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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Neuroscience. Author manuscript; available in PMC 2010 June 30.
Published in final edited form as:
PMCID: PMC2705209
NIHMSID: NIHMS105087

Afferent connections of the parabrachial nucleus in C57BL/6J mice

Abstract

Although the mouse is an experimental model with an increasing importance in various fields of Neuroscience, the characteristics of its central gustatory pathways have not yet been well documented. Recent electrophysiological studies using the rat and hamster have revealed that taste processing in the brainstem gustatory relays is under the strong influence of inputs from forebrain gustatory structures. In the present study, we investigated the organization of afferent projections to the mouse parabrachial nucleus (PbN), which is located at a key site between the brainstem and gustatory, viscerosensory and autonomic centers in the forebrain. We made injections of the retrograde tracer Fluorogold centered around the “waist” area of the PbN, whose neurons are known to be highly responsive to taste stimuli. Retrogradely labeled neurons were found in the infralimbic, dysgranular and agranular insular cortex as well as the claustrum; the bed nucleus of the stria terminalis and the substantia innominata; the central nucleus of the amygdala; the lateral and medial preoptic areas, the paraventricular, the dorsomedial, the ventromedial, the arcuate, and the lateral hypothalamic areas; the periaqueductal gray, the substantia nigra pars compacta, and the ventral tegmental area; the supratrigeminal nucleus, rostral and caudal nucleus of the solitary tract; the parvicellular intermediate and gigantocellular reticular nucleus; the caudal and interpolar divisions of the spinal trigeminal nucleus, dorsomedial spinal trigeminal nucleus, and the area postrema. Numbers of labeled neurons in the main components of the gustatory system including the insular cortex, bed nucleus of the stria terminalis, central nucleus of the amygdala, lateral hypothalamus, and rostral nucleus of the solitary tract were quantified. These results are basically consistent with those of the previous rat and hamster studies, but some species differences were found. Functional implications of these afferent inputs are discussed with an emphasis on their role in taste.

Keywords: taste system, cortex, amygdala, hypothalamus, bed nucleus of the stria terminalis, nucleus of the solitary tract

Introduction

A number of previous studies have elucidated the basic neuroanatomical characteristics of the central taste system in the rat and hamster, traditional model species in the field of gustatory neurobiology. In these model organisms, afferent fibers of the VIIth, IXth, and Xth cranial nerves convey gustatory information to the rostral nucleus of the solitary tract (NST) (Brining and Smith, 1996; Contreras et al., 1982; Hamilton and Norgren, 1984; Hayakawa et al., 2001; Torvik, 1956; Whitehead and Frank, 1983; Whitehead, 1986). From the NST, ascending fibers project to the pontine parabrachial nucleus (PbN) (Halsell et al., 1996; Herbert et al., 1990; Norgren, 1978; Norgren and Leonard, 1971; Travers, 1988; Whitehead, 1990). The PbN projects to the gustatory cortex via the ventroposteromedial nucleus of the thalamus (VPMpc), and to various limbic structures including the central nucleus of the amygdala (CeA), the bed nucleus of the stria terminalis (BST), and the lateral hypothalamus (LH) (Fulwiler and Saper, 1984; Halsell, 1992; Karimnamazi and Travers, 1998; Norgren and Leonard, 1973; Norgren, 1974; Norgren and Wolf 1976; Saper and Loewy, 1980). These same forebrain areas, excepting the VPMpc, project back to the NST and PbN (Allen et al., 1991; Halsell, 1992; Kang and Lundy, 2009; Krettek and Price, 1978; Moga et al., 1989, 1990a,b; Saggu and Lundy, 2008; Shipley, 1982; Shipley and Sanders, 1982; van der Kooy et al., 1984; Veening et al, 1978; Whitehead et al., 2000). Electrophysiological studies demonstrate that these descending projections play a role in modulating gustatory-evoked activity in brainstem nuclei (Cho et al., 2003; Di Lorenzo, 1990; Di Lorenzo and Monroe, 1992, 1995; Huang et al., 2003; Kang et al., 2004; Li et al., 2002, 2005; Li and Cho, 2006; Lundy and Norgren, 2001, 2004; Matsuo et al., 1984; Tokita et al., 2004; Smith et al., 2005).

The mouse also has become one of the most important model organisms for the study of the taste system, yielding a wealth of information about the genetic basis of gustatory and ingestive behavior (see, for review, Boughter and Bachmanov, 2007). Work stemming from strain comparisons and from gene-targeted models has enabled the recent advancement of molecular biological insights into the structure, development, and function of both peripheral and central taste systems (i.e. Chandrashekar et al., 2006).

Although previous reports concerning the gustatory abilities of mice are more or less confined to behavior and the peripheral gustatory nervous system, recent neurophysiological and c-fos immunohistochemical studies, some of them utilizing knockout or transgenic mice, have focused on the characterization of responses of taste neurons in the mouse NST and PbN (Hashimoto et al., 2009; McCaughey, 2007; Lemon and Margolskee, 2009; Travers et al., 2007). Moreover, a recent study using genetic tracing techniques demonstrated functionally segregated pathways for sweet and bitter receptor input in the mouse central nervous system (Sugita and Shiba, 2005).

The current state of knowledge of the neuroanatomical organization of the gustatory system in mice is limited as compared to traditional models such as rat or hamster. However there is evidence of intriguing species differences: A recent study has shown that mouse fungiform taste buds are innervated by only four or five geniculate ganglion neurons whose fibers converge on a single taste bud, whereas in rats and hamsters branching afferent nerve fibers innervate several buds on the anterior tongue (Zafini and Whitehead, 2006; Fish et al., 1944; Whiteside, 1927). Centrally, the distribution pattern of terminals of peripheral taste nerves in the mouse NST appears similar to that of rat and hamster although only a few studies have been conducted in the mouse so far (Åstrom, 1953; Ganchrow et al., 2007). Zaidi et al. (2008) injected transsynaptic anterograde pseudorabies virus into fungiform taste papillae in order to describe the pattern of synaptically connected pathways from the geniculate ganglion to the first two brainstem taste relays, i.e. the NST and PbN. They found that different geniculate ganglion cells are engaged in either the ascending taste pathway involving the gustatory subdivion of the NST and PbN (lemniscal pathway), or in local oromotor circuits involving the NST and reticular formation. Finally, Hashimoto et al. (2009) have demonstrated the possibility of a species difference in mouse parabrachial taste neuron responsiveness, and subnuclear projection pattern to the VPMpc, in comparison to rats and hamsters. Using both anatomical (WGA-HRP) and functional (c-fos immunohistochemistry) methods, they demonstrated that VPMpc-projection neurons in the mouse PbN were located more closely to the superior cerebellar peduncle than in the hamster, and that oral NaCl stimulation induced only weak c-fos expression in the waist area where NaCl induces both robust c-fos expression and electrophysiological taste responses in the rat (Shimura et al., 2002; Tokita et al., 2004, 2007; Travers, 2002).

Although these studies demonstrate that knowledge about the mouse central gustatory system is beginning to accumulate, the organization of afferent inputs to the PbN, a significant source of modulation of gustatory activity in the rat and hamster, has not yet been elucidated. In the present study, we investigated the afferent connection patterns of the mouse PbN, a key interface between brainstem and forebrain gustatory and visceral areas. We analyzed projections to the PbN both from the brainstem and forebrain areas by injection of a retrograde tracer into the whole PbN. Thus, the aim of this study is to offer anatomical data in the mouse that will help in understanding the comparative basis of taste behavior, and physiology.

Experimental Procedures

Subjects

A total of 12 male and female C57BL/6J mice (19 – 28 g) were used. The animals were maintained in a temperature- and humidity-controlled colony room on a 12 h light/12 h dark cycle (lights on at 0700 h, off at 1900 h), and were given ad libitum access to normal dry pellet (22/5 rodent diet, Harlan Teklad, Madison, WI) and water. This study was approved by the Animal Care and Use Committee at UTHSC, and and all experiments were carried out in accordance with the National Institute of Health Guide for Care and Use of Laboratory Animals (NIH Publications No. 80-23), revised 1996.

Surgery

Animals were anesthetized with Ketamine/Xylazine (100/10 ml/kg) and positioned in a stereotaxic frame (Stoelting, Wood Dale, IL). The scalp was opened with a midline incision, and the skull was leveled between bregma and lambda by adjusting the bite bar. The body temperature was maintained at 35 °C using a heating pad (Elenco electronics, Wheeling, IL). A glass micropipette (20–25 μm tip diameter) filled with 5% Fluorogold (FG) was lowered into the PbN (5.4 mm caudal, 1.2 mm lateral, 3.55 mm ventral to bregma) with a micromanipulator (SM-191, Narishige, Tokyo, Japan). FG was injected into the unilateral PBN either by iontophoresis (2 μA, 5 s on/off for 15 min; n = 7) or via a Picospritzer II (General Valve Corp., Fairfield, NJ) pressure injector system (60 nl, n = 5). The injection pipette was left in place for 10 min both before and after the injection was made. Although injections were not physiologically guided, we have recorded in vivo both single-unit and multi-unit taste activity at these same coordinates in similarly sized C57BL/6J male and female mice (data not shown). Supplemental anesthetic was administered as necessary throughout the surgery to maintain the animals under deep anesthesia. After recovery from surgery, none of the mice displayed abnormal behavior or locomotion.

Tissue preparation

After a 4-day survival period, mice were perfused transcardially with phosphate-buffered saline and 4% paraformaldehyde. The brains were removed and placed in 10% formalin and then transferred to a 30% buffered sucrose solution and stored at 4°C for at least 1 week. Coronal sections (40 μm) were cut serially using a freezing microtome and divided into two adjacent series. One series was stained with cresyl violet to reveal cytoarchitecture, and the adjacent series was used for observation of fluorescent tracer. Both series were mounted and coverslipped on silane-coated slides (Scientific Device Laboratory, Des Plaines, IL) with Cytoseal 60 (Richard-Allan Scientific, Kalamazoo, MI).

Microscopic analysis of sections

Fluorescent labeling in all sections was imaged and analyzed using a Leica (DMRXA2, Leica Microsystems, Bannockburn, IL) episcopic-fluorescence microscope equipped with a digital camera (Hamamatsu ORCA-ER) and imaging software (SimplePCI). The distribution of retrogradely labeled neurons by FG was established by plotting labeled neurons onto representative atlas sections (e.g. Figure 3). In select regions of the gustatory axis, including IC, BST, CeA, LH, and rNST, retrogradely labeled neurons were counted in each animal. The rostral – caudal extent of each area in each animal was determined, and fluorescent cell profiles were counted within each nucleus in every other section along the rostral – caudal axis.

Figure 3Figure 3Figure 3
Diagrams illustrating the distribution of labeled neurons in the brain (rostral to caudal, A–R) after FG injections into the PbN (in mouse 1). Each dot represents one neuron in a single 40-μm-thick section. Maps are adapted and modified ...

In all regions quantified, numbers of labeled neurons were compared with respect to ipsilateral-contralateral location (relative to injection site) with t-tests. Numbers of labeled neurons across gustatory regions, and NST subnuclei, were compared with a repeated measures ANOVA and Post hoc analysis where appropriate (Tukey’s test). The statistical rejection criterion (i.e., alpha) was set at 0.05.

Results

PbN injection site

Microscopic observation revealed that in all of the 12 animals used in this study injection sites encompassed both medial and lateral parts of the PbN including the “waist area” which is known to be highly responsive to taste stimuli in the rat and hamster. FG spread to some extent to the dorsal edge of the supratrigeminal nucleus, but there was no invasion into the locus coeruleus, cuneiform nucleus, or cerebellum. Examples of typical injections, and plots of the maximum extent of all injection sites are shown in Figure 1. Generally, injections made via pressure (n = 5) produced slightly larger injection volumes, and therefore a greater number of cells were labeled in projection sites. However, injections made via iontophoresis (n = 7), while somewhat smaller, produced an overall pattern of labeling that was identical to those made via pressure.

Figure 1
(A) Fluorescent images of a representative injection site centered around the taste-responsive (waist) region of the PbN from caudal (left) to rostral (right) level (mouse 3). Scale bar = 500 μm. (B) Schematic diagram indicating PbN subnuclei ...

Projections to PbN

Neurons retrogradely labeled with Fluorogold were found in both forebrain and brainstem. Examples of labeled neurons in several structures along the gustatory axis are shown in Figure 2. Labeled neurons were found in the dysgranular and agranular insular cortex (DI and AI) as well as the claustrum (Cl) (Fig. 2A); the BST (Fig. 2B); the CeA (Fig. 2C); the LH (Fig. 2D); and the NST (Fig. 2F).

Figure 2
Representative fluorescent images of labeled neurons in the major structures in the gustatory neural axis after an injection of FG into the PbN. All labeling is shown on the side ipsilateral to the injection site, except the PbN (E). A. Insular cortex. ...

Cortex

Retrogradely labeled neurons were found in layer V of the insular cortex along its whole rostrocaudal axis, preferentially in the ipsilateral dysgranular and agranular parts (Fig. 3A–G). Labeled neurons in the contralateral side were sparse. Some neurons were located in the somatosensory cortex, infralimbic and dorsal peduncular cortex (Fig. 3A–G). There was also dense labeling in the claustrum which is located medial to the insular cortex (Fig. 3A–G).

Ventral forebrain

Strong labeling was seen in various areas in the ventral forebrain such as the bed nucleus of the stria terminalis (BST), substantia innominata (SI), central nucleus of the amygdala (CeA) and hypothalamus. The BST as well as the CeA and LH were the forebrain regions where the most robust labeling was observed. Multiple BST subnuclei, especially the LD, LP, TLP and TLI, contained numerous labeled neurons (Fig. 3D–E). These neurons extended ventrally into the SI, lateral preoptic area, medial preoptic area, and medial sublentic external amygdala (Fig. 3E–F). Within the caudal CeA, labeled neurons were most numerous in the lateral division, but significant labeling appeared in the medial subdividion in the rostral CeA. Numbers of labeled neurons in the lateral division (115.25 ± 6.43) was significantly higher than in the medial subdivision (79.7 ± 4.80) at the rostrocaudal level of Fig. 3H (t-test, p < 0.05). No labeling was found in the lateral or basolateral amygdaloid subnuclei (Fig. 3G–H). Retrogradely labeled neurons in the BST and CeA were almost exclusively found ipsilateral to the injection site. Relatively heavy labeling was present in the paraventricular nucleus of the hypothalamus at the rostrocaudal level of the rostral edge of the ventromedial hypothalamic nucleus (Fig. 3G). There were dense labeled neurons in the lateral hypothalamus (LH) throughout its rostrocaudal extent (Fig. 3F–J). Labeling in the dorsomedial, ventromedial, arcuate, and median preoptic nucleus was weak (Fig. 3D–I).

Midbrain and pons

There was moderate labeling in the bilateral ventral tegmental area (Fig. 3K). In the periaqueductal gray (PAG), retrogradely labeled neurons were particularly numerous in the ipsilateral dorsolateral PAG (Fig. 3J–L). Ventral to the PAG, a few labeled neurons were found in the dorsal raphe nucleus (Fig. 3L). The lateral part of the compact zone of the substantia nigra contained many labeled neurons (Fig. 3K). In the contralateral PbN, there were some labeled neurons in the lateral aspect. Only moderate or weak labeling was found in the taste-responsive area in the PbN (Fig. 3M). Ventral to the PbN, the supratrigeminal nucleus contained many labeled cells on both sides (Fig. 3M).

Medulla

Numerous retrogradely labeled neurons were present throughout the rostrocaudal axis of the NST. The most extensive labeling was found in the rostral part of the NST. Ipsilateral dominance of labeling was greater in the rostral than in the caudal NST (Fig. 3N–R). Labeled neurons in the NST extended ventrally to the parvicellular, intermediate, and gigantocellular reticular nuclei and spinal trigeminal nucleus. Labeling in the reticular medullary formation was widespread, and became denser more rostrally. Strong labeling was seen in the caudal part of the area postrema, but it became very weak with slight ipsilateral dominance as it extended rostrally (Fig. 3Q). Many labeled neurons were found with a very slight ipsilateral dominance in the entire medullary reticular formation along the rostrocaudal axis (Fig. 3N–R). Labeling was most evident in the rostral parvicellular reticular nucleus (Fig. 3N–O). Numerous labeled neurons were located in the spinal trigeminal nucleus with moderate ipsilateral dominance. In the caudal spinal trigeminal nucleus, labeled cells were found preferentially in the outer laminae (Fig. 3R). Rostrally, labeling was widely seen in the spinal trigeminal nucleus as well as dorsomedial part of it (Fig. 3N–Q). Labeling was also found in cell bodies in the spinal trigeminal tract (Fig. 3P–Q).

Quantification of labeled neurons

Number of labeled neurons in the GC, BST, CeA, LH, and rostral NST (rNST) are summarized in Table 1. In all regions quantified, numbers of labeled neurons on the ipsilateral side were significantly higher than those of the contralateral side to the injection site (p < 0.01). Numbers of neurons per section in these areas are shown in Figure 4. Repeated measures ANOVA revealed a significant main effect of region (F[4,44] = 33.13, p < 0.01). Post hoc analysis showed that numbers of labeled neurons in the CeA were significantly higher than all other areas (p < 0.01).

Figure 4
The mean number of retrogradely labeled neurons in the insular cortex (IC), rostral nucleus of the solitary tract (rNST), bed nucleus of the stria terminalis (BST), lateral hypothalamus (LH) and central nucleus of the amygdala (CeA). *p < 0.01. ...
Table 1
Number of retrogradely labeled neurons per section in each animal

The rNST was further divided into 4 subdivisions (M, RC, RL and V) in accordance with previous reports using rat, hamster, and mouse (Fig. 4C and D) (Ganchrow, 2007; Gill et al., 1999; Halsell et al., 1996; Harrer and Travers, 1996; Whitehead, 1988, 1990; Whitehead et al., 1993; Zaidi et al., 2008) and numbers of labeled neurons in these regions were quantified. Repeated measures ANOVA revealed a significant main effect of region (F[3,33] = 57.69, p < 0.01). Post hoc analysis (Tukey’s test) demonstrated that numbers of labeled neurons in the RC were significantly higher than all other areas (p < 0.01). Neurons with different morphological characteristics such as elongate and stellate cells (Fig. 4A and B), which have been described in the rat, hamster and mouse rNST, were also observed in the present study (Halsell et al., 1996; King and Bradley, 1994; Whitehead, 1988, 1990; Whitehead et al., 1993; Zaidi et al., 2008).

Discussion

The anatomical organization of the mouse central taste system has been described by only a limited numbers of studies (Åstrom, 1953; Ganchrow et al., 2007; Hashimoto et al., 2009; Shipley, 1982; Shipley and Geinisman, 1982; Zaidi et al., 2008). The results of the present experiments were qualitatively similar to those of previous studies using other species of rodents (Allen et al., 1991; Halsell, 1992; Herbert et al., 1990; Kang and Lundy, 2009; Krettek and Price, 1978; Moga et al., 1989, 1990a,b; Ricardo and Koh, 1978; Saggu and Lundy, 2008; Saper, 1982a,b; Shipley, 1982; Shipley and Sanders, 1982; Travers, 1998; van der Kooy et al., 1984; Veening et al, 1978; Whitehead, 1990; Whitehead et al., 2000) by demonstrating that the mouse PbN receives afferent fibers from a variety of gustatory, visceral, autonomic, and oromotor regions in the brainstem and forebrain. This report offers the beginnings of a central anatomical basis for physiological and behavioral approaches in this important species.

Recent electrophysiological studies in the rat and hamster have focused on understanding the functional roles of descending projections from the higher gustatory centers to the PbN (Di Lorenzo; 1990, Di Lorenzo and Monroe, 1992; Li and Cho, 2006; Li et al., 2005; Lundy and Norgren, 2001, 2004; Matsuo et al., 1984; Tokita et al., 2004). These studies clearly indicate that parabrachial gustatory activity is under strong centrifugal influence. Although such experiments have not yet been conducted in the mouse, our results suggest that similar mechanisms also exist in this species. Because our injections targeted the taste-responsive waist area of the PbN, we focus predominantly on the role of these projections in taste processing; however, our tracer injections spread throughout other areas of the PbN, and it is important recognize that many of these afferent fibers will also play a role in non-taste sensory and visceral function.

Projections from the forebrain

Consistent with previous studies in the rat, we showed that the mouse infralimbic and insular cortex also have descending projections to the PbN (Moga et al., 1990a; Saper, 1982a,b; van der Kooy, 1984). Insular cortical neurons that send axons to the PbN were mainly located in the dysgranular and agranular regions, similar to previous studies (Allen et al., 1991; Kang and Lundy, 2009; Moga et al., 1990a; Saggu and Lundy, 2008; Saper, 1982a,b; Shipley and Sanders, 1982). These regions correspond to electrophysiologically identified taste-responsive insular cortex in the rat (Kosar et al., 1986), which is also known to send efferent fibers back to the rNST and medial PbN where gustatory information is processed (Whitehead et al., 2000).

Prominent labeling was found in both the CeA and the BST, as has been shown in the rat and hamster (Dong et al., 2001; Dong and Swanson, 2003; Halsell, 1992; Kang and Lundy, 2009; Kretekk and Price, 1978; Moga et al., 1989, 1990a; Saggu and Lundy, 2008; van der Kooy et al., 2004; Veening et al., 1984). Several independent findings showed that descending inputs from the CeA to the PbN can modulate taste activities (Huang et al., 2003; Kang et al., 2004; Li et al., 2005; Lundy and Norgren, 2001, 2004; Tokita et al., 2004). Veening et al. (1984) reported that by far the majority of retrogradely labeled neurons were observed in the medial subdivision of the CeA after injection of the retrograde tracers True Blue or bisbenzimide in the rat. In contrast, Halsell (1992) observed much denser labeling in the lateral subdivision than in the medial subdivision of the CeA after injection of WGA-HRP in the hamster. An intermediate result using rats was reported by Moga et al. (1990a), where they found that FG injections into medial PbN resulted in dense labeling in the medial division of the CeA. However, many neurons were also labeled following injections into the ventrolateral part of the PbN. As our FG injections encompassed almost the whole PbN it is impossible to show topographic differences in the projection patterns from various PbN subnuclei. However, we observed strong labeling in both medial and lateral divisions of the CeA. Caudally, labeling was strong in the lateral division and rostrally, labeling was strong in the medial division. The gustatory function of PbN-projecting neurons in the BST is unclear, but Li and Cho (2006) recently demonstrated that electrical stimulation of BST produced exclusively inhibitory effects on taste neurons in the hamster PbN.

It has been demonstrated that the PbN receives descending projections from the lateral hypothalamus (LH) in the rat (Berk and Finkelstein 1982; Moga et al., 1990a,b; Saper et al., 1979; Veening et al., 1987). In agreement with these studies, we showed numerous labeled neurons extending from the regions dorsal and lateral to the fornix to the ventrolateral part of the LH. These PbN-projecting neurons are known to contain various neuropeptides (Moga et al., 1990b). Recent studies have shown that the rat PbN-projecting neurons in the LH contain feeding-related neuropeptides such as corticotropin-releasing hormone, melanin-concentrating hormone and orexin (Kelly and Watts, 1998; Peyron et al., 1998; Touzani et al., 1993). This anatomical evidence suggests that the taste system and the LH “feeding center” have a close interaction (Yamamoto, 2008).

Moga et al. (1990a) reported that numerous cells in the median preoptic nucleus (MnPO) were labeled following FG injection into the rat PbN. Considering large FG injections in the present study, it is noteworthy that only a few scattered neurons in the median preoptic nucleus were retrogradely labeled. This slight discrepancy could be due to species differences between rat and mouse although its functional implication is not clear. PbN-MnPO connections are reported to be reciprocal and have been implicated in various physiological functions such as autonomic responses to noxious or thermal stimuli in the rat (Hermanson et al., 1998; Moga et al., 1990a; Nakamura and Morrison, 2008)

Projections from the pons and medulla

Retrogradely-labeled neurons in the PbN contralateral to the injection side were mainly located in the dorsal-half of the rostral PbN which is not highly responsive to taste stimuli (Halsell and Travers, 1997; Shimura et al., 2002; Tokita, 2004). In the typical taste-responsive zone in the PbN, the “waist” region, there were only a few labeled cells. These results were consistent with those of rats (Moga et al., 1990a) but not of hamster where no single labeled neurons were found in the contralateral PbN even after large HRP injection (Whitehead, 1990). It is suggested that interactions of gustatory information between the PbN on both sides are not frequent even though there seem to exist some species differences as to the strength of mutual connections.

Although FG injection into the PbN was too large to investigate subnuclear projection patterns, our results are generally consistent with previous reports showing that the PbN receives a massive projection from both rostral and caudal nucleus of the solitary tract (Cho et al., 2002; Cho and Li, 2008; Halsell et al., 2006; Herbert et al., 1990; Karimnamazi et al., 2002; Norgren, 1978; Whitehead, 1990; Williams et al., 1996). Projection from the NST was bilateral, but much stronger from the ipsilateral side to the injection than from the contralateral side as has been reported for the rat (Herbert et al., 1990; Karimnamazi et al., 2002; Norgren, 1978; Williams et al., 1996). However, hamster NST neurons are known to project almost exclusively to the ipsilateral PbN (Cho and Li, 2008; Travers, 1988; Whitehead, 1990). The percentage of PbN-projection neurons in each subnucleus in the rNST were very similar to those reported in the rat and hamster (Gill et al., 1999; Halsell et al., 1996). In the present study, 53.1 % of PbN-projection neurons were located in the RC, where there exists the heaviest synaptic endings of taste primary afferent axons (Ganchrow et al., 2007; May and Hill, 2006; Whitehead, 1988; Whitehead and Frank, 1983; Zaidi et al., 2008), and where taste-responsive neurons are located (Harrer and Travers, 1996; McPeeters et al., 1990; Travers and Norgren, 1995). Consistent with the previous reports using mouse (Zaidi et al., 2008), NST neurons with similar morphological characteristics (i.e. elongate and stellate cells) described in the rat and hamster were also found in the present study (Halsell et al., 1996; King and Bradley, 1994; Whitehead, 1988, 1990; Whitehead et al., 1993). Our results, generally similar to those of previous reports in the rat and hamster (Herbert et al., 1990; Whitehead, 1990), also showed that numerous cells are retrogradely labeled in the medullary reticular formation after FG injections into the PbN; this area is thought to contain pre-motor neurons controlling oromotor behaviors (DiNardo and Travers, 1997). This projection may be related to circuitry coordinating oromotor rejection or ingestive responses; trigeminal premoter neurons involved in mastication have been localized in the lateral part of the PbN (Inoue et al., 1992).

Reciprocal connections between the forebrain structures and PbN

It is noteworthy to indicate that the forebrain structures which send descending fibers to the PbN in the present study corresponds well to those which receive efferent inputs from the PbN in the rat and hamster (Fulwiler and Saper, 1984; Halsell, 1992; Saper and Loewy, 1980). Furthermore, the density of afferent and efferent connections is strongly correlated, i.e., many of the structures with dense inputs from the PbN tend to send dense fibers back to the PbN. Although a detailed study about efferent connections of the mouse PbN has not yet been done, findings from other rodent species strongly suggest that gustatory information is processed in a highly mutual fashion between the PbN and forebrain. Future studies may investigate these reciprocal connections in gene-targeted mouse models in pursuit of understanding the link between taste and motivational processes such as feeding or reward.

Figure 5
(A and B) Fluorescent images of a representative elongate (A) and stellate (B) cells located in the rostral central subdivision of rNST. Arrowheads indicate cell body and arrows indicate dendrites. Scale bars = 20 μm. (C) Fluorescent image of ...

Acknowledgments

This research was supported by NIH grant DC000353 to J.D.B.

Abbreviations

ac
anterior commisure
AcbC
nucleus accumbens core
AcbSh
nucleus accumbens shell
AI
agranular insular cortex
AID
agranular insular cortex, dorsal
AIV
agranular insular cortex, ventral
AP
area postrema
Arc
arcuate hypothalamic nucleus
BST
bed nucleus of the stria terminalis
MPI
medial division, posterointermediate part
MV
medial division, ventral part
LD
lateral division, dorsal part
LP
lateral division, posterior part
LTI
lateral division, intermediate part
LV
lateral division, ventral part
BLA
basolateral nucleus of the amygdala
cc
corpus callosum
CeA
central nucleus of the amygdala
CeC
central nucleus of the amygdala, capsular division
CeL
central nucleus of the amygdala, lateral division
CeM
central nucleus of the amygdala, medial division
CM
central medial thalamic nucleus
Cl
claustrum
CPu
caudate putamen
Cu
cuneate nucleus
DI
dysgranular insular cortex
DM
dorsomedial spinal trigeminal nucleus
DMH
dorsomedial nucleus of the hypothalamus
DP
dorsal peduncular cortex
DRD
dorsal raphe nucleus, dorsal part
DRV
dorsal raphe nucleus, ventral part
DRVL
dorsal raphe nucleus, ventrolateral part
Ect
ectorhinal cortex
ECu
external cuneate nucleus
En
endopiriform nuclueus
f
fornix
fr
fasciculus retroflexus
GI
granular insular cortex
Gi
gigantocellular reticular nucleus
IC
insular cortex
ic
internal capsule
icp
inferior cerebellar peduncle
IL
infralimbic cortex
IP
interpeduncular nucleus
IRt
intermediate reticular nucleus
LA
lateral nucleus of the amygdala
LH
lateral hypothalamus
LPO
lateral preoptic area
LRt
lateral reticular nucleus
LPAG
lateral periaqueductal gray
MD
mediodorsal thalamic nucleus
mlf
medila longitudinal fasciculus
MnPO
median preoptic nucleus
Mo5
motor trigeminal nucleus
MPA
medial preoptic area
MVe
medial vestibular nucleus
NST
nucleus of the solitary tract
M
medial subnucleus of the NST
RC
rostral central subnucleus of the NST
RL
rostral lateral subnucleus of the NST
rNST
rostral nucleus of the solitary tract
V
ventral subnucleus of the NST
PAG
periaqueductal gray
PbN
parabrachial nucleus
PbNm
medial parabrachial nucleus
PbNl
lateral parabrachial nucleus
CL
central lateral subnucleus
CM
central medial subnucleus
DL
dorsal lateral subnucleus
EL
external lateral subnucleus
EM
external medial subnucleus
VL
ventral lateral subnucleus
PCRt
parvicellular reticular nucleus
PCRtA
parvicellular reticular nucleus, alpha
Pir
piriform cortex
PF
parafascicular thalamic nucleus
PH
posterior hypothalamic area
PMnR
paramedian raphe nucleus
PnO
pontine reticular nucleus, oral part
PRh
perirhinal cortex
Pr5DM
principal sensory trigeminal nucleus, dorsomedial part
Pr5VL
principal sensory trigeminal nucleus, ventrolateral part
PS
parastrial nucleus
PV
paraventricular thalamic nucleus
PVA
paraventricular thalamic nucleus, anterior
PVH
paraventricular nucleus of the hypothalamus
py
pyramidal tract
RCh
retrochasmatic area
RN
red nucleus
SCol
superior colliculus
scp
superior cerebellar peduncle
SI
substantia innominata
SLEAM
sublentic external amygdala, medial
SNC
substantia nigra pars compacta
SpVe
spinal vestibular nucleus
S1
primary somatosensory cortex
S1BF
primary somatosensory cortex, barrel field
S2
secondary somatosensory cortex
sol
solitary tract
sp5
spinal trigeminal tract
SP5C
spinal trigeminal nucleus, caudal division
SP5I
spinal trigeminal nucleus, interpolar division
STh
subthalamic nucleus
SuM
supramammillary nucleus
Su5
supratrigeminal nucleus
VL
ventrolateral thalamic nucleus
VLPAG
ventrolateral periaqueductal gray
VMH
ventromedial nucleus of the hypothalamus
VP
ventral pallidum
VPM
ventral posteromedial nucleus of the thalamus
VPMpc
ventral posteromedial nucleus of the thalamus, parvicellular part
VTA
ventral tegmental area
ZI
zona incerta
12N
hypoglossal nucleus

Footnotes

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