Susan P. Travers

Ascending and descending projections from the rostral nucleus of the solitary tract originate from separate neuronal populations

Anterograde studies have shown that neurons within the rostral (gustatory) nucleus of the solitary tract project to the parabrachial nucleus, as well as to sites within the medulla including the reticular formation and caudal nucleus of the solitary tract. In order to determine the degree to which the same neurons contribute to both projections, injections of retrograde tracers were made simultaneously into both the parabrachial nuclei and medullary reticular formation of the rat. Only a small proportion of neurons were double labeled. Consistent with studies in hamster, labeled neurons projecting to the parabrachial nuclei in rat consisted of both stellate and elongate neurons, concentrated within the central subdivision of the rostral nucleus of the solitary tract. Injections into the medullary reticular formation also labeled both stellate and elongate neurons but these were concentrated in the ventral subdivision of the nucleus. The results of the present study demonstrate that different populations of neurons in the nucleus of the solitary tract contribute to ascending and descending pathways. This suggest a possible functional specialization within the nucleus of the solitary tract for those neurons whose output eventually reaches the forebrain compared to those neurons with local connections.

The Representation of Taste Quality in the Mammalian Nervous System

The process by which the mammalian nervous system represents the features of a sapid stimulus that lead to a perception of taste quality has long been controversial. The labeled-line (sparse coding) view differs from the across-neuron pattern (ensemble) counterpoint in proposing that activity in a given class of neurons is necessary and sufficient to generate a specific taste perception. This article critically reviews molecular, electro-physiological, and behavioral findings that bear on the issue. In the peripheral gustatory system, the authors conclude that most qualities appear to be signaled by labeled lines; however, elements of both types of coding characterize signaling of sodium salts. Given the heterogeneity of neuronal tuning functions in the brain, the central coding mechanism is less clear. Both sparse coding and neuronal ensemble models remain viable possibilities. Furthermore, temporal patterns of discharge could contribute additional information. Ultimately, until specific classes of neurons can be selectively manipulated and perceptual consequences assessed, it will be difficult to go beyond mere correlation and conclusively discern the validity of these coding models.

Topographic organization of Fos-like immunoreactivity in the rostral nucleus of the solitary tract evoked by gustatory stimulation with sucrose and quinine

Fos immunohistochemistry was used to elucidate the pattern of activation elicited by two qualitatively and hedonically distinct taste stimuli, sucrose and quinine, within the first-order gustatory relay, the rostral division of the nucleus of the solitary tract. Compared to unstimulated controls, both sucrose and quinine elicited significant increases in Fos-like immunoreactivity in the rostral central subnucleus, the region of the rostral solitary nucleus that receives the densest primary afferent input. Within the rostral central subnucleus, neurons that exhibited Fos-like immunoreactivity following quinine stimulation were concentrated medially, but neurons that exhibited Fos-like immunoreactivity following sucrose stimulation were distributed more evenly along the mediolateral axis. Despite their differential distribution, sucrose- and quinine-activated neurons also demonstrated notable intermingling. Further, the chemotopic arrangement was only partially consistent with what would be predicted if chemotopy was merely an outcome of orotopy. Our results suggest that a rough chemotopy characterizes the organization of taste responses in the nucleus of the solitary tract, and that the topographic pattern of taste afferent terminations in this nucleus is related to their chemosensitivity as well as to their peripheral spatial distribution.

Neurotransmitter phenotypes of intermediate zone reticular formation projections to the motor trigeminal and hypoglossal nuclei in the rat

Numerous studies suggest an essential role for the intermediate (IRt) and parvocellular (PCRt) reticular formation (RF) in consummatory ingestive responses. Although the IRt and PCRt contain a large proportion of neurons with projections to the oromotor nuclei, these areas of the RF are heterogeneous with respect to neurotransmitter phenotypes. Glutamatergic, GABAergic, cholinergic, and nitrergic neurons are all found in the PCRt and IRt, but the projections of neurons with these phenotypes to the motor trigeminal (mV) and hypoglossal nucleus (mXII) has not been fully evaluated. In the present study, after small injections of Fluorogold (FG) into mV and mXII, sections were processed immunohistochemically to detect retrogradely labeled FG neurons in combination with the synthetic enzymes for nitric oxide (nitric oxide synthase) or acetylcholine (choline acetyltransferase) or in situ hybridization for the synthetic enzyme for GABA (GAD65/67) or the brainstem vesicular transporter for glutamate (VGLUT2). In three additional cases, FG injections were made into one motor nucleus and cholera toxin (subunit b) injected in the other to determine the presence of dual projection neurons. Premotor neurons to mXII (pre‐mXII) were highly concentrated in the IRt. In contrast, there were nearly equal proportions of premotor‐trigeminal neurons (pre‐mV) in the IRt and PCRt. A high proportion of pre‐oromotor neurons were positive for VGLUT2 (pre‐mXII: 68%; pre‐mV: 53%) but GABAergic projections were differentially distributed with a greater projection to mV (25%) compared to mXII (8%). Significant populations of cholinergic and nitrergic neurons overlapped pre‐oromotor neurons, but there was sparse double‐labeling (<10%). The IRt also contained a high proportion of neurons that projected to both mV and MXII. These different classes of premotor neurons in the IRt and PCRt provide a substrate for the rhythmic activation of lingual and masticatory muscles. J. Comp. Neurol. 487:28–47, 2005.

Glossopharyngeal Nerve Transection Eliminates Quinine-Stimulated Fos-Like Immunoreactivity in the Nucleus of the Solitary Tract: Implications for a Functional Topography of Gustatory Nerve Input in Rats

The relationship between specific gustatory nerve activity and central patterns of taste-evoked neuronal activation is poorly understood. To address this issue within the first central synaptic relay in the gustatory system, we examined the distribution of neurons in the nucleus of the solitary tract (NST) activated by the intraoral infusion of quinine using Fos immunohistochemistry in rats with bilateral transection of the chorda tympani (CTX), bilateral transection of the glossopharyngeal nerve (GLX), or combined neurotomy (DBLX). Compared with nonstimulated and water-stimulated controls, quinine evoked significantly more Fos-like-immunoreactive (FLI) neurons across the rostrocaudal extent of the gustatory NST (gNST), especially within its dorsomedial portion (subfield 5). Although the somatosensory aspects of fluid stimulation contributed to the observed increase in FLI neurons, the elevated number and spatial distribution of FLI neurons in response to quinine were remarkably distinguishable from those in response to water. GLX and DBLX produced a dramatic attenuation of quinine-evoked FLI neurons and a shift in their spatial distribution such that their number and pattern were indiscernable from those observed in water-stimulated controls. Although CTX had no effect on the number of quinine-evoked FLI neurons within subfield 5 at intermediate levels of the gNST, it produced intermediate effects elsewhere; yet, the spatial distribution of the quinine-evoked FLI neurons was not altered by CTX. These findings suggest that the GL provides input to all FLI neurons responsive to quinine, however, some degree of convergence with CT input apparently occurs in this subpopulation of neurons. Although the role of these FLI neurons in taste-guided behavioral responses to quinine remains speculative, their possible function in oromotor reflex control is considered.

Gustatory and tactile stimulation of the posterior tongue activate overlapping but distinctive regions within the nucleus of the solitary tract

Both the gustatory and somatosensory systems provide necessary sensory input for the initiation and control of oromotor behaviors. Behavioral studies indicate that somatosensory input from the posterior tongue (PT) is important in initiating swallowing, whereas PT taste input is particularly important in gustatory rejection reflexes. However, there have been few studies of the central representation of PT gustatory or tactile responses. In the present study, electrophysiological multi-unit recording techniques were used to map the location of PT-mediated taste and tactile responses in the nucleus of the solitary tract (NST) of the rat. A stimulation technique that allows taste stimuli to be introduced directly and specifically into the papillae trenches was used to optimally activate PT taste receptors located within the circumvallate (CV) and foliate (FOL) papillae. The results demonstrated that non-PT responsive sites dominated the rostral half of the rostral division of NST (rNST), while PT-responsive sites dominated the caudal half. Some PT-responsive sites extended into the caudal NST. Both gustatory and tactile stimuli were effective at 28% of PT-responsive locations (taste-tactile sites), whereas at the remaining locations, only tactile stimulation was effective (tactile-only sites). Although these two types of PT-responsive sites exhibited some anatomical overlap, their distributions were distinctive, with taste-tactile sites restricted medially and the laterally located tactile-only sites offset caudally. On the other hand, responses arising from stimulation of the CV and FOL exhibited no anatomical organization, i.e., responses to stimulation of both papillae were coexistensive. On average, of the four tastants used (0.01 M Na saccharin, 0.3 M NaCl, 0.01 M quinine hydrochloride, 0.03 M HCl), HCl was the most effective stimulus for both the CV and FOL. The present results delimit the regions of the NST that provide a substrate for the gustatory and somatosensory limbs of PT-mediated oromotor reflexes.

Extranuclear projections of rNST neurons expressing gustatory–elicited Fos

Previous studies have demonstrated that gustatory stimulation evokes expression of the immediate–early gene, c–fos in the rostral division of the nucleus of the solitary tract (rNST) (Harrer and Travers [1996] Brain Res. 711:125–137; DiNardo and Travers [1997] J. Neurosci. 17:3826–3839; King et al. [1999] J. Neurosci. 19:3107–3121). The present investigation further defined the phenotype of those neurons by determining their projections, by using immunohistochemistry for the Fos protein and retrograde tracing with Fluoro–Gold. Tracer injections were made into the two major extranuclear targets of rNST, the parabrachial nucleus ( PBN ) and medullary reticular formation ( RF ). These structures are thought to play differential roles in higher–order discriminative and homeostatic ( PBN ) versus reflexive function ( RF ). After PBN injections, ∼18% of the Fos–like immunoreactive (FLI) neurons were double–labeled; after RF injections the proportion was 9%. Because only a minority of FLI neurons appear to project to targets outside NST, this suggests that most of these cells have local, intranuclear projections. Comparable proportions of cells were double–labeled after sucrose or quinine, consistent with roles for both tastants in higher–order and reflexive function. On the other hand, regardless of stimulus, twice as many FLI neurons projected to the PBN as to the RF . This could suggest that more FLI neurons contribute to functions mediated by the ascending pathway. However, the results of a recent study prompted a different hypothesis: Because glossopharyngeal nerve section similarly devastates quinine–induced FLI and oral rejection but leaves discriminative function unimpaired, it was proposed that FLI neurons are more important in driving oral motor behavior than discrimination (King et al. [1999] J. Neurosci. 19:3107–3121). A plausible hypothesis for reconciling this apparent discrepancy is that many FLI neurons make local projections in rNST, that in turn give rise to RF connections. J. Comp. Neurol. 427:124–138, 2000.

Bitter-Responsive Gustatory Neurons in the Rat Parabrachial Nucleus

Bitterness is a distinctive taste sensation, but central coding for this quality remains enigmatic. Although some receptor cells and peripheral fibers are selectively responsive to bitter ligands, central bitter responses are most typical in broadly tuned neurons. Recently we reported more specifically tuned bitter-best cells (B-best) in the nucleus of the solitary tract (NST). Most had glossopharyngeal receptive fields and few projected to the parabrachial nucleus (PBN), suggesting a role in reflexes. To determine their potential contribution to other functions, the present study investigated whether B-best neurons occur further centrally. Responses from 90 PBN neurons were recorded from anesthetized rats. Stimulation with four bitter tastants (quinine, denatonium, propylthiouracil, cycloheximide) and sweet, umami, salty, and sour ligands revealed a substantial proportion of B-best cells (22%). Receptive fields for B-best NST neurons were overwhelmingly foliate in origin, but in PBN, about half received foliate and nasoincisor duct input. Despite convergence, most B-best PBN neurons were as selectively tuned as their medullary counterparts and response profiles were reliable. Regardless of intensity, cycloheximide did not activate broadly tuned acid/sodium (AN) neurons but did elicit robust responses in B-best cells. However, stronger quinine activated AN neurons and concentrated electrolytes stimulated B-best cells, suggesting that B-best neurons might contribute to higher-order functions such as taste quality coding but work in conjunction with other cell types to unambiguously signal bitter-tasting ligands. In this ensemble, B-best neurons would help discriminate sour from bitter stimuli, whereas AN neurons might be more important in differentiating ionic from nonionic bitter stimuli.

Taste receptors on the anterior tongue and nasoincisor ducts of rats contribute synergistically to behavioral responses to sucrose

In four groups of rats, behavioral responsiveness to sucrose was tested by allowing them to lick solutions in a computer-controlled gustometer (10-s trials; 0.01-1.0 M). Rats with cautery lesions of the nasoincisor ducts (NID) behaved no differently from controls. After bilateral chorda tympani nerve (CT) section, which removes taste input from the anterior tongue (AT), rats demonstrated a marginal attenuation in their responsiveness to sucrose. Combining the two lesions, however, had the greatest effect on the concentration-response curve. By shifting the curve to the right and lowering the asymptotic licking rate, the combined lesion reduced the area under the curve by one third. The effects of the combined treatments were larger than would be predicted from the sum of either one alone. This presumably reflects the central convergence of primary afferent axons from the NID and AT. Neurophysiological data have demonstrated such convergence within the nucleus of the solitary tract.

Suppression of third ventricular NPY-elicited feeding following medullary reticular formation infusions of muscimol.

The appetitive component of feeding is controlled by forebrain substrates, but the consummatory behaviors of licking, mastication, and swallowing are organized in the brainstem. The target of forebrain appetitive signals is unclear but likely includes regions of the medullary reticular formation (RF). This study was undertaken to determine the necessity of different RF regions for mastication induced by a descending appetitive signal. We measured solid food intake in response to third ventricular (3V) infusions of the orexigenic peptide neuropeptide Y 3-36 in awake, freely moving rats and determined whether focal RF infusions of the GABAA agonist muscimol suppressed eating. RF infusions were centered in either the lateral tegmental field, comprising the intermediate (IRt) and parvocellular (PCRt) RF, or in the nucleus gigantocellularis (Gi). Infusions of NPY 3-36 (5 microg/5 microl) into 3V significantly increased feeding of solid food over a 90-min period compared with the noninfused condition (4.3 g +/- 0.56 vs. 0.57 g +/- 0.57, p < .001). NPY 3-36-induced food intake was suppressed (1.7 g +/- 0.48) by simultaneous infusions of muscimol (0.6 mM/100 nl) into the IRt/PCRt (p < .01). Coincident with the decrease in feeding was a decrease in the amplitude of anterior digastric muscle contractions in response to intraoral sucrose infusions. In contrast, infusions of muscimol into Gi had no discernible effect on food intake or EMG amplitude. These data suggest that the IRt/PCRt is essential for forebrain-initiated mastication, but that the Gi is not a necessary link in this pathway.