Subdivisions and neuron types of the nucleus of the solitary tract that project to the parabrachial nucleus in the hamster

The solitary nuclear complex (NST) consists of a number of subdivisions that differ in their cytoarchitectonic features as well as in the amounts of inputs they receive from lingual afferent axons. In this study horseradish peroxidase (HRP) was injected into the parabrachial nucleus (PBN) of the hamster to determine which of these subdivisions contain cells that project to the pons. In the rostral, gustatory division of the NST, the rostral central subdivision contains the greatest number of labelled pontine-projection neurons. The rostral lateral subdivision contains moderate numbers of labelled cells; progressively fewer labelled cells are in the ventral, medial, and dorsal subdivisions. In the caudal, general viscerosensory division of the NST, the caudal central subdivision contains the majority of labelled cells, although fewer than its rostral counterpart. Progressively fewer cells are labelled in the medial, laminar, ventrolateral, and lateral subdivisions; none in the dorsolateral subdivision. Small horseradish peroxidase injections into the pons revealed that cells of the rostral central and rostral lateral subdivisions of the NST project to the medial subdivision of the PBN, predominantly to caudal and ventral parts of the subdivision. Cells of the caudal central and medial subdivisions of the NST project to the central lateral subdivision of the PBN, predominantly to intermediate and rostral-dorsal parts of the subdivision. Outside the NST, cells in the spinal trigeminal nucleus and parvicellular reticular formation were also labelled after PBN injections. Within the rostral central and rostral lateral (gustatory) subdivisions of the NST at least two types of neurons, distinguished on the basis of dendritic and cell body morphology, were labelled after HRP injections that included the medial PBN. Elongate cells have ovoid-fusiform somata and dendrites oriented in the mediolateral plane parallel to primary afferent axons entering from the solitary tract. Stellate cells have triangular or polygonal cell bodies and three to five dendrites oriented in all directions, although one or two often extend mediolaterally. These results indicate that cytoarchitectonic subdivisions of the NST are distinguished by their efferent ascending connections. For each subdivision within the rostral, gustatory NST there is a correlation between the density of lingual inputs it receives and the density of pontine-projection neurons it contains. Within the rostral central subdivision, which contains the densest lingual inputs and the largest collection of PBN-projection neurons, cell types previously identified in studies with the Golgi method were found to send their axons to the PBN. The presence of two types of pontine-projection cells in the rostral central subdivision provides a structural basis for parallel information processing in the ascending gustatory system. Projections to the PBN from regions outside the NST provide opportunities for convergence, at the level of the pons, between inputs arising from gustatory/general viscerosensory subdivisions of the NST and from trigeminal sensory nuclei and the reticular formation.     

The parabrachial nucleus and conditioned taste aversion

The parabrachial nucleus (PBN) surrounds the brachium conjunctivum in the dorsolateral pons. Although composed of numerous subnuclei, the PBN is typically organized into medial and lateral subdivisions according to their location relative to the brachium. In rodents, the medial PBN is part of the central gustatory system, whereas the lateral PBN is a component of the visceral sensory system. Lesions of the PBN disrupt conditioned taste aversion, a critically important learning mechanism that prevents the repeated ingestion of toxic food. Relevant neurobehavioral literature is reviewed to elucidate the role of the PBN in taste aversion learning.     

Organization of parabrachial nucleus efferents to the thalamus and amygdala in the golden hamster.

While gustation in the hamster has been extensively studied at the behavioral and physiological level, very little is known about the central anatomy of the taste system. The purpose of this study was to trace the connections of the parabrachial nucleus (PBN) in the golden Syrian hamster (Mesocricetus auratus) using wheat germ agglutinin-conjugated horseradish peroxidase. The PBN is the site of the second central synapse for the ascending gustatory system and receives taste afferents from the nucleus of the solitary tract. Following large injections into the PBN, anterogradely transported label was seen in the lateral hypothalamus, dorsal thalamus, bed nucleus of the stria terminalis, and amygdala. The anatomy of the two primary targets, the ventral posteromedial thalamus and central nucleus of the amygdala, is described based on Nissl-stained material, and acetylcholinesterase and NADH dehydrogenase histochemistry. Injections into these two regions revealed different patterns of efferents within the PBN. Following injections into the thalamus, retrogradely labelled cell bodies were distributed throughout the PBN subdivisions bilaterally, but concentrated in the central medial (CM) and external lateral (EL) subdivisions. Following injections into the amygdala, retrogradely labelled cell bodies were primarily in the ipsilateral PBN EL, while anterogradely transported label was distributed throughout much of the ipsilateral PBN. The majority of CM efferents projecting to the thalamus were elongate cells, whereas the majority of CM efferents to the amygdala were round-oval cells. These results indicate that the ascending central gustatory system changes from a serial pathway (nucleus of the solitary tract-PBN) to a parallel organization consisting of two major projections, the parabrachio-thalamo-cortical and parabrachio-amygdaloid pathways.     

Medial versus lateral parabrachial nucleus lesions in the rat: effects on mercaptoacetate-induced feeding and conditioned taste aversion

The two experiments of the present study examined the influence of bilateral electrophysiologically-guided ibotenic acid lesions of the medial (gustatory) and lateral (viscerosensory) subdivisions of the parabrachial nucleus (PBN) on lipoprivic feeding and on the acquisition of a conditioned taste aversion. In Experiment 1, mercaptoacetate (0, 400, 600, or 800 micromol/kg) failed to enhance food intake in normal rats maintained and tested on standard laboratory chow. In the same procedure, rats with lesions of the medial or lateral PBN consumed less food during baseline but nonetheless were sensitive to the orexigenic action of mercaptoacetate. In Experiment 2, both types of PBN lesions prevented acquisition of a conditioned taste aversion induced by the oral self administration of lithium chloride. The results suggest that PBN neurons essential for conditioned taste aversion are not involved in the mercaptoacetate-induced feeding of rats maintained and tested on standard laboratory chow.     

Convergence of vagal and gustatory afferent input within the parabrachial nucleus of the rat

Our previous anatomical and electrophysiological studies demonstrated that first-order hepatic and gustatory afferents project to separate regions of the solitary nucleus (NST) and no intra-NST interaction of these two sensory systems could be demonstrated. However, iontophoretic injections of horseradish peroxidase into physiologically identified zones of the NST revealed that both of these regions send overlapping projections to the immediately subjacent parvocellular reticular formation as well as the postero-medial parabrachial nucleus (PBN). The present electrophysiological studies demonstrate that an interstitial zone of neurons in the caudal, medial PBN, indeed, receive convergent input from second-order gustatory and vagal afferents. Co-activation of these PBN units by the simultaneous arrival of both input sources frequently resulted in an additive interaction of evoked activity. PBN units lateral and caudal to this zone responded to vagal stimulation only, while units in the anterior and extreme medial portion of the PBN only responded to gustatory stimulation. By virtue of the efferent projections of the PBN, one might speculate that the convergence of information at this locus may, eventually, play a role in directing long term feeding behavior patterns such as learned taste aversion as well as the more transient changes in taste preference with visceral loading.     

Neurokinin-1 receptor immunoreactivity in the nucleus of the solitary tract in the hamster.

Substance P (SP) modulates the activity of taste-responsive neurons in the gustatory zone of the nucleus of the solitary tract (NST) in the hamster. The distribution of the neurokinin-1 (NK1) receptor (i.e. the SP receptor) was mapped and compared with the distribution of SP immunoreactivity to identify the sites of ligand-receptor interactions. NK1-immunoreactive puncta and somata were located mostly in the rostral lateral, upper half of the rostral central and medial NST subnuclei. These subnuclei also contained intense SP-immunoreactive puncta, and are known to receive substantial inputs via gustatory and somatosensory afferent fibers. The ventral subnucleus, which is involved in visceromotor reflexes accompanying ingestion, contained little NK1 or lighter SP-immunoreactivity. These findings suggest that SP modulates taste activity destined for the ascending gustatory pathway at the level of the first central synapse in the gustatory pathway.     

Medial versus lateral parabrachial nucleus lesions in the rat: effects on cholecystokinin- and D-fenfluramine-induced anorexia

The two major components of the pontine parabrachial nucleus (PBN), the medial (gustatory) and lateral (visceral) subdivisions, have been implicated in a variety of ingestive behaviors. The present study examined the influence of bilateral ibotenic acid lesions of the medial or lateral PBN on the anorectic effects of two systemically administered drug treatments. In Experiment 1, 24-h food-deprived rats where injected with sulfated cholecystokinin (26-33) (CCK; 0, 4.0, or 8.0 microg/kg) and then given 60 min access to food. In Experiment 2, the influence of D-fenfluramine (DFEN; 0, 0.5, 1.0, or 2.0 mg/kg) on deprivation-induced feeding was examined in the same rats using the same behavioral procedure as in Experiment 1. Lesions of the lateral PBN abolished CCK-, but not DFEN-induced anorexia whereas lesions of the medial PBN augmented DFEN-, but had no influence on CCK-induced anorexia. The results suggest that the satiating effects of CCK and DFEN are mediated through different mechanisms involving, respectively, visceral and orosensory processing.     

Medial versus lateral parabrachial nucleus lesions in the rat: effects on cholecystokinin- and -fenfluramine-induced anorexia

The two major components of the pontine parabrachial nucleus (PBN), the medial (gustatory) and lateral (visceral) subdivisions, have been implicated in a variety of ingestive behaviors. The present study examined the influence of bilateral ibotenic acid lesions of the medial or lateral PBN on the anorectic effects of two systemically administered drug treatments. In Experiment 1, 24-h food-deprived rats where injected with sulfated cholecystokinin_26-33 (CCK; 0, 4.0, or 8.0 μg/kg) and then given 60 min access to food. In Experiment 2, the influence of -fenfluramine (DFEN; 0, 0.5, 1.0, or 2.0 mg/kg) on deprivation-induced feeding was examined in the same rats using the same behavioral procedure as in Experiment 1. Lesions of the lateral PBN abolished CCK-, but not DFEN-induced anorexia whereas lesions of the medial PBN augmented DFEN-, but had no influence on CCK-induced anorexia. The results suggest that the satiating effects of CCK and DFEN are mediated through different mechanisms involving, respectively, visceral and orosensory processing.     

Anatomy of the gustatory system in the hamster: central projections of the chorda tympani and the lingual nerve

The sensory modalities of taste and touch, for the anterior tongue, are relegated to separate cranial nerves. The lingual branch of the trigeminal nerve mediates touch: the chorda tympani branch of the facial nerve mediates taste. The chorda tympani also contains efferent axons which originate in the superior salivatory nucleus. The central projections of these two nerves have been visualized in the hamster by anterograde labelling with horseradish peroxidase (HRP). Afferent fibers of the chorda tympani distribute to all rostral-caudal levels of the solitary nucleus. They synapse heavily in the dorsal half of the nucleus at its rostral extreme; synaptic endings are sparser and located laterally in caudal regions. These taste afferents travel caudally in the solitary tract and reach different levels by a series of collateral branches which extend medially in the the solitary nucleus, where they exhibit preterminal and terminal swellings. Taste afferent axons range in diameter from 0.2 micrometer to 1.5 micrometers. The thickest axons project exclusively to the rostral and intermediate subdivisions of the solitary nucleus; the find ones may distribute predominantly to the caudal subdivision. Afferent fibers of the lingual nerve terminate heavily in the dorsal one-third of the spinal nucleus of the trigeminal nerve and also as a dense patch in the lateral solitary nucleus at the midpoint between its rostral and caudal poles. This latter projection overlaps that of the chorda tympani. Thus the two sensory nerves which subserve taste and touch from coincident peripheral fields on the tongue converge centrally on the intermediate subdivision of the solitary nucleus. Efferent neurons of the superior salivatory nucleus were labelled retrogradely following application of HRP to the chorda tympani. These cells are located ipsilaterally in the medullary reticular formation ventral to the rostral pole of the solitary nucleus; their dendrites are oriented dorsoventrally. The efferent axons course dorsally, form a genu lateral to the facial somatomotor genu, and course ventrolaterally through the spinal nucleus of the trigeminal nerve to exit the brain ventral to the entering facial afferents.     

Insular and gustatory inputs to the caudal ventral striatum in primates

The ventral striatum mediates goal-directed behaviors based, in part, on inputs from the amygdala. However, striatal areas caudal to the ventral striatum also receive inputs from the amygdala. In primates, the amygdala projects to the central ventral putamen, lateral amygdalostriatal area, and caudal ventral putamen, suggesting that these regions are also "limbic-related." The anterior insula, which integrates sensory and amygdaloid inputs, projects to the classic ventral striatum. We used retrograde and anterograde tract tracing techniques to determine the extent to which specific subdivisions of the insula influence the caudal ventral striatum in the primate. The anterior (agranular and rostral dysgranular) insula has significant inputs to caudal ventral striatal regions that receive projections from the amygdala. In contrast, the posterior (granular) insula has sparse projections. Within the agranular insula, the posteromedial agranular (Iapm), lateral agranular (Ial), and posterolateral agranular (Iapl) subdivisions have the strongest inputs. These subdivisions mediate olfactory, gustatory, and visceral information processing (Carmichael and Price JL [1996b] J. Comp. Neurol. 363:642-640). In contrast, the intermediate agranular subdivision (Iai) is relatively devoid of visceral/gustatory inputs and has few inputs. In summary, caudal ventral striatal areas that receive amygdaloid inputs also receive significant innervation by agranular and dysgranular insula subdivisions that are themselves connected with the amygdala. Within this projection, the Ial, Iapm, and Iapl make the strongest contribution, suggesting that highly processed visceral/autonomic information, taste, and olfaction influence behavioral responses mediated by the caudal ventral striatum.     

Localization of parabrachial nucleus neurons projecting to the thalamus or the amygdala in the cat using horseradish peroxidase.

Topographical localization of parabrachial nucleus (PBN) neurons projecting directly to the thalamus or the amygdala was examined in the cat by the horseradish peroxidase (HRP) method. After HRP injection in the central nucleus of the amygdala, PBN neurons labeled with the enzyme were seen ipsilaterally in the ventral portion of the lateral PBN as well as in the medial PBN. When the HRP injections were centered on the parvocellular portion of the posteromedial ventral nucleus of the thalamus (VPMpc), HRP-labeled neurons were observed ipsilaterally in the dorsal portion of the lateral PBN as well as in the medial PBN. Within the medial PBN, the distribution of neurons projecting to the amygdala overlapped that of neurons projecting to VPMpc; the cell bodies of the former neurons, however, tended to be more elongated than the latter, and the mean of the average soma diameters of the former was significantly larger than the latter. On the other hand, in the lateral PBN no significant differences were noted between the means of the average soma diameters of neurons projecting to VPMpc and those projecting to the amygdala. The PBN neurons in the cat were presumed to transmit gustatory and general visceral information ipsilaterally to the thalamic taste region and the limbic areas in the basal forebrain.     

A search for the cortical gustatory area in the hamster

The gustatory area was searched in the cerebral cortex of the hamster by means of a combined approach using electrophysiological, behavioral, and histological experiments. The chorda tympani (CT), which innervates taste buds on the anterior part of the tongue, projected to a confined area anterior to the middle cerebral artery and just dorsal to the rhinal fissure. The trigeminal component of the lingual nerve (LN) area was located anterodorsal to the CT area, and the glossopharyngeal nerve (GN), which innervates taste buds on the posterior part of the tongue, was posterior to the CT area. The center of the CT and GN areas belonged to the dorsal part of the dysgranular insular cortex, and the LN area was within the primary somatosensory granular cortex. Bilateral symmetrical ablations of the CT and GN areas abolished the conditioned taste aversion (to sodium saccharin) that had been acquired before ablations, indicating a role of these areas in some cognitive processes of taste perception. Injections of horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) in the CT and GN areas, centered in the dysgranular insular cortex, revealed that this cortical region had major fiber connections with the contralateral homotypical cortical area, ipsilateral amygdala (central, lateral and basolateral nuclei), ipsilateral parvicellular part of the posteromedial ventral nucleus of the thalamus, bilateral parabrachial nucleus, contralateral nucleus of the solitary tract, raphe nuclei, and the locus ceruleus. Conversely, injections of WGA-HRP in these target areas showed anterograde and/or retrograde transport in the similar dysgranular insular cortex and additionally in the ventral part of the granular insular cortex. The present results suggest that the cortical gustatory area of the hamster is about 1.5 × 1.5 mm in size with the topographic organization between anterior and posterior parts of the tongue, and is located mainly in the dysgranular insular cortex around the middle cerebral artery.     

A subpopulation of neurons in the rat rostral nucleus of the solitary tract that project to the parabrachial nucleus express glutamate-like immunoreactivity

In rodents, gustatory information is transmitted from second order neurons in the rostral nucleus of the solitary tract (rNST) to the parabrachial nucleus (PBN) in the pons. The chemical nature of this projection is unknown. Therefore, the goal of the current study was to determine if rNST neurons that project to the PBN express glutamate-like immunoreactivity. Projection neurons were retrogradely labeled following stereotaxic injection of rhodamine-filled latex microspheres into the right PBN of seven rats while glutamate-immunoreactive (GLU-IR) structures were visualized in the same tissue using an immunoperoxidase procedure. The number of single- and double-labeled neurons located in the right (ipsilateral) and left rNST, in each of the nuclear subdivisions as well as their position along the rostral-caudal axis of the rNST was determined. GLU-IR cell bodies were located throughout the rNST. Although the rostral central subdivision contained the highest percentage (33.8%) of GLU-IR perikarya, immunolabeled neurons were most concentrated (number/area of subdivision) within the medial subnucleus. The rostral third of the rNST contained the fewest (20. 5%) and lowest density of GLU-IR cell bodies. The highest percentage of rNST neurons retrogradely labeled from the PBN were located ipsilateral (85.4%) to the pontine injection site, in the middle third of the nucleus (44.2%) and within the rostral central subdivision (52.4%). Overall, 18% of the labeled rNST projection neurons were GLU-IR. The distribution of double-labeled neurons mirrored that of the projection neurons with the largest number located in the ipsilateral rNST (84.5%), middle third of the nucleus (40.5%) and rostral central subdivision (64.7%). These results indicate that glutamate may be a main component of the ascending pathway from the rNST to the PBN. In addition, since GLU-IR neurons were located throughout the rNST and most were not retrogradely-labeled, the current results suggest that glutamate may be an important neurotrans-mitter within the medulla.     

Organization of taste-evoked activity in the hamster parabrachial nucleus.

Small groups of 3-4 neighboring taste neurons in the hamster parabrachial nucleus (PBN) were either generalists (42%) or specialists (58%). Generalists responded well to sucrose, NaCl, KCl, and their mixture but specialists responded to only one or two stimuli. PBN temporal response patterns resembled chorda tympani patterns, indicating that they were preserved across two synapses. Generalist neuron-groups were distributed throughout the central medial (CM) subdivision of PBN. Sucrose-sensitive neuron-groups, which responded best to mixtures, were restricted to rostral CM, whereas most NaCl-best neuron groups were in caudal CM. These results suggest a multifaceted functional organization of taste sensibilities in the PBN.     

Convergence onto hamster medullary taste neurons

Research has shown that gustatory afferents innervating different areas of the oral cavity converge onto single neurons in the nucleus tractus solitarii (NTS). However, most studies of gustatory physiology have only stimulated the receptors on the anterior tongue. No information exists on the responses of hamster NTS neurons to stimulation of receptors located in other areas of the oral cavity. The present investigation compared responses of hamster NTS neurons to stimulation of receptors on the anterior tongue and posterior oral cavity, and to stimulation of both receptor populations together. Of the neurons, 64% responded to both anterior tongue and posterior oral cavity stimulation. The remaining neurons responded exclusively to stimulation of one area. Cells responsive to both fields of stimulation were found throughout the rostral NTS. Cells responding to stimulation of only one field were anatomically separate. Most neurons (69%) were more responsive to anterior tongue than posterior oral cavity stimulation. The neural responses to stimulation of both fields simultaneously were complex. Frequently, a cell's response was intermediate between those produced by stimulation of either receptor population alone. In other cases the response was the same as the larger of the two individual responses. The breadth of responsiveness to the 4 basic taste stimuli (sucrose, NaCl, HCl and quinine-HCl) was similar for both receptor populations, but the breadth of tuning of an individual cell for one field of stimulation was not correlated with its breadth of responsiveness for the other. In contrast, the breadth of tuning following stimulation of the entire oral cavity was correlated with that following stimulation of the anterior tongue.     

Gustatory cortex in the rat. I. Physiological properties and cytoarchitecture

The precise cytoarchitectural localization of taste-elicited cortical responses in the rat was studied using a combination of anatomical and physiological techniques. Multi-unit responses to tongue tactile, thermal and gustatory stimuli were recorded along 97 electrode penetrations positioned parallel to the lateral convexity of the brain and marking lesions were placed at the sites of transitions in these functional properties. Lesions made at sites that received different sensory inputs were consistently located within different cytoarchitectural subdivisions. In this manner, taste cortex in the rat was localized to the agranular insular cytoarchitectural region, in contrast to its traditional assignation to granular insular cortex. Instead, tongue temperature was found to be represented in the cortical area previously termed gustatory, i.e., in ventral granular cortex where layer IV attenuates.     

Effects of early postnatal receptor damage on dendritic development in gustatory recipient zones of the rostral nucleus of the solitary tract.

The rostral gustatory zone of the nucleus of the solitary tract (NST) exhibits extensive anatomical development during the first 3 weeks of postnatal life, and this development requires the presence of intact gustatory receptors during a critical period. We have previously shown that unilateral damage induced to fungiform papillae of the anterior tongue at postnatal day 2 (P2) alters normal migration and ramification of chorda tympani (CT) axons in the rostral NST. In addition to alterations of axonal development, P2 receptor damage decreases the intraneuronal distance between neurons that project axons to the second-order central gustatory relay, located in the caudal parabrachial nucleus (PBN). This observation suggested that P2 receptor damage may alter both axonal development and dendritic development in the rostral gustatory NST. The present study evaluated potential changes in dendritic development of PBN projection neurons following either P2 or P10 receptor damage. Morphological studies were first conducted to quantitatively define somatic characteristics of neurons that project axons to the PBN. Independent experiments used fluorescent labeling combined with subsequent Golgi-impregnation to study dendritic architecture of identified PBN projection neurons. Results confirmed that P2 receptor damage alters dendritic development of PBN projection neurons located in CT terminal fields. Anterior tongue receptor damage at P2 (1) reduces planar length of first- and second-order dendritic branches, (2) reduces the mean number of second-order branches per neuron, and (3) reduces the density of spine processes on second-order dendritic branches. A critical period exists for these effects, similar to that reported for axonal development, insofar as P2 receptor damage alters dendritic development of PBN projection neurons, whereas P10 receptor damage does not. Dendrites of identified PBN projection neurons located in regions of the NST that receive primary afferent axons from the glossopharyngeal nerve are not affected by anterior tongue damage at P2. These results show that early postnatal receptor damage influences both pre- and postsynaptic development in the rostral gustatory NST. These anatomical changes are undoubtedly related to alterations in taste-guided behaviors that are observed following P2 receptor damage.     

Differential projections from gustatory responsive regions of the parabrachial nucleus to the medulla and forebrain

The present study combined extracellular electrophysiology with anterograde and retrograde tracing techniques to determine efferent projections from taste responsive sites within the parabrachial nucleus (PBN). Taste activity was recorded from two distinct regions of the PBN, the waist region consisting of the ventrolateral (VL) and central medial (CM) subnuclei, and the external region, consisting of the external medial (EM) and external lateral (EL) subnuclei. Ascending and descending projections from these two regions differed. Small biotinylated dextran injections placed in taste responsive sites in the waist area produced a prominent descending projection to the medullary parvocellular reticular formation, a projection nearly non-existent from the external region. Differences in ascending projections were more subtle. Projections to the thalamus were bilateral in all cases, however, the waist region had a larger ipsilateral thalamic projection than the external region and the external region had a larger contralateral projection compared to the waist. Central nucleus of amygdala (CNA) projections from the waist area were primarily from posterior tongue responsive sites in VL and terminated in the central medial and lateral CNA subnuclei; external region projections were distributed to the capsular region of CNA. Both the external and waist region projected to substantia innominata (SI). Different efferent projections from the two gustatory responsive regions of the PBN may reflect functional specialization of PBN subnuclei. Descending projections from orally responsive sites in the waist area project to the lateral parvocellular reticular formation, a region implicated in brainstem circuitry underlying consummatory components of ingestive function. The external region, contains cells responsive to pain and oral aversive stimuli, but does not apparently contribute directly to local brainstem functions. Rather, forebrain pathways appear critical to the expression of external region functions.     

Identification of human gustatory cortex by activation likelihood estimation

Over the last two decades, neuroimaging methods have identified a variety of taste-responsive brain regions. Their precise location, however, remains in dispute. For example, taste stimulation activates areas throughout the insula and overlying operculum, but identification of subregions has been inconsistent. Furthermore, literature reviews and summaries of gustatory brain activations tend to reiterate rather than resolve this ambiguity. Here, we used a new meta-analytic method [activation likelihood estimation (ALE)] to obtain a probability map of the location of gustatory brain activation across 15 studies. The map of activation likelihood values can also serve as a source of independent coordinates for future region-of-interest analyses. We observed significant cortical activation probabilities in: bilateral anterior insula and overlying frontal operculum, bilateral mid dorsal insula and overlying Rolandic operculum, and bilateral posterior insula/parietal operculum/postcentral gyrus, left lateral orbitofrontal cortex (OFC), right medial OFC, pregenual anterior cingulate cortex (prACC) and right mediodorsal thalamus. This analysis confirms the involvement of multiple cortical areas within insula and overlying operculum in gustatory processing and provides a functional "taste map" which can be used as an inclusive mask in the data analyses of future studies. In light of this new analysis, we discuss human central processing of gustatory stimuli and identify topics where increased research effort is warranted.     

Opioid modulation of taste responses in the nucleus of the solitary tract

Gustatory processing within the medulla is modulated by a number of physiologic and experiential factors. Several neurotransmitters, including excitatory amino acids, GABA, and substance P, are involved in synaptic processing within the rostral portion of the nucleus of the solitary tract (NST). Endogenous opiates have been implicated in the regulation of feeding behavior and in taste palatability and gustatory responses in the parabrachial nuclei are reduced by systemic morphine. In the present experiments, extracellular recording of neuronal activity within the NST in response to taste input was combined with local microinjection of met-enkephalin (Met-ENK) and naltrexone (NLTX) to determine the effect of these agents on gustatory activity. The anterior tongue was stimulated with anodal current pulses to determine the time course of drug action (n=85 cells) and with prototypical taste stimuli (0.032 M sucrose, NaCl, and quinine hydrochloride, and 0.0032 M citric acid) to investigate the effects of these opioid compounds on taste-evoked responses (n=80 cells). Among these 165 taste-responsive neurons in the NST, the activity of 39 (23.6%) was suppressed by Met-ENK. These effects were dose-dependent and blockable by NLTX, which alone was without effect, suggesting that opiates do not maintain a tonic inhibitory influence. Immunohistochemical experiments demonstrated both micro - and delta-opioid receptors within the gustatory portion of the NST; previous studies had shown numerous fiber terminals containing Met-ENK. These data suggest that endogenous opiates play an inhibitory role in gustatory processing within the medulla.