Gastric vagal efferent inhibition evoked by intravenous CRF is unrelated to simultaneously recorded vagal afferent activity in urethane-anesthetized rats

Corticotropin-releasing factor (CRF) injected peripherally or released in response to stressful challenges to the organism reduces gastric tone and contractility, in part by vagal pathways. However, information on the changes in gastric vagal impulse activity evoked by peripheral CRF administration is entirely lacking. Using a novel "dual recording" method in urethane-anesthetized rats, vagal efferent (VE) and afferent (VA) impulse activities were recorded simultaneously from separate, fine bundles dissected from the ventral gastric vagus nerve branch innervating the glandular stomach. Activity records for 38 VA single units (SUs) and 33 VE SUs were sorted from multiunit records obtained from 13 preparations. Intravenous (iv) administration of saline had no effect on multiunit VE activity, whereas CRF (1 microg/kg, iv) immediately inhibited VE activity, reaching a nadir of 54 +/- 8.0% of preinjection levels at 3.0 min postinjection. CRF (1 microg/kg, iv) inhibited 25/33 (75.8%) VE SUs and excited three of 33 (9.1%) VE SUs. In contrast to potent effects on VE activity, iv CRF did not alter multiunit VA activity. Single-unit analysis, however, revealed five of 38 (13.1%) VA SUs excited by iv CRF at widely varying latencies (suggesting an indirect mode of action) and one inhibited VA SU. VA SUs excited after iv CRF did not respond during gastric distention and vice versa. These experiments are the first to use simultaneous recording of gastric VA and VE units. The data demonstrate a predominantly inhibitory influence of iv CRF on VE outflow to the hindstomach, not driven by gastric vagovagal reflex activity.     

Capsaicin-sensitive vagal afferent neurons innervating the rat pancreas

The vagal afferent innervation of the rat pancreas was investigated by the use of retrograde axonal transport of horseradish peroxidase (HRP) injected into the pancreas through the common bile duct. Many labeled neuronal somata were found in the right and left nodose ganglia. The size distribution of the labeled neuronal population in the nodose ganglia was examined and compared with that obtained from rats pretreated with capsaicin. In rats treated neonatally with capsaicin the smallest neurons (up to 200 micron2) were completely absent and those belonging to the second and third classes (200-300, 300-400 micron2) were reduced in both vagi.     

Cholecystokinin-induced c-fos expression in the rat brain stem is influenced by vagal nerve integrity.

Exogenous cholecystokinin (CCK) activates brain stem neurons in the area postrema and nucleus of the tractus solitarius, primarily in regions where vagal afferent fibres terminate. The present experiments show that vagal sensory fibres mediate CCK-induced c-fos in brain stem neurons, based on the findings that perivagal capsaicin pre-treatment in seven out of eight cases reduced or ablated c-fos expression in these regions.     

Role of globus pallidus and substantia nigra efferent pathways in striatally evoked head turning in the rat

Summary These studies have examined the role of brain areas that receive efferent projections from the globus pallidus (GP) and substantia nigra (SN) in producing the contralateral head turning evoked by unilateral electrical stimulation of the neostriatum in the conscious rat. Two parameters were studied: the latency for a 90 ° head turn and changes in the normal latency evoked by administration of the GABA drugs picrotoxin and muscimol in GP. Electrolesions in the ipsilateral ventromedial and centromedian thalamic nuclei had no effect on the head turn parameters. Although small electrolesions in the SN slowed, but did not abolish the head turn, it prevented the changes in the response latency brought about by GABA drugs in GP. Treatment with 6-hydroxydopamine, which partly destroyed the nigrostriatal dopamine neurones, had no effect on the head turn. Areas of the brainstem that receive basal ganglia efferents were lesioned. An electrolesion of the nucleus tegmenti pedunculopontinus had no effect on the head turn latencies. The head turning was abolished by a lesion in the lateral periaqueductal grey (PAG); a more rostral PAG lesion, on the same level as SN, was ineffective. It is concluded that the head turning is mediated by basal ganglia efferents which pass close to the nigra without synapsing and project to the PAG. The GABA-sensitive GP efferents which modulate the response, probably project to SN.     

Gustatory neural circuitry in the hamster brain stem

The nucleus of the solitary tract (NST) and the parabrachial nuclei (PbN) are the first and second central relays for the taste pathway, respectively. Taste neurons in the NST project to the PbN, which further transmits taste information to the rostral taste centers. Nevertheless, details of the neural connections among the brain stem gustatory nuclei are obscure. Here, we investigated these relationships in the hamster brain stem. Three electrode assemblies were used to record the activity of taste neurons extracellularly and then to electrically stimulate these same areas in the order: left PbN, right PbN, and right NST. A fourth electrode, a glass micropipette, was used to record from gustatory cells in the left NST. Results showed extensive bilateral communication between brain stem nuclei at the same level: 1) 10% of 96 NST neurons projected to the contralateral NST and 58% received synaptic input from the contralateral NST; and 2) 12% of 43 PbN neurons projected to the contralateral PbN and 21% received synaptic input from the contralateral PbN. Results also showed extensive communication between levels: 1) as expected, the majority of 119 NST neurons, 82%, projected to the ipsilateral PbN, but 85% of the 20 NST neurons tested received synaptic input from the ipsilateral PbN, as did 59% of 22 NST neurons that did not project to the PbN; and 2) although few, 3%, of 119 NST cells projected to the contralateral PbN and 38% received synaptic input from the contralateral PbN. These results demonstrated that taste neurons in the NST not only project to, but also receive descending input from the bilateral PbN and that gustatory neurons in the NST and PbN also communicate with the corresponding nucleus on the contralateral side.     

Mushroom body efferent neurons responsible for aversive olfactory memory retrieval in Drosophila

Aversive olfactory memory is formed in the mushroom bodies in Drosophila melanogaster. Memory retrieval requires mushroom body output, but the manner in which a memory trace in the mushroom body drives conditioned avoidance of a learned odor remains unknown. To identify neurons that are involved in olfactory memory retrieval, we performed an anatomical and functional screen of defined sets of mushroom body output neurons. We found that MB-V2 neurons were essential for retrieval of both short- and long-lasting memory, but not for memory formation or memory consolidation. MB-V2 neurons are cholinergic efferent neurons that project from the mushroom body vertical lobes to the middle superiormedial protocerebrum and the lateral horn. Notably, the odor response of MB-V2 neurons was modified after conditioning. As the lateral horn has been implicated in innate responses to repellent odorants, we propose that MB-V2 neurons recruit the olfactory pathway involved in innate odor avoidance during memory retrieval.     

Some observations on responses evoked by pinna stimulation in efferent and afferent fibres innervating hind limb muscle spindles of the rat

Summary Pinna stimulation has long been known to evoke reflex changes of discharge in efferents to the hind limb and hence changes in muscle spindle discharges. The present experiments were made in the rat to determine the involvement of the static and dynamic fusimotor systems in the pinna reflex.We first observed fusimotor activity indirectly, by recording spindle responses to various length changes with and without concurrent pinna stimulation. Afferent responses were clearly influenced by static fusimotion during the reflex; evidence for dynamic fusimotion was sought but not found. Ipsilateral and contralateral stimuli appeared equally effective in evoking this static fusimotion.The magnitudes of afferent responses differed markedly between muscles. Observations were made simultaneously on activities recorded directly from efferents to peroneal and soleus muscles. Several efferents were spontaneously active in each nerve; pinna stimulation usually enhanced their activities and aroused also several others, previously quiescent. The frequencies of discharge in efferents to peroneus were usually higher than in those to soleus. This must in part be responsible for differences in afferent responses. The spontaneously active and activated fibres together formed about one quarter to one third of the total motoneurone pool and had conduction velocities restricted to the lower end of the conduction velocity spectrum for fibres.     

Cardio-respiratory reflexes evoked by phenylbiguanide in rats involve vagal afferents which are not sensitive to capsaicin

Aim: Stimulation of pulmonary C fibre receptors by phenylbiguanide (PBG, 5-HT₃ agonist) produces hypotension, bradycardia and tachypnoea or apnoea. However, tachypnoeic or apnoeic responses are not consistent. Therefore, this study was undertaken to delineate the actions of PBG on respiration and compared with those evoked by capsaicin (TRPV1 agonist). Methods: Blood pressure, respiratory excursions and ECG were recorded in urethane anaesthetized adult rats. The effect of PBG or capsaicin was evaluated before and after ondansetron (5-HT₃ antagonist), capsazepine (TRPV1 antagonist) or bilateral vagotomy. In addition, their effect on vagal afferent activity was also evaluated. Results: Bolus injection of PBG produced concentration-dependent (0.1–100 μg kg⁻¹) hypotensive and bradycardiac responses, while there was tachypnoea at lower concentrations (0.1–3 μg kg⁻¹) and apnoea at higher concentrations (10–100 μg kg⁻¹). After vagotomy or after exposure to ondansetron both tachypnoeic and apnoeic responses were abolished along with cardiovascular responses. However, capsazepine (3 mg kg⁻¹) did not block the PBG-induced reflex responses. Capsaicin (0.1–10 μg kg⁻¹), on the other hand, produced a concentration-dependent apnoea, hypotension and bradycardia but tachypnoea was not observed. Ondansetron failed to block the capsaicin-induced reflex response while bilateral vagotomy abolished bradycardiac and hypotensive responses and attenuated the apnoeic response. In another series, vagal afferent activity and cardio-respiratory changes evoked by PBG were blocked by ondansetron. However, capsaicin failed to activate the PBG-sensitive vagal afferents even though cardio-respiratory alterations were observed. Conclusions: The present observations indicate that PBG produced tachypnoea at a lower concentration and apnoea at a higher concentration involving vagal afferents which are different from those excited by capsaicin.     

Accelerated mobilization and formation of histamine in the gastric mucosa evoked by vagal excitation

1. The changes in the rate of histamine formation and in the histamine content of the parietal cell containing region of the gastric mucosa have been studied in rats under the influence of agents which evoke or abolish vagal excitation.2. The hypoglycaemia producing agents, insulin and 2-deoxyglucose (2-DG), raised the mucosal histamine-forming capacity (HFC) in a way similar to that previously observed on re-feeding, gastrin injection, and distension of the stomach wall.3. In cats, insulin injection elicited an elevation of mucosal HFC similar to the corresponding effect of insulin in rats.4. Hoechst 9980, which inhibits post-ganglionic cholinergic transmission, counteracted the elevation of mucosal HFC following vagal excitation, but did not inhibit changes produced by gastrin, thus indicating the absence of a cholinergic intermediary link between gastrin and changes in mucosal histamine.5. It is emphasized that although re-feeding, vagus excitation, gastrin and distension all produce similar changes in mucosal histamine, the clarification of the precise role of histamine as a natural stimulant for the parietal cells may require a fresh kind of approach.     

Analysis of the circuitry responsible for primary afferent depolarization in the trigeminal spinal nucleus caudalis of cats

Summary Depth analysis was performed on the field potential evoked by stimulation of the infraorbital nerve in the trigeminal spinal nucleus caudalis and the subjacent lateral reticular formation of cats. It was shown by dye marking of the recording positions that each subnucleus of the nucleus caudalis (subnucleus marginalis, gelatinosus and magnocellularis) and the reticular formation could be differentiated from one another by the characteristics of the peripherally evoked field potentials.Responses of neurons were extracellularly recorded in the subnuclei gelatinosus and magnocellularis of the nucleus caudalis and in the reticular formation to stimulation of the trigeminal sensory branches (the frontal, infraorbital and lingual nerves), the nucleus ventralis posteromedialis of the thalamus and the cerebral cortex. The properties of the neurons were studied in relation to their thresholds, latencies, receptive fields (sensory branches effective for spike generation) and frequency-following capacities. These responses were then compared with properties of the PAD induced in the fibers terminating in the nucleus caudalis by similar peripheral and central stimulation.It was found that the neurons in the subnucleus magnocellularis were the most likely candidates for the interneurons mediating the peripherally evoked disynaptic PAD in the trigeminal nerve fibers terminating in the nucleus caudalis.     

Sympathetic efferent pathways projecting bilaterally to the vas deferens in the rat

ABSTRACT Background: The laterality of the signals passing through the splanchnic nerves to the vas deferens has not been well studied. Methods: The present study was designed to determine the bilateral distribution of sympathetic nerves to the rat vasa deferentia by measuring intravasal pressure (VP) responses to electrical stimulation of left lumbar splanchnic nerves (LSN) following consecutive transections of more distal nerves. Results: L₂-L₆ LSN stimulation increased VP bilaterally. Left VP responses decreased slightly (<20%) after section of the right hypogastric nerve (HGN) and then were abolished by subsequent section of branches (B-M-APG) between the left major pelvic (MPG) and accessory pelvic ganglia (APG). Left VP responses were decreased by >80% after section of left HGN, not changed further by subsequent section of commissural branches (CB-MPG) between the MPG, and completely eliminated by section of commissural branches between the APG (CB-APG). Right VP responses were decreased slightly (<20%) by section of the left HGN and then abolished by section of the right B-M-APG. These responses were also decreased by >70% by section of right HGN, not changed by section of CB-MPG, but then completely eliminated by section of CB-APG. Conclusions: These results indicate that the left lumbar sympathetic pathway to the vas deferens is distributed bilaterally and exhibits two crossing points at the level of the inferior mesenteric ganglion and APG. Anat. Rec. 248:291-299, 1997. © 1997 Wiley-Liss, Inc.     

Ca2+ transient evoked by chemical stimulation is enhanced by PGE2 in vagal sensory neurons: role of cAMP/PKA signaling pathway

The effect of prostaglandin E(2) (PGE(2)) on chemical stimulation-evoked calcium (Ca(2+)) transient was investigated in isolated vagal sensory neurons of the rat using fura-2-based ratiometric Ca(2+) imaging. Application of capsaicin (3 x 10(-8) to 10(-7) M; 15 s) caused a rapid surge of intracellular Ca(2+) concentration in small- and medium-size neurons; the response was reproducible when >10 min elapsed between two challenges and was absent in nominally Ca(2+)-free solution. After pretreatment with PGE(2) (3 x 10(-7) M; 5 min), the peak of this capsaicin-evoked Ca(2+) transient was increased by almost fourfold, and its duration was also prolonged. This augmented response to capsaicin induced by PGE(2) gradually declined but remained higher than control after 15-min washout. Similarly, PGE(2) pretreatment also markedly enhanced the Ca(2+) transients induced by other chemical stimulants to C neurons, such as phenylbiguanide (PBG), adenosine 5'-triphosphate (ATP), and KCl. The Ca(2+) transients evoked by PBG, ATP, and KCl were potentiated after the pretreatment with PGE(2) to 242, 204, and 163% of their control, respectively. This potentiating effect of PGE(2) could be mimicked by forskolin (10(-6) M; 5 min), an activator of adenylyl cyclase, and 8-(4-chlorophenylthio)adenosine-3'-5'-cyclic monophosphate (CPT-cAMP; 3 x 10(-6) M, 10 min), a membrane-permeable cAMP analogue. Furthermore, the potentiating effects of PGE(2), forskolin, and CPT-cAMP were abolished by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89; 10(-5) M; 15-20 min), a protein kinase A (PKA) inhibitor. In summary, these results show that PGE(2) reversibly potentiates the chemical stimuli-evoked Ca(2+) transients in cultured rat vagal sensory neurons, and this potentiating effect is mediated through the cyclic AMP/PKA transduction cascade.