces pancreas islet size.

The sympathetic nervous system is crucial for the regulation of visceral organ function. For instance, the activation of the sympathetic nervous system promotes glycogenolysis in the liver and modulates glucagon and insulin release from the pancreas, thereby raising blood glucose levels. A decrease in sympathetic nerve activity has the opposite effect. Although such acute effects of sympathetic activity changes have been studied, their long-term outcomes have not been previously examined. In this study, we removed the celiac/superior mesenteric ganglia, where sympathetic postganglionic neurons innervating pancreas and liver locate, and examined its effects on glucose homeostasis and islet size several weeks after surgery. Consistent with the reduction in gluconeogenesis, glucose tolerance improved in gangliectomized mice. However, contrary to our expectation that the inhibition of pancreatic function by sympathetic nerves would be relieved with gangliectomy, insulin or C-peptide release did not increase. Examining the size distribution of pancreatic islets, we identified that the gangliectomy led to a size reduction in large islets and a decrease in the proportion of α and ß cells within each islet, as analyzed by immunostaining for insulin and glucagon, respectively. These results indicate that the absence of sympathetic nerve activity reduces the size of the pancreatic islets within a few weeks to reinstate the homeostatic mechanism of blood glucose levels.

Neural crest origin of sympathetic neurons at the dawn of vertebrates.

The neural crest is an embryonic stem cell population unique to vertebrates1 whose expansion and diversification are thought to have promoted vertebrate evolution by enabling emergence of new cell types and structures such as jaws and peripheral ganglia2. Although jawless vertebrates have sensory ganglia, convention has it that trunk sympathetic chain ganglia arose only in jawed vertebrates3-8. Here, by contrast, we report the presence of trunk sympathetic neurons in the sea lamprey, Petromyzon marinus, an extant jawless vertebrate. These neurons arise from sympathoblasts near the dorsal aorta that undergo noradrenergic specification through a transcriptional program homologous to that described in gnathostomes. Lamprey sympathoblasts populate the extracardiac space and extend along the length of the trunk in bilateral streams, expressing the catecholamine biosynthetic pathway enzymes tyrosine hydroxylase and dopamine ß-hydroxylase. CM-DiI lineage tracing analysis further confirmed that these cells derive from the trunk neural crest. RNA sequencing of isolated ammocoete trunk sympathoblasts revealed gene profiles characteristic of sympathetic neuron function. Our findings challenge the prevailing dogma that posits that sympathetic ganglia are a gnathostome innovation, instead suggesting that a late-developing rudimentary sympathetic nervous system may have been characteristic of the earliest vertebrates.

Blockade of sympathetic ganglia improves vascular dysfunction in septic shock.

Sepsis/septic shock activates the sympathetic nervous system (SNS) to deal with the infection stress. However, an imbalanced or maladaptive response due to excessive or uncontrolled activation characterizes autonomic dysfunction. Our hypothesis was that reducing this excessive activation of the autonomic nervous system would impact positively in sepsis. Using ganglionic blockers as a pharmacological approach, the main aim of the present report was to assess the role of ganglionic transmission in the vascular dysfunction associated with sepsis.Sepsis was induced in rats by cecal ligation and puncture (CLP). One hour after CLP surgery, rats were treated subcutaneously with hexamethonium (15 mg/kg; ganglionic blocker), pentolinium (5 mg/kg; a blocker with a higher selectivity for sympathetic ganglia compared to hexamethonium), or vehicle (PBS). Basal blood pressure and the response to adrenergic agonists were evaluated at 6 and 24 h after CLP surgery. Reactivity to vasoconstrictors, nitric oxide (NO) synthase 2 (NOS-2) expression, IL-1 and TNF plasma levels, and density of α1 adrenergic receptors were evaluated in the aorta 24 h after CLP.Septic shock resulted in hypotension and hyporesponsiveness to norepinephrine and phenylephrine, increased plasma cytokine levels and NOS-2 expression in the aorta, and decreased α1 receptor density in the same vessel. Pentolinium but not hexamethonium recovered responsiveness and α1 adrenergic receptor density in the aorta. Both blockers normalized the in vivo response to vasoconstrictors, and reduced plasma IL-1 and NOx levels and NOS-2 expression in the aorta.Blockade of ganglionic sympathetic transmission reduced the vascular dysfunction in experimental sepsis. This beneficial effect seems to be, at least in part, due to the preservation of α1 adrenergic receptor density and to reduced NOS-2 expression and may lead to adjuvant ways to treat human sepsis.

Immunohistochemical phenotype of sensory neurons associated with sympathetic plexuses in the trigeminal ganglia of adult nerve growth factor transgenic mice.

Following peripheral nerve injury, postganglionic sympathetic axons sprout into the affected sensory ganglia and form perineuronal sympathetic plexuses with somata of sensory neurons. This sympathosensory coupling contributes to the onset and persistence of injury-induced chronic pain. We have documented the presence of similar sympathetic plexuses in the trigeminal ganglia of adult mice that ectopically overexpress nerve growth factor (NGF), in the absence of nerve injury. In this study, we sought to further define the phenotype(s) of these trigeminal sensory neurons having sympathetic plexuses in our transgenic mice. Using quantitative immunofluorescence staining analyses, we show that the invading sympathetic axons specifically target sensory somata immunopositive for several biomarkers: NGF high-affinity receptor tyrosine kinase A (trkA), calcitonin gene-related peptide (CGRP), neurofilament heavy chain (NFH), and P2X purinoceptor 3 (P2X3). Based on these phenotypic characteristics, the majority of the sensory somata surrounded by sympathetic plexuses are likely to be NGF-responsive nociceptors (i.e., trkA expressing) that are peptidergic (i.e., CGRP expressing), myelinated (i.e., NFH expressing), and ATP sensitive (i.e., P2X3 expressing). Our data also show that very few sympathetic plexuses surround sensory somata expressing other nociceptive (pain) biomarkers, including substance P and acid-sensing ion channel 3. No sympathetic plexuses are associated with sensory somata that display isolectin B4 binding. Though the cellular mechanisms that trigger the formation of sympathetic plexus (with and without nerve injury) remain unknown, our new observations yield an unexpected specificity with which invading sympathetic axons appear to target a precise subtype of nociceptors. This selectivity likely contributes to pain development and maintenance associated with sympathosensory coupling.

Targeted ablation of the left middle cervical ganglion prevents ventricular arrhythmias and cardiac injury induced by AMI.

Cardiac sympathetic overactivation is a critical driver in the progression of acute myocardial infarction (AMI). The left middle cervical ganglion (LMCG) is an important extracardiac sympathetic ganglion. However, the regulatory effects of LMCG on AMI have not yet been fully documented. In the present study, we detected that the LMCG was innervated by abundant sympathetic components and exerted an excitatory effect on the cardiac sympathetic nervous system in response to stimulation. In canine models of AMI, targeted ablation of LMCG reduced the sympathetic indexes of heart rate variability and serum norepinephrine, resulting in suppressed cardiac sympathetic activity. Moreover, LMCG ablation could improve ventricular electrophysiological stability, evidenced by the prolonged ventricular effective refractory period, elevated action potential duration, increased ventricular fibrillation threshold, and enhanced connexin43 expression, consequently showing antiarrhythmic effects. Additionally, compared with the control group, myocardial infarction size, circulating cardiac troponin I, and myocardial apoptosis were significantly reduced, accompanied by preserved cardiac function in canines subjected to LMCG ablation. Finally, we performed the left stellate ganglion (LSG) ablation and compared its effects with LMCG destruction. The results indicated that LMCG ablation prevented ventricular electrophysiological instability, cardiac sympathetic activation, and AMI-induced ventricular arrhythmias with similar efficiency as LSG denervation. In conclusion, this study demonstrated that LMCG ablation suppressed cardiac sympathetic activity, stabilized ventricular electrophysiological properties and mitigated cardiomyocyte death, resultantly preventing ischemia-induced ventricular arrhythmias, myocardial injury, and cardiac dysfunction. Neuromodulation therapy targeting LMCG represented a promising strategy for the treatment of AMI.

Reference gene recommendations and PACAP receptor expression in murine sympathetic ganglia of the autonomic nervous system that innervate adipose tissues after chronic cold exposure.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an important regulator of the stress response in mammals, influencing both the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). PACAP has been reported to influence energy homeostasis, including adaptive thermogenesis, an energy burning process in adipose tissue regulated by the SNS in response to cold stress and overfeeding. While research suggests PACAP acts centrally at the level of the hypothalamus, knowledge of PACAP's role within the sympathetic nerves innervating adipose tissues in response to metabolic stressors is limited. This work shows, for the first time, gene expression of PACAP receptors in stellate ganglia and highlights some differential expression with housing temperature. Additionally, we present our dissection protocol, analysis of tyrosine hydroxylase gene expression as a molecular biomarker for catecholamine producing tissue and recommend three stable reference genes for the normalization of quantitative real time-polymerase chain reaction (qRT-PCR) data when working with this tissue. This study adds to information about neuropeptide receptor expression in peripheral ganglia of the sympathetic nervous system innervating adipose tissue and provides insight into PACAP's role in the regulation of energy metabolism.

Downregulation of Bmal1 Expression in Celiac Ganglia Protects against Hepatic Ischemia-Reperfusion Injury.

Hepatic ischemia-reperfusion injury (HIRI) significantly contributes to liver dysfunction following liver transplantation and hepatectomy. However, the role of the celiac ganglion (CG) in HIRI remains unclear. Adeno-associated virus was used to silence Bmal1 expression in the CG of twelve beagles that were randomly assigned to the Bmal1 knockdown group (KO-Bmal1) and the control group. After four weeks, a canine HIRI model was established, and CG, liver tissue, and serum samples were collected for analysis. The virus significantly downregulated Bmal1 expression in the CG. Immunofluorescence staining confirmed a lower proportion of c-fos+ and NGF+ neurons in TH+ cells in the KO-Bmal1 group than in the control group. The KO-Bmal1 group exhibited lower Suzuki scores and serum ALT and AST levels than the control group. Bmal1 knockdown significantly reduced liver fat reserve, hepatocyte apoptosis, and liver fibrosis, and it increased liver glycogen accumulation. We also observed that Bmal1 downregulation inhibited the hepatic neurotransmitter norepinephrine, neuropeptide Y levels, and sympathetic nerve activity in HIRI. Finally, we confirmed that decreased Bmal1 expression in CG reduces TNF-α, IL-1ß, and MDA levels and increases GSH levels in the liver. The downregulation of Bmal1 expression in CG suppresses neural activity and improves hepatocyte injury in the beagle model after HIRI.

Diversity of satellite glia in sympathetic and sensory ganglia.

Satellite glia are the major glial type found in sympathetic and sensory ganglia in the peripheral nervous system, and specifically, contact neuronal cell bodies. Sympathetic and sensory neurons differ in morphological, molecular, and electrophysiological properties. However, the molecular diversity of the associated satellite glial cells remains unclear. Here, using single-cell RNA sequencing analysis, we identify five different populations of satellite glia from sympathetic and sensory ganglia. We define three shared populations of satellite glia enriched in immune-response genes, immediate-early genes, and ion channels/ECM-interactors, respectively. Sensory- and sympathetic-specific satellite glia are differentially enriched for modulators of lipid synthesis and metabolism. Sensory glia are also specifically enriched for genes involved in glutamate turnover. Furthermore, satellite glia and Schwann cells can be distinguished by unique transcriptional signatures. This study reveals the remarkable heterogeneity of satellite glia in the peripheral nervous system.

Interplay between nitric oxide and gonadotrophin-releasing hormone in the neuromodulation of the corpus luteum during late pregnancy in the rat.

BACKGROUND: Nitric oxide and GnRH are biological factors that participate in the regulation of reproductive functions. To our knowledge, there are no studies that link NO and GnRH in the sympathetic ganglia. Thus, the aim of the present work was to investigate the influence of NO on GnRH release from the coeliac ganglion and its effect on luteal regression at the end of pregnancy in the rat. METHODS: The ex vivo system composed by the coeliac ganglion, the superior ovarian nerve, and the ovary of rats on day 21 of pregnancy was incubated for 180 min with the addition, into the ganglionic compartment, of L-NG-nitro arginine methyl ester (L-NAME), a non-selective NO synthase inhibitor. The control group consisted in untreated organ systems. RESULTS: The addition of L-NAME in the coeliac ganglion compartment decreased NO as well as GnRH release from the coeliac ganglion. In the ovarian compartment, and with respect to the control group, we observed a reduced release of GnRH, NO, and noradrenaline, but an increased production of progesterone, estradiol, and expression of their limiting biosynthetic enzymes, 3ß-HSD and P450 aromatase, respectively. The inhibition of NO production by L-NAME in the coeliac ganglion compartment also reduced luteal apoptosis, lipid peroxidation, and nitrotyrosine, whereas it increased the total antioxidant capacity within the corpora lutea. CONCLUSION: Collectively, the results indicate that NO production by the coeliac ganglion modulates the physiology of the ovary and luteal regression during late pregnancy in rats.

Prion type 2 selection in sporadic Creutzfeldt-Jakob disease affecting peripheral ganglia.

In sporadic Creutzfeldt-Jakob disease (sCJD), the pathological changes appear to be restricted to the central nervous system. Only involvement of the trigeminal ganglion is widely accepted. The present study systematically examined the involvement of peripheral ganglia in sCJD utilizing the currently most sensitive technique for detecting prions in tissue morphologically. The trigeminal, nodose, stellate, and celiac ganglia, as well as ganglia of the cervical, thoracic and lumbar sympathetic trunk of 40 patients were analyzed with the paraffin-embedded tissue (PET)-blot method. Apart from the trigeminal ganglion, which contained protein aggregates in five of 19 prion type 1 patients, evidence of prion protein aggregation was only found in patients associated with type 2 prions. With the PET-blot, aggregates of prion protein type 2 were found in all trigeminal (17/17), in some nodose (5 of 7) and thoracic (3 of 6) ganglia, as well as in a few celiac (4 of 19) and lumbar (1 of 5) ganglia of sCJD patients. Whereas aggregates of both prion types may spread to dorsal root ganglia, more CNS-distant ganglia seem to be only involved in patients accumulating prion type 2. Whether the prion type association is due to selection by prion type-dependent replication, or due to a prion type-dependent property of axonal spread remains to be resolved in further studies.

Generation, Characterization, and Application of Inducible Proliferative Adult Human Epicardium-Derived Cells.

RATIONALE: In recent decades, the great potential of human epicardium-derived cells (EPDCs) as an endogenous cell source for cardiac regeneration has been recognized. The limited availability and low proliferation capacity of primary human EPDCs and phenotypic differences between EPDCs obtained from different individuals hampers their reproducible use for experimental studies. AIM: To generate and characterize inducible proliferative adult human EPDCs for use in fundamental and applied research. METHODS AND RESULTS: Inducible proliferation of human EPDCs was achieved by doxycycline-controlled expression of simian virus 40 large T antigen (LT) with a repressor-based lentiviral Tet-On system. In the presence of doxycycline, these inducible EPDCs (iEPDCs) displayed high and long-term proliferation capacity. After doxycycline removal, LT expression ceased and the iEPDCs regained their cuboidal epithelial morphology. Similar to primary EPDCs, iEPDCs underwent an epithelial-to-mesenchymal transition (EMT) after stimulation with transforming growth factor ß3. This was confirmed by reverse transcription-quantitative polymerase chain reaction analysis of epithelial and mesenchymal marker gene expression and (immuno) cytochemical staining. Collagen gel-based cell invasion assays demonstrated that mesenchymal iEPDCs, like primary EPDCs, possess increased invasion and migration capacities as compared to their epithelial counterparts. Mesenchymal iEPDCs co-cultured with sympathetic ganglia stimulated neurite outgrowth similarly to primary EPDCs. CONCLUSION: Using an inducible LT expression system, inducible proliferative adult human EPDCs were generated displaying high proliferative capacity in the presence of doxycycline. These iEPDCs maintain essential epicardial characteristics with respect to morphology, EMT ability, and paracrine signaling following doxycycline removal. This renders iEPDCs a highly useful new in vitro model for studying human epicardial properties.

Sympathetic innervation of the mouse kidney and liver arising from prevertebral ganglia.

The sympathetic nervous system (SNS) plays a crucial role in the regulation of renal and hepatic functions. Although sympathetic nerves to the kidney and liver have been identified in many species, specific details are lacking in the mouse. In the absence of detailed information of sympathetic prevertebral innervation of specific organs, selective manipulation of a specific function will remain challenging. Despite providing major postganglionic inputs to abdominal organs, limited data are available about the mouse celiac-superior mesenteric complex. We used tyrosine hydroxylase (TH) and dopamine ß-hydroxylase (DbH) reporter mice to visualize abdominal prevertebral ganglia. We found that both the TH and DbH reporter mice are useful models for identification of ganglia and nerve bundles. We further tested if the celiac-superior mesenteric complex provides differential inputs to the mouse kidney and liver. The retrograde viral tracer, pseudorabies virus (PRV)-152 was injected into the cortex of the left kidney or the main lobe of the liver to identify kidney-projecting and liver-projecting neurons in the celiac-superior mesenteric complex. iDISCO immunostaining and tissue clearing were used to visualize unprecedented anatomical detail of kidney-related and liver-related postganglionic neurons in the celiac-superior mesenteric complex and aorticorenal and suprarenal ganglia compared with TH-positive neurons. Kidney-projecting neurons were restricted to the suprarenal and aorticorenal ganglia, whereas only sparse labeling was observed in the celiac-superior mesenteric complex. In contrast, liver-projecting postganglionic neurons were observed in the celiac-superior mesenteric complex and aorticorenal and suprarenal ganglia, suggesting spatial separation between the sympathetic innervation of the mouse kidney and liver.

Neuromodulatory effect of GnRH from coeliac ganglion on luteal regression in the late pregnant rat.

The GnRH/GnRH receptor system has been found in several extrapituitary tissues, although its physiological significance has not yet been well established. Taking into account that the peripheral neural system can act as a modulator of pregnancy corpus luteum, the objective was to physiologically investigate the presence of the GnRH system in coeliac ganglion (CG) and to analyse its possible involvement in luteal regression through the superior ovarian nerve (SON) at the end of pregnancy in the rat. The integrated ex vivo CG-SON-Ovary system of rats on day 21 of pregnancy was used. Cetrorelix (CTX), a GnRH receptor antagonist, was added into the ganglionic compartment while the control systems were untreated. Ganglionic GnRH release was detected under basal conditions. Then, the CTX addition in CG increased it, which would indicate the blockade of the receptor. In turn, CTX in CG caused an increase in ovarian progesterone release. Furthermore, the luteal cells showed an increase in the expression of Hsd3b1 and a decrease in the expression of Akr1c3 (progesterone synthesis and degradation enzymes, respectively), reduced TUNEL staining according to an increase in the antioxidant defence system activity and low lipid peroxide levels. The ovarian and ganglionic nitric oxide (NO) release increased, while the luteal nitrotyrosine content, measured as nitrosative stress marker, decreased. CTX in CG decreased the ovarian noradrenaline release. The present study provides evidence that GnRH from CG may trigger neuronal signals that promote the luteal regression in late pregnancy by affecting the release of NO and noradrenaline in the ovary.

Effect of Electrical Stimulation of Cervical Sympathetic Ganglia on Intraocular Pressure Regulation According to Different Circadian Rhythms in Rats.

Purpose: The purpose of this study was to investigate the relationship between circadian rhythm and intraocular pressure (IOP), and to explore whether electrical stimulation of cervical sympathetic ganglia (SCG) can regulate IOP via neurotransmitter distribution around the Schlemm's canal (SC) in rats. Methods: Sprague Dawley rats were housed under normal (N-normal), constant dark (N-dark), and constant light (N-light) rhythms (n = 6 per group). Electrical stimulation (intermittent wave [20 hertz {Hz}, 2 mA, 10 minutes]) was used to stimulate the SCG. Atropine sulfate eye gel was applied three times a day. DiI was injected into the SCG and anterior chamber. The cross-sectional area and circumference of SC were evaluated using hematoxylin-eosin staining. Immunofluorescence staining was used to evaluate dopamine-ß-hydroxylase (DßH) expression in SC endothelial (SCE) cells. Results: N-Dark increased the IOP, decreased the cross-sectional area of SC, and increased DßH levels in SCE cells. Nerve projection between SC and SCG was detected, and electrical stimulation of SCG upregulated DßH expression in SCE cells. Under normal and constant light rhythms, electrical stimulation of SCG increased DßH and decreased the cross-sectional area and circumference of SC, while simultaneously increasing IOP and decreasing IOP fluctuations. After paralyzing the ciliary muscles, electrical stimulation of SCG decreased the cross-sectional area and circumference of SC under normal and constant light rhythms. Conclusions: N-Dark increased DßH in SCE cells, reduced the cross-sectional area of SC, and increased IOP. Under the normal and light rhythms, electrical stimulation of SCG increased DßH in SCE cells, reduced the cross-sectional area and circumference of SC, and in turn elevated IOP and decreased IOP fluctuations.

Functional segregation within the pelvic nerve of male rats: a meso- and microscopic analysis.

The pelvic splanchnic nerves are essential for pelvic organ function and have been proposed as targets for neuromodulation. We have focused on the rodent homologue of these nerves, the pelvic nerves. Our goal was to define within the pelvic nerve the projections of organ-specific sensory axons labelled by microinjection of neural tracer (cholera toxin, subunit B) into the bladder, urethra or rectum. We also examined the location of peptidergic sensory axons within the pelvic nerves to determine whether they aggregated separately from sacral preganglionic and paravertebral sympathetic postganglionic axons travelling in the same nerve. To address these aims, microscopy was performed on the major pelvic ganglion (MPG) with attached pelvic nerves, microdissected from young adult male Sprague-Dawley rats (6-8 weeks old) and processed as whole mounts for fluorescence immunohistochemistry. The pelvic nerves were typically composed of five discrete fascicles. Each fascicle contained peptidergic sensory, cholinergic preganglionic and noradrenergic postganglionic axons. Sensory axons innervating the lower urinary tract (LUT) consistently projected in specific fascicles within the pelvic nerves, whereas sensory axons innervating the rectum projected in a complementary group of fascicles. These discrete aggregations of organ-specific sensory projections could be followed along the full length of the pelvic nerves. From the junction of the pelvic nerve with the MPG, sensory axons immunoreactive for calcitonin gene-related peptide (CGRP) showed several distinct patterns of projection: some projected directly to the cavernous nerve, others projected directly across the surface of the MPG to the accessory nerves and a third class entered the MPG, encircling specific cholinergic neurons projecting to the LUT. A subpopulation of preganglionic inputs to noradrenergic MPG neurons also showed CGRP immunoreactivity. Together, these studies reveal new molecular and structural features of the pelvic nerves and suggest functional targets of sensory nerves in the MPG. These anatomical data will facilitate the design of experimental bioengineering strategies to specifically modulate each axon class.

Human epicardium-derived cells reinforce cardiac sympathetic innervation.

RATIONALE: After cardiac damage, excessive neurite outgrowth (sympathetic hyperinnervation) can occur, which is related to ventricular arrhythmias/sudden cardiac death. Post-damage reactivation of epicardium causes epicardium-derived cells (EPDCs) to acquire a mesenchymal character, contributing to cardiac regeneration. Whether EPDCs also contribute to cardiac re/hyperinnervation, is unknown. AIM: To investigate whether mesenchymal EPDCs influence cardiac sympathetic innervation. METHODS AND RESULTS: Sympathetic ganglia were co-cultured with mesenchymal EPDCs and/or myocardium, and neurite outgrowth and sprouting density were assessed. Results showed a significant increase in neurite density and directional (i.e. towards myocardium) outgrowth when ganglia were co-cultured with a combination of EPDCs and myocardium, as compared to cultures with EPDCs or myocardium alone. In absence of myocardium, this outgrowth was not directional. Neurite differentiation of PC12 cells in conditioned medium confirmed these results via a paracrine effect, in accordance with expression of neurotrophic factors in myocardial explants co-cultured with EPDCs. Of interest, EPDCs increased the expression of nerve growth factor (NGF) in cultured, but not in fresh myocardium, possibly due to an "ischemic state" of cultured myocardium, supported by TUNEL and Hif1α expression. Cardiac tissues after myocardial infarction showed robust NGF expression in the infarcted, but not remote area. CONCLUSION: Neurite outgrowth and density increases significantly in the presence of EPDCs by a paracrine effect, indicating a new role for EPDCs in the occurrence of sympathetic re/hyperinnervation after cardiac damage.

Long-term potentiation is differentially expressed in rostral and caudal neurons in the superior cervical ganglion of normal and hypertensive rats.

Neurons in the superior cervical ganglia (SCG) are classified as rostral and caudal according to their regional locations. Although diverse phenotypes have been reported for these two subpopulations, differences in neuroplasticity, like long-term potentiation (LTP), have not been characterized. Here, we explored possible regional differences of LTP expression in rostral and caudal neurons of the SCG in control rats, Wistar and Wistar Kyoto (WKy), and in the spontaneously hypertensive rats (SHR) as a model of hypertension. We characterized the expression of gLTP evoked by a tetanic train (40 Hz, 3 s) in an in vitro SCG preparation. gLTP was recorded in rostral and caudal neurons at 8-weeks-old (wo) in Wistar rats, 6-wo and 12-wo in SHR and WKy rats. We found that gLTP was differentially expressed; gLTP was larger in caudal neurons in Wistar and adult WKy rats. In adult 12-wo hypertensive SHR, gLTP was expressed in caudal but not in rostral neurons. In contrast, in 6-wo pre-hypertensive SHR, gLTP was expressed in rostral but not in caudal neurons; while in 6-wo WKy, gLTP was expressed in caudal but not in rostral neurons. The lack of gLTP expression in caudal neurons of 6-wo SHR was not due to a GABAergic modulation because several GABA-A receptor antagonists failed to unmask gLTP. Data show that neuroplasticity, particularly gLTP expression, varied according to the ganglionic region. We propose that differential regional expression of gLTP may be correlated with selective innervation on different target organs.

The Vagus Nerve and the Celiaco-mesenteric Ganglia Participate in the Feeding Responses Evoked by Non-sulfated Cholecystokinin-8 in Male Sprague Dawley Rats.

We have shown that non-sulfated cholecystokinin-8 (NS CCK-8) reduces food intake in adult male Sprague Dawley rats by activating cholecystokinin-B receptor (CCK-BR). Here, we tested the hypothesis that the vagus nerve and the celiaco-mesenteric ganglia may play a role in this reduction. The hypothesis stems from the following facts. The vagus and the celiaco-mesenteric ganglia contain NS CCK-8, they express and have binding sites for CCK-BR, NS CCK-8 activates CCK-BR on afferent vagal and sympathetic fibers and the two structures link the gastrointestinal tract to central feeding nuclei in the brain, which also contain the peptide and CCK-BR. To test this hypothesis, three groups of free-feeding rats, vagotomy (VGX), celiaco-mesenteric ganglionectomy (CMGX) and sham-operated, received NS CCK-8 (0, 0.5 and 1 nmol/kg) intraperitoneally prior to the onset of the dark cycle and various feeding behaviors were recorded. We found that in sham-operated rats both doses of NS CCK-8 reduced meal size (MS), prolonged the intermeal interval (IMI, time between first and second meal), increased satiety ratio (SR = IMI/MS), reduced 24-h food intake and reduced the number of meals relative to saline control. In the VGX and the CMGX groups, all of the previous responses were attenuated. Consistent with our hypothesis, the findings of the current work suggest a role for the vagus nerve and the celiaco-mesenteric ganglia in the feeding responses evoked by NS CCK-8.

Changes of the Expression of Neuronal NO-Synthase in Rat Sympathetic Ganglia during Ontogeny.

Expression of neuronal NO synthase in the sympathetic cranial cervical ganglion and stellate ganglion in rats during postnatal ontogeny was studied by immunohistochemistry and Western blotting. In the sympathetic ganglia, neuronal NO synthase-immunoreactive neurons were absent in all rats. In the stellate and cranial cervical ganglia, the expression of neuronal NO synthase and the density of immunoreactive fibers increased in early postnatal ontogeny from the moment of birth to the age of 30 days and then decreased. Thus, we observed heterochroneous expression of neuronal NOS in the preganglionic somata in the spinal cord and in the preganglionic fibers in the sympathetic ganglia during ontogeny.