Effect of electrical stimulation of the nucleus of the solitary tract on the development of electrical amygdaloid kindling in the cat

PURPOSE: This work analyzed the effect of electrical stimulation of the nucleus of the solitary tract (NTS) on the development of electrical amygdaloid kindling (AK) in freely moving cats. METHODS: Nine male adult cats with implanted electrodes in both amygdalae (basolateral nucleus), both lateral geniculate bodies, left NTS, and both prefrontal cortices were used. Electromyogram and electrooculogram also were recorded. The AK was performed every 24 h (1-s train, 1-ms pulses, 60 Hz, 300-600 microA). The NTS was stimulated previously for 1 min (0.5-ms pulses, 30 Hz, 150-300 microA), just before the AK at 10:00 a.m., and then every 60 min, 4 times, from 11:00 a.m. to 2:00 p.m. On different days, all NTS stimulation was suspended, and AK was continued until stage VI kindling was reached. RESULTS: Behavioral changes produced by the stimulation of the NTS were blinking, immobility periods with upward sight, licking, and swallowing. Animals with simultaneous stimulation of NTS and AK did not reach stage VI, remaining in behavioral stages I-III. Stage VI was reached after NTS stimulation was intentionally suspended. The amplitude, duration, and the propagation of the amygdaloid afterdischarge did not exhibit progressive evolution during NTS stimulation. A regression analysis was performed between the number of days with only AK stimulation and days with simultaneous NTS stimulation, which showed a positive correlation (values of r = 0.84). CONCLUSIONS: Our results suggest that NTS stimulation interferes with the development of convulsive evolution and secondary generalization. This delay effect may be due to the activation of the locus ceruleus and some areas of the midbrain reticular formation, among other structures, which has been demonstrated to inhibit experimental convulsive seizures.     

Preemptive effect of nucleus of the solitary tract stimulation on amygdaloid kindling in freely moving cats

Purpose: The nucleus of the solitary tract (NTS) is a primary site where vagal afferents terminate. The aim of this study was to analyze the preemptive effect of NTS electrical stimulation on daily amygdaloid kindling (AK) in freely moving cats. Methods: Seven adult male cats were used. Bipolar electrodes were stereotaxically implanted into both amygdalae, lateral geniculate bodies, hippocampi, and prefrontal cortices. In addition, a bipolar stainless steel electrode was implanted in the left NTS. Cats were recorded under the following experimental conditions: The NTS was stimulated for 6 days before the initiation of AK (1 min on/5 min off, 1 h total). AK was performed by stimulating the amygdala every 24 h (1 s, 60 Hz, 1 ms) until behavioral stage VI was reached. Results: The number of stimulations to reach stage VI in control animals was 23.4 ± 3.7, in lateral tegmental field (LTF) animals was 17.0 ± 2.1 days. Animals subjected to preemptive NTS stimulation showed a significant increase (53.8 ± 5.9). In addition, behavioral development was retarded, with an increase in the number of stimulations required to reach stage III. In this group, overall kindling development was delayed, and amygdaloid afterdischarge duration did not show a progressive increase as was observed in the control group. Discussion: Our results indicate that preemptive NTS electrical stimulation interferes with epileptogenesis. This anticonvulsive effect could be related to the activation of certain structures that inhibit seizure development. Therefore, results suggest that NTS mediates the anticonvulsive effect of vagus nerve stimulation.     

Subnuclear organization of the human caudal nucleus of the solitary tract

The caudal human nucleus of the solitary tract (NTS) is composed of 10 subnuclei. The commissural subnucleus spans the midline below the obex, merging rostrally into the medial subnucleus. The other subnuclei of the NTS are best seen just above the obex. The ventrolateral subnucleus contains large, darkly staining neurons. The interstitial subnucleus consists of neurons lying in groups intermingled with the fibers of the tract. The lateral subnucleus is small at caudal levels, merging with the interstitial subnucleus more rostrally. The dorsal subnucleus contains large melanotic neurons and encircles the substantia gelatinosus, a round, cell-poor subnucleus. The ventromedial subnucleus curls around the medial and ventral edge of the tract. The intermediate subnucleus, laying ventrolateral to the dorsal motor nucleus of the vagus, also contains melanotic neurons. The subpostremal subnucleus separates the area postrema from the NTS proper. The medial subnucleus is the largest subnucleus in the caudal NTS, containing medium-sized fusiform neurons. Adoption of a uniform cytoarchitectural map of the caudal NTS will permit more accurate comparisons between human and nonhuman studies.     

Transfer of information about taste from the nucleus of the solitary tract to the parabrachial nucleus of the pons

In the study of the neural code for gustation, the relative sensitivity of a cell to a variety of taste stimuli is defined as its response profile. To study the construction of response profiles from incoming signals, electrophysiological responses to NaCl, HCl, quinine-HCl, sucrose and Na saccharin were recorded simultaneously in pairs of single cells: one in the nucleus of the solitary tract (NTS) and the other in the parabrachial nucleus of the pons (PbN), respectively the first and second synapses in the central pathway for gustation. Of 37 units recorded in the NTS and 32 in the PbN, 12 (32%) pairs showed evidence of functional connectivity. Although PbN responses were significantly larger than those in the NTS in general, no amplification of NTS activity was apparent among those units that were functionally connected. Analysis of NTS–PbN connectivity patterns suggests that PbN units receive input from NTS units with response profiles that are both similar and different from their own pattern of sensitivities. Further analysis suggests that the stimulus-selectivity of the response profile of a PbN unit may be determined by stimulus-selective input from NTS cells that show similar response profiles. However, input from NTS cells with response profiles different from their own appears to be non-stimulus-selective. Analysis of the organization of response profiles in the two structures suggests that the cells in both the NTS and PbN cannot be easily distinguished by their patterns of sensitivity to taste stimuli.     

Cholecystokinin in the nucleus of the solitary tract of the rat: evidence for its vagal origin

Nerve fibers and terminals immunoreactive for cholecystokinin (CCK) were demonstrated in the nucleus of the solitary tract (NTS) of the rat using light and electron microscopic immunocytochemistry. The following morphological and biochemical evidence suggests that CCK in the NTS seems to be of extrinsic, most probably vagal, origin: (1) axon fragments of the intracranial vagus were identified by immunostaining on their way to the solitary tract; (2) CCK-immunostaining could be localized in nerve terminals in the nucleus of the solitary tract, where only a very few immunopositive dendrites or cell bodies were present; and (3) transecting the major neuronal afferents (via solitary tract and/or more laterally) resulted in a complete disappearance of radioimmunoassayable CCK from the nucleus of the solitary tract.     

Intramedullary connections of the rostral nucleus of the solitary tract in the hamster

The rostral nucleus of the solitary tract (NST) figures prominently in the gustatory system, giving rise to ascending taste pathways that are well documented. Less is known of the local connections of the rostral NST with sites in the medulla. This study defines the intramedullary connections of the rostral NST in the hamster. Small iontophoretic injections of horseradish peroxidase (HRP), confined to the rostral NST, resulted in Golgi-like filling of axons that exited the NST or that interconnected cytoarchitectonic subdivisions within the NST complex. The NST efferent axons terminated sparsely in the trigeminal, facial and hypoglossal motor nuclei, but axons and endings were heavily distributed in the parvicellular reticular formation ventral to the NST. HRP injections centered in this part of the reticular formation resulted in heavy projections to the orofacial motor nuclei. Intranuclear connections, labelled after NST injections, linked NST subdivisions that receive primary afferent taste inputs to subdivisions involved in (1) projections to the preoromotor reticular formation, (2) projections to swallowing motor neurons, (3) activation of preganglionic parasympathetic neurons, and (4) general viscerosensation. In general, the connections defined in the present study provide anatomical details about the substrate for gustatory-motor and gustatory-visceral interactions.     

Subtypes of metabotropic glutamate receptors in the nucleus of the solitary tract of rats

We have determined the role of subgroups of metabotropic glutamate receptors (mGluRs) in the nucleus of the solitary tract (NTS) of normotensive Wistar rats. Unilateral microinjection of (S)-3, 5-dihydroxyphenylglycine (3,5-DHPG), an agonist of group I mGluRs, into the NTS significantly decreased mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) (-19. 4+/-2.6 mmHg, -16.4+/-5.1 beats/min, and -30.6+/-5.7% by 1 nmol). Microinjection of (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 1 nmol), a putative antagonist of group I mGluRs, into the NTS caused transient decreases in MAP and RSNA, followed by sustained increases in MAP (+8.3+/-2.4 mmHg) and RSNA (+27.7+/-10.8%). Pretreatment with AIDA failed to prevent the cardiovascular and RSNA responses to microinjection of 3,5-DHPG. Unilateral microinjection of (S)-4-carboxy-3-hydroxyphenylglycine (4C3HPG), an agonist of group II mGluRs, into the NTS also significantly decreased MAP, HR, and RSNA, whose responses were not inhibited by pre-microinjection of (2S)-alpha-ethylglutamic acid (EGLU; 2 nmol), a putative antagonist of group II mGluRs. On the other hand, unilateral microinjection of L(+)-2-amino-4-phosphonobutyric acid (L-AP4), an agonist of group III mGluRs, into the NTS caused dose-related decreases in MAP (-8. 3+/-1.5 mmHg by 0.1 nmol and -45.1+/-3.4 mmHg by 0.3 nmol), HR, and RSNA (-21.3+/-3.9% by 0.1 nmol and -77.2+/-6.5% by 0.3 nmol), whose responses were suppressed by pre-microinjection of (R, S)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG; 0.3 nmol), an antagonist of group III mGluRs. These results suggest that all subgroups of mGluRs participate in cardiovascular and sympathetic regulations in the NTS of rats, and that endogenous group I mGluRs in the NTS may contribute to tonic cardiovascular and sympathetic regulations.     

Role of the paraventricular nucleus in the projection from the nucleus of the solitary tract to the olfactory bulb

Electrophysiological experiments were performed on anesthetized rats to determine the effects of lesions of the paraventricular nucleus on the amplitude of evoked potentials recorded in the periglomerular layer of the olfactory bulb after nucleus of the solitary tract electrical stimulation. Lesions of the paraventricular nucleus enhance the amplitude of both the positive and negative components of the evoked potential in the olfactory bulb. The pathway from the paraventricular nucleus to the olfactory bulb seems to exert a suppressive influence over the projection from the nucleus of the solitary tract to the olfactory bulb under these conditions.     

Trigeminal modulation of gustatory neurons in the nucleus of the solitary tract

Electrophysiological methods were used to investigate the effects of trigeminal nerve stimulation or transection on responses of single gustatory neurons in the nucleus of the solitary tract (NTS) to tastants (NaCl, sucrose, citric acid, monosodium glutamate) in pentobarbital-anesthetized rats. Unilateral transection of the lingual nerve, or the mandibular branch of the trigeminal nerve, resulted in significant reductions (by 21 and 29%, respectively; P<0.01) in tastant-evoked responses, with no further effect following bilateral transection. Electrical stimulation of the central cut end of the mandibular nerve directly excited nine of 14 gustatory NTS units. For these units, central mandibular stimulation facilitated the tastant-evoked responses in six, depressed responses in three, and had no effect in five. Facilitation of tastant-evoked responses peaked 4 min after mandibular stimulation and recovered within 8 min. Electrical stimulation of the peripheral cut end of the mandibular nerve significantly reduced tastant-evoked responses in nine other NTS units, with a maximal reduction at 4 min post-stimulation followed by recovery. Stimulation of the superior cervical sympathetic ganglion did not affect NTS tastant-evoked responses. These results suggest the presence of complex central modulation of NTS neurons by trigeminal afferents, as well as a peripheral depressant effect on gustatory processing possibly mediated via neuropeptide release from trigeminal nerve endings in the tongue.     

Artificial rearing alters development of the nucleus of the solitary tract

Previous studies have shown that damage induced to fungiform papillae of the anterior tongue at postnatal day 2 (P2) alters both pre- and postsynaptic development of gustatory recipient zones within the rostral nucleus of the solitary tract (NST). The present study was conducted to determine whether or not artificial rearing (AR) manipulations, which reduce normal orochemical stimulation during early postnatal development, would be sufficient to produce alterations in anatomical development of the rostral gustatory NST. Two groups of Long-Evans hooded rats were examined. One group received normal rearing with a lactating dam from birth to weaning (mother reared; MR). A second group of animals received artificial rearing via intragastric cannulae between the ages of P4 and P14, and were thereafter returned to lactating dams until the age of weaning (P21). Following weaning and maturation to adulthood (P49), the organization of gustatory afferent terminal fields in the NST was examined using fluorescent tracing procedures which permit the simultaneous visualization of gustatory afferent terminal fields arising from the seventh and ninth cranial nerves. Results show that AR manipulations between the ages of P4 and P14 produce alterations in development of gustatory afferent terminal fields in the NST that are essentially similar to those observed following early postnatal receptor damage. These results confirm previous suggestions that orochemical stimulation during a limited portion of rats' postnatal life is essential in inducing normal presynaptic development in the gustatory NST.     

Perinatal undernutrition increases meal size and neuronal activation of the nucleus of the solitary tract in response to feeding stimulation in adult rats

During the early periods of development, i.e., gestation and lactation, the influences of stimulus such as undernutrition can lead to several behavioural and morphofunctional damages to organs and systems in general, including pathways and structures that control energy balance and feeding behaviour. Although a large body of evidences have shown the effects of this stimulus on structures such as hypothalamus, only few studies have directed their attention to the long-term effects of undernutrition on the nucleus of the solitary tract (NTS). The aim of this study was to investigate the effects of early undernutrition on the NTS and control of food intake in adulthood. Male Wistar rats were divided into two groups according to the diet offered to the dams during gestation and lactation: control group (C, diet containing 17% casein) or isocaloric low-protein group (LP, diet containing 8% casein). On 35 or 180 days, we evaluated the rats’ body weight, food intake, behavioural satiety sequence and c-Fos protein expression in the NTS in response to food stimulus. Based on these assessments, it was found that perinatal undernutrition promoted an increase in food intake and the number of activated cells in rostral and, mainly, medial NTS in response to food stimulation in adulthood. These results indicated that the NTS is a structure particularly vulnerable to the influences of nutritional manipulation in the early stages of development with effects on food control in adulthood.     

Murine strain differences in taste responsivity and organization of the rostral nucleus of the solitary tract

Taste responsivity and organization of fungiform papillae, geniculate ganglion neurons and gustatory recipient zones of the nucleus of the solitary tract (NST) were examined in C57BL/6NCrlBR (C57) mice, BALB/c6NCrlBR (BALB/c) mice and CB6F1/CrlBr (CB6) mice, an F1 hybrid cross between BALB/c and C57 mice. Results from behavioral studies confirm that C57 and CB6 mice exhibit higher preferences to sucrose and lower preferences to NaCl, as compared to BALB/c mice. No strain differences were confirmed for aversion responses to citric acid or quinine HCl taste stimuli. Anatomical analyses show that the number and organization of fungiform papillae do not reliably differ between C57, BALB/c, and CB6 mice, nor do volumes of glossopharyngeal terminal fields in the NST. However, strain-specific differences exist in the number of neurons contained in the geniculate ganglion, volume of chorda tympani (CT) terminal fields in the rostral NST, and number of NST neurons contained in CT terminal fields. BALB/c and CB6 mice possess a greater number of geniculate ganglion neurons and larger CT terminal fields, as compared to C57 mice. However, strain differences in the number of geniculate ganglion neurons and terminal field volume are not obviously correlated with strain differences in gustatory responsivity. The only reliable relationship confirmed between taste responsivity and neuroanatomical organization of the rostral NST relates to the absolute number of neurons contained in CT terminal fields, and corresponding neuronal density within CT terminal fields. Chorda tympani terminal fields of C57 and CB6 mice contain an average of 379 neurons, whereas CT terminal fields of BALB/c mice contain an average of 531 neurons.(ABSTRACT TRUNCATED AT 250 WORDS)     

Organization of GABA and GABA-transaminase containing neurons in the gustatory zone of the nucleus of the solitary tract

Previous cytoarchitectural and electron micrographic studies have indicated that the gustatory zone of the nucleus of the solitary tract (NST) may contain local circuit neurons. It is known that neurons of the caudal "visceroceptive" NST contain GABA, glutamic acid decarboxylase (EC 4.1.1.15), and GABA-transaminase (GABA-T; 4-aminobutyrate: 2-oxoglutarate aminotransferase; EC 2.6.1.19). The present study was conducted to determine whether or not neurons in the gustatory zone of the NST of rat contain GABA and the principle degradative enzyme of GABA, GABA-T. Transganglionic transport of horseradish peroxidase (HRP) was used to identify chorda tympani (CT) nerve terminal fields. Immunohistochemical studies were combined with transport experiments to evaluate the organization of GABA immunoreactive neurons in CT terminal fields. Results show that GABA immunoreactive neurons and puncta are located within CT terminal fields. These neurons evince small ovoid morphologies resembling Golgi interneurons, and comprise an average of 18% of total neurons in CT terminal fields. Independent histochemical studies reveal that approximately 82% of GABA immunoreactive neurons within CT terminal fields exhibit GABA-T activity. Retrograde transport of HRP was used in additional studies to evaluate whether or not axons of putative GABAergic neurons project to the second-order central gustatory relay located in the caudal parabrachial nucleus (PBNc), to the caudal NST, or to regions surrounding the rostral or caudal NST. Combined studies indicate that GABA immunoreactive neurons in the gustatory NST do not project axons to the PBNc, to the caudal NST, or to regions adjacent to the rostral or caudal NST.(ABSTRACT TRUNCATED AT 250 WORDS)     

Organisation of the visceral solitary tract nucleus in the ferret as defined by the distribution of choline acetyltransferase and nerve growth factor receptor immunoreactivity

The cholinergic innervation of the visceral component of the nucleus of the solitary tract in the ferret was investigated by using choline acetyltransferase immunocytochemistry. The subdivisions of the ferret solitary tract nucleus as defined by Nissl architectonics were found to correspond to most of those previously assigned to the cat solitary tract nucleus. The subnuclei of the ferret solitary tract nucleus were also outlined by using immunohistochemical and histochemical methods to stain for nerve growth factor (NGF) receptor and acetylcholinesterase, respectively. In particular, the gelatinosus and interstitial subnuclei stain intensely for NGF receptor immunoreactivity and for acetylcholinesterase activity. Since abundant NGF receptor immunoreactivity is observed also in the nodose ganglion and in the solitary tract, it was assumed that the gelatinosus and the interstitial subnuclei represent the principal sites of termination of primary visceral afferents. A rich choline acetyltransferase-positive terminal axonal arborization was located in all of the subdivisions of the solitary tract nucleus but was found to be lacking in the gelatinosus and interstitial subnuclei. A small number of giant choline acetyltransferase-positive axon terminals was seen in the subnucleus gelatinosus but was assumed to be of doubtful functional significance because these terminals derive from only one or two large axons on each side of the brain. The weak cholinergic innervation of the gelatinosus and interstitial subnuclei and the stronger innervation of the other subnuclei suggest that acetylcholine has a more important role in the secondary rather than the primary processing of afferent visceral information. Because the distribution of acetylcholinesterase activity in the nucleus of the solitary tract matches that of the NGF receptor immunoreactivity rather than that of the cholinergic acetyltransferase immunoreactivity, a non-cholinergic function for acetylcholinesterase may dominate in the solitary tract nucleus of the ferret.     

Neuronal architecture of the nucleus of the solitary tract in the hamster

This study provides a scheme for subdividing the nucleus of the solitary tract of the hamster on the basis of cytoarchitectonic criteria, cell measurements, and neuronal cell types identified with the Golgi method. Reduced silver-stained sections revealed the feltlike neuropil that characterizes the nucleus of the solitary tract and were used to define the boundaries of the nuclear complex. Adjacent sections stained for Nissl substance revealed ten subdivisions, each with a characteristic neuronal architecture based on cell sizes, shapes, and packing density. Some subdivisions, e.g., the ventral and medial subnuclei, were identified at all rostrocaudal levels of the nuclear complex, while other subdivisions, e.g., the caudally located dorsolateral and ventrolateral subnuclei, were restricted to particular levels. Golgi preparations were counterstained for Nissl substance, thus allowing dendro- and cytoarchitecture to be compared directly. This material permitted the identification of a number of functionally relevant features of the neuronal constituents of the subdivisions. This approach, employing three cytological methods, has permitted the assembly of a detailed atlas of the nucleus of the solitary tract. The subdivisions of the present atlas have been compared with their likely counterparts identified in previous investigations of the mammalian nucleus of the solitary tract. In order to relate cytoarchitecture with primary afferent termination sites and to define the gustatory-recipient subdivisions, the differential relationships of the subdivisions with lingual afferent projections in the hamster are also described. The present parcellation scheme is intended to facilitate anatomical and physiological investigations of the types of circuits that compose the medullary gustatory and general visceral sensory systems.     

Spinal and vagal influences on the responses of rat solitary nucleus neurons to stimulation of uterus, cervix and vagina

Neurons in the rat solitary nucleus (NTS) respond to mechanical stimulation of the uterine horn, cervix and vagina [7]. The present study examined how these responses were affected by bilateral vagotomy and/or T10-T12 spinal transection for 12 single NTS neurons recorded in 12 rats anesthetized with halothane/nitrous oxide. Spinal transections eliminated all responses. Vagotomies eliminated responses only to uterine horn stimulation and either reduced the excitatory or enhanced the inhibitory responses to cervix and vaginal stimuli. These results suggest that NTS neuronal responses to cervix and vaginal stimulation depend upon input from the spinal dorsal horn and are facilitated by vagal input, whereas responses to uterine horn stimulation may require both spinal and vagal input.     

迷走神经刺激术对脑干孤束核部位GABA含量的影响

目的：探讨迷走神经刺激术（VNS）抗癫痫作用的机制是否为VNS引起孤束核部位GABA含量变化。方法：通过Waters高效液相色谱系统分析32只接受不同持续时间迷走神经刺激的大鼠脑干孤束核部位,主要兴奋及抑制性氨基酸含量的变化。结果：1小时持续刺激组孤束核部位GABA含量,较对照组升高且差异有显著意义。结论：迷走神经刺激术可能通过升高孤束核部位的GABA含量起到抗癫痫作用。     

Insular cortex projection to the nucleus of the solitary tract and brainstem visceromotor regions in the mouse

Anterograde transport of horseradish peroxidase (HRP) and HRP conjugated to wheat germ agglutinin (WGA-HRP) demonstrated a substantial, bilateral projection from insular cortex to the nucleus of the solitary tract (NTS) in the mouse. Injections that labeled the projection were restricted to the cortical sector homologous to taste-visceral cortex in the rat and label was antero- and retrogradely transported to several subcortical structures along ascending taste-visceral pathways. Multiple, small injections in this cortical region labeled fibers and terminals throughout the rostro-caudal extent of NTS. Small, single injection showed that the projection is topologically organized: Rostral points along the cortical strip project to rostral parts of NTS, intermediate points to the intermediate levels of NTS and caudal parts of the cortical field to caudal parts of NTS. In NTS the primary cranial nerve afferents distribute along a rostral to caudal gradient with the VII nerve rostral, the IX intermediate and the Xth caudal [2,6,37]. The present results indicate that the cortical sensory representation of these cranial nerve afferents reflects their topographic distribution in NTS. This suggests that there is an organized anatomical substrate by which the cerebral cortex may selectively influence the central processing of both gustatory and visceral afferent information in the primary CNS relay for these modalities. This insulofugal pathway also terminates in parts of NTS and additional medullary areas that contain preganglionic parasympathetic motoneurons. This appears to be the first anatomical demonstration of a projection from any part of the cerebral cortex to parasympathetic motor nuclei. The pathway provides a substantial direct channel by which higher cortical activity may modulate parasympathetic function.     

Substance P-containing trigeminal sensory neurons project to the nucleus of the solitary tract

Intense substance P-like immunoreactivity (SPLI) was identified in fiber bundles coursing between the spinal nucleus of the trigeminal nerve and the ventrolateral nucleus of the solitary tract at the level of the area postrema. These bundles were apparent only when tissue was stained for substance P immunoreactivity and were not visible in preparations treated with antisera to somatostatin or neurotensin. Following unilateral section of the trigeminal nerve, the SPLI-containing fiber bundles were absent ipsilateral to the nerve section. The fibers were absent bilaterally in rats which were previously injected with capsaicin. Unilateral removal of the nodose ganglion did not diminish the intensity or apparent number of SPLI fibers. These data indicate the presence of a trigeminosolitary projection which is composed of primary trigeminal sensory neurons containing substance P. The results provide an anatomical route by which substance P of trigeminal origin may modulate vagal or glossopharyngeal sensory information.