Biomedical subjects

R Norgren

Publications and source records attributed to R Norgren.

At least 19 recordsLinked to original sources

PubMed2006

Gustatory reward and the nucleus accumbens.

The concept of reward is central to psychology, but remains a cipher for neuroscience. Considerable evidence implicates dopamine in the process of reward and much of the data derives from the nucleus accumbens. Gustatory stimuli are widely used for animal studies of reward, but the connections between the taste and reward systems are unknown. In a series of experiments, our laboratory has addressed this issue using functional neurochemistry and neuroanatomy. First, using microdialysis probes, we demonstrated that sapid sucrose releases dopamine in the nucleus accumbens. The effect is dependent on oral stimulation and concentration. We subsequently determined that this response was independent of the thalamocortical gustatory system, but substantially blunted by damage to the parabrachial limbic taste projection. Further experiments using c-fos histochemistry confirmed that the limbic pathway was the prime carrier for the gustatory afferent activity that drives accumbens dopamine release.

Afferent Pathways↗

PubMed2005

Regional activation in the rat brain during visceral stimulation detected by c-fos expression and fMRI.

AIM: The aim of the study was to determine and compare the areas of brain activated in response to colorectal distention (CRD) using functional magnetic resonance imaging (fMRI) and c-fos protein expression. METHODS: For fMRI study (3.0 T magnet), anaesthetized rats underwent phasic CRD, synchronized with fMRI acquisition. Stimulation consisted of eight cycles of balloon deflation (90 s) and inflation (30 s), at 40, 60 or 80 mmHg of pressure. For c-fos study two sets of experiments were performed on anaesthetized rats: comparing (A) brain activation in rats with the inserted colorectal balloon (n = 5), to the rats without the balloon (n = 5); and (B) rats with inserted balloon (n = 10), to the rats with inserted and distended balloon (n = 10). The pressure of 80 mmHg was applied for 2 h of 30 s inflation and 90 s deflation, alternating cycles. RESULTS: Functional MRI revealed significant activation in the amygdala, hypothalamus, thalamus, cerebellum and hippocampus. Significant increase in c-fos expression was observed in amygdala and thalamus in the first set of experiments, and hypothalamus and parabrachial nuclei in the second. CONCLUSION: The two methods are not interchangeable but appeared to be complementary: fMRI was more sensitive, whereas c-fos had much greater resolution.

Animals↗

PubMed2003

Intracranial renin alters gustatory neural responses in the nucleus of the solitary tract of rats.

Activation of the renin-angiotensin system in the brain is considered important in the arousal and expression of sodium appetite. To clarify the effects of directly activating this hormonal cascade, taste neurons in the nucleus of the solitary tract of rats were tested with a battery of sapid stimuli after intracerebroventricular injection of renin or its vehicle. The rats were chronically prepared but lightly anesthetized during the recording procedure. Eighty-five taste neurons were tested: 46 after renin injections and 39 after vehicle. Neural activity was counted for 5.0-s periods without stimulation (spontaneous) and during stimulation with water and sapid chemicals. The averaged responses to each of the standard stimuli (0.1 M NaCl, 0.3 M sucrose, 0.01 M citric acid, and 0.01 M quinine hydrochloride) did not differ significantly between the two conditions. When the rats were tested with a concentration range of NaCl, however, after renin the average responses to the hypertonic 0.3 and 1.0 M stimuli were reduced to 74 and 70%, respectively, compared with those after vehicle injections. A similar tendency was evident for the subsample of neurons that responded best to NaCl, but the effect was smaller. These data are consistent with, but not as dramatic as, those reported after dietary-induced sodium appetite.

Animals↗

PubMed2001

Accumbens dopamine mechanisms in sucrose intake.

Extracellular levels of dopamine (DA) and monoamine metabolites were measured in the nucleus accumbens (NAcc) during sucrose licking using microdialysis in freely moving rats. The converse relationship also was tested. Using bilateral reverse microdialysis, D1 and D2 receptor antagonists (SCH23390, sulpiride) and the DA uptake blocker nomifensine were introduced into NAcc while measuring both ingestive behavior and neurochemistry. Licking of 0.3 M sucrose caused a 305% (+/-69%) increase in NAcc DA compared with water intake. Reverse microdialysis of nomifensine at a dose that increased accumbens DA levels (1484+/-346%) led to an increase of sucrose intake (152.5+/-5.4%). Concurrent infusions of the D1 and D2 blockers with nomifensine brought sucrose ingestion back near to control levels (114.8+/-3.7%). The higher dose of the D2 antagonist sulpiride also increased DA levels and sucrose intake. In contrast, the lower dose of the D2, and both doses of the D1 antagonist had no chemical or behavioral effects. These results showed release of NAcc DA in response to sucrose licking and the converse, an augmentation of the behavior by uptake blockade. The same data, however, failed to prove that tonic, local accumbens D1 and D2 receptor activity influenced this ingestive behavior.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

Parabrachial nucleus lesions block taste and attenuate flavor preference and aversion conditioning in rats.

Rats with ibotenic acid lesions of the parabrachial nucleus (PBN) failed to learn a taste aversion induced by lithium chloride (LiCl) toxicosis. The same rats also did not learn to prefer a taste that was paired with intragastric (IG) carbohydrate infusions during 22 hr/day trials. The PBN-lesioned rats did learn to prefer a flavor (odor + taste) paired with the IG carbohydrate infusions over a different flavor paired with IG water. The PBN-lesioned rats also learned to avoid a flavor paired with IG LiCl infusions during 22 hr/day trials. The flavor preference and aversion, however, were less pronounced than those displayed by control rats. These data indicate that the PBN is essential for forming orosensory-viscerosensory associations when taste is the primary cue but is less critical when more complex flavor cues are available.

Animals↗

PubMed2001

Pontine gustatory activity is altered by electrical stimulation in the central nucleus of the amygdala.

Visceral signals and experience modulate the responses of brain stem neurons to gustatory stimuli. Both behavioral and anatomical evidence suggests that this modulation may involve descending input from the forebrain. The present study investigates the centrifugal control of gustatory neural activity in the parabrachial nucleus (PBN). Extracellular responses were recorded from 51 single PBN neurons during application of sucrose, NaCl, NaCl mixed with amiloride, citric acid, and QHCl with or without concurrent electrical stimulation in the ipsilateral central nucleus of the amygdala (CeA). Based on the sapid stimulus that evoked the greatest discharge, 3 neurons were classified as sucrose-best, 32 as NaCl-best, and 16 as citric acid-best. In most of the neurons sampled, response rates to an effective stimulus were either inhibited or unchanged during electrical stimulation of the CeA. Stimulation in the CeA was without effect in two sucrose-best neurons, nine NaCl-best neurons, and one citric acid-best neuron. Suppression was evident in 1 sucrose-best neuron, 18 NaCl-best neurons, and 15 citric acid-best neurons. In NaCl-best neurons inhibited by CeA stimulation, the magnitude of the effect was similar for spontaneous activity and responses to the five taste stimuli. Nonetheless, the inhibitory modulation of gustatory sensitivity increased the relative effectiveness of NaCl resulting in narrower chemical selectivity. For citric acid-best neurons, the magnitude of inhibition produced by CeA activation increased with an increase in stimulus effectiveness. The responses to citric acid were inhibited significantly more than the responses to all other stimuli with the exception of NaCl mixed with amiloride. The overall effect was to change these CA-best neurons to CA/NaCl-best neurons. In a smaller subset of NaCl-best neurons (n = 5), CeA stimulation augmented the responsiveness to NaCl but was without effect on the other stimuli or on baseline activity. It appears that electrical stimulation in the CeA modulates response intensity, as well as the type of gustatory information that is transmitted in a subset of NaCl-best neurons. These findings provide an additional link between the amygdala and the PBN in the control of NaCl intake, modulating the response and the chemical selectivity of an amiloride-sensitive Na+ detecting input pathway.

Amiloride↗

PubMed2000

Projections of the parabrachial nucleus in the old world monkey.

The efferent projections of the pontine parabrachial nucleus (PBN) were examined in the Old World monkey (Macaca fascicularis) using tritiated amino acid autoradiography and horseradish peroxidase histochemistry. Parabrachiofugal fibers ascended to the forebrain along three pathways: the central tegmental tract, the ventral ascending catecholaminergic pathway, and a pathway located on the midline between the medial longitudinal fasciculi. The PBN projected heavily to the central nucleus of the amygdala and the lateral division of the bed nucleus of the stria terminalis and moderately to the ventral tegmental area and the substantia nigra. Light terminal label also was present within the dorsomedial, ventromedial, lateral, supramammillary, and infundibular nuclei of the hypothalamus and the annular nucleus and the dorsal raphe nucleus within the brain stem. The overall pattern of terminal label was similar to that previously reported for nonprimate species, but several differences were notable. In monkey the projection to the ventrobasal thalamus did not coincide with the region that contains gustatory-responsive neurons. In rats, these parabrachiothalamic fibers convey gustatory activity but in the monkey these fibers may carry visceral afferent information. The projections from the PBN to the hypothalamus in the monkey were neither as widespread nor as intense as in the rat, and the monkey lacks a projection from the PBN to the frontal and insular cortices.

Afferent Pathways↗

PubMed1999

Effect of intraduodenal lipid on parabrachial gustatory coding in awake rats.

Intestinal fat differentially suppresses sham feeding of liquid diets and preferred gustatory stimuli. Although the behavioral effect is robust, no electrophysiological evidence exists to account for its neural basis. Therefore, we investigated the effect of intestinal fat on gustatory coding in the pontine parabrachial nuclei (PBN) by recording from single neurons in awake rats before, during, and after intraduodenal infusions of lipid (Intralipid; 10 ml, 5 kcal). Intraduodenal lipid did not alter the response profiles of PBN taste neurons. It did, however, produce an overall decrease in response magnitude (-16.25%; n = 43), with the largest reduction to sucrose (-30%; n = 43). The most pronounced suppression occurred in sucrose-best neurons in response to sucrose (-55%; n = 19), and this effect was largest for the sucrose-specific cells (-77%; n = 3). After lipid infusions, nonspecific neurons in both the sucrose-best and NaCl-best categories also responded less to their best stimulus (sucrose, -46%; n = 16; NaCl, -35%; n = 13). In contrast, no significant changes were found in NaCl-specific cells in response to NaCl. All effects appeared with short latency ( approximately 5 min) and were reversible within the time frame of a meal. In controls, duodenal infusions of saline did not cause any changes in taste responsiveness. These results suggest that intestinal fat has specific effects on taste coding in the PBN that may contribute to the intake suppression of palatable food observed in behavioral studies. The similar, short latency of both the behavioral and neural effects supports the hypothesis of a preabsorptive site of action.

Animals↗

PubMed1998

Intestinal fat suppressed intake of fat longer than intestinal sucrose.

Although animals eventually stop eating when only experiencing the oro-sensory stimuli from a food, they stop eating much more rapidly if they also receive postgastric stimuli simultaneously. This suggests that the postgastric effects of a nutrient influence the hedonic value of food or motivation to consume that food, and thus, can influence food selection within the time frame of a meal. In this experiment, rats were equipped with a gastric fistula and duodenal cannula. This combination allowed them to receive the same oro-sensory stimuli, but different postgastric nutrients. While ingesting either a fat (Intralipid) or carbohydrate (sucrose) solution, both of which drained from the gastric fistula, the rats received a duodenal infusion of either sucrose (10 mLs, 0.24 kcals/mL), fat (10 mLs, 0.25 kcals/mL) or saline (10 mLs, 0 kcals/mL). While ingesting the Intralipid, a duodenal infusion of fat suppressed intake quicker and longer than an infusion of sucrose. While the animals ingested sucrose, sucrose and fat suppressed intake equivalently.

Animals↗

PubMed1998

Ibotenic acid lesions of the parabrachial nucleus and conditioned taste aversion: further evidence for an associative deficit in rats.

Rats with extensive ibotenic acid lesions centered in the gustatory zone of the pontine parabrachial nucleus (PBN) failed to acquire a conditioned taste aversion (CTA) induced by lithium chloride (LiCl) toxicosis (Experiments 1 and 4). This deficit cannot be explained as an inability to either perceive or process gustatory information because lesioned rats that failed to acquire a CTA readily acquired a conditioned flavor preference (Experiment 2). Similarly, the CTA deficit cannot be attributed to an inability to experience or process visceral input because PBN-lesioned rats that failed to acquire a CTA successfully learned an aversion to a trigeminal stimulus, capsaicin, when paired with LiCl-induced illness (Experiment 3). This pattern of results supports the view that cell bodies within the PBN are essential for the associative processes that govern CTA learning.

Animals↗

PubMed1998

The parabrachial nucleus is essential for acquisition of a conditioned odor aversion in rats.

Rats with bilateral ibotenic acid lesions of the gustatory zone of the parabrachial nuclei (PBN) failed to acquire a conditioned taste aversion (CTA) in Experiment 1. They also failed to acquire a conditioned odor aversion (COA) when the olfactory cue was presented on an odor disk in Experiment 2 or when it was presented in water in Experiment 3. The failure to acquire the COA was not due to an inability to detect or use olfactory stimuli because the lesioned rats displayed neophobia to a novel odor in Experiment 3 and used an olfactory cue to predict the availability of an aversive capsaicin solution in Experiment 4. Together, the results demonstrate that, as with CTA learning, PBN cell bodies are essential for the establishment of a specific association between an olfactory conditioned stimulus and a lithium chloride unconditioned stimulus.

Analysis of Variance↗

PubMed1997

Identification of rat brainstem multisynaptic connections to the oral motor nuclei using pseudorabies virus. I. Masticatory muscle motor systems.

Oromotor behavior results from the complex interaction between jaw, facial, and lingual muscles. The experiments in this and subsequent papers identify the sources of multisynaptic input to the trigeminal, facial, and hypoglossal motor nuclei. In the current experiments, pseudorabies virus (PRV-Ba) was injected into the jaw-opening (anterior digastric and mylohyoid) and jaw-closing muscles (masseter, medial pterygoid, and temporalis) in bilaterally sympathectomized rats. Injection volumes ranged from 2 to 21 microl with average titers of 2.8 x 10(8) pfu/ml and maximum survival times of 96 h. The labeling patterns and distributions were consistent between each of the individual muscles and muscle groups. A predictable myotopic labeling pattern was produced in the trigeminal motor nucleus (Mo 5). Transneuronally labeled neurons occurred in regions known to project directly to Mo 5 motoneurons including the principal trigeminal sensory and supratrigeminal areas, Kölliker-Fuse region, nucleus subcoeruleus, and the parvicellular reticular formation. Maximum survival times revealed polysynaptic connections from the periaqueductal gray, laterodorsal and pedunculopontine tegmental areas, and the substantia nigra in the midbrain, ventromedial pontine reticular regions including the gigantocellular region and pars alpha and ventralis in the pons and medulla, and the nucleus of the solitary tract, paratrigeminal region, and paramedian field in the medulla. Thus, the results define the structure of the multisynaptic brainstem neural circuits controlling mandibular movement in the rat.

Animals↗

PubMed1997

Identification of rat brainstem multisynaptic connections to the oral motor nuclei in the rat using pseudorabies virus. II. Facial muscle motor systems.

The present experiments continue our investigations of the higher order afferent systems controlling the orofacial musculature. Pseudorabies virus (PRV) was injected into the buccinator, platysma, posterior digastric, and zygomatic muscles in bilaterally sympathectomized rats. Injection volumes ranged from 6 to 12 microl with average titers of 7 x 10(8) pfu/ml and maximum survival times of 96 h. The labeling patterns and distributions were similar across the individual muscles and between muscle groups (perioral vs. posterior digastric), as well as in comparison to the results from previous masticatory muscle injections. Injections produced a predictable myotopic labeling pattern in the facial motor nucleus (Mo 7) and transneuronally in regions known to project directly to Mo 7 including the red nucleus, ventrolateral parabrachial region, principal trigeminal sensory nucleus, supratrigeminal area, and the parvicellular reticular formation. Maximum survival times revealed more distant connections from a variety of nuclear zones including the periaqueductal gray, laterodorsal and pedunculopontine tegmental areas, and the substantia nigra in the midbrain, ventromedial reticular regions including the gigantocellular region and pars alpha and ventralis in the pons and medulla, and the nucleus of the solitary tract, spinal trigeminal nucleus caudalis, paratrigeminal region, and paramedian field in the medulla. The similarity of the labeling patterns and distributions of the higher order afferents resulting from PRV facial and masticatory muscle injections identifies the neural circuits that may coordinate the activity of these muscle groups during oral motor behavior.

Animals↗

PubMed1997

Identification of rat brainstem multisynaptic connections to the oral motor nuclei using pseudorabies virus. III. Lingual muscle motor systems.

The present experiments complete our investigations of higher order afferent control of the orofacial muscles by examining the premotor systems controlling the lingual musculature. Pseudorabies virus (PRV) was injected into the extrinsic (protruders: genioglossus and geniohyoid; retractors: hyoglossus and styloglossus) and intrinsic tongue muscles in bilaterally sympathectomized rats. Injection volumes ranged from 1 to 12 microl with average titers of 4 x 10(8) pfu/ml and maximum survival times of 90 h. Consistent labeling patterns and distributions occurred across each of the individual muscles and between extrinsic and intrinsic muscle groups, as well as in comparison to the results from the previous masticatory and facial muscle experiments. Virus injections produced a predictable myotopic labeling pattern in the hypoglossal nucleus (Mo 12). Transneuronally labeled neurons occurred in regions known to project directly to Mo 12 motoneurons including the nucleus subcoeruleus, trigeminal sensory areas, parvicellular reticular formation, and the dorsal medullary reticular fields. Maximum survival times revealed more distant connections from medial and lateral reticular zones including the periaqueductal gray, dorsal raphe, laterodorsal and pedunculopontine tegmental areas, and substantia nigra in the midbrain, the gigantocellular region, pontine nucleus caudalis and ventralis, and lateral paragigantocellular region in the pons, and the nucleus of the solitary tract, paratrigeminal region, and paramedian field in the medulla. Thus, injections of PRV into the orofacial muscles revealed a complex, but remarkably uniform network of multisynaptic connections in the brainstem that control and coordinate the activity of the masticatory, facial, and lingual muscles.

Animals↗

PubMed1997

Reward comparison in chronic decerebrate rats.

The simultaneous contrast paradigm was used to evaluate responsiveness to a low (0.05 M) and a high (0.5 M) concentration of sucrose under two conditions in intact and chronic decerebrate rats. In one condition the low concentration was presented on one day and the high concentration on another. In the other condition presentation of the two concentration was alternated within the same daily session. In each case there was a total of 40 trials/day during which the stimulus was delivered intraorally for 2 s at a rate of 1.5 ml/min with a 30-s intertrial interval. The results showed that the intact rats always licked more for the high than for the low concentration of sucrose but that the magnitude of the effect was larger when given the opportunity to compare the two concentrations within the same daily session. The decerebrate rats produced a similar pattern, but the concentration effect was evident only when the stimuli were alternated within the same daily session. These data stand as the first evidence that the isolated caudal brain stem is adequate for the expression of a behavior that depends on comparison processes involving short-term memory.

Animals↗

PubMed1997

Repeated sodium depletion affects gustatory neural responses in the nucleus of the solitary tract of rats.

Furosemide sodium depletions were induced repeatedly to determine the effects on gustatory neural responses in the nucleus of the solitary tract (NST) of chronically prepared, but lightly anesthetized, rats. Sodium-replete and sodium-deplete conditions were alternated four times in each rat. When rats were under depleted conditions, the responses to NaCl were significantly greater than in sodium-replete conditions. This effect was attributable primarily to an increase in the magnitude of response of those neurons that responded better to NaCl than to the other standard stimuli (sucrose, citric acid, and quinine hydrochloride). In addition, the largest change in responsiveness of the NaCl-best neurons occurred during the third and fourth sodium depletions. These results are essentially opposite to those reported for NST neurons when sodium appetite is induced by dietary sodium restriction. This suggests that the coding of intensity in the gustatory system is dependent not only on the animal's deprivation condition, but also the method through which the deprivation is produced.

Animals↗

PubMed1997

Parabrachial neural coding of taste stimuli in awake rats.

Parabrachial neural coding of taste stimuli in awake rats. J. Neurophysiol. 78: 2254-2268, 1997. In awake, behaving rats, the activity of 74 single neurons in the pontine parabrachial nucleus (PBN) was recorded in response to sapid stimulation by 15 chemicals. Of these, 44 taste cells were tested with all 15 stimuli. Based on their responsiveness to 4 standard stimuli, these neurons were categorized as follows: 23 NaCl-best, 15 sucrose-best, 5 citric acid-best, and 1 quinine HCl-best. Several forms of multivariate analyses indicated that the taste responses matched both the behavioral responses to and, less well, the chemical structure of, the sapid stimuli. A hierarchical cluster analysis of the neurons substantially confirmed the best-stimulus categorization, but separated the NaCl-best cells into those that responded more to Na+-containing salts and those that responded more to Cl--containing salts. The cells that responded best to the Na+ moiety actually were somewhat more correlated with the sucrose-best cells than with those that responded to the Cl--containing stimuli. Citric acid-best neurons and the lone quinine-best unit formed a single cluster of neurons that responded well to acids, as well as to NH4Cl and, to a lesser extent, NaNO3. A factor analysis of the neuronal response profiles revealed that three factors accounted for 78.8% of the variance in the sample. Similar analyses of the stimuli suggested that PBN neurons respond to four or five sets of stimuli related by their chemical makeup or by human psychophysical reports. The capacity of rats to make these discriminations has been documented by other behavioral studies in which rodents generalize across sapid chemicals within each of 5 stimulus categories. Furthermore, a simulation analysis of the neural data replicated behavioral results that used amiloride, a Na+ channel blocker, in which rats generalized NaCl to non-Na+, Cl- salts. Thus, using a variety of analyses, in awake rats, the activity of PBN taste neurons tracks their behavioral responses to a variety of chemical stimuli.

Amiloride↗

PubMed1997

Brainstem lesions and gustatory function: I. The role of the nucleus of the solitary tract during a brief intake test in rats.

Using an automated gustometer, licking behavior in rats was evaluated for a range of concentrations of appetitive and aversive stimuli in rats following electrolytic lesions in the rostral nucleus of the solitary tract (NST). Lesions of the NST flattened the concentration-response function for all gustatory stimuli. They attenuated the concentration-response function for MgCl2, QHCI, and NH(4)Cl by shifting it to the right by 0.5 log unit, attenuated the function for citric acid and Polycose by shifting it to the right by 1.5 log units, and fully eliminated the function for sucrose and NaCl. This failure to respond appropriately, however, was specific to gustatory stimuli because all rats reduced ingestive responding when presented with increasing concentrations of capsaicin, a trigeminal stimulus. Together, the data show that the NST is critical for responding appropriately to changes in intensity of a gustatory, but not a trigeminal, stimulus.

Animals↗