Hindbrain Noradrenergic Lesions Attenuate Anorexia and Alter Central cFos Expression in Rats after Gastric Viscerosensory Stimulation

Behavioral, autonomic, and endocrine outputs of the CNS are subject to important feedback modulation by viscerosensory signals that are conveyed initially to the hindbrain nucleus of the solitary tract (NST). In the present study, noradrenergic (NA) neurons [i.e., those that express the NA synthetic enzyme dopamine β hydroxylase (DbH)] in the caudal NST were lesioned to determine their role in mediating anorexic responses to gastric stimulation and in conveying gastric sensory signals to the hypothalamus and amygdala. For this purpose, saporin toxin conjugated to an antibody against DbH was microinjected bilaterally into the caudal NST in adult rats. Control rats received similar microinjections of vehicle. Several weeks later, rats were tested for the ability of systemic cholecystokinin octapeptide (CCK) (0 or 10 μg/kg) to inhibit food intake. CCK-induced anorexia was significantly attenuated in toxin-treated rats. Rats subsequently were used in a terminal cFos study to determine central neural activation patterns after systemic CCK or vehicle and to evaluate lesion extent. Toxin-induced loss of DbH-positive NST neurons was positively correlated with loss of CCK-induced anorexia. Hypothalamic cFos expression was markedly attenuated in lesioned rats after CCK treatment, whereas CCK-induced neural activation in the parabrachial nucleus and amygdala appeared normal. These findings suggest that hindbrain NA neurons are an integral component of brainstem circuits that mediate CCK-induced anorexia and also are necessary for hypothalamic but not parabrachial or amygdala responses to gastric sensory stimulation

The role of nucleus of the solitary tract glucagon-like peptide-1 and prolactin-releasing peptide neurons in stress: anatomy, physiology and cellular interactions

Neuroendocrine, behavioural and autonomic responses to stressful stimuli are orchestrated by complex neural circuits. The caudal nucleus of the solitary tract (cNTS) in the dorsomedial hindbrain is uniquely positioned to integrate signals of both interoceptive and psychogenic stress. Within the cNTS, glucagon-like peptide-1 (GLP-1) and prolactin-releasing peptide (PrRP) neurons play crucial roles in organising neural responses to a broad range of stressors. In this review we discuss the anatomical and functional overlap between PrRP and GLP-1 neurons. We outline their co-activation in response to stressful stimuli and their importance as mediators of behavioural and physiological stress responses. Finally, we review evidence that PrRP neurons are downstream of GLP-1 neurons and outline unexplored areas of the research field. Based on the current state-of-knowledge, PrRP and GLP-1 neurons may be compelling targets in the treatment of stress-related disorders

Progressive postnatal assembly of limbic-autonomic circuits revealed by central transneuronal transport of pseudorabies virus

The development of neuronal projections to a target and the establishment of synaptic connections with that target can be temporally distinct events, which typically are distinguished by functional assessments. We have applied a novel neuroanatomical approach to characterize the development of limbic forebrain synaptic inputs to autonomic neurons in neonatal rats. Transneuronal labeling of preautonomic forebrain neurons was achieved by inoculating the ventral stomach wall with pseudorabies virus (PRV) on postnatal day 1 (P1), P4, or P8. In each age group, PRV-positive neurons were present in autonomic and preautonomic regions of the spinal cord and brainstem 62-64 hr after inoculation. Transneuronal forebrain labeling in rats injected on P8 was similar to the transneuronal labeling reported previously in adult rats and included neurons in the medial and lateral hypothalamus, amygdala, bed nucleus of the stria terminalis, and visceral cortices. However, no cortex labeling and only modest amygdala and bed nucleus labeling were observed in rats injected with PRV on P4, and only medial hypothalamic labeling was observed in rats injected on P1. Additional tracing experiments involving central injections of PRV or cholera toxin β indicated that lateral hypothalamic and telencephalic regions projected to the medullary dorsal vagal complex several days before establishing synaptic connections with gastric-related autonomic neurons. These results demonstrate a novel strategy for evaluating synaptic connectivity in developing neural circuits and show a temporally segregated postnatal emergence of medial hypothalamic, lateral hypothalamic, and telencephalic synaptic inputs to central autonomic neurons

Psychogenic stress activates C-Fos in nucleus accumbens-projecting neurons of the hippocampal ventral subiculum

Background: The ventral subiculum is known to be activated by the presentation of novel stressors. It has been hypothesized that neuronal ensembles at the ventral aspect of the hippocampal formation are involved in context-dependent processing and can guide the learning of appropriate action selections in response to threatening contexts. Artificial activation of the ventral subiculum can excite medium spiny neurons of the nucleus accumbens and can increase the excitability of mesolimbic dopamine neurons via a polysynaptic pathway through the basal ganglia. However, it remains unknown whether this circuit can be activated by aversive experience, and if so, whether ventral subiculum engages nucleus accumbens monosynaptically. Methods: To address this, the retrograde tracer fluorogold was used in rats to label neurons projecting to the caudomedial nucleus accumbens. One to 2 weeks later, the same rats were exposed to psychogenic stress (i.e., acute restraint in a novel test room) or served as nonhandled controls, followed by dual immunocytochemical localization of retrogradely transported tracer and nuclear Fos. Results: Compared with controls, rats exposed to psychogenic stress displayed more fluorogold-positive ventral subiculum neurons that were double-labeled for Fos. Conclusion: This study establishes that the direct pathway from ventral subiculum to the caudomedial nucleus accumbens is activated by stressful experience

Influence of Temperature, Air Velocity, and Ultrasound Application on Drying Kinetics of Grape Seeds

The objective of this work was to determine the influence of temperature, air velocity, and ultrasound application on the drying kinetics of grape seeds. The drying kinetics were determined at 1.0, 1.5, 2.0, and 3.0 m/s and at 40, 50, 60, and 70 C. At 1.0 and 1.5 m/s, the experiments were carried out with and without ultrasound application. To establish the influence of the variables on the drying kinetics, the results were modeled by means of both the Peleg and a diffusion model. The activation energy was determined (Arrhenius equation). For an air velocity of over 1.5 m/s, it was determined that the external resistance to mass transfer was negligible. No influence of ultrasound application was observed, probably due to the fact that grape seeds are very hard and have a low level of porosity.The authors of this article acknowledge financial support from the Valencian Government ("Generalitat Valenciana,'' Valencia, Spain, PROMETEO/2010/062).Clemente Polo, G.; Sanjuán Pellicer, MN.; Cárcel Carrión, JA.; Mulet Pons, A. (2014). Influence of Temperature, Air Velocity, and Ultrasound Application on Drying Kinetics of Grape Seeds. Drying Technology. 32(1):68-76. https://doi.org/10.1080/07373937.2013.811592S687632

Prolactin-releasing peptide affects gastric motor function in rat by modulating synaptic transmission in the dorsal vagal complex

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66249/1/jphysiol.2004.072736.pd

Central and peripheral GLP-1 systems independently suppress eating

The anorexigenic peptide glucagon-like peptide-1 (GLP-1) is secreted from gut enteroendocrine cells and brain preproglucagon (PPG) neurons, which, respectively, define the peripheral and central GLP-1 systems. PPG neurons in the nucleus tractus solitarii (NTS) are widely assumed to link the peripheral and central GLP-1 systems in a unified gut–brain satiation circuit. However, direct evidence for this hypothesis is lacking, and the necessary circuitry remains to be demonstrated. Here we show that PPGNTS neurons encode satiation in mice, consistent with vagal signalling of gastrointestinal distension. However, PPGNTS neurons predominantly receive vagal input from oxytocin-receptor-expressing vagal neurons, rather than those expressing GLP-1 receptors. PPGNTS neurons are not necessary for eating suppression by GLP-1 receptor agonists, and concurrent PPGNTS neuron activation suppresses eating more potently than semaglutide alone. We conclude that central and peripheral GLP-1 systems suppress eating via independent gut–brain circuits, providing a rationale for pharmacological activation of PPGNTS neurons in combination with GLP-1 receptor agonists as an obesity treatment strategy

GLP-1 neurons form a local synaptic circuit within the rodent nucleus of the solitary tract

Glutamatergic neurons that express pre‐proglucagon (PPG) and are immunopositive (+) for glucagon‐like peptide‐1 (i.e., GLP‐1+ neurons) are located within the caudal nucleus of the solitary tract (cNTS) and medullary reticular formation in rats and mice. GLP‐1 neurons give rise to an extensive central network in which GLP‐1 receptor (GLP‐1R) signaling suppresses food intake, attenuates rewarding, increases avoidance, and stimulates stress responses, partly via GLP‐1R signaling within the cNTS. In mice, noradrenergic (A2) cNTS neurons express GLP‐1R, whereas PPG neurons do not. In this study, confocal microscopy in rats confirmed that prolactin‐releasing peptide (PrRP)+ A2 neurons are closely apposed by GLP‐1+ axonal varicosities. Surprisingly, GLP‐1+ appositions were also observed on dendrites of PPG/GLP‐1+ neurons in both species, and electron microscopy in rats revealed that GLP‐1+ boutons form asymmetric synaptic contacts with GLP‐1+ dendrites. However, RNAscope confirmed that rat GLP‐1 neurons do not express GLP‐1R mRNA. Similarly, Ca²⁺ imaging of somatic and dendritic responses in mouse ex vivo slices confirmed that PPG neurons do not respond directly to GLP‐1, and a mouse crossbreeding strategy revealed that <1% of PPG neurons co‐express GLP‐1R. Collectively, these data suggest that GLP‐1R signaling pathways modulate the activity of PrRP+ A2 neurons, and also reveal a local “feed‐forward” synaptic network among GLP‐1 neurons that apparently does not use GLP‐1R signaling

A2 Noradrenergic Lesions Prevent Renal Sympathoinhibition Induced by Hypernatremia in Rats

Renal vasodilation and sympathoinhibition are recognized responses induced by hypernatremia, but the central neural pathways underlying such responses are not yet entirely understood. Several findings suggest that A2 noradrenergic neurons, which are found in the nucleus of the solitary tract (NTS), play a role in the pathways that contribute to body fluid homeostasis and cardiovascular regulation. The purpose of this study was to determine the effects of selective lesions of A2 neurons on the renal vasodilation and sympathoinhibition induced by hypertonic saline (HS) infusion. Male Wistar rats (280–350 g) received an injection into the NTS of anti-dopamine-beta-hydroxylase-saporin (A2 lesion; 6.3 ng in 60 nl; n = 6) or free saporin (sham; 1.3 ng in 60 nl; n = 7). Two weeks later, the rats were anesthetized (urethane 1.2 g⋅kg−1 b.wt., i.v.) and the blood pressure, renal blood flow (RBF), renal vascular conductance (RVC) and renal sympathetic nerve activity (RSNA) were recorded. In sham rats, the HS infusion (3 M NaCl, 1.8 ml⋅kg−1 b.wt., i.v.) induced transient hypertension (peak at 10 min after HS; 9±2.7 mmHg) and increases in the RBF and RVC (141±7.9% and 140±7.9% of baseline at 60 min after HS, respectively). HS infusion also decreased the RSNA (−45±5.0% at 10 min after HS) throughout the experimental period. In the A2-lesioned rats, the HS infusion induced transient hypertension (6±1.4 mmHg at 10 min after HS), as well as increased RBF and RVC (133±5.2% and 134±6.9% of baseline at 60 min after HS, respectively). However, in these rats, the HS failed to reduce the RSNA (115±3.1% at 10 min after HS). The extent of the catecholaminergic lesions was confirmed by immunocytochemistry. These results suggest that A2 noradrenergic neurons are components of the neural pathways regulating the composition of the extracellular fluid compartment and are selectively involved in hypernatremia-induced sympathoinhibition