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Injections of picrotoxin and bicuculline into the amygdaloid complex of the rat: an electroencephalographic, behavioural and morphological analysis.

Bicuculline methiodide (0.5-3 nmol) and picrotoxin (0.5-4 nmol) were injected uni- or bilaterally into the rat amygdala and the resulting behavioural, electroencephalographic and morphological alterations were studied. In rats treated unilaterally with lowest doses of either bicuculline or picrotoxin (0.5 and 1 nmol) increase in the locomotor activity, occasional myoclonus of the hindlimbs and wet dog shakes were observed. At doses of 2-3 nmol, both gamma-aminobutyrate antagonists produced a sequence of repetitively occurring behavioural alterations including limbic gustatory automatisms, tremor and myoclonus of the forelimbs, head nodding and rearing, that developed over 15-30 min and built up progressively into the recurrent motor limbic seizures lasting for 1-6 h. In animals injected bilaterally with either bicuculline (0.5-3 nmol) or picrotoxin (0.5-3 nmol) motor limbic seizures rapidly developed into the status epilepticus lasting for several hours. Bicuculline and picrotoxin produced both ictal and interictal epileptiform activity in the electroencephalogram. A spectrum of electroencephalographic changes consisted of high voltage fast activity, slow and fast voltage spiking, paraoxysmal bursts and periods of postictal depression. The earliest electrographic alterations appeared in the amygdala and then rapidly spread to cortical areas. Electrographic seizures started 1-10 min after unilateral injections of large doses of bicuculline and pictrotoxin (2-4 nmol). Ictal periods lasted for 1-2 min, recurred every 5-10 min and were followed by periods of depression of the electrographic activity. Bilateral injections of large doses of both gamma-aminobutyrate antagonists (2-3 nmol) resulted in the status epilepticus. Morphological examination of frontal forebrain sections with light microscopy revealed a widespread damage to the amygdala, olfactory cortex, substantia nigra, thalamus, hippocampus and neocortex. Pretreatment of animals with diazepam prevented the build-up of convulsive activity and brain damage produced by bicuculline or picrotoxin. Muscimol retarded the appearance and shortened the duration of convulsive activity, but did not alter the sequence and intensity of seizures. The results indicate that gamma-aminobutyrate antagonists, bicuculline and picrotoxin when directly applied to the amygdala can elicit in rats motor limbic seizures, epileptic changes in the electroencephalogram indicative of repetitive limbic seizures, and status epilepticus accompanied by seizure-related brain damage.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗

Taste discriminations in rats lacking anterior insular gustatory neocortex.

Previous neurobehavioral investigations have demonstrated that the anterior insular gustatory neocortex (AIGN) mediates taste-illness learning. The present experiment evaluated taste discriminations in rats lacking AIGN. Two groups of rats received distinct surgical treatments. One-half of the animals received bilateral electrolytic lesion placements in the AIGN: Remaining animals received anesthesia and scalp incisions only. Following postoperative recovery animals received standard two-bottle preference tests with various concentrations of sucrose to evaluate gustatory reactivity. Animals thereafter received two-bottle discrimination tests with selected sucrose concentrations. At the conclusion of preference tests and discrimination tests with sucrose, preference tests and discrimination tests were conducted with sodium chloride. Following those tests animals received taste aversion conditioning to determine whether or not AIGN lesions impaired taste-illness learning. Results of two-bottle taste tests indicated that AIGN lesions do not obviously alter taste reactivity nor taste discriminations to preferred concentrations of sucrose and NaCl. Anterior insular lesions did, however, impair normal taste aversion learning. These results, in combination with those of previous investigators, provide further evidence that the AIGN preferentially contributes to taste learning functions.

Animals↗

Improved methods for fMRI studies of combined taste and aroma stimuli.

Previous neuroimaging studies of the cortical representation of gustatory and olfactory stimuli have often delivered tastants to the mouth in very small quantities or stimulated olfaction orthonasally. In studies of retro-nasal olfaction, swallowing was generally delayed to reduce head motion artefacts. The present fMRI study aims to improve upon such methodological limitations to allow investigation of the cortical representation of flavour (taste and aroma combination) as it typically occurs during the consumption of liquid foods. For this purpose we used (1) a novel, automated, sprayed stimulus delivery system and a larger volume of liquid sample (containing sweet tastants and banana/pear aroma volatiles) to achieve more extensive stimulation of the oral cavity taste receptors, (2) a pseudo-natural delivery paradigm that included prompt swallowing after each sample delivery to obtain physiological retro-nasal olfactory stimulation, (3) fMRI acquisition with wide brain coverage and double-echo EPI to improve sensitivity. We validated our paradigm for the delivery of volatiles using atmospheric pressure chemical ionisation mass spectrometry. This showed that the main retro-nasal delivery of volatiles in the paradigm occurs immediately after the swallow. Several brain areas were found to be activated, including the insula, frontal operculum, rolandic operculum/parietal lobe, piriform, dorsolateral prefrontal cortex, anterior cingulate cortex, ventro-medial thalamus, hippocampus and medial orbitofrontal cortex.

Adult↗

Neocortical involvement in the acquisition and retention of learned alcohol aversions in rats.

In one experiment, rats lacking gustatory neocortex (GN) were compared with control (both normal and control lesion) rats in the acquisition of a learned alcohol aversion. In a second experiment, the effect of GN ablations on preoperatively learned alcohol aversions was examined. Results showed that rats lacking GN both learned and retained alcohol aversions in a normal manner. These same GN rats, however, extinguished the alcohol aversions significantly faster than controls. These results are in contrast to previous data which indicated that the integrity of the GN was necessary for normal acquisition and retention of learned taste aversions. It is suggested that the odor qualities present in the alcohol stimulus account for the relatively normal performance of GN rats.

Alcohol Drinking↗

Efferent connections of the substantia innominata in the rat.

The efferent connections of the substantia innominata (SI) were investigated employing the anterograde axonal transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). The projections of the SI largely reciprocate the afferent connections described by Grove (J. Comp. Neurol. 277:315-346, '88) and thus further distinguish a dorsal and a ventral division in the SI. Efferents from both the dorsal and ventral divisions of the SI descend as far caudal as the ventral tegmental area, substantia nigra, and peripeduncular area, but projections to pontine and medullary structures appear to originate mainly from the dorsal SI. Within the amygdala and hypothalamus, which receive widespread innervation from the SI, the dorsal SI projects preferentially to the lateral part of the bed nucleus of the stria terminalis; the lateral, basolateral, and central nuclei of the amygdala; the lateral preoptic area; paraventricular nucleus of the hypothalamus; and certain parts of the lateral hypothalamus, prominently including the perifornical and caudolateral zones described previously. The ventral SI projects more heavily to the medial part of the bed nucleus of the stria terminalis; the anterior amygdaloid area; a ventromedial amygdaloid region that includes but is not limited to the medial nucleus; the lateral and medial preoptic areas; and the anterior hypothalamus. Modest projections reach the lateral hypothalamus, with at least a slight preference for the medial part of the region, and the ventromedial and arcuate hypothalamic nuclei. Both SI divisions appear to innervate the dorsomedial and posterior hypothalamus and the supramammillary region. In the thalamus, the subparafascicular, gustatory, and midline nuclei receive a light innervation from the SI, which projects more densely to the medial part of the mediodorsal nucleus and the reticular nucleus. Cortical efferents from at least the midrostrocaudal part of the SI are distributed primarily in piriform, infralimbic, prelimbic, anterior cingulate, granular and agranular insular, perirhinal, and entorhinal cortices as well as in the main and accessory olfactory bulbs. The cells of origin for many projections arising from the SI were identified as cholinergic or noncholinergic by combining the retrograde transport of WGA-HRP with histochemical and immunohistochemical procedures to demonstrate acetylcholinesterase activity or choline acetyltransferase immunoreactivity. Most of the descending efferents of the SI appear to arise primarily or exclusively from noncholinergic cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Taste and olfactory intensity perception changes following left insular stroke.

The authors tested suprathreshold intensity perception of gustatory and olfactory stimuli in a 70-year-old right-handed man following a left posterior insular stroke and compared his results with those of age-matched controls. Both modalities revealed significant differences between left (ipsilateral to lesion) and right (contralateral) ratings of intensity. In both gustation and olfaction, these differences were driven primarily by trends toward increased contralateral sensitivity relative to controls. Intensity changes were most pronounced for unpleasant odors and for tastes perceived strongly as either pleasant (sweet) or unpleasant (salty, bitter). These results show that a left posterior insula lesion may affect taste and olfactory perception similarly by increasing sensitivity contralateral to the lesion. One possible mechanism is release from inhibition at the cortical level.

Aged↗

Cortical substrates of taste aversion learning: dorsal prepiriform (insular) lesions disrupt taste aversion learning.

The functional relation between restricted damage to ventral primary somatosensory neocortex and the ability of rats to acquire conditioned taste aversion (CTA( was examined by a combination of behavioral and neurohistological techniques. Lesions confined exclusively to the established gustatory neocortex (GN) did not disrupt CTA acquisition, nor did lesions confined to suprarhinal cortical areas ventral to the GN. Lesions that encroached on dorsal prepiriform and insular cortices produced CTA acquisition deficits and damaged a large proportion of efferent projections to the prefrontal and precentral neocortex. In a second experiment, lesions of dorsal prepiriform and insular cortices did not modify taste preference-aversion threshold to any of the four taste modalities. It is concluded tha ventral somatosensory neocortical fields, including the established GN, do not mediate CTA acquisition and that rhinal cortices ventral and posterior to the GN are preferentially involved in associative learning for tastes and illness.

Animals↗

Release of acetylcholine, gamma-aminobutyrate, dopamine and glutamate, and activity of some related enzymes, in rat gustatory neocortex.

The gustatory neocortex (GN), final relay along the gustatory pathway, is a region of the brain involved in the neural integration of feeding behavior. Since information on the neurotransmitters in this nucleus is scarce, the aim of the present work was to establish whether acetylcholine (ACh), gamma-aminobutyric acid (GABA), dopamine and glutamate may act as transmitters within this structure. It was found that GN slices are able to release labeled GABA, ACh and glutamate but not dopamine. Additionally, it was possible to detect significant glutamic acid decarboxylase, choline acetyltransferase and acetylcholinesterase activities in GN homogenates. The activity of the two enzymes involved in acetylcholine metabolism was higher than that observed in other cortical regions. These findings suggest that GABA, ACh and glutamate probably are neurotransmitters in the GN, whereas dopamine is not.

Acetylcholine↗

Projections from the rhomboid nucleus of the bed nuclei of the stria terminalis: implications for cerebral hemisphere regulation of ingestive behaviors.

The basic organization of an exceptionally complex pattern of axonal projections from one distinct cell group of the bed nuclei of the stria terminalis, the rhomboid nucleus (BSTrh), was analyzed with the PHAL anterograde tract-tracing method in rats. Brain areas that receive a strong to moderate input from the BSTrh fall into nine general categories: central autonomic control network (central amygdalar nucleus, descending hypothalamic paraventricular nucleus, parasubthalamic nucleus and dorsal lateral hypothalamic area, ventrolateral periaqueductal gray, lateral parabrachial nucleus and caudal nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and salivatory nuclei), gustatory system (rostral nucleus of the solitary tract and medial parabrachial nucleus), neuroendocrine system (periventricular and paraventricular hypothalamic nuclei, hypothalamic visceromotor pattern generator network), orofaciopharyngeal motor control (rostral tip of the dorsal nucleus ambiguus, parvicellular reticular nucleus, retrorubral area, and lateral mesencephalic reticular nucleus), respiratory control (lateral nucleus of the solitary tract), locomotor or exploratory behavior control and reward prediction (nucleus accumbens, substantia innominata, and ventral tegmental area), ingestive behavior control (descending paraventricular nucleus and dorsal lateral hypothalamic area), thalamocortical feedback loops (medial-midline-intralaminar thalamus), and behavioral state control (dorsal raphé and locus coeruleus). Its pattern of axonal projections and its position in the basal telencephalon suggest that the BSTrh is part of a striatopallidal differentiation involved in modulating the expression of ingestive behaviors, although it may have other functions as well.

Animals↗

Odor cue mediation of alcohol aversion learning in rats lacking gustatory neocortex.

Normal rats presented with a 5% alcohol solution followed by lithium chloride-induced illness quickly learned to avoid drinking alcohol. After training, the rats also avoided drinking water in the presence of the alcohol odor alone, whether tested immediately or 1 month later. In Experiment 1, rats with gustatory neocortex (GN) ablations also developed strong alcohol aversions when the alcohol solution was paired with illness. They also showed normal avoidance of drinking in the presence of the alcohol odor alone when tested soon after training. In Experiment 2, when normal rats were trained to avoid alcohol, given GN ablations, and then tested for retention 1 month later, avoidance of drinking water in the presence of the odor alone was significant but attenuated somewhat in relation to trained control rats. These data support the hypothesis that rats lacking GN partially acquire alcohol aversions by using odor cues and confirm that associative learning is intact in these rats despite the fact that GN rats display significant deficits in aversion learning when only tastes are paired with illness.

Alcohol Drinking↗

Neurons in the primate orbitofrontal cortex respond to fat texture independently of viscosity.

The primate orbitofrontal cortex (OFC) is a site of convergence from primary taste, olfactory, and somatosensory cortical areas. We describe the responses of a population of single neurons in the OFC that respond to orally applied fat (e.g., safflower oil) and to substances with a similar texture but different chemical composition, such as mineral oil (hydrocarbon) and silicone oil [(Si(CH3)2O)n]. These findings provide evidence that the neurons respond to the oral texture of fat, sensed by the somatosensory system. Use of an oral viscosity stimulus consisting of carboxymethyl-cellulose in the range 1-10,000 centipoise (cP) showed that the responses of these fat-sensitive neurons are not related to stimulus viscosity. Thus a textural component independent of viscosity and related to the slick or oily property is being used to activate these oral fat-sensitive neurons. Moreover, a separate population of neurons responds to viscosity (produced, e.g., by the carboxymethyl-cellulose series), but not to fat with the same viscosity. Thus there is a dissociation between texture channels used to sense fat viscosity and non-fat-produced viscosity. Further, free fatty acids such as linoleic acid do not activate these neurons, providing further evidence that the oral fat-sensing mechanism through which these OFC neurons are activated is not gustatory but textural. Most of this population of fat-sensitive neurons receive convergent taste inputs. These results provide evidence about how oral fat is sensed and are relevant to understanding the physiological and pathophysiological processes related to fat intake.

Action Potentials↗

Alcohol preference in rats lacking gustatory neocortex.

Ingestion of alcohol solutions (in concentrations from 0.5 to 12% v/v) was examined in three experiments where rats lacking gustatory neocortex (GN) were compared with intact and control lesion rats. Two experiments tested alcohol consumption during a restricted schedule of fluid access with one or two bottle tests. The last experiment involved testing with continuous access to water and alcohol solutions in two bottle tests. Subgroups of rats in each experiment were presented with either an ascending or descending order of concentrations. In all experiments, GN rats consumed less total fluid during testing (relative to control rats). In general, GN rats exhibited similar patterns of alcohol consumption as that found in control rats. Where differences between GN rats and control rats were found, GN rats consumed more alcohol than control rats during tests with restricted fluid access. During continuous fluid access, however, no significant differences between GN rats and control rats were found.

Alcohol Drinking↗

The anatomy of epileptic auras: focal pathology and surgical outcome.

An aura is generally understood to be the beginning of a seizure. Yet, following successful surgery for intractable epilepsy, patients may have persistent auras even though they are otherwise seizure free. Ninety patients with intractable seizures and auras underwent resective surgery. Forty-three patients had hippocampal sclerosis and 47 had temporal or extratemporal lesions such as glial tumors or vascular malformations. The semiology of the auras was found to have value in localization but not lateralization of the pathology. Epigastric auras as well as gustatory and olfactory auras were significantly more frequent in patients with hippocampal sclerosis than in those with temporal or extratemporal lesions. Auras of vertigo or dizziness were most frequent in patients with extratemporal pathology. There was a significant difference between the pathology groups in the efficacy of resection in eliminating the auras. Of the patients with hippocampal sclerosis who were rendered seizure free, 18.9% had persistent auras, whereas only one (2.6%) of the patients with temporal or extratemporal lesions who were rendered seizure free had persistent auras. These findings suggest that for patients with hippocampal sclerosis an anatomical dissociation between seizure and aura may occur, whereas this dissociation is not present in patients with lesions. Patients suspected of having hippocampal sclerosis should be counseled preoperatively as to the significant likelihood of persistent auras even if seizures are successfully abolished.

Brain Diseases↗

[Bilateral ageusia after left insular and opercular ischemic stroke].

Gustatory disorders after ischemic stroke is an uncommon event, generally occurring unilaterally, ipsilateral or contralateral to the stroke depending on the site of the lesion. We report a patient who developed bilateral agueusia after a unilateral insular stroke. This 70-year-old right-handed man developed a sudden onset left opercular syndrome in March 1999 with right hemiphyosethesia. Magnetic resonance imaging revealed a left insular and opercular stroke. Anarthria, swallowing and sensorial disorders regressed in a few weeks, but taste disturbances led to a 6 kg weight loss. After six months, the symptoms disappeared. To our knowledge, 32 cases of taste disorders after stroke have been reported. For most of the cases, the agueusia was unilateral. Our case illustrated the predominance of the left cortical hemisphere for taste perception in the right-handed subject.

Aged↗

Corticofugal influence on taste responses in the parabrachial pons of the rat.

Although the anatomy of centrifugal input to gustatory neural structures has been described, little is known of the physiological mechanisms that convey this influence or of their functional significance. As a first step in the investigation of these issues, the effect of a reversible lesion in the gustatory neocortex (GN) on the neural code for taste in the parabrachial nucleus of the pons (PbN) was studied in rats. Electrophysiological responses to taste stimuli bathed over the tongue were recorded from single units in the PbN before, after and following recovery from an infusion of procaine-HCl into the GN. Test stimuli consisted of sapid solutions of NaCl (0.1 M), HCl (0.01 M), sucrose (0.5 M), Na-saccharin (0.004 M) and quinine-HCl (0.01 M). Infusions of procaine into the GN were correlated with both specific and nonspecific effects on the responsivity to gustatory stimuli in the PbN. Specific effects included: (1) changes in the magnitude of response to some tastants, but not others, in a given PbN unit, (2) changes in the across unit patterns produced by sweet stimuli and (3) the appearance of OFF responses in a subset of PbN units. Nonspecific effects were evidenced by changes in the spontaneous rates of activity and by enhancement or suppression of responses across all the tastants tested in a subset of PbN units. Comparison of these results with reports on the effects of decerebration suggests that some of these effects may be accounted for by interruption of the descending input from the GN to the PbN. In addition, the stimulus-specific effects that were noted following procaine infusion into the GN provide support for the suggestion that the GN specifically modifies the electrophysiological patterns that are evoked by salient taste stimuli.

Animals↗

Corticofugal input to taste-responsive units in the parabrachial pons.

Taste responses in units in the parabrachial nucleus of the pons (PbN) that receive direct projections from the gustatory neocortex (GN) were examined in the rat. Electrical stimulation was applied to the GN with bipolar stimulating electrodes. Time-locked responses to GN stimulation were observed in 19 of 62 (31%) taste-responsive units identified in the PbN. Of these, 17 units produced excitatory responses following GN stimulation and 2 units showed evidence of inhibition. No evidence of antidromic activation of PbN units was apparent. These results are consistent with descriptions of the anatomical projections from the GN to the PbN and demonstrate that some portion of taste-responsive neural elements within the PbN receive direct cortical input. PbN units that followed GN stimulation could not be distinguished from those that did not follow either by their spontaneous rates or their response profiles. These results suggest that axons from the GN do not select targets within the PbN based on the particular response properties.

Animals↗

[Olfactory evoked potentials and contingent negative variation in expert assessment of disordered sense of smell].

Normally, the sense of smell is assessed by means of traditional subjective tests (sniff test, gustatory smell test, and trigeminus test). When results are inconclusive, an objective smell test is indicated. Simultaneously registering olfactory evoked potentials (OEP) and contingent negative variation (CNV) permits evaluation of both odor perception and odor discrimination. We can even objectively assess the false olfactory sensations in parosmia patients who are unable to discriminate between different odors. In this study, the results of 59 patients with olfactory disorders are presented. Head trauma and upper respiratory infections were the most common causes of the patients' complaints. In twelve cases, lack of cooperation and patient unrest prevented us from evaluating the data. In anosmia, the objective results agreed completely with the patient's subjective assessment. In hyposmia and parosmia, the results agreed with the patient's subjective assessment in most cases; here we were able to arrive at a more specific diagnosis in several cases. The objective smell test can be used to supplement subjective methods and thus provide more reliable assessment of olfactory disorders.

Attention↗

Parabrachial gustatory lesions impair taste aversion learning in rats.

Lesions in the gustatory zone of the parabrachial nuclei (PBN) severely impair acquisition of a conditioned taste aversion (CTA) in rats. To test whether this deficit has a memorial basis, intact rats (n = 15) and rats with PBN lesions (PBNX; n = 10) received seven intraoral taste stimulus infusions (30 s, 0.5 ml) distributed over a 30.5-min period after either LiCl or NaCl injection. This task measures the rapid formation of a CTA and has minimum demands on memory. LiCl-injected intact rats progressively changed their oromotor response profile from one of ingestion to one of aversion. NaCl-injected intact rats did not change their ingestive pattern of responding. In contrast, there was no difference between LiCl- and NaCl-injected PBNX rats. These same PBNX rats failed to avoid licking the taste stimulus when tested in a different paradigm. A simple impairment in a memorial process is not likely the basis for the CTA deficit.

Afferent Pathways↗