Solitary Tract Nucleus Neurons Research Articles

Norepinephrinergic and nitroxidergic neurons of vasomotor nuclei in hypertensive rats.

The distributions of norepinephrinergic and nitroxidergic neurons in solitary tract nucleus, locus coeruleus, and in the small-celled and gigantocellular reticular nuclei were examined in sham-operated and experimental Wistar rats with induced renovascular hypertension. In control rats, the greatest population of norepinephrinergic cells was revealed in the projections of locus coeruleus and reticular gigantocellular nuclei, while the larger number of nitroxidergic neurons were observed in the solitary tract and the small-celled nuclei. During renovascular hypertension, the earliest and the most pronounced changes in luminescence intensity and the number of nitroxidergic neurons were observed in the solitary tract nucleus, while the changes in locus coeruleus were minimal. The significant changes in similar parameters of norepinephrinergic neurons were documented only in reticular gigantocellular nucleus and locus coeruleus, but they were delayed and less pronounced in comparison with the changes of nitroxidergic neurons.

Cannabinoid 1 and transient receptor potential vanilloid 1 receptors discretely modulate evoked glutamate separately from spontaneous glutamate transmission.

Action potentials trigger synaptic terminals to synchronously release vesicles, but some vesicles release spontaneously. G-protein-coupled receptors (GPCRs) can modulate both of these processes. At cranial primary afferent terminals, the GPCR cannabinoid 1 (CB1) is often coexpressed with transient receptor potential vanilloid 1 (TRPV1), a nonselective cation channel present on most afferents. Here we tested whether CB1 activation modulates synchronous, action potential-evoked (eEPSCs) and/or spontaneous (sEPSCs) EPSCs at solitary tract nucleus neurons. In rat horizontal brainstem slices, activation of solitary tract (ST) primary afferents generated ST-eEPSCs that were rapidly and reversibly inhibited from most afferents by activation of CB1 with arachidonyl-2'-chloroethylamide (ACEA) or WIN 55,212-2 [R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl) methanone monomethanesulfonate]. The CB1 antagonist/inverse agonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide] blocked these responses. Despite profound depression of ST-eEPSCs during CB1 activation, sEPSCs in these same neurons were unaltered. Changes in temperature changed sEPSC frequency only from TRPV1(+) afferents (i.e., thermal sEPSC responses only occurred in TRPV1(+) afferents). CB1 activation failed to alter these thermal sEPSC responses. However, the endogenous arachidonate metabolite N-arachidonyldopamine (NADA) promiscuously activated both CB1 and TRPV1 receptors. NADA inhibited ST-eEPSCs while simultaneously increasing sEPSC frequency, and thermally triggered sEPSC increases in neurons with TRPV1(+) afferents. We found no evidence for CB1/TRPV1 interactions suggesting independent regulation of two separate vesicle pools. Together, these data demonstrate that action potential-evoked synchronous glutamate release is modulated separately from TRPV1-mediated glutamate release despite coexistence in the same central terminations. This two-pool arrangement allows independent and opposite modulation of glutamate release by single lipid metabolites.

Responses of Solitary Tract Nucleus Neurons to Nociceptive Stimuli of the Large Intestine in Rats

Immunohistochemical and neurophysiological experiments on rats were performed to study the responses of solitary tract nucleus neurons to nociceptive stimulation of the large intestine and to identify the role of nitric oxide in these processes. Nociceptive distension of the colorectal part of the intestine was found to induce significant increases in the level of expression of c-fos proteins, mainly in the medial, commissural, parvocellular, and dorsomedial subnuclei of the solitary tract. Neurophysiological experiments showed that non-painful colorectal distension induced mild excitatory responses in cells in these structures, these being exclusively of the phasic type. Painful stimulation of the intestine was accompanied by significant increases in the responses of these neurons and activation of neurons with tonic responses. Blockade of neuronal NO synthase led to significant decreases in neuron responses to nociceptive distension of the intestine and the number of cells with tonic responses. It is suggested that neurons with NO-dependent tonic responses may be directly associated with the transmission of pain information from the large intestine.

Focal synaptic recruitment to second order solitary tract nucleus neurons with minimal electrical shocks

Second order neurons in the solitary tract (ST) nucleus (NTS) receive vagal primary afferent as well as input from other central neurons. Less is known about non‐ST inputs. In horizontal brainstem slices, ST activation evoked low jitter EPSCs (σ of latency; 101±6 μs) identifying 2nd order NTS neurons (n=38), ST‐EPSCs (amplitude 213±25 pA) never failed. Using a fine glass focal electrode, minimal electrical shocks activated local inputs that did not interact with ST‐EPSCs (failed collisions). Probing the surface of the slice 10–400 μm from voltage clamped cells, focal shocks at minimal intensities evoked mostly EPSCs (30/38 cells). Focal‐EPSCs were unitary, all‐or‐none (amplitude 176±22 pA; jitter 102±5 μs; 0% failure rate) and blocked by the non‐NMDA antagonist NBQX, indicating that minimal focal shocks selectively recruit monosynaptic glutamatergic inputs. High focal intensities evoked complex PSCs consistent with recruitment of multiple inputs, many exhibiting high jitter (>200 μs), indicating polysynaptic pathways. In NBQX, focal stimulation (5/38 cells) recruited unitary, low‐jitter (138±22 μs) IPSCs with highly variable amplitudes (184±49 pA) and frequent failures (47±16%). GABAA receptor antagonist SR95531 blocked IPSCs. This approach allows for selective recruitment of converging inputs to NTS neurons and indicates that GABA release has lower release probability than afferent glutamate.

Optical tracking of phenotypically diverse individual synapses on solitary tract nucleus neurons

The solitary tract nucleus (NTS) is the termination site for cranial visceral afferents–peripheral primary afferent neurons which differ by phenotype (e.g. myelinated and unmyelinated). These afferents have very uniform glutamate release properties calculated by variance mean analysis. In the present study, we optical measured the inter-terminal release properties across individual boutons by assessing vesicle membrane turnover with the dye FM1–43. Single neurons were mechanically micro-harvested from medial NTS without enzyme treatment. The TRPV1 agonist capsaicin (CAP, 100 nM) was used to identify afferent, CAP-sensitive terminals arising from unmyelinated afferents. Isolated NTS neurons retained both glutamatergic and inhibitory terminals that generated EPSCs and IPSCs, respectively. Visible puncta on the neurons were stained positively with monoclonal antibody for synaptophysin, a presynaptic marker. Elevating extracellular K + concentration to 10 mM increased synaptic release measured at individual terminals by FM1–43. Within single neurons, CAP destained some but not other individual terminals. FM1–43 positive terminals that were resistant to CAP could be destained with K + solution. Individual terminals responded to depolarization with similar vesicle turnover kinetics. Thus, vesicular release was relatively homogenous across individual release sites. Surprisingly, conventionally high K + concentrations (> 50 mM) produced erratic synaptic responses and at 90 mM K + overt neuron swelling—results that suggest precautions about assuming consistent K + responses in all neurons. The present work demonstrates remarkably uniform glutamate release between individual unmyelinated terminals and suggests that the homogeneous EPSC release properties of solitary tract afferents result from highly uniform release properties across multiple contacts on NTS neurons.

Presynaptic actions of propofol enhance inhibitory synaptic transmission in isolated solitary tract nucleus neurons

General anesthetics variably enhance inhibitory synaptic transmission that relies on (-aminobutyric acid (GABA) and GABA A receptor function with distinct differences across brain regions. Activation of “extra-synaptic” GABA A receptors produces a tonic current considered the most sensitive target for general anesthetics, particularly in forebrain neurons. To evaluate the contribution of poor drug access to neurons in slices, we tested the intravenous anesthetic propofol in mechanically isolated neurons from the solitary tract nucleus (NTS). Setting chloride concentrations to E Cl = − 29 mV made GABA currents inward at holding potentials of − 60 mV. Propofol triggered pronounced but slowly-developing tonic currents that reversed with 5 min washing. Effective concentrations in isolated cells were lower than in slices and propofol enhanced phasic IPSCs more potently than tonic currents (1 μM increased phasic decay-time constant vs. > 3 μM tonic currents). Propofol increased IPSC frequency (> 3 μM), a presynaptic action. Bicuculline blocked all propofol actions. Gabazine blocked only phasic IPSCs. IPSCs persisted in TTX and/or cadmium but these agents prevented propofol-induced increases in IPSC frequency. Furosemide (> 1 mM) reversibly blocked propofol-evoked IPSC frequency changes without altering waveforms. We conclude that presynaptic actions of propofol depend on a depolarizing chloride gradient across presynaptic inhibitory terminals. Our results in isolated neurons indicate that propofol pharmacokinetics intrinsically trigger the tonic currents slowly and the time course is not related to slow permeation or delivery. Unlike forebrain, phasic NTS GABA A receptors are more sensitive to propofol than tonic receptors but that presynaptic GABA A receptor mechanisms regulate GABA release.

Characteristics of Rostral Solitary Tract Nucleus Neurons With Identified Afferent Connections That Project to the Parabrachial Nucleus in Rats

Afferent information derived from oral chemoreceptors is transmitted to second-order neurons in the rostral solitary tract nucleus (rNST) and then relayed to other CNS locations responsible for complex sensory and motor behaviors. Here we investigate the characteristics of rNST neurons sending information rostrally to the parabrachial nucleus (PBN). Afferent connections to these rNST-PBN projection neurons were identified by anterograde labeling of the chorda tympani (CT), glossopharyngeal (IX), and lingual (LV) nerves. We used voltage- and current-clamp recordings in brain slices to characterize the expression of both the transient A-type potassium current, IKA and the hyperpolarization-activated inward current, Ih, important determinants of neuronal repetitive discharge characteristics. The majority of rNST-PBN neurons express IKA, and these IKA-expressing neurons predominate in CT and IX terminal fields but were expressed in approximately half of the neurons in the LV field. rNST-PBN neurons expressing Ih were evenly distributed among CT, IX and LV terminal fields. However, expression patterns of IKA and Ih differed among CT, IX, and LV fields. IKA-expressing neurons frequently coexpress Ih in CT and IX terminal fields, whereas neurons in LV terminal field often express only Ih. After GABAA receptor block all rNST-PBN neurons responded to afferent stimulation with all-or-none excitatory synaptic responses. rNST-PBN neurons had either multipolar or elongate morphologies and were distributed throughout the rNST, but multipolar neurons were more often encountered in CT and IX terminal fields. No correlation was found between the biophysical and morphological characteristics of the rNST-PBN projection neurons in each terminal field.

Organization and Properties of GABAergic Neurons in Solitary Tract Nucleus (NTS)

Cranial visceral afferents enter the brain at the solitary tract nucleus (NTS). GABAergic neurons are scattered throughout the NTS, but their relation to solitary tract (ST) afferent pathways is imprecisely known. We hypothesized that most GABAergic NTS neurons would be connected only indirectly to the ST. We identified GABAergic neurons in brain stem horizontal slices using transgenic mice in which enhanced green fluorescent protein (EGFP) expression was linked to glutamic acid decarboxylase expression (GAD(+)). Finely graded electrical shocks to ST recruit ST-synchronized synaptic events with all-or-none thresholds and individual waveforms did not change with greater suprathreshold intensities--evidence consistent with initiation by single afferent axons. Most (approximately 70%) GAD(+) neurons received ST-evoked excitatory postsynaptic currents (EPSCs) that had minimally variant latencies (jitter, SD of latency <200 micros) and waveforms consistent with single, direct ST connections (i.e., monosynaptic). Increasing stimulus intensity evoked additional ST-synchronized synaptic responses with jitters >200 micros including inhibitory postsynaptic currents (IPSCs), indicating indirect connections (polysynaptic). Shocks of suprathreshold intensity delivered adjacent (50-300 microm) to the ST failed to excite non-ST inputs to second-order neurons, suggesting a paucity of axons passing near to ST that connected to these neurons. Despite expectations, we found similar ST synaptic patterns in GAD(+) and unlabeled neurons. Generally, ST information that arrived indirectly had small amplitudes (EPSCs and IPSCs) and frequency-dependent failures that reached >50% for IPSCs to bursts of stimuli. This ST afferent pathway organization is strongly use-dependent--a property that may tune signal propagation within and beyond NTS.

Intestinal electric stimulation modulates neuronal activity in the nucleus of the solitary tract in rats

Intestinal electric stimulation (IES) has been shown to produce an inhibitory effect on gastric motility and secretion. The possible central mechanism of this entero-gastric inhibitory effect induced by IES is unknown. The objective of this study was to evaluate the effects of various IES on the activity of neurons in nucleus tractus solitarii (NTS). We examined the extracellular neuronal activity in NTS of the medulla in pentobarbital anesthetized, paralyzed, ventilated male adult rats. The aortic depressor, superior laryngeal, and carotid sinus nerves were crushed or sectioned bilaterally to avoid neuronal responses in NTS to cardiovascular baroreceptors. After NTS neurons with gastric input were identified, responses of single neurons in NTS to IES were determined. IES with different parameters was performed via a pair of platinum electrodes sutured onto the serosal surface of the duodenum 2 cm below the pylorus. IES with different parameters activated 39–72% of the solitary tract nucleus neurons responsive to gastric distension. Moreover, we demonstrated that IES activated the neuronal activity in NTS, which was stimulation energy dependent. The modulatory effect of IES on the central neurons receiving vagal inputs may contribute to the neural mechanisms of IES therapy for the treatment of patients with obesity and gastrointestinal motility disorders.

The role of the septal nuclei in controlling the activity of vagosensitive neurons in the solitary tract nucleus in cats.

Studies on cats anesthetized with a mixture of Nembutal and chloralose were performed to study the descending influences of single, paired, and frequent stimulation of the lateral septal nucleus (LSN) and bed nucleus of the stria terminalis (BNST) on the activity of viscerosensory neurons in the solitary tract nucleus, identified by stimulation of the cervical part of the vagus nerve. Of 70 units recorded in the solitary tract nucleus, 50 were identified as primary and secondary input vagus neurons. Single stimuli applied to the septal nuclei induced initial excitation in 30% (15 units) of vagus neurons. The latent period of these responses was 5-25 msec. Presentation of paired stimuli showed that loss of the ability to respond to the second stimulus occurred at interstimulus intervals of 10-200 and sometimes 300 msec. A total of 34% (17 units) of solitary tract nucleus neurons showed tonic changes in spontaneous activity in response to rhythmic stimulation. Increasing the stimulation frequency to 10-20 Hz led to very different changes in the spontaneous rhythm, i.e., wave-like changes (decreases and increases in frequency, secondary suppression) or complete inhibition, sometimes lasting up to 10 sec after stimulation ended. A small number of units (five) showed a blocking effect of septal discharges on the visceral afferent input in conditions of paired stimulation. These results lead to the conclusion that the LSN and BNST are involved in modulating the activity of bulbar viscerosensory neurons, though their influences are mediated mainly via oligo- and polysynaptic pathways via other limbic structures (hypothalamus, amygdala).

Angiotensin potentiates excitatory sensory synaptic transmission to medial solitary tract nucleus neurons.

Femtomole doses of angiotensin (ANG) II microinjected into nucleus tractus solitarii (nTS) decrease blood pressure and heart rate, mimicking activation of the baroreflex, whereas higher doses depress this reflex. ANG II might generate cardioinhibitory responses by augmenting cardiovascular afferent synaptic transmission onto nTS neurons. Intracellular recordings were obtained from 99 dorsal medial nTS region neurons in rat medulla horizontal slices to investigate whether ANG II modulated short-latency excitatory postsynaptic potentials (EPSPs) evoked by solitary tract (TS) stimulation. ANG II (200 fmol) increased TS-evoked EPSP amplitudes 20-200% with minimal membrane depolarization in 12 neurons excited by ANG II and glutamate, but not substance P (group A). Blockade of non-N-methyl-d-aspartate receptors eliminated TS-evoked EPSPs and responses to ANG II. ANG II did not alter TS-evoked EPSPs in 14 other neurons depolarized substantially by ANG II and substance P (group B). ANG II appeared to selectively augment presynaptic sensory transmission in one class of nTS neurons but had only postsynaptic effects on another group of cells. Thus ANG II is likely to modulate cardiovascular function by more than one nTS neuronal pathway.

Medial prefrontal cortex depressor response: role of the solitary tract nucleus in the rat

The depressor response elicited by unilateral low intensity electrical stimulation of the rat ventral medial prefrontal cortex may be mediated by a connection with the solitary tract nucleus. We tested this hypothesis by (i) examining the influence of medial prefrontal cortex stimulation on the induction of Fos-like immunoreactivity in neurons in the medulla oblongata, and (ii) by testing the effect of inhibition of solitary tract nucleus neurons on the medial prefrontal cortex stimulation-evoked depressor response. Depressor responses (>10 mmHg) were elicited by electrical stimulation of the medial prefrontal cortex every minute for 1 h (`Stimulated' group). Control animals were treated identically but did not receive electrical stimulation (`Unstimulated' group). Neurons exhibiting Fos-like immunoreactivity were abundant at the stimulation site which included the infralimbic area, and dorsal peduncular cortex. Medullary Fos-like immunoreactivity observed in the `Stimulated' and `Unstimulated' groups exceeded levels observed in untreated rats and was detected in the rostral, caudal and intermediate areas of the ventrolateral medulla, and the commissural, intermediate, medial and lateral regions of the solitary tract nucleus, as well as the medial vestibular nucleus, and the dorsal motor nucleus of the vagus. The number of neurons displaying Fos-like immunoreactivity in the ipsilateral solitary tract nucleus and caudal ventrolateral medulla of the `Stimulated' group was found to be significantly elevated compared to the contralateral side ( P<0.05), and the `Unstimulated' group bilaterally. Inhibition of solitary tract nucleus neurons using bilateral injections of the GABA A receptor agonist muscimol (44 pmol/25 nl) inhibited the sympathetic vasomotor baroreflex and attenuated the depressor and sympathoinhibitory response to medial prefrontal cortex stimulation by 62% and 65%, respectively. These findings suggest that the projection from the medial prefrontal cortex to the solitary tract nucleus is excitatory and support the hypothesis that the depressor response elicited by medial prefrontal cortex stimulation is mediated, in part, by a cortico-solitary projection which activates the intramedullary baroreflex pathway.

Responses of solitary tract nucleus neurons to taste and mechanical stimulations of the oral cavity in decerebrate rats.

Physiological characteristics of 45 taste and 15 mechanoreceptive units were examined in the solitary tract nucleus (NTS) of rats decerebrated at the pre- or midcollicular level, and compared with previous findings in the intact rat. The rostro-caudal extent of the area, where taste and mechanoreceptive neurons were recorded, was almost the same in the decerebrate rat as that in intact rat. The spontaneous discharge rate was significantly lower in the decerebrate rat than in the intact rat. The taste profile of the NTS units in decerebrate rats was quite different from that in intact rats; significant decreases in correlation coefficients were found between certain pairs of taste stimuli and spontaneous discharge rate, e.g. NaCl-quinine, sucrose-quinine. A large number of taste (18 of 31) and mechanoreceptive (12 of 15) units examined had receptive fields (RFs) on the palate, and four taste and two mechanoreceptive units on the circumvallate area. This contrasts with the findings in the intact rat. Some taste (n = 1) and mechanoreceptive units (n = 2) had large RFs. Taste units with different RF locations showed different taste profiles. Acute i.v. injection of amobarbital sodium affected only the response magnitude of taste units, suggesting that most of the differences between intact and decerebrate rats might be caused by decerebration. The present findings indicate that neural structures above the pre- or midcollicular level have tonic inhibitory or facilitatory effects on the response properties of NTS taste units.

Taste relay neurons in the solitary tract nucleus of rats

Impulse discharges of 82 solitary tract nucleus neurons, in response to natural stimulation of the oral cavity, were recorded. Among these, 52 units responded to taste stimuli and 30 units to mechanical stimuli. When the caudal end of the parabrachial nucleus was stimulated ipsilaterally, 16 taste and 5 mechanoreceptive units were excited antidromically. Response types of rostrally projecting taste neurons were not different from those of the non-projecting ones, and both of them were similar to that of the chorda tympani.

Projection to parabrachial nucleus of solitary tract nucleus neurons activated by tongue afferents in rats.

Eighty-eight solitary tract nucleus neurons of anesthetized rats were recorded extracellularly, and investigated by the spike responses to stimulation of the three tongue afferents and the ipsilateral parabrachial nucleus. Among them, 21 neurons were found to receive antidromic invasions from the parabrachial nucleus. Moreover, they were mostly excited by stimulation of the nerves innervating the anterior tongue.

Synaptic processing of taste-quality information in the nucleus tractus solitarius of the rate.

Synaptic processing of taste-quality information in the nucleus tractus solitarius of the rate.