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Correlation between acetylcholine release and recovery of conditioned taste aversion induced by fetal neocortex grafts.

Rats with lesions of the gustatory neocortex (GN) show deficits in the acquisition of taste aversion. Fetal GN grafts to a lesioned animal restore taste aversion learning and establish connections with the host brain. In this work, we examined whether the grafts are biochemically functional and whether this fact can be related to behavioral recovery. Gustatory or occipital cortices from rat fetuses were transplanted to GN-lesioned rats. Two months later, taste aversion recovery was tested and the release of labeled gamma-aminobutyric acid (GABA), acetylcholine (ACh), dopamine and glutamate from the grafted tissue was assayed. Fetal GN grafts promoted recovery of learning and released GABA, ACh and glutamate in response to K+ depolarization. Occipital cortex grafts did not induce behavioral recovery, although they were capable of releasing GABA. In contrast, these grafts did not release ACh. Moreover, GN-grafted rats in which behavioral recovery was not seen also failed to release ACh. These results are in agreement with previous findings that cholinergic transmission is important in the GN and suggest that ACh may play a role in the graft-mediated behavioral recovery observed in this model.

Acetylcholine↗

Disturbed GABAergic transmission in mutant Han-Wistar rats: further evidence for basal ganglia dysfunction.

A mutant strain of Wistar rats which carries an autosomal gene defect is characterized by a progressively developing hyperexcitability, tremor, olfactory and gustatory movements, bradykinesia, ataxia and a pathologically increased muscle tone of hindlimbs which can be measured by recording tonic activity in the electromyogram (EMG) of the gastrocnemius-soleus muscle. The activity of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) and the receptor binding of GABA as estimated by [3H]GABA binding to synaptic membranes were examined in olfactory bulbs, frontal cerebral cortex, corpus striatum, hippocampus, thalamus, hypothalamus, tectum, substantia nigra, medulla oblongata, cerebellum, and pons of mutant rats. Mutant rats exhibit a lower activity of GAD in synaptosomal fractions of olfactory bulbs and substantia nigra whereas GAD activity within the pons was increased. The changes in the activity of GAD were accompanied by alterations in [3H]GABA binding to synaptic membranes: GABA binding was significantly elevated in the olfactory bulbs and the substantia nigra, but it was markedly reduced in the pons. The functional importance of impaired nigral GABAergic transmission in mutant rats was demonstrated by the fact that intranigral injection of the GABA agonist muscimol reduced the tonic extension of the hindlimbs as indicated by reduced tonic EMG activity of the gastrocnemius-soleus muscle, while intranigral injection of the GABA antagonist bicuculline increased the disturbance.

Animals↗

Fetal brain transplants induce recuperation of taste aversion learning.

Rats showing disrupted taste aversion due to gustatory neocortex or amygdala lesions were transplanted into the lesioned area with homologous brain tissue obtained from 17-day-old fetuses. Comparisons of taste aversions scores before and after the graft, revealed that the grafted animals significantly recuperated taste aversions, whereas cortical lesioned animals without grafts did not. Surprisingly, however, amygdala-lesioned animals without graft presented spontaneous recovery. These results not only support the hypothesis that fetal brain transplants can restore cognitive functions, but also that there are some fundamental functional differences between the gustatory neocortex and the amygdala in the regulation of the processes involved in the acquisition and retention of taste aversion.

Amygdala↗

Calcitonin gene-related peptide (CGRP) in the rat central nervous system: patterns of immunoreactivity and receptor binding sites.

The distribution of immunoreactive (IR) axons and neurons in the rat central nervous system (CNS) has been studied with an antiserum directed against the C-terminal sequence of rat a-calcitonin gene-related peptide (CGRP) and a durable peroxidase reaction product for detailed analysis in relation to normal cytoarchitecture. These materials were studied and illustrated in the three principal axes in relation to cell-stained adjacent sections in normal as well as colchicine- and capsaicin-treated animals, although no fundamental differences in pattern were evident in neurotoxin-treated rats. The patterns of CGRP-IR were then compared with autoradiograms of specific, high affinity receptor binding sites for 125I-human a-CGRP. CGRP-IR labeling in motor systems includes the vast majority of motoneurons, enabling facile identification of isolated 'accessory' populations. Preganglionic parasympathetic nuclei revealed only labeling of a small proportion of neurons. By contrast, the sensory systems revealed a diversity of labeling patterns precluding simple generalizations. Peripheral input ranges from extensive labeling of thin somatic afferents, feeble to moderate gustatory and olfactory afferents to a total absence of auditory afferents, yet IR axons and neurons can be found in selective distribution within each of these sensory systems. Patterns of IR in various integrative centers, e.g. cerebellum, basal ganglia and hypothalamus, reveal selectivity that fails to conform to conventional descriptions of functional systems. Some regions display unexpected patterns, e.g. vertical stripes in cerebellar cortex. CGRP receptor binding sites (RB) are found in many of the sites where IR axons terminate and in some cases, e.g. motor neurons, which express intraneuronal IR. The main sensory systems reveal a variety of RB patterns, only a few of which can be related to sites of IR axon terminals. Many apparent 'mismatches' between IR and RB are illustrated and discussed in the context of functional peptide expression or in quasi-hormonal terms. It is suggested that the principle of CGRP-IR axon distribution in peripheral tissues, where synapses are lacking, might also apply to the CNS and that neither the locus of IR-axon terminals nor RB sites need indicate transmitter action for impulse information transfer. CGRP is a widely distributed neuromodulator probably subserving a role in both synaptic and metabolic regulation, depending on the specific requirements of the diverse distribution of its receptors.

Animals↗

Blockade of N-methyl-D-aspartate receptors in the insular cortex disrupts taste aversion and spatial memory formation.

The present experiments examined the effects of direct intracortical microinjections of the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid directly into the insular cortex of rats, before or immediately after training of conditioned taste aversion and the water maze spatial learning task. In the first series of experiments animals received bilateral injections of 2-amino-5-phosphonovaleric acid prior to taste aversion conditioning or spatial training. A strong disruptive effect was found in the acquisition of training tasks. To determine the possible involvement of N-methyl-D-aspartate receptors in the early post-training processes taking place in the cortex during both learning paradigms, in a second series of experiments, animals received bilateral 2-amino-5-phosphonovaleric acid microinjections 30, 60 or 120 min after the acquisition trial, and 15 min before the retention test. For spatial learning successive treatments were independently done either starting at the onset of the asymptotic phase of the learning curve, 0, 30 or 120 min after finishing the training session, as well as 15 min before the retention test trial. The conditioned taste aversion task remained sensitive to N-methyl-D-aspartate blockade during a period of at least 2 h after the first presentation of the gustatory stimulus, while in the case of the spatial learning task, a gradually decreasing effect was observed from the onset of the asymptotic phase onwards. Taken together, these results provide direct evidence for N-methyl-D-aspartate receptor involvement in cortical regulation of memory formation. Furthermore, our results suggest that in the same cortical region, a different time-course for the activation of N-methyl-D-aspartate-dependent mechanisms occurs during the early formation of cortically mediated memories, depending on the particular behavioural task.

2-Amino-5-phosphonovalerate↗

Altered processing of novel information in N-CAM-deficient mice.

N-CAM-deficient mice display anatomical and electrophysiological abnormalities in the CNS and behavioral deficits. Here, we address the question whether information processing is altered in these mice by analysis of the expression of c-fos and arg 3.1/arc in N-CAM-deficient mice after presentation of saccharin as novel or familiar and water as neutral gustatory stimulus. When compared to their wild-type control littermates, increased expression of c-fos mRNA in the amygdala after the novel taste and of arg 3.1/arc mRNA in the dentate gyrus 4.5 h after the neutral taste was detected in the absence of N-CAM. Furthermore, the novelty-induced increase in arg 3.1/arc expression in the cingulate cortex 4.5 h after the novel taste was not observed in N-CAM-deficient mice. These data suggest that information processing mediated by immediate-early gene expression is altered in N-CAM-deficient mice.

Amygdala↗

Functional imaging of neural responses to expectancy and experience of monetary gains and losses.

Neural responses accompanying anticipation and experience of monetary gains and losses were monitored by functional magnetic resonance imaging. Trials comprised an initial "prospect" (expectancy) phase, when a set of three monetary amounts was displayed, and a subsequent "outcome" phase, when one of these amounts was awarded. Hemodynamic responses in the sublenticular extended amygdala (SLEA) and orbital gyrus tracked the expected values of the prospects, and responses to the highest value set of outcomes increased monotonically with monetary value in the nucleus accumbens, SLEA, and hypothalamus. Responses to prospects and outcomes were generally, but not always, seen in the same regions. The overlap of the observed activations with those seen previously in response to tactile stimuli, gustatory stimuli, and euphoria-inducing drugs is consistent with a contribution of common circuitry to the processing of diverse rewards.

Adult↗

Gustatory processing is dynamic and distributed.

The process of gustatory coding consists of neural responses that provide information about the quantity and quality of food, its generalized sensation, its hedonic value, and whether it should be swallowed. Many of the models presently used to analyze gustatory signals are static in that they use the average neural firing rate as a measure of activity and are unimodal in the sense they are thought to only involve chemosensory information. We have recently elaborated upon a dynamic model of gustatory coding that involves interactions between neurons in single as well as in spatially separate, gustatory and somatosensory regions. We propose that the specifics of gustatory responses grow not only out of information ascending from taste receptor cells, but also from the cycling of information around a massively interconnected system.

Action Potentials↗

Novelty-induced increased expression of immediate-early genes c-fos and arg 3.1 in the mouse brain.

The detection of novel stimuli is a memory-dependent process. The presented stimulus has to be compared with memory contents to judge its novelty. In addition, the novelty of stimuli activates attention-related processes that facilitate memory formation. To determine the involvement of limbic and neocortical brain structures in novelty detection, we exposed mice to a novel gustatory stimulus (0.5% saccharin) added to their drinking fluid. We then compared the novelty-induced expression of the two immediate-early genes (IEGs) c-fos and arg 3.1, with their expression in mice familiarized with the same stimulus or mice not exposed to that stimulus. Exposure to taste novelty increased expression of c-fos and arg 3.1 mRNA in the cingulate cortex and deep layers of the parietal cortex. In addition, c-fos mRNA expression was increased in the amygdala and arg 3.1 mRNA was increased in the dentate gyrus. Expression of c-fos and arg 3.1 was elevated 30 min after the exposure to novelty. For arg 3.1, a second peak of expression was found 4.5 h after presentation of the novel stimulus. Our results indicate that the amygdala, the dentate gyrus, and the cingulate and parietal cortices may be involved in novelty detection and associated cognitive events, and suggest that c-fos and arg 3.1 play distinct roles in these processes.

Animals↗

Cerebral activation focusing on strong tasting food: a functional magnetic resonance imaging study.

Very little research has been conducted on taste imagery because of the difficulty of doing so. We conducted a functional magnetic resonance imaging study to observe cerebral activation patterns produced in volunteers concentrating on pickled plums (umeboshi), a traditional Japanese food with a strong and sour taste. Activation was observed in the right insula, the bilateral opercula, the bilateral orbitofrontal cortices and the left Broca's area. Activation in the insula (primary gustatory area) was very weak and limited to one side. The activation pattern was similar to that of taste perception. Our results showed that it is possible for humans to imagine tastes.

Adult↗

[Epileptic auras: classification, pathophysiology, practical usefulness, differential diagnosis and controversials].

OBJECTIVE: To examine those aspects of the epileptic auras that may contribute to improve our understanding of this epileptic manifestation. DEVELOPMENT: Epileptic aura is that portion of the seizure which occurs before consciousness is loss and for which memory is retained afterwards. In the case of simple partial seizures, the aura is the entire seizure. This epileptic phenomenon is the consequence of the activation of functional cortex by abnormal, unilateral, circumscribed and brief neuronal discharge. Surface electroencephalogram frequently fails to detect any changes during an isolated aura. The incidence of auras in partial epilepsy remains imprecise and there are marked discrepancies among authors. Viscerosensorial and experiential auras are most often seen in temporal lobe epilepsy. Feeling of fear is the commonest affective symptom associated with epileptic discharges from mesial temporal origin. Special sensory auras including visual, gustatory and vertiginous are more frequently described in extratemporal epilepsy. Olfactory auras are rare, however, when they occur the most likely etiology is a tumor involving the amygdala and hippocampus. Somatosensory auras include sensations of tingling or numbness, electrical feeling or very occasionally, pain. There is not agreement with the classification of determined auras such as motor, cephalic and sexual. The differential diagnosis is enormously heterogeneous including vestibular disfunction, migraine, stroke, autonomic disturbances, drug intoxications and psychiatric disorders. CONCLUSION: The clinical manifestations of the epileptic auras are extraordinarily diverses and, therefore, the knowledge of their pathophysiology, characteristics, incidence and association with differents types of focal epilepsy are the clue to obtain a precise diagnosis.

Diagnosis, Differential↗

Functional MRI detection of activation in the primary gustatory cortices in humans.

Magnetoencephalography (MEG) has recently revealed that the transitions between the parietal operculum (Pop) and the insula (area G) and the ventral end of the central sulcus (cs) were activated with the shortest latency by instrumental gustatory stimulation, which suggests that the location of the primary gustatory area is in these two regions. However, studies using other noninvasive brain-imaging methods such as positron-emission tomography or functional magnetic resonance imaging (fMRI) with manual application of tastants into the mouth have been unable to confirm this. The present study examined cortical activation by repetitive stimulation of the tongue tip with 1 M NaCl with a computer-controlled stimulator and used fMRI to detect it. In individual brains, activations were detected with multiple comparisons (false discovery rate) across the whole brain corrected (threshold at P < 0.05) at both area G and frontal operculum (Fop) in 8 of 11 subjects and at the rolandic operculum (Rop) in 7 subjects. Activations were also found at the ventral end of the cs (n = 3). Group analysis with random-effect models (multiple comparison using familywise error in regions of interest, P < 0.02) revealed activation at area G in both hemispheres and in the Fop, Rop, and ventral end of the cs on the left side. The present study revealed no activation on the gyrus of the external cerebral surface except for the Rop. Taking MEG findings into consideration, the present findings strongly indicate that the primary gustatory area is present at both the transition between the Pop and insula and the Rop including the gray matter within a ventral part of the cs.

Adult↗

Neuronal activities in the reward phase in primary and higher-order gustatory cortices of monkeys.

We examined neuronal activities in the reward phase of a taste discrimination GO/NOGO task and the reversal from the primary (PGC; areas G, 3 and 1-2) and higher order gustatory cortices (HGC, PrCO and OFC) in the monkey. Sucrose was given as reward for both GO (lever pressing during LED) and NOGO responses when correct. Three ON responses, synchronous with sucrose onset at correct or LED offset at incorrect trials were found: C- and I- types increased discharges only at correct or incorrect trials, while C-I type changed discharges at both. Of the latter two classes were noted; Class I increased discharges at correct and decreased them at incorrect trials, and Class II increased discharges at both. C-type and Class I were most numerous in both PGC and HGC except for the OFC in which Class II responses predominated. I-type was rare. Onset latencies at correct and incorrect trials were significantly correlated in the HGC but not in the PGC. It was suggested that C-type responses represented the gustatory nature of reward, I-type neurons error signals, and that Class I of C-I type indicated the arrival or omission of the reward, and Class II anticipation of reward delivery.

Action Potentials↗

Congenital bilateral perisylvian syndrome: MR findings.

The insula of Reil is seen on every MR imaging study of the brain. It is interesting to be familiar with the insular anatomy, as the insula is often involved in brain pathology and it is a location in the brain with multiple vital functions, such as gustatory sensation, motor planning of speech, vestibular function, and cardiovascular para/orthosympathetic balance. We describe the anatomy of the insula and correlate the anatomy on MR imaging obtained at 1.5T. We illustrate the clinical importance of the insula by a case report.

Brain Diseases↗

Convulsant action of naloxone in the rat amygdala.

Increasing doses of naloxone hydrochloride (100-1000 nmol) were micro-injected unilaterally into the rat amygdala and the behavioral, neuropathological and electrographic responses were studied. Microinjections of low doses of naloxone (100-250 nmol) produced staring, gustatory automatisms and wet shakes whereas higher doses additionally resulted in motor limbic seizures and status epilepticus. The electroencephalogram showed a sequence of alterations characterised by high voltage fast activity, spiking, bursts of polyspiking, electrographic seizures and postictal depression which first appeared in the amygdala and rapidly spread to hippocampal and cortical areas. The neuropathological analysis of frontal forebrain sections by means of light microscopy revealed seizure-related brain damage in amygdala, olfactory cortex, thalamus, hippocampal formation, substantia nigra and neocortex. Diazepam, 10 mg/kg i.p., when given prior to the microinjection of naloxone into the amygdala, abolished the epileptogenic and neurotoxic effects of the drug. The results suggest that naloxone, when microinjected into rat amygdala elicits electrographic and motor limbic seizures followed by seizure-related brain damage.

Amygdala↗

Distribution of calcitonin gene-related peptide immunoreactivity in relation to the rat central somatosensory projection.

The distribution of the neuropeptide calcitonin gene-related peptide (CGRP) was studied in relation to the known subcortical somatosensory pathways and contiguous systems in the central nervous system (CNS) of rats by using peroxidase histochemical methods in order to relate zones of immunoreactivity (IR) to cytoarchitecture. CGRP is the most ubiquitous peptide found to date in sensory ganglion cells: principally small and medium-size neurons emitting thin axons inferred to be largely nociceptive in function on the basis of the peripheral distribution of their terminals. Its apparent absence in sympathetic axons provides an especially useful sensory marker. The distribution of CGRP-IR axons displays remarkable selectivity at each level of the CNS. The trigeminal root distributes axons primarily to the pericornual layers (laminae I and II) of spinal V nucleus caudalis and to subnucleus oralis, evading the subnucleus interpolaris and contributing only few axons to principal V. Although there are only a few CGRP-IR somata at each level, heavily labeled axon trajectories can be traced to the nuclei of the solitary tract, the parabrachial nuclei, several sectors of the caudal medial thalamus, and the central nucleus of the amygdala. A sector of labeled neuron somata lies contiguous to each of these axon terminal zones, the largest of which is a thalamic nucleus containing cells of distinctive dendritic architecture extending from the periaqueductal gray across the posterior group nuclei to the peripeduncular nucleus, forming a linear array at the mesodiencephalic junction. The relation of CGRP-IR axonal distribution to spinothalamic, visceral, and gustatory systems is discussed in the context of a specialized "chemosensory" component of the thin-fiber somatosensory system.

Animals↗

Localization of the tachykinin neurokinin B precursor peptide in rat brain by immunocytochemistry and in situ hybridization.

Tachykinins exert a broad range of actions in the mammalian nervous system. While much is known about the localization of peptides derived from one of the two mammalian tachykinin genes (substance P- and neurokinin A-encoding preprotachykinin), little has been reported on the localization of peptides derived from a second tachykinin gene encoding neurokinin B. Using an antiserum raised against a 30-residue peptide fragment (Peptide 2) of the protein precursor to neurokinin B, we have mapped the distribution of Peptide 2 by immunocytochemistry. Peptide 2 antiserum specificity was determined by western blot analysis (which showed antibody cross-reactivity to a neurokinin B fusion protein from a cloned neurokinin B-encoding complementary DNA) and by the elimination of immunoreactive product in brain tissue sections upon preabsorption with a 10 microM concentration of Peptide 2 peptide. In addition, we report on the distribution of neurokinin B-messenger RNA with a full-length complementary RNA probe to localize cells that express the neurokinin B precursor. Peptide 2 immunoreactivity and neurokinin B-messenger RNA-positive cells were found, in some instances, paralleling the distribution of substance P and in other cases existing separately from substance P. Peptide 2 immunoreactivity as well as neurokinin B-messenger RNA-positive cells were found in the main olfactory bulb, cortex, olfactory tubercle, nucleus accumbens, hippocampus, bed nucleus of the stria terminalis, amygdala, medial habenula, periaqueductal gray, superior and inferior colliculus, and nucleus of the spinal trigeminal tract. Whereas substance P is found throughout the rat brain, neurokinin B appears to be partitioned more to forebrain than to brainstem structures. The marked differences in the distribution of both tachykinins in the rat central nervous system suggests that neurokinin B may play an important role in olfactory, gustatory, visceral, and neuroendocrine processing of information.

Amino Acid Sequence↗

Some introductory notes on the organization of the forebrain in tetrapods.

As an introduction to the main theme of this conference an overview of the organization of the tetrapod forebrain is presented with emphasis on the telencephalic representation of sensory and motor functions. In all classes of tetrapods, olfactory, visual, octavolateral, somatosensory and gustatory information reaches the telencephalon. Major differences exist in the telencephalic targets of sensory information between amphibians and amniotes. In amphibians, three targets are found: the lateral pallium for olfactory input, the medial pallium for visual and multisensory input, and the lateral subpallium for visual, octavolateral and somatosensory information. The forebrains of reptiles and mammals are similar in that the dorsal surface of their cerebral hemisphere is formed by a pallium with three major segments: (a) an olfactory, lateral cortex; (b) a 'limbic' cortex that forms the dorsomedial wall of the hemisphere, and (c) an intermediate cortex that is composed entirely of isocortex in mammals, but in reptiles (and birds) consists of at least part of the dorsal cortex (in birds the Wulst) and a large intraventricular protrusion, i.e. the dorsal ventricular ridge. In birds, the entire lateral wall of the hemisphere is involved in this expansion. The intermediate pallial segment receives sensory projections from the thalamus and contains modality-specific sensory areas in reptiles, birds and mammals. The most important differences between the intermediate pallial segment of amniotes concern motor systems.

Animals↗