Opioid modulation of taste responses in the nucleus of the solitary tract

Gustatory processing within the medulla is modulated by a number of physiologic and experiential factors. Several neurotransmitters, including excitatory amino acids, GABA, and substance P, are involved in synaptic processing within the rostral portion of the nucleus of the solitary tract (NST). Endogenous opiates have been implicated in the regulation of feeding behavior and in taste palatability and gustatory responses in the parabrachial nuclei are reduced by systemic morphine. In the present experiments, extracellular recording of neuronal activity within the NST in response to taste input was combined with local microinjection of met-enkephalin (Met-ENK) and naltrexone (NLTX) to determine the effect of these agents on gustatory activity. The anterior tongue was stimulated with anodal current pulses to determine the time course of drug action (n=85 cells) and with prototypical taste stimuli (0.032 M sucrose, NaCl, and quinine hydrochloride, and 0.0032 M citric acid) to investigate the effects of these opioid compounds on taste-evoked responses (n=80 cells). Among these 165 taste-responsive neurons in the NST, the activity of 39 (23.6%) was suppressed by Met-ENK. These effects were dose-dependent and blockable by NLTX, which alone was without effect, suggesting that opiates do not maintain a tonic inhibitory influence. Immunohistochemical experiments demonstrated both micro - and delta-opioid receptors within the gustatory portion of the NST; previous studies had shown numerous fiber terminals containing Met-ENK. These data suggest that endogenous opiates play an inhibitory role in gustatory processing within the medulla.     

Neurons in the posterior insular cortex are responsive to gustatory stimulation of the pharyngolarynx, baroreceptor and chemoreceptor stimulation, and tail pinch in rats

Extracellular unit responses to gustatory stimulation of the pharyngolaryngeal region, baroreceptor and chemoreceptor stimulation, and tail pinch were recorded from the insular cortex of anesthetized and paralyzed rats. Of the 32 neurons identified, 28 responded to at least one of the nine stimuli used in the present study. Of the 32 neurons, 11 showed an excitatory response to tail pinch, 13 showed an inhibitory response, and the remaining eight had no response. Of the 32 neurons, eight responded to baroreceptor stimulation by an intravenous (i.v.) injection of methoxamine hydrochloride (Mex), four were excitatory and four were inhibitory. Thirteen neurons were excited and six neurons were inhibited by an arterial chemoreceptor stimulation by an i.v. injection of sodium cyanide (NaCN). Twenty-two neurons were responsive to at least one of the gustatory stimuli (deionized water, 1.0 M NaCl, 30 mM HCl, 30 mM quinine HCl, and 1.0 M sucrose); five to 11 excitatory neurons and three to seven inhibitory neurons for each stimulus. A large number of the neurons (25/32) received converging inputs from more than one stimulus among the nine stimuli used in the present study. Most neurons (23/32) received converging inputs from different modalities (gustatory, visceral, and tail pinch). The neurons responded were located in the insular cortex between 2.0 mm anterior and 0.2 mm posterior to the anterior edge of the joining of the anterior commissure (AC); the mean location was 1.2 mm (n=28) anterior to the AC. This indicates that most of the neurons identified in the present study seem to be located in the region posterior to the taste area and anterior to the visceral area in the insular cortex. These results indicate that the insular cortex neurons distributing between the taste area and the visceral area receive convergent inputs from gustatory, baroreceptor, chemoreceptor, and nociceptive organs.     

Organization of GABA and GABA-transaminase containing neurons in the gustatory zone of the nucleus of the solitary tract

Previous cytoarchitectural and electron micrographic studies have indicated that the gustatory zone of the nucleus of the solitary tract (NST) may contain local circuit neurons. It is known that neurons of the caudal "visceroceptive" NST contain GABA, glutamic acid decarboxylase (EC 4.1.1.15), and GABA-transaminase (GABA-T; 4-aminobutyrate: 2-oxoglutarate aminotransferase; EC 2.6.1.19). The present study was conducted to determine whether or not neurons in the gustatory zone of the NST of rat contain GABA and the principle degradative enzyme of GABA, GABA-T. Transganglionic transport of horseradish peroxidase (HRP) was used to identify chorda tympani (CT) nerve terminal fields. Immunohistochemical studies were combined with transport experiments to evaluate the organization of GABA immunoreactive neurons in CT terminal fields. Results show that GABA immunoreactive neurons and puncta are located within CT terminal fields. These neurons evince small ovoid morphologies resembling Golgi interneurons, and comprise an average of 18% of total neurons in CT terminal fields. Independent histochemical studies reveal that approximately 82% of GABA immunoreactive neurons within CT terminal fields exhibit GABA-T activity. Retrograde transport of HRP was used in additional studies to evaluate whether or not axons of putative GABAergic neurons project to the second-order central gustatory relay located in the caudal parabrachial nucleus (PBNc), to the caudal NST, or to regions surrounding the rostral or caudal NST. Combined studies indicate that GABA immunoreactive neurons in the gustatory NST do not project axons to the PBNc, to the caudal NST, or to regions adjacent to the rostral or caudal NST.(ABSTRACT TRUNCATED AT 250 WORDS)     

Re-examination of the human taste region: a positron emission tomography study.

There is considerable uncertainty regarding the cortical areas in the human brain that are involved in gustatory processing. Evidence from nonhuman primates indicates that parts of the peri-central opercular region (secondary somatosensory cortex) and insular cortex may be important for gustatory processing. The aim of the study was to examine changes in cerebral blood flow during gustatory stimulation (with sucrose or water) in the insulo-opercular region of the human brain with positron emission tomography using only movement of the tongue and mouth as control conditions. This is important because subtractions of responses to one gustatory stimulus from those to another may mask gustatory activity that is common to both stimuli, even when the control stimulus is an apparently tasteless one (e.g. water). Bilateral increases in activity were observed in the insulo-opercular region and, consistent with animal work, they indicate that there are a number of separate foci within this general area where primary gustatory inputs may be processed.     

Cortical responses to electrical and gustatory stimuli in the rabbit.

The distribution of surface positive cortical potentials evoked by electrical stimulation of the chorda tympani, glossopharyngeal and lingual nerves which innervate the tongue was mapped in rabbits. All projections were bilateral. Judging from the extent of the cortical response area and the amplitude and latency of the responses, the major projection of the chorda tympani was ipsilateral, whereas that of the lingual and the glossopharyngeal nerves was contralateral. Both the chorda tympani and the glossopharyngeal nerve project to a confined area in the insular cortex and the lingual nerve projects to the appropriate part of the somatotopic pattern of somatic sensory area I. Further, a single unit study was undertaken to characterize the response of units in the cerebral cortex which was induced by gustatory stimulation of the anterior tongue, Twenty-four gustatory units were found in the insular cortex and the claustrum. The gustatory units were divided into an early response type (21 units) and a late response type (3 units) based on latency measurements. Gustatory units were also classified according to discharge patterns into excitation type (21 units) and inhibition type (4 units). Eleven units responded to 1 or 2 kinds of conventional taste stimuli, and 13 units responded to more than 3 different taste stimuli. Sensitivities of cortical units to the 4 conventional taste stimuli were found to be mutually independent and randomly distributed among cortical units. The frequency of discharges increased in the excitation type units and decreased in the inhibition type units monotonically with the excitation type units and decreased in the inhibition type units monotonically with an increse of NaCl concentration exfept at the highest concentrations.     

Gustatory cortex in the rat. I. Physiological properties and cytoarchitecture

The precise cytoarchitectural localization of taste-elicited cortical responses in the rat was studied using a combination of anatomical and physiological techniques. Multi-unit responses to tongue tactile, thermal and gustatory stimuli were recorded along 97 electrode penetrations positioned parallel to the lateral convexity of the brain and marking lesions were placed at the sites of transitions in these functional properties. Lesions made at sites that received different sensory inputs were consistently located within different cytoarchitectural subdivisions. In this manner, taste cortex in the rat was localized to the agranular insular cytoarchitectural region, in contrast to its traditional assignation to granular insular cortex. Instead, tongue temperature was found to be represented in the cortical area previously termed gustatory, i.e., in ventral granular cortex where layer IV attenuates.     

Cortical and thalamic afferent connections of the insular and adjacent cortex of the rat

Thalamic and cortical afferents to the insular and perirhinal cortex of the rat were investigated. Unilateral injections of horseradish peroxidase (HRP) were made iontophoretically along the rhinal sulcus. HRP injections covered or invaded areas along the rhinal fissure from about the level of the middle cerebral artery to the posterior end of the fissure. The most anterior injection labeled a few cells in the mediodorsal nucleus. More posterior injections labeled neurons in the basal portion of the nucleus ventralis medialis, thus suggesting that this cortical region constitutes the rat's gustatory (insular) cortex. We consider the cortex situated posterior to the gustatory cortex in and above the rhinal sulcus as the core region of the rat's (associative) insular cortex, as this cortex receives afferents from the regions of and between the nuclei suprageniculatus and geniculatus medialis, pars magnocellularis. It includes parts of the cortex termed perirhinal in other studies. The cortex dorsal and posterior to the insular cortex we consider auditory cortex, as it receives afferents from the principal part of the medial geniculate nucleus, and the cortex ventral to the insular cortex (below the fundus of the rhinal sulcus) we consider to constitute the prepiriform cortex, which is athalamic. The posterior part of the perirhinal cortex (area 35) receives afferents from nonspecific thalamic nuclei (midline nuclei). Cortical afferents to the injection loci arise from a number of regions, above all from regions of the medial and sulcal prefrontal cortex. Those injections confined to the projection cortex of the suprageniculate-magnocellular medial geniculate nuclear complex also led to labeling in contralateral prefrontal regions, particularly in area 25 (infralimbic region). A comparison of our results with those on the insular cortex of cats and monkeys suggests that on the basis of thalamocortical connections, topographical relations, and involvements of neurons in information processing and overt behavior, the insular cortex has to be regarded as a heterogeneous region which may be separated into prefrontal insular, gustatory (somatosensory) insular, and associative insular portions.     

Taste-evoked Fos expression in nitrergic neurons in the nucleus of the solitary tract and reticular formation of the rat

The current investigation used double labeling for NADPHd and Fos-like immunoreactivity to define the relationship between nitric oxide synthase-containing neural elements and taste-activated neurons in the nucleus of the solitary tract (NST) and subjacent reticular formation (RF). Stimulation of awake rats with citric acid and quinine resulted in significant increases in the numbers of double-labeled neurons in both the NST and RF, suggesting that some medullary gustatory neurons utilize nitric oxide (NO) as a transmitter. Overall, double-labeled neurons were most numerous in the caudal reaches of the gustatory zone of the NST, where taste neurons receive inputs from the IXth nerve, suggesting a preferential role for NO neurons in processing gustatory inputs from the posterior oral cavity. However, double-labeled neurons also exhibited a preferential distribution depending on the gustatory stimulus. In the NST, double-labeled neurons were most numerous in the rostral central subnucleus after either stimulus but had a medial bias after quinine stimulation. In the RF, after citric acid stimulation, there was a cluster of double-labeled neurons with distinctive large soma in the parvicellular division of the lateral RF, subjacent to the rostral tip of NST. In contrast, in response to quinine, there was a cluster of double-labeled neurons with much smaller soma in the intermediate zone of the medial RF, a few hundred micrometers caudal to the citric acid cluster. These differential distributions of double-labeled neurons in the NST and RF suggest a role for NO in stimulus-specific gustatory autonomic and oromotor reflex circuits.     

Hunger Modulates the Responses to Gustatory Stimuli of Single Neurons in the Caudolateral Orbitofrontal Cortex of the Macaque Monkey

1. In order to determine whether the responsiveness of neurons in the caudolateral orbitofrontal cortex (a secondary cortical gustatory area) is influenced by hunger, the activity evoked by prototypical taste stimuli (glucose, NaCl, HCl, and quinine hydrochloride) and fruit juice was recorded in single neurons in this cortical area before, while, and after cynomolgous macaque monkeys were fed to satiety with glucose or fruit juice. 2. It was found that the responses of the neurons to the taste of the glucose decreased to zero while the monkey ate it to satiety during the course of which his behaviour turned from avid acceptance to active rejection. 3. This modulation of responsiveness of the gustatory responses of the neurons to satiety was not due to peripheral adaptation in the gustatory system or to altered efficacy of gustatory stimulation after satiety was reached, because modulation of neuronal responsiveness by satiety was not seen at earlier stages of the gustatory system, including the nucleus of the solitary tract, the frontal opercular taste cortex, and the insular taste cortex. 4. The decreases in the responsiveness of the neurons were relatively specific to the food with which the monkey had been fed to satiety. For example, in seven experiments in which the monkey was fed glucose solution, neuronal responsiveness decreased to the taste of the glucose but not to the taste of blackcurrant juice. Conversely, in two experiments in which the monkey was fed to satiety with fruit juice, the responses of the neurons decreased to fruit juice but not to glucose. 5. These and earlier findings lead to a proposed neurophysiological mechanism for sensory-specific satiety in which the information coded by single neurons in the gustatory system becomes more specific through the processing stages consisting of the nucleus of the solitary tract, the taste thalamus, and the frontal opercular and insular taste primary taste cortices, until neuronal responses become relatively specific for the food tasted in the caudolateral orbitofrontal cortex (secondary) taste area. Then sensory-specific satiety occurs because in this caudolateral orbitofrontal cortex taste area (but not earlier in the taste system) it is a property of the synapses that repeated stimulation results in a decreased neuronal response. 6. Evidence was obtained that gustatory processing involved in thirst also becomes interfaced to motivation in the caudolateral orbitofrontal cortex taste projection area, in that neuronal responses here to water were decreased to zero while water was drunk until satiety was produced.     

A search for the cortical gustatory area in the hamster

The gustatory area was searched in the cerebral cortex of the hamster by means of a combined approach using electrophysiological, behavioral, and histological experiments. The chorda tympani (CT), which innervates taste buds on the anterior part of the tongue, projected to a confined area anterior to the middle cerebral artery and just dorsal to the rhinal fissure. The trigeminal component of the lingual nerve (LN) area was located anterodorsal to the CT area, and the glossopharyngeal nerve (GN), which innervates taste buds on the posterior part of the tongue, was posterior to the CT area. The center of the CT and GN areas belonged to the dorsal part of the dysgranular insular cortex, and the LN area was within the primary somatosensory granular cortex. Bilateral symmetrical ablations of the CT and GN areas abolished the conditioned taste aversion (to sodium saccharin) that had been acquired before ablations, indicating a role of these areas in some cognitive processes of taste perception. Injections of horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) in the CT and GN areas, centered in the dysgranular insular cortex, revealed that this cortical region had major fiber connections with the contralateral homotypical cortical area, ipsilateral amygdala (central, lateral and basolateral nuclei), ipsilateral parvicellular part of the posteromedial ventral nucleus of the thalamus, bilateral parabrachial nucleus, contralateral nucleus of the solitary tract, raphe nuclei, and the locus ceruleus. Conversely, injections of WGA-HRP in these target areas showed anterograde and/or retrograde transport in the similar dysgranular insular cortex and additionally in the ventral part of the granular insular cortex. The present results suggest that the cortical gustatory area of the hamster is about 1.5 × 1.5 mm in size with the topographic organization between anterior and posterior parts of the tongue, and is located mainly in the dysgranular insular cortex around the middle cerebral artery.     

Postnatal development of the rostral solitary nucleus in rat: dendritic morphology and mitochondrial enzyme activity

Morphological and metabolic development of the gustatory zone of the rostral nucleus of the solitary tract (NST) was examined in rat. Transganglionic transport of horseradish peroxidase (HRP) was used to visualize the organization of gustatory projections to the rostral gustatory NST in rats aged postnatal day 1 (P1) to P34. Golgi impregnation studies were performed to analyze morphological development of dendrites in regions of the rostral NST that were identified as anterior tongue terminal fields. Results demonstrate that afferent fibers of the anterior tongue project to the rostral NST in rats as young as P1. The volume of NST terminal fields increased from P1 to approximately P16-P20, and was adult-like after approximately P20. Developmental increases in terminal field volume resulted from a preferential expansion in the rostrocaudal plane. Planar length of first-order dendrites associated with fusiform, multipolar, and ovoid neurons, and second-order dendrites of fusiform and ovoid neurons, increased approximately three-fold between P4 and P16-20. First-order dendritic length for all morphological types was adult-like after approximately 20-25 days of age, whereas second-order dendritic length of multipolar neurons increased significantly between P30 and P60-70. Histochemical studies confirmed that activity of the mitochondrial respiratory enzymes cytochrome c oxidase (EC 1.9.3.1), succinate dehydrogenase (EC 1.3.99.1), and NADH-dehydrogenase (EC 1.6.99.3) increased monotonically during the developmental period in which planar growth of first-order dendrites was observed. The present results, in combination with results from previous studies, indicate that morphological and metabolic development fo the NST occurs concomitantly with morphological development of taste receptors and peripheral gustatory nerves.(ABSTRACT TRUNCATED AT 250 WORDS)     

Taste neurons in the cortex of the alert cynomolgus monkey.

The activity of single neurons in the gustatory cortex of alert cynomolgus monkeys was analyzed. Taste-evoked activity in response to the four prototypical taste stimuli was recorded from a cortical gustatory area comprising the frontal operculum and adjoining anterior insula. Spontaneous activity for 364 gustatory neurons was 3.9 +/- 4.9 (mean +/- SD) spikes/s. Mean net (gross minus spontaneous) discharge rates for all gustatory neurons were: 1.0 M glucose = 4.9 +/- 11.6, 0.3 M NaCl = 3.2 +/- 7.1, M quinine HCl = 2.6 +/- 5.8, and 0.01 M HCl = 1.7 +/- 4.6. The results from intensity-response functions imply that the perception of each basic taste quality in the nonhuman primate is based on the activity of the appropriate neural subgroup rather than on the mean activity of all taste cells. Therefore a more meaningful index of the effectiveness of a stimulus may be the discharge rate it evokes from the subset of gustatory neurons for which it is the best stimulus. Glucose was the best stimulus for 142 cells (including ties), from which it elicited a mean net response of 10.3 spikes/s; NaCl was best for 107 neurons which gave a mean 8.7 spikes/s; quinine HCl evoked 6.2 spikes/s from the 74 cells that responded best to it; HCl elicited 5.9 spikes/s from the 49 neurons for which it served as best stimulus. The response characteristics of cortical taste cells indicate heterogeneous features, and significantly different patterns from those reported in other nonchemical sensory systems.     

Immunocytochemical staining of GABA in the insular lobe of the savanna baboon: a light microscopic study

The free floating peroxidase antiperoxidase (PAP) technique has been applied to sections of the baboon insular cortex using an antibody for gamma-aminobutyric acid (GABA). Immunostaining was localized to neuronal processes, punctate structures in the neuropil, and neuroglial cells in the subcortical white matter. GABAergic neurons were present in all cortical layers (especially layers II, III, and V/VI), in the subcortical white matter, and at all insular levels. Individual GABA-immunostained nerve cell bodies were non-pyramidal in type, often vertically oriented, round or pear-shaped, and 7.5-12.5 microns in their major transverse diameter. In the deepest cortical layers larger GABA-positive neurons were present. Horizontal GABA-positive cells were rarely identified. Immunostained neurons with apically oriented processes, basally directed processes, bipolar neurons, and multipolar neurons (10-12.5 microns in major transverse diameter) were also identified. Pyramidal shaped cells (measuring 17.5-18.5 micron) and the proximal portions of their processes were often outlined by puncta. GABA-immunostained cells in the subcortical white matter typically had a long but narrow shape. These GABAergic neurons are considered to be intrinsic or local circuit neurons.     

Immature Neurons and GABA Networks May Contribute to Epileptogenesis in Pediatric Cortical Dysplasia

Summary:  Cortical dysplasia (CD), a frequent pathological substrate of pediatric epilepsy surgery patients, has a number of similarities with immature cortex, such as reduced Mg²⁺ sensitivity of N-methyl-D-aspartate (NMDA) receptors and the persistence of subplate-like neurons and undifferentiated cells. Because γ-aminobutyric acid (GABA) is the main neurotransmitter in early cortical development, we hypothesized increased GABA receptor-mediated synaptic function in CD tissue. Infrared videomicroscopy and whole-cell patch clamp recordings were used to characterize the morphology and electrophysiological properties of immature and normal-appearing neurons in slices from cortical tissue samples resected for the treatment of pharmacoresistant epilepsy in children (0.2–14 years). In addition, we examined spontaneous and evoked synaptic activity, as well as responses to exogenous GABA application. We demonstrate both the presence of immature pyramidal neurons and networks in young CD tissue and the predominance of GABA synaptic activity. In addition, spontaneous GABA depolarizations frequently induced action potentials, supporting a potential excitatory role of GABA in CD. Evoked synaptic responses mediated by GABA were also prominent, and bath application of 4-aminopyridine induced rhythmic depolarizations that were blocked by bicuculline. Finally, responses to exogenous application of GABA had depolarized reversal potentials in severe compared to mild and non-CD cases. The present data support the hypothesis that CD shares features of immature cortex, with predominant and potentially excitatory GABA_A receptor-mediated neurotransmission. These results could partially explain the increased excitability of the cortical network in pediatric CD.     

Restoration of quinine‐stimulated fos‐immunoreactive neurons in the central nucleus of the amygdala and gustatory cortex following reinnervation or cross‐reinnervation of the lingual taste nerves in rats

Remarkably, when lingual gustatory nerves are surgically rerouted to inappropriate taste fields in the tongue, some taste functions recover. We previously demonstrated that quinine‐stimulated oromotor rejection reflexes and neural activity (assessed by Fos immunoreactivity) in subregions of hindbrain gustatory nuclei were restored if the posterior tongue, which contains receptor cells that respond strongly to bitter compounds, was cross‐reinnervated by the chorda tympani nerve. Such functional recovery was not seen if instead, the anterior tongue, where receptor cells are less responsive to bitter compounds, was cross‐reinnervated by the glossopharyngeal nerve, even though this nerve typically responds robustly to bitter substances. Thus, recovery depended more on the taste field being reinnervated than on the nerve itself. Here, the distribution of quinine‐stimulated Fos‐immunoreactive neurons in two taste‐associated forebrain areas was examined in these same rats. In the central nucleus of the amygdala (CeA), a rostrocaudal gradient characterized the normal quinine‐stimulated Fos response, with the greatest number of labeled cells situated rostrally. Quinine‐stimulated neurons were found throughout the gustatory cortex, but a “hot spot” was observed in its anterior–posterior center in subregions approximating the dysgranular/agranular layers. Fos neurons here and in the rostral CeA were highly correlated with quinine‐elicited gapes. Denervation of the posterior tongue eliminated, and its reinnervation by either nerve restored, numbers of quinine‐stimulated labeled cells in the rostralmost CeA and in the subregion approximating the dysgranular gustatory cortex. These results underscore the remarkable plasticity of the gustatory system and also help clarify the functional anatomy of neural circuits activated by bitter taste stimulation. J. Comp. Neurol. 522:2498–2517, 2014. © 2014 Wiley Periodicals, Inc.     

Excitatory Amino Acid Pathway from the Hippocampus to the Prefrontal Cortex. Contribution of AMPA Receptors in Hippocampo-prefrontal Cortex Transmission

Previous experiments in the rat have demonstrated that field CA1 and the subiculum project to the prefrontal cortex and that this direct unilateral pathway is excitatory. In the present study, anatomical and electrophysiological approaches were used to determine the transmitter mediating the excitatory responses in prefrontal cortex neurons to low-frequency stimulation of the hippocampus. The method of selective retrograde d-[3H]aspartate labelling was used to identify putative glutamatergic and/or aspartatergic hippocampal afferent fibres to the prefrontal cortex. Unilateral microinjection of d-[3H]aspartate into the prelimbic area of the prefrontal cortex resulted in the retrograde labelling of a fraction of hippocampal neurons. Some labelled cell bodies were distributed in field CA1 and the subiculum but larger numbers of neurons were detected in the ventral and intermediary subiculum. In a second series of experiments, the excitatory transmission from the hippocampus to the prefrontal cortex was pharmacologically analysed to provide further evidence for the involvement of glutamate and/or aspartate in the pathway. All prefrontal cortex neurons responding to the stimulation of the hippocampus were activated by selective agonists of the glutamate receptor subtypes alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-d-aspartate (NMDA), and these effects were selectively antagonized by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonopentanoic acid (APV) respectively. Most of the excitatory responses of prefrontal cortex neurons to single and paired-pulse stimulation of the hippocampus were antagonized by CNQX. APV only affected the excitatory response in a few cells. These results suggest that the hippocampal input to the prefrontal cortex utilizes glutamate and/or aspartate as a transmitter. Even though prefrontal cortex neurons responding to the stimulation of the hippocampus appear to have both AMPA and NMDA receptors, low-frequency stimulation of the hippocampo-prefrontal cortex pathway activates cortical neurons mostly through AMPA receptors.     

Cortical association areas in the gustatory system

The existence, location and interrelationships of cortical gustatory association areas in primates and rodents are discussed. Based on previous proposals, and on anatomical, physiological and lesion data, we propose that in addition to primary gustatory cortex, located in primate opercular cortex and rodent granular insular cortex, three association areas exist. A secondary area is located in dysgranular insular cortex, a tertiary area in agranular insular cortex, and the terminus of the cortical gustatory analyzer is located in perirhinal cortex. We propose that the subjective awareness of flavor is most probably due to neuronal activities in agranular insular cortex.     

Reciprocal functional connections of the olfactory bulbs and other olfactory related areas with the prefrontal cortex

Reciprocal putative connections of the prefrontal cortex (PFC) (agranular insular, ventral and lateral orbital region) with the ipsi and contralateral main olfactory bulb (IOB; COB), the mediodorsal thalamic nucleus (MD), the basolateral amygdaloid nucleus (BLA) and the piriform cortex (PC) were investigated with electrophysiological techniques. Evoked field responses and orthodromic unit driving, generated in PFC following electrical stimulation of the above mentioned structures, were abolished following topical application of KCl, except for COB evoked mass potentials. Thus, locally generated activity was elicited in agranular insular cortex following IOB activation, the same region where recently, the taste cortex in the rat was localized. Since gustatory-visceral afferent information reaches insular cortex via 2-3 synaptic relays, autonomic, olfactory and gustatory inputs may interact at this level, and, as suggested previously for the mouse, play a key integrative role in flavor perception. Antidromically invaded neurons, 47% of which were identified by the collision-extinction technique, were also found in PFC areas which overlapped to a considerable extent with those from which orthodromic unit responses were obtained. In particular, closely spaced neurons in ventrolateral orbital (VLO) and lateral orbital (LO) regions were antidromically invaded following IOB and PC shocks; some neurons antidromically discharged by IOB were also transsynaptically activated following PC stimulation. These findings are in agreement with recent neuroanatomical studies which demonstrate axonal projections from PFC neurons to the IOB and COB in the rat and South American armadillo. In addition, stimulation of PFC regions dorsal to the rhinal fissure mostly inhibited spontaneous unit discharges recorded at the mitral cell layer of the IOB, suggesting that this effect may be partially mediated by excitatory inputs of prefrontal axons onto granule cells. The conduction properties, antidromic thresholds and activity-dependent variations in conduction velocity (CV) of bulbopetal neurons in prefrontal cortex were found to be similar to those exhibited by cells projecting to the IOB from olfactory peduncle regions, but not to those present in bulbopetal neurons of the horizontal limb of diagonal band, indicating that the OB may be subjected to centrifugal control by at least two cell groups differing in both histochemical and electrophysiological properties.     

Estrogen attenuates neuronal excitability in the insular cortex following middle cerebral artery occlusion

The current investigation examined the role of estrogen in the insular cortex (IC) under both normal and ischemic conditions. Experiments were done in anaesthetized male Sprague-Dawley rats. The effect of systemic 17beta-estradiol (estrogen) administration on levels of amino acids and of endogenous estrogen obtained by microdialysis and its effect on neuronal activity of cells located in the insular cortex were measured in the absence of, and following permanent occlusion of, the right middle cerebral artery (MCA). In normal rats, intravenous (i.v.) injection of estrogen resulted in a significant increase (greater than 25 spikes/bin) in the spontaneous activity of neurons located within the insular cortex, while there was a significant decrease in gamma-aminobutyric acid (GABA) levels measured in IC dialysate. Middle cerebral artery occlusion (MCAO) resulted in a biphasic response consisting of a transient increase in the extracellular concentration of glutamate, aspartate, and GABA, followed by sustained elevations in glutamate and aspartate, but reduced GABA levels 4 h post-MCAO. MCAO also resulted in a significant increase in neuronal activity in the IC (from 28 +/- 9 to 120 +/- 88 spikes/bin). This MCAO-induced excitation was completely blocked following the prior intravenous administration of estrogen. Systemic estrogen administration also resulted in a delay in the progression and decrease in the final infarct volume by approximately 56%. Taken together, these results suggest that under normal conditions, estrogen excites neurons in the insular cortex by decreasing GABA release (disinhibition) and it plays a role in attenuating the MCAO-induced excitability and death of these neurons.     

Primary somatosensory cortex modulation of tactile responses in nucleus gracilis cells of rats

Corticofugal influences from the primary somatosensory cortex to the gracilis nuclei were studied with single unit recordings performed in urethane-anaesthetized rats. Two types of neurons were identified: low firing rate (LF) neurons, which could be activated antidromically by medial lemniscus stimulation; and high firing rate (HF) neurons. The effects of electrically stimulating the contralateral primary somatosensory cortex were studied in two situations: when the stimulated cortical area and specific gracilis cells had overlapping receptive fields and when the receptive fields of the cells and primary somatosensory cortex did not overlap. Cortical stimulation facilitated cortical and tactile responses in most gracilis neurons (68% and 58% for LF and HF neurons, respectively) with overlapping receptive fields. When receptive fields were different, cortical stimulation inhibited tactile response in most LF neurons (58%) and some HF neurons (20%). Trains of cortical shocks during sensory stimulation demonstrated that the facilitatory and inhibitory effects outlasted the stimulation period by 5 min. The facilitatory effect was decreased by iontophoretic application of the N-methyl-D-aspartate (NMDA) receptor antagonist APV (50 mm). However, APV did not modify the intensity of the tactile response inhibition in cells with nonoverlapping receptive fields, although, its duration was decreased (<5 min). Iontophoretic application of the gamma-aminobutyric acid (GABA)(A) antagonist bicuculline (20 mm) blocked the cortically evoked inhibition in cells with nonoverlapping receptive fields. The results indicate that the somatosensory cortex precisely controls somatosensory transmission throughout the gracilis nucleus by means of NMDA and GABA(A) receptor activation.