Chemical Senses Vol. 30 No. suppl 1 © Oxford University
Press 2005; all rights reserved
Reflex Topography in the Nucleus of the Solitary Tract
The Ohio State University, College of Dentistry, Section of Oral Biology, 305 W. 12th Avenue, Columbus, OH 43210, USA
Correspondence to be sent to: Susan Travers, e-mail: travers.3{at}osu.edu
Key words: chemotopy, Fos, gapes, rejection, taste
 |
Introduction and methods |
|---|
 Top Introduction and methods Results and DiscussionAcknowledgementsReferences |
|---|
The diverse influences that taste signals exert on organisms give rise to a complex anatomy. The first-order taste relay, the rostral nucleus of the solitary tract (rNST), is the origin for local reflex pathways, and ascending pathways important in motivational and cognitive functions. The intrinsic organization of the nucleus is characterized by topographic specialization. Cells with different morphologies, projections, receptive fields and responsiveness to taste versus oral tactile stimuli are preferentially distributed. Notably, however, a map of quality has not been evident.
Taste stimuli encompass not only food-related chemicals that promote ingestion, but
also potentially toxic, often bitter, molecules that provide powerful signals to prevent
intake. Based on Fos immunohistochemistry, we argue that there is a topographic
representation of the bitter taste quality in rNST but one restricted to a subpopulation
of neurons with a special function. In the Fos studies summarized below, taste stimuli
(~7 ml/30 min) were infused through intraoral cannule into awake rats and their brains
processed using immunohistochemical techniques to detect the Fos protein. Control groups
were unstimulated and/or water-stimulated animals (see
Harrer and Travers, 1996
;
Travers and Hu, 2000;
Travers, 2002;
Chan et al., 2004).
|
Results and Discussion |
|---|
|
TopIntroduction and methodsResults and DiscussionAcknowledgementsReferences |
|---|
The initial study compared two tastants with opposite effects on ingestion: sucrose (1.0 M) and QHCl (3 mM). There was a differential distribution of Fos-like immunoreactive (FLI) neurons. Sucrose elicited FLI more evenly distributed along the mediolateral axis, compared to QHCl, which elicited FLI more restricted medially (Harrer and Travers, 1996
). Subsequent studies indicated that
the QHCl pattern was maintained across concentration (Travers, 2002) and different bitter stimuli (Chan et al., 2004). Additional data
indicated that citric acid (30 and 100 mM) also evoked a different FLI distribution than
QHCl (Travers, 2002;
Chan et al., 2004) but one
similar to sucrose. With the NST divided into mediolateral thirds, there were two FLI
patterns. Bitter stimuli evoked more FLI in the medial third of NST but sucrose, citric
acid, water or no stimulation all were associated with maximal FLI in the middle
subfield, with fewer Fos-positive neurons in the control groups. Thus the topographic
organization does not extend to all qualities, since citric acid and sucrose evoke
different sensations (‘sour’ and ‘sweet’) but similar FLI
distributions. Neither does it represent a simple preferred-avoided axis, since both QHCl
and citric acid are avoided in preference tests but elicit distinctive FLI.
Important insights were gained by studying another standard tastant. Surprisingly,
0.3 M NaCl, a potent stimulus, elicited FLI indistinguishable from water (Travers, 2002), demonstrating that not all activated taste
neurons are revealed by Fos. This further implies that although QHCl, sucrose and citric
acid are effective in eliciting Fos, the observed neurons may represent only a subset of
the activated populations. As such, it is possible that these neurons have specialized
functions. The clearest hypothesis derives from FLI neurons observed after bitter
stimulation.
Decerebrate rats display FLI in the typical pattern following QHCl stimulation
(Travers et al., 1999), but
IXth nerve transection greatly reduces the number of FLI neurons and obliterates their
distinctive medial distribution (King et
al., 1999). Behaviorally, decerebration obliterates voluntary QHCl
behaviors, but the reflex rejection response, described by
Grill and Norgren (1978), are
virtually untouched. In contrast, IXth nerve transection spares voluntary QHCl avoidance
(Pfaffmann, 1952) and performance in
discriminative tasks (St. John and Spector,
1998), but reflex rejection is severely compromised (Travers et al., 1987). The persistence of
QHCl-elicited FLI and oral rejection after decerebration, in contrast to the blunting of
Fos and this behavior after IXth nerve section, is consistent with the hypothesis that
neurons expressing Fos after QHCl stimulation are a subset of bitter-activated neurons
with a critical role in reflex rejection (King
et al., 1999). Furthermore, since a particular NST region, the
medial third, preferentially expresses Fos after bitter stimulation, we suggest the
reflex has a topographic representation in NST. This hypothesis is also consistent with
the relative effectiveness of various stimuli in eliciting reflex rejection, including
one exception to the unique nature of the ‘bitter’ pattern. In two cases, an
error resulted in infusion of a very high concentration of NaCl (~1.7 M), and revealed
robust FLI with a medial, ‘bitter-like’ topography. Reliable behavioral
observations on one case indicated clearly that rejection had occurred. This salt
concentration constitutes a trigeminal, as well as a gustatory stimulus, but
significantly, capsaicin (100 µM), a potent trigeminal non-gustatory
stimulus, yielded sparse FLI in rNST without a preferential medial distribution and only
minimal gaping (DiNardo, 1997). Thus,
FLI in the medial NST is best associated with stimuli that evoke the gustatory rejection
reflex.
Reflex rejection is not synonymous with gapes, but gapes are the most salient component of the rat rejection response and the most often quantified. Recent unpublished observations in the mouse demonstrate that intraoral QHCl evokes few gapes, and instead chin rubs and suppression of licking characterize rejection in this species. Nevertheless, QHCl evoked FLI in the mouse NST that closely resembled that in the rat in its cardinal feature, a pronounced increase in the medial third of NST. These results emphasize that the medial NST is not specifically associated with gapes, but the entire sequence of gustatory rejection.
Aside from the correlation between FLI and behavior, another approach to defining the
function of these neurons is to establish their projections. Dual-retrograde tracing
suggests that mostly separate populations of rNST cells project to the parabrachial
nucleus (PBN) and the reticular formation (RF) subjacent to NST (Halsell et al., 1996). Functional inactivation
demonstrates that the RF is necessary for gustatory-elicited oromotor responses,
including reflex rejection (Chen et al.,
2001). If cells expressing Fos after bitter stimulation contribute
preferentially to oromotor rejection, a greater proportion might project to the RF than
PBN. However, double-labeling with Fos immunohistochemistry combined with retrograde
tracing revealed instead that approximately twice as many gustatory-activated FLI cells
projected to PBN. In fact, only about one-third of the Fos cells contacted either target,
suggesting that a substantial proportion are interneurons.
These anatomical results suggest that Fos-activated neurons in the medial subfield
trigger oromotor rejection via more complex circuits. A number of pathways could act in
parallel. Although older data suggested that PBN lesions had little impact on gustatory
oromotor reflexes (Flynn et al.,
1991), two recent studies (Matsuo
et al., 2001;
King et al., 2004) suggest
that lesions or glutaminergic blockade in PBN suppress gapes. Thus an
NST–PBN–RF projection is likely involved in oromotor rejection. In addition,
a possible local pathway is for FLI cells in the medial subfield to make intranuclear
connections to other NST cells that do not express FLI but that do project to the RF. The
lack of Fos might mean that the higher-order NST neurons do not have the requisite
intracellular signaling pathways, or that intranuclear connections are primarily
inhibitory. Preliminary data (n = 1) with in-situ hybridization for GAD65
does suggest that some NST cells that express FLI after QHCl stimulation are inhibitory.
A second possibility is that the connections between the NST and RF occur over very short
distances, making them difficult to study precisely with extracellular tracing methods.
Indeed a striking feature of the FLI elicited after bitter stimulation in awake animals
is that Fos-positive cells extend in a continuous swath from the medial NST ventrally and
laterally into the RF, suggestive of a multi-stage short connection pathway. Within this
distribution, we have preliminary evidence for NST-RF communication via extension of RF
dendrites into NST. With double-staining for NADPHd, a marker for nitric oxide synthase,
Fos-activated nitrergic cells in the dorsal RF immediately subjacent to NST were observed
to send dendrites toward and sometimes into the overlying nucleus (Travers, 2000).
In summary, these data provide evidence for a novel type of topography in the first-order gustatory nucleus. The critical variable underlying this topography appears related to a specific gustatory behavior– reflex rejection of potentially toxic foodstuffs. To the extent that these stimuli are most closely tied to bitter taste, this is a type of chemotopy. However, because reflex rejection is just one function of bitter tastants, it is more accurate to label this as a reflex topography. The suggested circuit by which these neurons exert their effects are speculative. However, the fact that we can functionally define neurons implicated in a specific behavior should help to resolve the critical connections and their mechanisms.
|
Acknowledgements |
|---|
|
TopIntroduction and methodsResults and DiscussionAcknowledgementsReferences |
|---|
Supported by DC00416 to S.P.T. and DC00417 to J.B.T.
|
References |
|---|
|
TopIntroduction and methodsResults and DiscussionAcknowledgementsReferences |
|---|
Chan, C.Y., Yoo, J.E. and Travers, S.P. (2004) Diverse bitter stimuli elicit highly similar patterns of Fos-like immunoreactivity in the nucleus of the solitary tract. Chem. Senses, 29, 573–581.
Chen, Z., Travers, S.P. and Travers, J.B. (2001) Muscimol infusions in the brain stem reticular formation reversibly block ingestion in the awake rat. Am. J. Physiol. Regul. Integr. Comp. Physiol., 280, R1085–1094.
DiNardo, L.A. (1997) Identification of specific medullary reticular formation areas involved in consummatory oromotor reflex control in the rat using Fos immunohistochemistry. Doctoral dissertation, Department of Psychology, Ohio State University, Columbus, OH, p. 173.
Flynn, F.W., Grill, H.J., Schulkin, J. and Norgren, R. (1991) Central gustatory lesions: II. Effects on sodium appetite, taste aversion learning, and feeding behaviors. Behav. Neurosci., 105, 944–954.[CrossRef][Web of Science][Medline]
Grill, H.J. and Norgren, R. (1978) The taste reactivity test. II. Mimetic responses to gustatory stimuli in chronic thalamic and chronic decerebrate rats. Brain Res., 143, 281–297.[CrossRef][Web of Science][Medline]
Halsell, C.B., Travers, S.P. and Travers, J.B. (1996) Ascending and descending projections from the rostral nucleus of the solitary tract originate from separate neuronal populations. Neuroscience, 72, 185–197.[CrossRef][Web of Science][Medline]
Harrer, M.I. and Travers, S.P. (1996) Topographic organization of Fos-like immunoreactivity in the rostral nucleus of the solitary tract evoked by gustatory stimulation with sucrose and quinine. Brain Res., 711, 125–137.[CrossRef][Web of Science][Medline]
King, C.T., Travers, S.P., Rowland, N.E, Garcea, M. and Spector, A.C. (1999) 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. J. Neurosci., 19, 3107–3121.
King, M.S., Keller, G.S. and Uflacker, A.B. (2004) Blocking glutamate receptors in the parabrachial nucleus reduces avesive oromotor responses to quinine in conscious rats. Achems Abstr., XXVI, 54.
Matsuo, R., Yamauchi, Y., Kobashi, M., Funahashi, M., Mitoh, Y. and Adachi, A. (2001) Role of parabrachial nucleus in submandibular salivary secretion induced by bitter taste stimulation in rats. Auton. Neurosci., 88, 61–73.[Medline]
Pfaffmann, C. (1952) Taste preference and aversion following lingual denervation. J. Comp. Physiol. Psychol., 45, 393–400.[CrossRef][Web of Science][Medline]
St. John, S.J. and Spector, A.C. (1998) Behavioral discrimination between quinine and KCl is dependent on input from the seventh cranial nerve: implications for the functional roles of the gustatory nerves in rats. J. Neurosci., 18, 4353–4362.
Travers, S.P. (2000) Co-localization of gustatory-elicited Fos-like immunoreactivity and NADPH in the NST and medullary reticular formation. Soc. Neurosci. Abstr., 26, 1972.
Travers, S.P. (2002) Quinine and citric acid elicit distinctive Fos-like immunoreactivity in the rat nucleus of the solitary tract. Am. J. Physiol. Regul. Integr. Comp. Physiol., 282, R1798–R1810.
Travers, J.B. and Hu, X. (2000) Title of article? Journal Title, 00, 000–000.
Travers, J.B., Grill H.J. and Norgren, R. (1987) The effects of glossopharyngeal and chorda tympani nerve cuts on the ingestion and rejection of sapid stimuli: an electromyographic analysis in the rat. Behav. Brain Res., 25, 233–246.[CrossRef][Web of Science][Medline]
Travers, J.B., Urbanek, K. and Grill, H.J. (1999) Fos-like immunoreactivity in the brain stem following oral quinine stimulation in decerebrate rats. Am. J. Physiol., 277, R384–R394.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. San Gabriel, T. Maekawa, H. Uneyama, and K. Torii Metabotropic glutamate receptor type 1 in taste tissue Am. J. Clinical Nutrition, September 1, 2009; 90(3): 743S - 746S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Travers, K Herman, J Yoo, and S. Travers Taste Reactivity and Fos Expression in GAD1-EGFP Transgenic Mice Chem Senses, February 1, 2007; 32(2): 129 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Geran and S. P. Travers Single Neurons in the Nucleus of the Solitary Tract Respond Selectively to Bitter Taste Stimuli J Neurophysiol, November 1, 2006; 96(5): 2513 - 2527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Spector and S. P. Travers The representation of taste quality in the Mammalian nervous system. Behav Cogn Neurosci Rev, September 1, 2005; 4(3): 143 - 191. [Abstract] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||