Rostral Nucleus Of The Solitary Tract Research Articles

Different taste map for amiloride sensitivity, response frequency, and threshold to NaCl in the rostral nucleus of the solitary tract in rats.

Studies on taste bud cells and brain stem relay nuclei suggest that alternative pathways convey information regarding different taste qualities. Building on the hypothesis that amiloride (epithelial Na channel antagonist)-sensitive neurons respond to palatable salt (low-concentration) and amiloride-insensitive neurons respond to aversive salt (high-concentration), we investigated the histological distribution of taste-sensitive neurons in the rostral nucleus of the solitary tract in rats and their NaCl and amiloride sensitivities. We recorded neuronal activity in extracellular single units using multi-barrel glass micropipettes and reconstructed their locations on the rostrocaudal and mediolateral axes. Seventy-three taste-sensitive neurons were categorized into the best-taste category. The amiloride sensitivities of the 31 neurons were examined for 0.1, 0.2, 0.4, and 0.8 M NaCl. The neuronal distribution of amiloride-sensitive neurons was located in the lateral region, while amiloride-insensitive neurons were located in the medial region. The amiloride-sensitive neurons responded to low salt concentrations, signaling the NaCl levels required by body fluids. Amiloride-insensitive neurons were silent at low salt concentrations but may function as warning signals for high salt concentrations. Low-threshold and/or high-response neurons were located in the rostrolateral region. In contrast, high-threshold and/or low-response neurons were located in the caudal-medial region.

A Novel Mechanism for T1R-Independent Taste Responses to Concentrated Sugars.

Recent findings from our laboratory demonstrated that the rostral nucleus of the solitary tract (rNST) retains some responsiveness to sugars in double-knock-out mice lacking either the T1R1+T1R3 (KO1+3) or T1R2+T1R3 (KO2+3) taste receptor heterodimers. Here, we extended these findings in the parabrachial nucleus (PBN) of male and female KO1+3 mice using warm stimuli to optimize sugar responses and employing additional concentrations and pharmacological agents to probe mechanisms. PBN T1R-independent sugar responses, including those to concentrated glucose, were more evident than in rNST. Similar to the NST, there were no "sugar-best" neurons in KO1+3 mice. Nevertheless, 1000 mm glucose activated nearly 55% of PBN neurons, with responses usually occurring in neurons that also displayed acid and amiloride-insensitive NaCl responses. In wild-type (WT) mice, concentrated sugars activated the same electrolyte-sensitive neurons but also "sugar-best" cells. Regardless of genotype, phlorizin, an inhibitor of the sodium-glucose co-transporter (SGLT), a component of a hypothesized alternate glucose-sensing mechanism, did not diminish responses to 1000 mm glucose. The efficacy of concentrated sugars for driving neurons broadly responsive to electrolytes implied an origin from Type III taste bud cells. To test this, we used the carbonic anhydrase (CA) inhibitor dorzolamide (DRZ), previously shown to inhibit amiloride-insensitive sodium responses arising from Type III taste bud cells. Dorzolamide had no effect on sugar-elicited responses in WT sugar-best PBN neurons but strongly suppressed them in WT and KO1+3 electrolyte-generalist neurons. These findings suggest a novel T1R-independent mechanism for hyperosmotic sugars, involving a CA-dependent mechanism in Type III taste bud cells.SIGNIFICANCE STATEMENT Since the discovery of Tas1r receptors for sugars and artificial sweeteners, evidence has accrued that mice lacking these receptors maintain some behavioral, physiological, and neural responsiveness to sugars. But the substrate(s) has remained elusive. Here, we recorded from parabrachial nucleus (PBN) taste neurons and identified T1R-independent responses to hyperosmotic sugars dependent on carbonic anhydrase (CA) and occurring primarily in neurons broadly responsive to NaCl and acid, implying an origin from Type III taste bud cells. The effectiveness of different sugars in driving these T1R-independent responses did not correlate with their efficacy in driving licking, suggesting they evoke a nonsweet sensation. Nevertheless, these salient responses are likely to comprise an adequate cue for learned preferences that occur in the absence of T1R receptors.

Characteristics and Impact of the rNST GABA Network on Neural and Behavioral Taste Responses.

The rostral nucleus of the solitary tract (rNST), the initial CNS site for processing gustatory information, is comprised of two major cell types, glutamatergic excitatory and GABAergic inhibitory neurons. Although many investigators have described taste responses of rNST neurons, the phenotypes of these cells were unknown. To directly compare the response characteristics of both inhibitory and noninhibitory neurons, we recorded from mice expressing Channelrhodopsin-2 (ChR2) under the control of GAD65, a synthetic enzyme for GABA. We observed that chemosensitive profiles of GABAergic taste neurons (G+TASTE) were similar to non-GABA taste neurons (G-TASTE) but had much lower response rates. We further observed a novel subpopulation of GABA cells located more ventrally in the nucleus that were unresponsive to taste stimulation (G+UNR), suggesting pathways for inhibition initiated by centrifugal sources. This preparation also allowed us to determine how optogenetic activation of the rNST GABA network impacted the taste responses of G-TASTE neurons. Activating rNST inhibitory circuitry suppressed gustatory responses of G-TASTE neurons across all qualities and chemosensitive types of neurons. Although the tuning curves of identified G-TASTE were modestly sharpened, the overall shape of response profiles and the ensemble pattern remained highly stable. These neurophysiological effects were consistent with the behavioral consequences of activating GAD65-expressing inhibitory neurons using DREADDs. In a brief-access licking task, concentration-response curves to both palatable (sucrose, maltrin) and unpalatable (quinine) stimuli were shifted to the right when GABA neurons were activated. Thus, the rNST GABAergic network is poised to modulate taste intensity across the qualitative and hedonic spectrum.

Regulation of Rostral Nucleus of the Solitary Tract Responses to Afferent Input by A-type K+ Current

Responses in the rostral (gustatory) nucleus of the solitary tract (rNST) are modified by synaptic interactions within the nucleus and the constitutive membrane properties of the neurons themselves. The potassium current IA is one potential source of modulation. In the caudal NST, projection neurons with IA show lower fidelity to afferent stimulation compared to cells without. We explored the role of an A-type K+ current (IA) in modulating the response to afferent stimulation and GABA-mediated inhibition in the rNST using whole cell patch clamp recording in transgenic mice that expressed channelrhodopsin (ChR2 H134R) in GABAergic neurons. The presence of IA was determined in current clamp and the response to electrical stimulation of afferent fibers in the solitary tract was assessed before and after treatment with the specific Kv4 channel blocker AmmTX3. Blocking IA significantly increased the response to afferent stimulation by 53%. Using dynamic clamp to create a synthetic IA conductance, we demonstrated a significant 14% decrease in responsiveness to afferent stimulation in cells lacking IA. Because IA reduced excitability and is hyperpolarization-sensitive, we examined whether IA contributed to the inhibition resulting from optogenetic release of GABA. Although blocking IA decreased the percent suppression induced by GABA, this effect was attributable to the increased responsiveness resulting from AmmTX3, not to a change in the absolute magnitude of suppression. We conclude that rNST responses to afferent input are regulated independently by IA and GABA.

Ultrastructure of Rat Rostral Nucleus of the Solitary Tract Terminals in the Parabrachial Nucleus and Medullary Reticular Formation.

Neurons in the rostral nucleus of the solitary tract (rNST) receive taste information from the tongue and relay it mainly to the parabrachial nucleus (PBN) and the medullary reticular formation (RF) through two functionally different neural circuits. To help understand how the information from the rNST neurons is transmitted within these brainstem relay nuclei in the taste pathway, we examined the terminals of the rNST neurons in the PBN and RF by use of anterograde horseradish peroxidase (HRP) labeling, postembedding immunogold staining for glutamate, serial section electron microscopy, and quantitative analysis. Most of the anterogradely labeled, glutamate-immunopositive axon terminals made a synaptic contact with only a single postsynaptic element in PBN and RF, suggesting that the sensory information from rNST neurons, at the individual terminal level, is not passed to multiple target cells. Labeled terminals were usually presynaptic to distal dendritic shafts in both target nuclei. However, the frequency of labeled terminals that contacted dendritic spines was significantly higher in the PBN than in the RF, and the frequency of labeled terminals that contacted somata or proximal dendrites was significantly higher in the RF than in the PBN. Labeled terminals receiving axoaxonic synapses, which are a morphological substrate for presynaptic modulation frequently found in primary sensory afferents, were not observed. These findings suggest that the sensory information from rNST neurons is processed in a relatively simple manner in both PBN and RF, but in a distinctly different manner in the PBN as opposed to the RF.

The Pattern of Fos-Like Immunoreactivity Expressed Within the Nucleus of the Solitary Tract Is Associated With Individual Variation in the Taste Quality of a Stimulus.

Outbred rats differ in their preference for the artificial sweetener sucralose. Psychophysical assessments have shown that the taste of sucralose is differentially generalized to either sucrose or a sucrose-quinine (QHCl) mixture in sucralose preferers (SP) and sucralose avoiders (SA), respectively. It remains to be determined if these differences in the psychophysical assessment of the taste of sucralose are due to an insensitivity to any bitter-like taste component of sucralose in SP or reduced sensitivity to a sweet-like component in SA that may mask any putative aversive side-taste in SP. Here, we exploited the proposed chemotopic organization of the rostral nucleus of the solitary tract (rNTS) to further parse out the root differences in the perception of the salient taste qualities of sucralose using Fos-like immunoreactivity (FLI) to approximate neural activation following intraoral delivery of sucrose, QHCl, and sucralose solutions in previously categorized SA and SP. First, we confirmed previous reports that the medial third of the NTS is primarily responsive to intraoral infusions of the bitter taste stimulus QHCl while sucrose produces a more diffuse pattern of FLI. Upon comparing the FLI generated by intraoral sucralose, we found that the pattern in SA was indistinguishable from that of QHCl while SP displayed a pattern of FLI more representative of a sucrose-QHCl mixture. We conclude that SA, relative to SP, may be less sensitive to the sucrose-like properties of sucralose and that an enhanced sensitivity to these sucrose-like qualities may mask a QHCl-like quality in SP.

Enhancing GABAergic Tone in the Rostral Nucleus of the Solitary Tract Reconfigures Sensorimotor Neural Activity.

Recent work has shown that most cells in the rostral, gustatory portion of the nucleus tractus solitarius (rNTS) in awake, freely licking rats show lick-related firing. However, the relationship between taste-related and lick-related activity in rNTS remains unclear. Here, we tested whether GABA-derived inhibitory activity regulates the balance of lick- and taste-driven neuronal activity. Combinatorial viral tools were used to restrict the expression of channelrhodopsin 2-enhanced yellow fluorescent protein to GAD1+ GABAergic neurons. Viral infusions were bilateral in rNTS. A fiber-optic fiber attached to a bundle of drivable microwires was later implanted into the rNTS. After recovery, water-deprived rats were presented with taste stimuli in an experimental chamber. Trials were five consecutive taste licks [NaCl, KCl, NH4Cl, sucrose, monosodium glutamate/inosine-5'-monophosphate, citric acid, quinine, or artificial saliva (AS)] separated by five AS rinse licks on a variable ratio 5 schedule. Each taste lick triggered a 1 s train of laser light (25 Hz; 473 nm; 8-10 mW) in a random half of the trials. In all, 113 cells were recorded in the rNTS, 50 cells responded to one or more taste stimuli without GABA enhancement. Selective changes in response magnitude (spike count) within cells shifted across-unit patterns but preserved interstimulus relationships. Cells where enhanced GABAergic tone increased lick coherence conveyed more information distinguishing basic taste qualities and different salts than other cells. In addition, GABA activation significantly amplified the amount of information that discriminated palatable versus unpalatable tastants. By dynamically regulating lick coherence and remodeling the across-unit response patterns to taste, enhancing GABAergic tone in rNTS reconfigures the neural activity reflecting sensation and movement.

Kv4 channel expression and kinetics in GABAergic and non-GABAergic rNST neurons.

The rostral nucleus of the solitary tract (rNST) serves as the first central relay in the gustatory system. In addition to synaptic interactions, central processing is also influenced by the ion channel composition of individual neurons. For example, voltage-gated K+ channels such as outward K+ current (IA) can modify the integrative properties of neurons. IA currents are prevalent in rNST projection cells but are also found to a lesser extent in GABAergic interneurons. However, characterization of the kinetic properties of IA, the molecular basis of these currents, as well as the consequences of IA on spiking properties of identified rNST cells is lacking. Here, we show that IA in rNST GABAergic (G+) and non-GABAergic (G-) neurons share a common molecular basis. In both cell types, there was a reduction in IA following treatment with the specific Kv4 channel blocker AmmTx3. However, the kinetics of activation and inactivation of IA in the two cell types were different with G- neurons having significantly more negative half-maximal activation and inactivation values. Likewise, under current clamp, G- cells had significantly longer delays to spike initiation in response to a depolarizing stimulus preceded by a hyperpolarizing prepulse. Computational modeling and dynamic clamp suggest that differences in the activation half-maximum may account for the differences in delay. We further observed evidence for a window current under both voltage clamp and current clamp protocols. We speculate that the location of Kv4.3 channels on dendrites, together with a window current for IA at rest, serves to regulate excitatory afferent inputs.NEW & NOTEWORTHY Here, we demonstrate that the transient outward K+ current IA occurs in both GABAergic and non-GABAergic neurons via Kv4.3 channels in the rostral (gustatory) solitary nucleus. Although found in both cell types, IA is more prevalent in non-GABAergic cells; a larger conductance at more negative potentials leads to a greater impact on spike initiation compared with GABAergic neurons. An IA window current further suggests that IA can regulate excitatory afferent input to the nucleus.

Two neuronal groups for NaCl with differential taste response properties and topographical distributions in the rat parabrachial nucleus.

It is crucial for animals to discriminate between palatable (safe) and aversive (toxic) tastants. The mechanisms underlying neuronal discrimination of taste stimuli remain unclear. We examined relations between taste response properties (spike counts, response duration, and coefficient of variation [CV]) and location of taste‐sensitive neurons in the pontine parabrachial nucleus (PBN). Extracellular single units’ activity in the PBN of Wistar rats was recorded using multibarrel glass micropipettes under urethane anesthesia. Forty taste‐sensitive neurons were classified as NaCl (N)‐best (n = 15), NaCl/HCl (NH)‐best (n = 14), HCl (H)‐best (n = 8), and sucrose (S)‐best (n = 3) neurons. The net response to NaCl (15.2 ± 2.3 spikes/s) among the N‐best neurons was significantly larger than that among the NH‐best (4.5 ± 0.8 spikes/s) neurons. The response duration (4.5 ± 0.2 s) of the N‐best neurons to NaCl was significantly longer than that of the NH‐best (2.2 ± 0.3 s) neurons. These differences in the spike counts and the response durations between the two neuronal types in the PBN were similar to that previously reported in the rostral nucleus of the solitary tract (rNST). The CVs in the N‐best and the NH‐best neurons were significantly smaller in the PBN than those in the rNST. Histologically, most N‐best neurons (12/13, 92%) were localized to the medial region, while NH‐best neurons (11/13, 85%) were primarily found within the brachium conjunctivum. These results suggest that NaCl‐specific taste information is transmitted by two distinct neuronal groups (N‐best and NH‐best), with different taste properties and locations within rNST to PBN tractography. Future studies on the higher order nuclei for taste could reveal more palatable and aversive taste pathways.

Astrocytic response to neural injury is larger during development than in adulthood and is not predicated upon the presence of microglia

While contributions of microglia and astrocytes are regularly studied in various injury models, how these contributions differ across development remains less clear. We previously demonstrated developmental differences in microglial profiles across development in an injury model of the gustatory system. Nerves of the rat gustatory system have limited capacity to regenerate if injured during neonatal ages but show robust recovery if the injury occurs in adulthood. Using this developmentally disparate model of regenerative capacity, we quantified microglia and astrocytes in the rostral nucleus of the solitary tract (rNTS) following transection of the gustatory chorda tympani nerve (CTX) of neonatal and adult rats. We found that neonatal CTX induced an attenuated microglia response but a larger astrocyte response compared to adult CTX. To elucidate the interplay between the microglia and astrocyte responses in the CTX model, we used our novel intraperitoneal injection protocol for the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia in the neonatal and adult rat brain prior to and after CTX. PLX5622 depleted microglia by 80–90% within 3 days of treatment, which increased to > 90% by 7 days. After 14 days of PLX5622 treatment, microglia were depleted by > 96% in both neonates and adults while preserving baseline astrocyte quantity. Microglia depletion eliminated the adult astrocyte response to CTX, while the neonatal astrocyte response after injury remained robust. Our results show injecting PLX5622 is a viable means to deplete microglia in neonatal and adult rats and suggest developmentally distinct mechanisms for astrogliosis following neural injury.

Heterogeneity of neuronal responses in the nucleus of the solitary tract suggests sensorimotor integration in the neural code for taste.

Theories of neural coding in the taste system typically rely exclusively on data gleaned from taste-responsive cells. However, even in the nucleus tractus solitarius (NTS), the first stage of central processing, neurons with taste selectivity coexist with neurons whose activity is linked to motor behavior related to ingestion. We recorded from a large ( n = 324) sample of NTS neurons recorded in awake rats, examining both their taste selectivity and the association of their activity with licking. All subjects were implanted with a bundle of microelectrodes aimed at the NTS and allowed to recover. Following moderate water deprivation, rats were placed in an experimental chamber where tastants or artificial saliva (AS) were delivered from a lick spout. Electrophysiological responses were recorded, and waveforms from single cells were isolated offline. Results showed that only a minority of NTS cells responded to taste stimuli as determined by conventional firing-rate measures. In contrast, most cells, including taste-responsive cells, tracked the lick pattern, as evidenced by significant lick coherence in the 5- to 7-Hz range. Several quantitative measures of taste selectivity and lick relatedness showed that the population formed a continuum, ranging from cells dominated by taste responses to those dominated by lick relatedness. Moreover, even neurons whose responses were highly correlated with lick activity could convey substantial information about taste quality. In all, data point to a blurred boundary between taste-dominated and lick-related cells in NTS, suggesting that information from the taste of food and from the movements it evokes are seamlessly integrated. NEW & NOTEWORTHY Neurons in the rostral nucleus of the solitary tract (NTS) are known to encode information about taste. However, recordings from awake rats reveal that only a minority of NTS cells respond exclusively to taste stimuli. The majority of neurons track behaviors associated with food consumption, and even strongly lick-related neurons could convey information about taste quality. These findings suggest that the NTS integrates information from both taste and behavior to identify food.

Neurons with diverse phenotypes project from the caudal to the rostral nucleus of the solitary tract.

The nucleus of the solitary tract is a potential site for taste-visceral interactions. Connections from the caudal, visceral area of the nucleus (cNST) to the rostral, gustatory zone (rNST) have been described, but the phenotype of cells giving rise to the projection(s) and their distribution among rNST subdivisions are unknown. To determine these characteristics of the intrasolitary pathway, we injected pan-neuronal and floxed AAV viruses into the cNST of mice expressing cre in glutamatergic, GABAergic, or catecholaminergic neurons. Particular attention was paid to the terminal field distribution in rNST subdivisions by simultaneously visualizing P2X2 localized to gustatory afferent terminals. All three phenotypically identified pathways terminated in rNST, with the density greatest for glutamatergic and sparsest for catecholaminergic projections, observations supported by retrograde tracing. Interestingly, cNST neurons had more prominent projections to rNST regions medial and ventral to P2X2 staining, i.e., the medial and ventral subdivisions. In addition, GABAergic neurons projected robustly to the lateral subdivision and adjacent parts of the reticular formation and spinal trigeminal nucleus. Although cNST neurons also projected to the P2X2-rich central subdivision, such projections were sparser. These findings suggest that cNST visceral signals exert stronger excitatory and inhibitory influences on local autonomic and reflex pathways associated with the medial and ventral subdivisions compared to weaker modulation of ascending pathways arising from the central subdivision and ultimately destined for the forebrain.

A computational analysis of signal fidelity in the rostral nucleus of the solitary tract.

Neurons in the rostral nucleus of the solitary tract (rNST) convey taste information to both local circuits and pathways destined for forebrain structures. This nucleus is more than a simple relay, however, because rNST neurons differ in response rates and tuning curves relative to primary afferent fibers. To systematically study the impact of convergence and inhibition on firing frequency and breadth of tuning (BOT) in rNST, we constructed a mathematical model of its two major cell types: projection neurons and inhibitory neurons. First, we fit a conductance-based neuronal model to data derived from whole cell patch-clamp recordings of inhibitory and noninhibitory neurons in a mouse expressing Venus under the control of the VGAT promoter. We then used in vivo chorda tympani (CT) taste responses as afferent input to modeled neurons and assessed how the degree and type of convergence influenced model cell output frequency and BOT for comparison with in vivo gustatory responses from the rNST. Finally, we assessed how presynaptic and postsynaptic inhibition impacted model cell output. The results of our simulations demonstrated 1) increasing numbers of convergent afferents (2-10) result in a proportional increase in best-stimulus firing frequency but only a modest increase in BOT, 2) convergence of afferent input selected from the same best-stimulus class of CT afferents produced a better fit to real data from the rNST compared with convergence of randomly selected afferent input, and 3) inhibition narrowed the BOT to more realistically model the in vivo rNST data. NEW & NOTEWORTHY Using a combination of in vivo and in vitro neurophysiology together with conductance-based modeling, we show how patterns of convergence and inhibition interact in the rostral (gustatory) solitary nucleus to maintain signal fidelity. Although increasing convergence led to a systematic increase in firing frequency, tuning specificity was maintained with a pattern of afferent inputs sharing the best-stimulus compared with random inputs. Tonic inhibition further enhanced response fidelity.

Microglia density decreases in the rat rostral nucleus of the solitary tract across development and increases in an age-dependent manner following denervation

Microglia are critical for developmental pruning and immune response to injury, and are implicated in facilitating neural plasticity. The rodent gustatory system is highly plastic, particularly during development, and outcomes following nerve injury are more severe in developing animals. The mechanisms underlying developmental plasticity in the taste system are largely unknown, making microglia an attractive candidate. To better elucidate microglia’s role in the taste system, we examined these cells in the rostral nucleus of the solitary tract (rNTS) during normal development and following transection of the chorda tympani taste nerve (CTX). Rats aged 5, 10, 25, or 50days received unilateral CTX or no surgery and were sacrificed four days later. Brain tissue was stained for Iba1 or CD68, and both the density and morphology of microglia were assessed on the intact and transected sides of the rNTS. We found that the intact rNTS of neonatal rats (9–14days) shows a high density of microglia, most of which appear reactive. By 29days of age, microglia density significantly decreased to levels not significantly different from adults and microglia morphology had matured, with most cells appearing ramified. CD68-negative microglia density increased following CTX and was most pronounced for juvenile and adult rats. Our results show that microglia density is highest during times of normal gustatory afferent pruning. Furthermore, the quantity of the microglia response is higher in the mature system than in neonates. These findings link increased microglia presence with instances of normal developmental and injury induced alterations in the rNTS.

Immunocytochemical organization and sour taste activation in the rostral nucleus of the solitary tract of mice.

Sensory inputs from the oropharynx terminate in both the trigeminal brainstem complex and the rostral part of the nucleus of the solitary tract (nTS). Taste information is conveyed via the facial and glossopharyngeal nerves, while general mucosal innervation is carried by the trigeminal and glossopharyngeal nerves. In contrast, the caudal nTS receives general visceral information largely from the vagus nerve. Although the caudal nTS shows clear morphological and molecularly delimited subdivisions, the rostral part does not. Thus, linking taste-induced patterns of activity to morphological subdivisions in the nTS is challenging. To test whether molecularly defined features of the rostral nTS correlate with patterns of taste-induced activity, we combined immunohistochemistry for markers of various visceral afferent and efferent systems with c-Fos-based activity maps generated by stimulation with a sour tastant, 30 mM citric acid. We further dissociated taste-related activity from activity arising from acid-sensitive general mucosal innervation by comparing acid-evoked c-Fos in wild-type and "taste blind" P2X2 /P2X3 double knockout (P2X-dbl KO) mice. In wild-type mice, citric acid stimulation evoked significant c-Fos activation in the central part of the rostral nTS-activity that was largely absent in the P2X-dbl KO mice. P2X-dbl KO mice, like wild-type mice, did exhibit acid-induced c-Fos activity in the dorsomedial trigeminal brainstem nucleus situated laterally adjacent to the rostral nTS. This dorsomedial nucleus also showed substantial innervation by trigeminal nerve fibers immunoreactive for calcitonin gene-related peptide (CGRP), a marker for polymodal nociceptors, suggesting that trigeminal general mucosal innervation carries information about acids in the oral cavity. J. Comp. Neurol. 525:271-290, 2017. © 2016 Wiley Periodicals, Inc.

Inhibitory modulation of optogenetically identified neuron subtypes in the rostral solitary nucleus.

Inhibition is presumed to play an important role in gustatory processing in the rostral nucleus of the solitary tract (rNST). One source of inhibition, GABA, is abundant within the nucleus and comes both from local, intrasolitary sources and from outside the nucleus. In addition to the receptor-mediated effects of GABA on rNST neurons, the hyperpolarization-sensitive currents, Ih and IA, have the potential to further modulate afferent signals. To elucidate the effects of GABAergic modulation on solitary tract (ST)-evoked responses in phenotypically defined rNST neurons and to define the presence of IA and Ih in the same cells, we combined in vitro recording and optogenetics in a transgenic mouse model. This mouse expresses channelrhodopsin 2 (ChR2) in GAD65-expressing GABAergic neurons throughout the rNST. GABA positive (GABA+) neurons differed from GABA negative (GABA-) neurons in their response to membrane depolarization and ST stimulation. GABA+ neurons had lower thresholds to direct membrane depolarization compared with GABA- neurons, but GABA- neurons responded more faithfully to ST stimulation. Both IA and Ih were present in subsets of GABA+ and GABA- neurons. Interestingly, GABA+ neurons with Ih were more responsive to afferent stimulation than inhibitory neurons devoid of these currents, whereas GABA- neurons with IA were more subject to inhibitory modulation. These results suggest that the voltage-gated channels underlying IA and Ih play an important role in modulating rNST output through a circuit of feedforward inhibition.

Brainstem metabotropic glutamate receptors reduce food intake and activate dorsal pontine and medullar structures after peripheral bacterial lipopolysaccharide administration

During infection-induced inflammation food intake is reduced. Vagal and brainstem pathways are important both in feeding regulation and immune-to-brain communication. Glutamate is released by vagal afferent terminals in the nucleus of the solitary tract and by its neurons projecting to the parabrachial nuclei. We therefore studied the role of brainstem glutamate receptors in spontaneous food intake of healthy animals and during sickness-associated hypophagia after peripheral administration of bacterial lipopolysaccharides or interleukin-1beta. Brainstem group I and II metabotropic, but not ionotropic, glutamate receptor antagonism increased food intake both in saline- and lipopolysaccharide-treated rats. In these animals, expression of the cellular activation marker c-Fos in the lateral parabrachial nuclei and lipopolysaccharide-induced activation of the nucleus of the solitary tract rostral to the area postrema were suppressed. Group I metabotropic glutamate receptors did not colocalize with c-Fos or neurons regulating gastric function in these structures. Group I metabotropic glutamate receptors were, however, found on raphé magnus neurons that were part of the brainstem circuit innervating the stomach and on trigeminal and hypoglossal motor neurons. In conclusion, our findings show that brainstem metabotropic glutamate receptors reduce food intake and activate the lateral parabrachial nuclei as well as the rostral nucleus of the solitary tract after peripheral bacterial lipopolysaccharide administration. They also provide insight into potential group I metabotropic glutamate receptor-dependent brainstem circuits mediating these effects.

Proceedings of the 2015 ASPEN Research Workshop-Taste Signaling.

This article summarizes research findings from 6 experts in the field of taste and feeding that were presented at the 2015 American Society for Parenteral and Enteral Nutrition Research Workshop. The theme was focused on the interaction of taste signals with those of a postingestive origin and how this contributes to regulation of food intake through both physiological and learning processes. Gastric bypass results in exceptional loss of fat mass and increases in circulating levels of key gut peptides, some of which are also expressed along with their cognate receptors in taste buds. Changes in taste preference and food selection in both bariatric surgery patients and rodent models have been reported. Accordingly, the effects of this surgery on taste-related behavior were examined. The conservation of receptor and peptide signaling mechanisms in gustatory and extraoral tissues was discussed in the context of taste responsiveness and the regulation of metabolism. New findings detailing the features of neural circuits between the caudal nucleus of the solitary tract (NST), receiving visceral input from the vagus nerve, and the rostral NST, receiving taste input, were discussed, as was how early life experience with taste stimuli and learned associations between flavor and postoral consequences of nutrients can exert potent and long-lasting effects on feeding.

Activation of microglia in the nucleus of the solitary tract by inferior alveolar nerve injury

There are reports on hypoesthesia and anesthesia in taste sensation persisting for several months or even years after dental anesthesia, pulpectomy and tooth extraction. Taste disorders following dental treatments are usually attributed to peripheral injury of taste (the chorda tympani) nerve fibers running with the lingual nerve fibers near the mandibular molars. 2 However, taste impairment in patients who received treatment of the maxillary anterior teeth cannot be explained by peripheral nerve injury, because the chorda tympani nerve fibers neither innervate nor run through the anterior surgical site. The inferior alveolar nerve, a branch of the trigeminal nerve, innervates dental pulp and periodontal tissue. Peripheral fibers of the inferior alveolar nerve are injured upon dental treatments such as pulpectomy and tooth extraction. In particular, there is a risk that the nerve trunk is crushed or torn upon extraction of mandibular third molars, because the IAN runs in the mandibular canal in close proximity to the molar root tips. Following peripheral nerve injury, glial cells respond at the primary nerve terminals in the central nervous system. In animal models of inferior alveolar nerve injury, microglia appear in the trigeminal spinal subnucleus caudalis and spinal dorsal horn and release substances that affect neuronal excitability. Inhibition of microglial activation suppresses development of pain hypersensitivity, suggesting that active microglia cause abnormal pain sensation by alteration of excitability in neurons processing somatosensory information. The inferior alveolar nerve also terminates in synapses with neurons of the rostral nucleus of the solitary tract where taste afferents terminate. In light of these observations, inferior alveolar nerve injury may activate microglia in the rostral nucleus of the solitary tract and the active microglia may alter neuronal excitability of the NST neurons that process taste information conveyed by taste afferents resulting in Activation of microglia in the nucleus of the solitary tract by inferior alveolar nerve injury

Consumption of a High Fat Diet Inhibits Sympathetic Outflow to Brown Adipose Tissue via Activation of Neurons in the Rostral Nucleus of the Solitary Tract

The recognition of significant depots of BAT in adult humans, the inverse correlation between active BAT and obesity, and the ability of white adipose depots to be “converted” to a more “brown-like...