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Biomedical subjects

R Norgren

Publications and source records attributed to R Norgren.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

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

Brainstem lesions and gustatory function: II. The role of the nucleus of the solitary tract in Na+ appetite, conditioned taste aversion, and conditioned odor aversion in rats.

Rats with lesions of the nucleus of the solitary tract (NST) that demonstrated flat concentration-response functions for NaCl and sucrose (T. Shimura, P. S. Grigson, & R. Norgren, 1997) expressed a significant (albeit reduced) salt appetite following sodium depletion, and a normal conditioned taste aversion (CTA) for alanine when paired with lithium chloride-induced toxicosis. Rats with lesions of the NST also could acquire a conditioned odor aversion, but the CTA to alanine was not mediated by odor cues because other rats with NST lesions also demonstrated normal CTA learning even when made anosmic with zinc sulfate. Together, the data suggest that the rostral NST is essential for responding appropriately to increasing concentrations of a tastant, but not for the chemical identification necessary for sodium appetite and CTA learning.

Afferent Pathways

Brainstem lesions and gustatory function: III. The role of the nucleus of the solitary tract and the parabrachial nucleus in retention of a conditioned taste aversion in rats.

Bilateral electrolytic lesions of the nucleus of the solitary tract (NST) or ibotenic acid lesions of the pontine parabrachial nuclei (PBN) failed to disrupt retention of a preoperatively acquired conditioned taste aversion (CTA) to 0.3 M alanine. For both sham- and NST-lesioned rats, the CTA persisted following 3 nonreinforced conditioned stimulus (CS) presentations. For PBN-lesioned rats, retention was more labile. The preoperatively acquired CTA was extinguished by the 3rd nonreinforced CS exposure. When assessed postoperatively using a novel CS, NST-lesioned rats acquired a new CTA, although they were rendered anosmic with zinc sulfate (P. S. Grigson, T. Shimura, & R. Norgren, 1997). Rats with PBN lesions, however, failed to acquire a second CTA postoperatively. Thus, the PBN is essential for the acquisition of a CTA, but neither of the brainstem gustatory nuclei need be intact for the retention of a preoperatively acquired CTA.

Animals

Gustatory functions, sodium appetite, and conditioned taste aversion survive excitotoxic lesions of the thalamic taste area.

Rats with bilateral, electrophysiologically guided, ibotenic acid lesions of the gustatory thalamus (THLX) were tested for their ability to perform a variety of taste-guided behaviors. First, in daily 30-min sessions, the rats were given repeated 10-s access periods to a range of concentrations of sucrose, NaCl, or QHCl, plus water. Both the control and the THLX rats exhibited similar concentration-response functions, regardless of hydrational state. Next, on 3 trials, the rats were given 15 min access to 0.3 M l-alanine and then injected with LiCl (0.15 M, 1.33 ml/100 g body weight ip). All rats learned a taste aversion following 1 pairing with LiCl. Finally, on 3 separate occasions, the rats were injected with furosemide, and Na(+)-appetite was evaluated 24 hr later. All rats expressed an equivalent sodium appetite after the first furosemide injection, but only the control rats increased intake of 0.51 M NaCl with repeated sodium depletions. These observations reinforce prior data implying that an intact gustatory thalamus is not necessary for the expression of some taste-guided behaviors.

Animals

Intestinal fat differentially suppresses sham feeding of different gustatory stimuli.

To determine the intestinal contribution to short-term satiety for solutions of varying palatability, 10 ml of either 0.15 M NaCl or lipid (Intralipid: 0.125, 0.25, 0.5, and 1.0 kcal/ml) was infused at a rate of 0.5 ml/min into the duodenum of rats that were sham feeding either a liquid diet (0.5 kcal/ml), 0.3 M sucrose (0.4 kcal/ml), or a 0.1 M solution of glucose polymers (Polycose 0.4 kcal/ml). Differences in palatability were estimated by the total consumption of each solution over 90 min in a one-bottle test. The intake of solutions maximally ingested during the saline infusions (Polycose > Sucrose > liquid diet) was the most sensitive to the lipid infusions. All four lipid concentrations suppressed intake of Polycose, the solution consumed the most; the three highest concentrations suppressed intake of sucrose (intermediate consumption), and only the two highest concentrations suppressed intake of the complete diet, the solution consumed the least. Nevertheless, the duration of suppression was shorter for the solutions the rats drank the most. For the solution the rats drank the least (liquid diet), the two high concentrations of lipid that suppressed intake did so for the entire experimental period, whereas for Polycose, al lipid infusions suppressed intake, but it recovered to control levels for all but the highest concentration. Other studies have reported that increasing diet palatability shortens the duration of satiety. The current results suggest that this effect may reflect the duration of intake suppression elicited by nutrients in the intestine.

Animals

Parabrachial nucleus lesions impair feeding response elicited by 2,5-anhydro-D-mannitol.

Systemic injection of the fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) elicits a feeding response and induces c-fos activity in the parabrachial nuclei (PBN). We used bilateral ibotenic acid lesions of PBN to determine whether the activation inferred from c-fos activity was causally related to the feeding response. The relationship between the PBN lesion and feeding behavior was also examined with the glucose analogue 2-deoxy-D-glucose (2-DG). The PBN lesions interfered with the feeding response to 2,5-AM but spared the feeding response to 2-DG. Rats were also tested in a conditioned taste-aversion paradigm. Differences were observed in the relationship between lesion extent and behavioral deficit for feeding responses to 2,5-AM and taste-guided intake after taste-aversion conditioning. These data provide the first demonstration that central lesions can disrupt feeding responses to peripherally acting 2,5-AM. The results suggest that the neural substrate for this response differs from that mediating taste-aversion conditioning and from that involved in the feeding response to 2-DG.

Animals

Sodium-deficient diet reduces gustatory activity in the nucleus of the solitary tract of behaving rats.

The activity of single taste neurons was recorded from the nucleus of the solitary tract before (n = 41) and after (n = 58) awake, behaving rats were switched to a sodium-free diet. During sodium deprivation, the spontaneous activity of the neurons increased (142%), but responses to water and sapid stimuli decreased. For all neurons in the sample, the mean response to water decreased to 72% of its predeprivation level, NaCl dropped to 53%, sucrose to 41%, citric acid to 68%, and quinine HCl to 84%. Despite the drop in magnitude, the response profiles of the taste neurons were not changed by the dietary condition. In the Na-replete state, 61% of the activity elicited by NaCl occurred in NaCl-best cells and 33% in sucrose-best neurons. In the depleted state, these values were 60 and 26%, respectively. Nevertheless, at the highest concentrations tested, deprivation did alter the relative responsiveness of the gustatory neurons to sucrose and NaCl in specific categories of neurons. Compared with acute preparations, dietary sodium deprivation in awake, behaving rats produced a more general reduction in the gustatory responses of neurons in the nucleus of the solitary tract. The largest reductions in elicited activity occurred for the "best stimulus" of a particular neuron, thus leading to smaller differences in response magnitude across stimuli, particularly at the highest concentrations tested.

Animals

Organization of orosensory responses in the nucleus of the solitary tract of rat.

1. The receptive field and topographic organization of single orosensory neurons located throughout the rostral division of the nucleus of the solitary tract (rNST) was studied by determining their responsiveness to gustatory stimulation of the entire oral cavity and to gustatory and mechanical stimulation of restricted oral regions. The rNST contained roughly equal numbers of two distinct populations of orosensory neurons, one responsive exclusively to oral mechanical stimulation (M neurons), the other to gustatory stimulation (G neurons). Some G neurons also responded to oral somatosensory stimuli, but usually less vigorously than to gustatory stimuli. The distribution of these two populations of rNST neurons was topographically organized: G neurons were centered anteriorly and medially to M neurons. 2. Eight of 44 G neurons responded only when the whole oral cavity was stimulated, but the remaining 36 cells responded to circumscribed stimulation of taste buds on the anterior tongue (AT), foliate papillae of the posterior tongue, nasoincisor ducts, retromolar mucosa (RM), or soft palate (SP). Overall, AT and SP stimulation were the most effective, and RM stimulation the least effective, for activating nucleus of the solitary tract (NST) G neurons. 3. Approximately half of the G neurons for which a receptive field could be defined (N = 36) responded to stimulation of a single taste receptor subpopulation, but the remaining neurons received convergent input from two or more taste bud groups. The receptive field configurations for convergent G neurons were orderly: convergence occurred preferentially between receptor subpopulations either within the anterior oral cavity (AO) or the posterior oral cavity (PO). An AO-PO distinction also was reflected in the topographic organization of gustatory responses. The mean location of neurons responding optimally to AO gustatory stimulation was more anterior in the NST, and also tended to be more lateral and ventral than the location of neurons that responded optimally to PO stimulation. 4. Forty-four rNST M neurons responded to innocuous mechanical stimulation of restricted areas of the tongue, palate, buccal mucosa, or periodontium. Stimulation of the hard palate and circumvallate papilla were most effective, whereas periodontal stimulation was least effective for activating these cells. 5. A majority (32 of 44) of rNST M neurons responded to stimulation of more than one of the oral sites tested.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Gustatory detection thresholds after parabrachial nuclei lesions in rats.

Rats with either electrolytic (Experiment 1) or excitotoxic lesions (Experiment 2) that had been electrophysiologically centered in the gustatory zone of the parabrachial nuclei (PBN) were tested for sucrose and NaCl taste detection thresholds in a conditioned avoidance task. With 1 exception, all of these rats had previously shown severe deficits in acquiring an LiCl-based conditioned taste aversion (CTA) to sucrose, NaCl, or alanine. The rats with excitotoxic lesions also had failed to express a depletion-induced sodium appetite. Despite the uniformity of these deficits, the rats with lesions exhibited varied performance in the detectability task. Roughly 1/3 of the rats did not perform competently, 1/3 had elevated thresholds, and 1/3 showed no or only marginal impairments in taste detectability. These findings demonstrate that the elimination of CTA following PBN lesions is not necessarily linked to an impairment in taste signal detection. Thus, PBN-induced deficits on 1 taste-related task do not entirely correspond with impairments on another.

Animals