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Absence of differential associative responses to novel and familiar taste stimuli in rats lacking gustatory neocortex.

Rats lacking gustatory neocortex (n = 24) and normal rats (n = 24) were familiarized to either hydrochloric acid (10(-1.6) M) or quinine hydrochloride (10(-4) M) solutions during free-drinking trials. They were trained subsequently to avoid either the familiar or the novel taste stimulus, using a balanced design, by pairing the to-be-associated taste with ip injections of apomorphine hydrochloride. Balanced, nonpaired presentations of the other taste solution and water were presented also. Normal rats more efficiently learned to avoid the novel compared with the familiar taste. Rats with gustatory neocortex lesions did not differentiate novel from familiar tastes. They learned aversions to both in a manner highly similar to the aversion learning of familiar tastes by the normal group. Therefore, rats lacking gustatory neocortex displayed an associative deficiency, relative to normal, only when they were trained on novel stimuli. This observation supports an earlier suggestion that gustatory neocortex lesions disrupt the conditionability of taste stimuli by reducing or eliminating responses to taste novelty. This suggestion is supported further by the absence of a "neophobic" response in the operated rats to the first presentation of a taste stimulus.

Animals↗

Interaction of gustatory and lingual somatosensory perceptions at the cortical level in the human: a functional magnetic resonance imaging study.

The present study has investigated interaction at the cortical level in the human between two major components of flavor perception, pure chemical gustatory and lingual somatosensory perception. Twelve subjects participated in a functional magnetic resonance imaging study and tasted six stimuli, applied on the whole tongue, among which four were pure gustatory stimuli (NaCl, aspartame, quinine and HCl, pH 2.4 or 2.2) and two were both taste and lingual somatosensory stimuli, i.e. somato-gustatory stimuli (HCl, pH 1.6 or 1.5, and aluminum potassium sulfate). Functional images were acquired with an echo planar sequence on a 3 T system and were individually processed by correlation with the temporal perception profile. Both sets of stimuli showed activation in the same cortical areas, namely the insula, the rolandic operculum (base of the pre- and post-central gyri), the frontal operculum and the temporal operculum, confirming a wide overlap of taste and lingual somatosensory representations. However, the relative activation across areas and the analysis of co-activated areas across all runs for each set of stimuli allowed discrimination of taste and somatosensory modalities. Factor analysis of correspondences indicated different patterns of activation across the sub-insular and opercular regions, depending on the gustatory or somato-gustatory nature of the stimuli. For gustatory stimuli different activation patterns for the superior and inferior parts of the insula suggested a difference in function between these two insular sub-regions. Furthermore, the left inferior insula was co-activated with the left angular gyrus, a structure involved in semantic processing. In contrast, only somato-gustatory stimuli specifically produced a simultaneous and symmetrical activation of both the left and right rolandic opercula, which include a part of the sensory homunculus dedicated to the tactile representation of oral structures.

Adult↗

The seventh cranial nerve of the rat. Visualization of efferent and afferent pathways by cobalt precipitation.

The cobalt sulphide precipitation technique, in conjunction with Timm's intensification procedure, was used to delineate the afferent and efferent intramedullary pathways of the seventh cranial nerve complex in the rat. The branchial motor nucleus with the accompanying first part, genu, and second part of the root are described. The motor branches to the superficial facial musculature do not contain fibres of geniculate ganglion origin or fibres which terminate in the spinal trigeminal nucleus. The motor branches to the deep facial muscles arise from the dorsal part of the branchial motor nucleus and traverse to the midline medial to the genu, then project under the genu into the lateral reticular formation before exiting with the facial nerve. The salivatory and lacrimal nuclei and their intramedullary pathways are described. Sensory fibres from the cutaneous auricular branch enter the spinal trigeminal tract and most of the chorda tympani gustatory fibres enter the fasciculus solitarius. A smaller number of gustatory fibres extend medially to the region of the salivatory nucleus. Fibres of greater superficial petrosal origin also enter the fasciculus solitarius as well as the medial reticular formation. These findings are discussed in relation to previous anatomical, physiological and clinical reports.

Animals↗

Flavor-illness aversions: gustatory neocortex ablations disrupt taste but not taste-potentiated odor cues.

Two experiments evaluated the contribution of the gustatory neocortex (GN) to the potentiation of odor by taste during illness-induced aversions in rats. In Experiment 1, rats lacking GN and control rats were given an odor, a taste, or an odor-taste compound cue followed by intragastric gavage of lithium chloride. Prior to conditioning, neophobia for flavored solutions was absent in rats with GN lesions. After pairing with LiCl, GN rats developed normal conditioned odor aversions (Experiment 1B), whereas conditioned taste aversions were attenuated (Experiment 1A) or totally blocked (Experiment 1B). Potentiation of odor by taste after compound conditioning was evident in both control and GN rats, although GN lesions attenuated the effect slightly in Experiment 1B. In Experiment 2, normal rats were given compound conditioning to induce potentiated odor aversions and then given GN lesions prior to tests with the odor and taste components. Taste aversion retention was disrupted totally by GN ablation; potentiated odor aversions were retained by both groups, although the GN group extinguished faster. Gustatory neocortex ablations produced differential effects on odor and taste, disrupting taste memorial and associative processes but leaving odor conditioning and the potentiation of odor by taste processes relatively unaffected. Integrity of the GN apparently is not necessary for the acquisition or retention of potentiation odor aversions.

Animals↗

Afferent connections of the parvocellular reticular formation: a horseradish peroxidase study in the rat.

The afferent connections of the parvocellular reticular formation were systematically investigated in the rat with the aid of retrograde and anterograde horseradish peroxidase tracer techniques. The results indicate that the parvocellular reticular formation receives its main input from several territories of the cerebral cortex (namely the first motor, primary somatosensory and granular insular areas), districts of the reticular formation (including its contralateral counterpart, the intermediate reticular nucleus, the nucleus of Probst's bundle, the dorsal paragigantocellular nucleus, the alpha part of the gigantocellular reticular nucleus, the dorsal and ventral reticular nuclei of the medulla, and the mesencephalic reticular formation), the supratrigeminal nucleus and the deep cerebellar nuclei. Moderate to substantial input to the parvocellular reticular formation appears to come from the central amygdaloid nucleus, the parvocellular division of the red nucleus, and the orofacial and gustatory sensory cell groups (comprising the mesencephalic, principal and spinal trigeminal nuclei, and the rostral part of the nucleus of the solitary tract), whereas many other structures, including the substantia innominata, the field H2 of Forel, hypothalamic nuclei, the superior colliculus, the substantia nigra pars reticulata, the retrorubral field and the parabrachial complex, seem to represent relatively modest additional input sources. Some of these projections appear to be topographically distributed within the parvocellular reticular formation. From the present results it appears that the parvocellular reticular formation receives afferents from a restricted group of sensory structures. This finding calls into question the traditional characterization of the parvocellular reticular formation as an intermediate link between the sensory nuclei of the cranial nerves and the medial magnocellular reticular districts, identified as the effector components of the reticular apparatus. Some of the possible physiological correlates of the fiber connections of the parvocellular reticular formation in the context of oral motor behaviors, autonomic regulations, respiratory phenomena and sleep-waking mechanisms are briefly discussed.

Afferent Pathways↗

Conditioned taste aversion as a learning and memory paradigm.

Conditioned taste aversion (CTA) is a well established learning and memory paradigm in rats and mice that is considered to be a special form of classical conditioning. Rodents--as well as many other species including man--learn to associate a novel taste (CS) with nausea (US), and as a consequence avoid drinking fluid with this specific taste. In contrast to other types of classical conditioning, even CS-US intervals lasting several hours lead to an aversion to the gustatory CS. With increasing CS-US delay duration, however, the aversion against the CS gradually decreases. Mice differ from rats in their reaction to the CS as well as the US. They tolerate a much higher concentration of saccharin and they do not show any clear signs of nausea when injected with the US. Advantages of this task are its relative independence of motor behavior, well described pathways for the CS and partly the US, and the wealth of available anatomical and pharmacological data implying several brain structures (e.g. parabrachial nucleus, amygdala, insular cortex), neurotransmitters and their receptors (e.g. cholinergic system, NMDA-receptors), and cellular processes (e.g. expression of immediate early genes, Ras-MAP kinase signaling pathway, CREB phosphorilation, protein tyrosine phosphorilation, protein synthesis) in CTA. The CTA paradigm has also been successfully used to phenotype mouse mutants.

Animals↗

Impairment of the gustatory engram by generalised seizure activity without associated loss of conditioned taste aversion.

Three experiments are reported concerning the disruption of conditioned taste aversion (CTA) by generalised seizure activity (GSA) induced by electroconvulsive shock (ECS). Rats were taught CTAs by pairing either strong or weak taste cues (10% or 2.5% sucrose solutions) with either strong (0.15 M) or weak (0.05 M) doses of LiCl. In Experiment 1 it is shown that a 2.5% sucrose cue combined with a weak dose of LiCl will reproduce the disruptive effect of GSA when the CTA is established using a 10% sucrose cue. Likewise, a CTA acquired using a 2.5% sucrose cue paired with a strong dose of LiCl will simulate the failure of GSA to disrupt a CTA which has been established with a 10% sucrose cue. These findings support the theory that GSA acts to disrupt CTA by weakening the gustatory engram and an apparent inability to disrupt CTA by GSA does not necessarily signify that the gustatory engram itself remains intact. In Experiment 2, a CTA was established to a 2.5% sucrose cue using the more toxic dose of LiCl. It is shown that GSA will cause a substantial learning loss irrespective of whether it is interpolated within the taste-illness interval, or after the aversion has been acquired. It is concluded that the gustatory engram continues to reside in an active labile state even after the CTA has been established. In Experiment 3 it was estimated that the memory of the 2.5% sucrose cue must have been reduced to just over half of its original strength in order to create the learning loss reported in Experiment 2.

Animals↗

Insular cortex and neighboring fields in the cat: a redefinition based on cortical microarchitecture and connections with the thalamus.

The insular areas of the cerebral cortex in carnivores remain vaguely defined and fragmentarily characterized. We have examined the cortical microarchitecture and thalamic connections of the insular region in cats, as a part of a broader study aimed to clarify their subdivisions, functional affiliations, and eventual similarities with other mammals. We report that cortical areas, which resemble the insular fields of other mammals, are located in the cat's orbital gyrus and anterior rhinal sulcus. Our data suggest four such areas: (a) a "ventral agranular insular area" in the lower bank of the anterior rhinal sulcus, architectonically transitional between iso- and allocortex and sparsely connected to the thalamus, mainly with midline nuclei; (b) a "dorsal agranular insular area" in the upper bank of the anterior rhinal sulcus, linked to the mediodorsal, ventromedial, parafascicular and midline nuclei; (c) a "dysgranular insular area" in the anteroventral half of the orbital gyrus, characterized by its connections with gustatory and viscerosensory portions of the ventroposterior complex and with the ventrolateral nucleus; and (d) a "granular insular area", dorsocaudal in the orbital gyrus, which is chiefly bound to spinothalamic-recipient thalamic nuclei such as the posterior medial and the ventroposterior inferior. Three further fields are situated caudally to the insular areas. The anterior sylvian gyrus and dorsal lip of the pseudosylvian sulcus, which we designate "anterior sylvian area", is connected to the ventromedial, suprageniculate, and lateralis medialis nuclei. The fundus and ventral bank of the pseudosylvian sulcus, or "parainsular area", is associated with caudal portions of the medial geniculate complex. The rostral part of the ventral bank of the anterior ectosylvian sulcus, referred to as "ventral anterior ectosylvian area", is heavily interconnected with the lateral posterior-pulvinar complex and the ventromedial nucleus. Present results reveal that these areas interact with a wide array of sensory, motor, and limbic thalamic nuclei. In addition, these data provide a consistent basis for comparisons with cortical fields in other mammals.

Animals↗

Cortical unit responses to chemical stimulation of the oral cavity in the rat.

The gustatory sensitivity of individual cortical neurons in the rat was examined using a wide range of chemical stimuli. Several subsets of cortical taste cells were identified based on similarities in their response profiles. Although adjacent cortical neurons can differ in their responsiveness to individual tastants, some overlap in taste sensitivities is usually observed.

Afferent Pathways↗

A modality-specific somatosensory area within the insula of the rhesus monkey.

Response properties of neurons in the monkey's granular insula (Ig) were examined with somatic, auditory, visual, and gustatory stimuli. Results indicate that a major portion of Ig is a somatic processing area exclusively, with units that have large and often bilateral receptive fields, consistent with the view that this area serves as a higher-order, modality-specific link in the somatosensory-limbic pathway.

Acoustic Stimulation↗

Spatio-temporal dynamics of brain activated regions during drinking behavior in rats.

Spatio-temporal dynamics of activated brain areas induced by drinking were investigated and visualized in behaving rats using functional magnetic resonance imaging (fMRI). The rats were trained to drink in the magnet bore, and the images were taken during and after drinking glucose and distilled water. During glucose ingestion, the signal intensity was increased continuously and maximally in the lateral hypothalamic area (LHA) and the ventromedial hypothalamus (VMH). Somewhat less intense activation in the central nucleus of the amygdala (AMc), and transient activation in the piriform cortex and the mediodorsal nucleus of the thalamus were observed. The signal intensities of other regions measured were largely unchanged. During post-ingestive periods, the signals re-increased in the hypothalamic areas and AMc. When water was given, LHA and VMH were similarly activated, however, the signal intensity in the amygdala was not significantly increased. The results indicate that these brain regions are activated differentially during drinking behavior, and that LHA and VMH play a central role in the control of not only feeding but also drinking. The regional activities in LHA and VMH are not principally related to the gustatory sensation, and the reactivation after drinking may be related to satisfaction or post-ingestive nutritional information. Also, the responses of AMc are probably due to reward value difference. To the best of our knowledge, this is the first report of mapping of brain areas using fMRI in behaving rats. The improved method described in this study for collecting fMRI data in behaving animals will be useful for studying functional network during animal behavior.

Animals↗

Role of the perirhinal cortex in rats' conditioned taste aversion response memorization.

The role of the perirhinal cortex (PC) in conditioned taste aversion (CTA) learning was investigated in Long Evans rats. CTA was induced by the intraperitoneal administration of LiCl 60 min after saccharin-sweetened water drinking. The PC was reversibly inactivated by the stereotaxic administration of tetrodotoxin (TTX) 60 min before saccharin drinking, immediately after saccharin drinking (Experiment 1), 6 or 24 hr after LiCl administration (Experiment 2), and 60 min before CTA retrieval testing (Experiment 3). Only pre-saccharin drinking PC inactivation disrupted CTA. Thus, PC integrity is necessary only during the earliest phases of CTA mnemonic processing, that is, taste information acquisition and early gustatory memory elaboration. The results are discussed in relation to PC connectivity and PC temporal involvement in the memorization process of other aversive responses.

Animals↗

Induction of the intronic enhancer of the human ciliary neurotrophic factor receptor (CNTFRalpha) gene by the TR4 orphan receptor. A member of steroid receptor superfamily.

A conserved hormone response element, CNTFR-DR1 (5'-AGGTCAGAGGTCAGG-3'), has been identified in the 5th intron of the alpha component of the ciliary neurotrophic factor receptor (CNTFRalpha) gene for the human TR4 orphan receptor (TR4). Electrophoretic mobility shift assay showed a specific binding with high affinity (Kd = 0.066 nM) between TR4 and the CNTFR-DR1. A reporter gene assay using chloramphenicol acetyltransferase demonstrated that the 5th intron of CNTFRalpha has an enhancer activity which could be induced by TR4 in a dose-dependent manner. Furthermore, our in situ hybridization data showed that abundant TR4 transcripts were detected in adult brain, in regions of cortical and hippocampal neurons, as well as in many developing neural structures, including brain, spinal cord, ganglia (sympathetic and sensory), and neuronal epithelia (retinal, otic, olfactory, and gustatory). The striking similarities in the expression patterns of TR4 and CNTFRalpha in the developing and postnatal nervous systems further support the potential role of TR4 in neurogenesis. Collectively, these data suggest that the human CNTFRalpha gene could represent the first identified neural-specific gene induced by TR4.

Adult↗

Taste and olfactory modulation of feeding related neurons in behaving monkey.

Single neuron activity in the monkey lateral hypothalamus (LHA) was recorded by multibarreled electrode during a bar press feeding task. Activity of glucose-sensitive (GS) neurons decreased during bar press (BP) and reward (RW) periods. The inhibition was caused by activation of beta-adrenoceptors and opioid receptors respectively. Glucose-insensitive (GIS) neurons were excited during BP and RW, and at cue light (CL). Excitation at CL and BP was caused by activation of dopaminergic receptors. Among GS neurons, 66% responded to taste and 88% to odor. These responses were 39% and 52% in GIS neurons. GS neurons responded predominantly to two or more taste and odor stimuli while GIS neurons responded to only one stimulant. GS neurons have dense mutual connections with the prefrontal area, and GIS neurons are connected with the motor area. Gustatory and olfactory stimulation elicited responses in 67% of GS neurons and in only 21% of GIS neurons. Data suggest that GS and GIS neurons may have different functions in feeding: GS neurons process endogenous chemical information and integrated chemical sensations, and GIS neurons process external information processing, motor control and discriminative chemical sensations.

Animals↗

Neural activities in the fronto-opercular cortex of macaque monkeys during tasting and mastication.

We recorded responses from 298 units in the fronto-opercular cortex (Fop) of three Japanese macaque monkeys. The units were activated while animals were drinking or eating. Three types of units could be defined: units with transient responses to the delivery of all the fluid into the mouth (ON-type units; n = 123); units activated in association with certain oral movements, e.g., licking (MO-type units; n = 90); and units responsive specifically to a certain fluid (taste units; n = 85). In both ON-type and MO-type units were included mechanoreceptive units with receptive fields in the oral cavity, mainly on the tongue and teeth. All but two taste units responded exclusively to gustatory stimuli. ON-type units were found mainly in the precentral opercular area (PrCO), and MO-type units were recorded predominantly in PrCO and area 6. Taste units were concentrated at the gustatory area and at a part of area 1-2. These results indicate the lack of convergence of somatic and taste input on single neurons. In awake monkeys, Fop units of a given function tended to be clustered at certain loci, thereby forming separate functional regions.

Animals↗

Clonidine in the prepyriform cortex blocked anorectic response to amino acid imbalance.

Ingestion of imbalanced amino acid diets (IMB) has been associated with a decrease in norepinephrine (NE) concentration in the prepyriform cortex (PPC), an area essential for the anorectic response to IMB. Decreased NE could result from activity-induced release (and subsequent metabolism) of the transmitter. If activity of the NE system is important in the rat's anorectic response to IMB, reduced NE activity should result in increased IMB intake. Therefore, the feeding response to IMB was measured after injecting clonidine (Clon) into the PPC to inhibit NE release. At 3 and 6 h after Clon (1.0 and 1.5 micrograms/rat) injections, IMB intake was increased from 69 (the usual response to IMB in untreated animals) to > 100% of control intake. Effective injection sites did not include the gustatory neocortex, an area important for conditioned taste aversions. Thus activation of the NE system in the PPC may be associated with the initial reduced intake of IMB, suggesting that NE activity in the PPC has a role in the neural mechanisms that subserve recognition of amino acid deficiency.

Amino Acids↗

Fos and Egr1 expression in the rat brain in response to olfactory cue after taste-potentiated odor aversion retrieval.

When an odor is paired with a delayed illness, rats acquire a relatively weak odor aversion. In contrast, rats develop a strong aversion to an olfactory cue paired with delayed illness if it is presented simultaneously with a gustatory cue. Such a conditioning effect has been referred to as taste-potentiated odor aversion learning (TPOA). TPOA is an interesting model for studying neural mechanisms of plasticity because of its robustness and rapid acquisition. However, the neural substrate involved in TPOA retrieval has not been well characterized. To address this question, we used immunocytochemical detection of inducible transcription factors encoded by the immediate-early genes Fos and Egr1. Thirsty male rats were conditioned to TPOA learning, and they were submitted to retrieval in the presence of the learned odor 3 d later. Significant increases in both Fos and Egr1 expressions were observed in basolateral amygdala, insular cortex, and hippocampus in aversive rats in comparison with the all the control groups. The pattern of neuronal activity seemed unlikely to be related to the sole LiCl injection. Lastly, opposite patterns of Fos and Egr1 were noted in the entorhinal cortex and the central nucleus of amygdala, suggesting a differential involvement of these markers in retrieval of TPOA.

Animals↗

fMRI activation in response to odorants orally delivered in aqueous solutions.

During food intake flavor perception results from simultaneous stimulation of the gustatory, olfactory and trigeminal systems. Olfactory stimulation occurs mainly through the retronasal pathway and the resulting perception is often interpreted as a taste perception, thus leading to the well-known sensory confusion between taste and olfaction. The present experiment was designed to study, with functional magnetic resonance imaging (fMRI), the cortical representation of olfactory perception in humans in response to retronasal stimulation by odorants delivered in aqueous solution. Psychophysical evaluation confirmed that the stimuli acted as pure olfactory stimuli through the retronasal pathway and did not present any taste component. Results showed activation in all brain regions previously described with neuroimaging techniques using olfactory stimulation with an odorized air flow. Piriform and orbitofrontal cortex were found activated as well as the hippocampal region, the amygdala, the insular lobe, the cingulate gyrus and the cerebellum. These results demonstrate the feasibility of efficiently stimulating the olfactory system in an fMRI scanner through the retronasal pathway with liquids delivered to the oral cavity. The presentation of olfactory stimuli in liquids to the mouth is a realistic model for the study of food-related flavor perception. This stimulation protocol furthermore allows presenting taste and olfactory stimuli separately or combined, thus allowing for direct comparisons between single modality representation, taste or olfaction, and representation of multi-modality mixtures.

Administration, Oral↗