Zoltán Karádi

Adrenal medullary cells transmute into dopaminergic neurons in dopamine-depleted rat caudate and ameliorate motor disturbances

Adrenal medullary cell suspensions, derived from newborn rats (postnatal day 1-6), were implanted into the head of the caudate nucleus in 35 rats with unilateral 6-hydroxydopamine (6-OHDA) lesions in the nigrostriatal dopamine (DA) pathway. Behavioral recovery from Met-amphetamine induced circling, cell growth and morphological features (tyrosine hydroxylase positive cells), and release of adrenaline (Ad), noradrenaline (NA), DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were investigated for 40 weeks after transplantation. Met-amphetamine induced circling decreased significantly in 43% (15/35) of the rats. The decrease was concurrent with transmutation of the tyrosine hydroxylase-like immunopositive (THLI) cells into mature neurons that had abundant elongated neurites with varicosities and synapses on neuronal elements in the host caudate. In the absence of behavioral recovery (57%, 20/35) THLI cells were very scant. DA, DOPAC and HVA were reduced more than 90% in perfusates collected by in vivo dialysis from the striata of the animals that were not improved by transplant. These levels recovered to 20-50% of controls in animals whose behavior recovered. Ad and NA were not detected in the perfusates of either recovered or non-recovered animals. The results suggest that some grafted adrenal medullary cells transform into dopaminergic neurons and the release of DA from these grafted cells functionally affects behavior improvement for at least 40 weeks.

Olfactory coding in the monkey lateral hypothalamus: Behavioral and neurochemical properties of odor-responding neurons

The activity of glucose-sensitive (GS) and glucose-insensitive (GIS) neurons was recorded in the lateral hypothalamic area (LHA) of monkeys during olfactory stimulation, a conditioned alimentary bar press task, and microelectrophoretic application of catecholamines. Olfactory stimuli evoked response of 88% of the GS neurons, and 52% of the GIS cells responded to odors. The GS neurons were more broadly tuned across odorants than the GIS cells, and their responses to various smells with distinct hedonic value were also differential. The odor-responding GS neurons were depressed during the bar press and reward periods of the task, and were mainly inhibited by dopamine. The odor-responding GIS cell activity increased in response to cue light and tone, and was facilitated by dopamine. Histological examinations disclosed topographic dissociation of the odor-responding GS and GIS cells: the former were located in more ventromedial regions than the latter. The results indicate that the GS neurons integrate multiple chemosensory inputs from both endogenous and exogenous sources in the regulation of feeding: whereas the GIS cells distinguish among fewer, more specific cues to control food acquisition behavior.

Complex attributes of lateral hypothalamic neurons in the regulation of feeding of alert rhesus monkeys

To elucidate the roles of glucose-sensitive (GS) and glucose-insensitive (GIS) cells of the lateral hypothalamic area (LHA), single neuron activity was recorded during 1) microelectrophoretic administration of chemicals, 2) a conditioned bar press feeding task, 3) gustatory, 4) olfactory, and 5) electrical brain stimulation. GS and GIS neurons showed different firing rate changes during phases of the task, and the responses were highly influenced by the palatability of the food and the motivational (hunger or satiety) state of the animal. The two groups of cells also differed in their responsiveness to gustatory and olfactory stimuli: GS neurons were more likely to respond to tastes and odors than GIS cells. Taste- and odor-responsive GS neurons were primarily suppressed by electrophoretically applied noradrenaline and were localized ventromedially within the LHA. The chemosensitive GIS cells, being organized along a dorsolateral axis, were especially excited by dopamine. The two sets of neurons had distinct connections with associative (orbitofrontal, prefrontal) cortical areas. GS and GIS cells, thus, appear to have differential and complex attributes in the control of feeding.

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.

Functional heterogeneity of the monkey lateral hypothalamus in the control of feeding

Regional differences in the effects of electrical (ES) and chemical stimulation on execution of a bar-press feeding task, and in neuronal activity related to feeding, glucose sensitivity, and odor responsiveness were examined in the lateral hypothalamic area (LHA) of monkeys. In satiated animals, ES of the far lateral and ventral LHA induced bar-press feeding. In hungry animals, ES of the dorsal LHA suppressed the feeding task only during the stimulation period, but prolonged feeding suppression that occurred after ES of the ventromedial LHA. Microinjection of Na-glutamate into LHA sites where ES was effective in suppressing feeding had no effect, but it was effective in the medial hypothalamus. Glucose-sensitive (GS) neurons decreased in activity during bar pressing and/or during the ingestion period. Glucose-insensitive (GIS) neurons showed a cue-related excitation more often than GS neurons. Odor-responding GS and GIS cells were localized in ventromedial and lateral LHA sites, respectively. The present study suggests the regional heterogeneity of the LHA in feeding regulation, depending on both hunger and satiety states.

A method for gustatory stimulus delivery in awake rhesus monkeys

A novel taste stimulus delivery technique along with a simple electronic onset marking system, designed for complex, neurophysiological-behavioral experiments in awake monkeys, are described. Intraoral implantation of a polyethylene tubing fistula enabled us to perform repeated, well-standardized application of various taste solutions to broad areas of gustatory receptors on the tongue, palate, pharynx and epiglottis while activity of single neurons was extracellularly recorded in behaving rhesus monkeys. By introducing an electronic marking onset and duration of the stimulation could be determined.

A medialis ventrolateralis praefrontalis (orbitofrontalis) kéreg glükózmonitorozó idegsejtjei szerepet játszanak a homeosztázis fenntartásában

Absztrakt: Bevezetes: A medialis orbitofrontalis kereg fontos szerepet jatszik a taplalkozas es az anyagcsere szabalyozasaban. Az itt talalhato glukozmonitorozo idegsejtek e folyamatokbeli erintettsege, jellemző műkodesi sajatossagaik azonban meg kevesse ismertek. Celkitűzes: Kiserletsorozatunkban e kemoszenzoros idegsejtek funkcionalis jelentőseget kivantuk megvilagitani. Modszer: A multibarrel mikroelektroforetikus technika segitsegevel elektrofiziologiai kiserleteket folytattunk, valamint a glukozmonitorozo neuronok sztreptozotocinnal valo szelektiv elpusztitasa utan anyagcsere-vizsgalatokat vegeztunk. Eredmenyek: A vizsgalt sejtek mintegy 15%-a bizonyult az előagyi glukozmonitorozo ideghalozat elemenek. E glukozmonitorozo es a glukozra valaszkeszseget nem mutato, ugynevezett glukozinszenzitiv idegsejtek elterő neurotranszmitter- es izerzekenyseget mutattak. Akut glukoztolerancia-tesztben, a sztreptozotocinnal kezelt patkanyok 30 es 60 perces vercukorertekei a kontrollallatokeinal szignifikansan magasa...INTRODUCTIONnThe medial orbitofrontal cortex is involved in the regulation of feeding and metabolism. Little is known, however, about the role of local glucose-monitoring neurons in these processes, and our knowledge is also poor about characteristics of these cells.nnnAIMnThe functional significance of these chemosensory neurons was to be elucidated.nnnMETHODnElectrophysiology, by the multibarreled microelectrophoretic technique, and metabolic investigations, after streptozotocin induced selective destruction of the chemosensory neurons, were employed.nnnRESULTSnFifteen percent of the neurons responded to glucose, and these chemosensory cells displayed differential neurotransmitter and taste sensitivities. In acute glucose tolerance test, at the 30th and 60th minutes, blood glucose level in the streptozotocin-treated rats was significantly higher than that in the controls. The plasma triglyceride concentrations were also higher in the streptozotocin-treated group.nnnCONCLUSIONSnGlucose-monitoring neurons of the medial orbitofrontal cortex integrate internal and external environmental signals, and monitor metabolic processes, thus, are indispensable to maintain the healthy homeostasis. Orv Hetil. 2017; 158(18): 692-700.

Umami Taste in the Forebrain of the Alert Macaque

“Umami” is the term proposed by Ikeda in 1909 to represent the taste of glutamate, the salt of the amino acid he had isolated from flavor-enhancing sea tangle. It has since been shown to be transduced by specific protein receptor molecules in a variety of animals [1]. Peripheral and central taste neurons are responsive to monosodium glutamate (MSG), and some show exclusive sensitivity to it. In multidimensional taste spaces generated from either human psychophysical or rat electrophysiologic data, MSG lies beyond the tetrahedron created by connecting the positions of the four traditional basic taste stimuli [2,3]. This fact implies that the taste of MSG cannot be accounted for by any combination of these basic stimuli. MSG is typically situated closer to NaCI than it is to sucrose, HCI, or quinine, suggesting a salty component to its taste. Yet when sodium transduction was disrupted in the rat by lingual application of amiloride, the impact on MSG’s response was minimal, and its neural code remained unaltered [4]. Therefore MSG presumably elicits a taste quality that transcends saltiness—one whose identity is sustained even as saltiness is largely blocked.

Gustatory and Olfactory Responses of Chemosensitive Pallidal Neurons

The globus pallidus (GP), a key structure of the extrapyramidal motor system, is known to be intimately involved in the central regulation of body weight and food and fluid intake behaviors [1–3]. In addition to its roles in the motor control of eating and drinking [4,5], it is important in metabolic regulation [6,7], as well as in feeding-associated sensorymotor and perceptual processes [1,4,8]. These functions of the GP are, at least partially, mediated by catecholaminergic (CA) forebrain mechanisms, most importantly by the nigrostriatal and mesolimbicmesocortical dopamine (DA) systems [1,4,9]. The close functional-morphological interrelations of the GP and the lateral hypothalamic area (LHA) [2,10] and the availability of information on related properties of neurons of the latter [11–13], indicate the necessity for investigating feeding-associated attributes of GP neurons, with particular regard to their sensitivity to glucose. Despite the abundance of related data in the literature, our knowledge is very poor concerning the chemical characteristics of GP cells. To date, information on the endogenous and exogenous chemosensitivity of pallidal neurons in the primate is very limited. The present studies, therefore, aimed to reveal the complex chemosensory properties of GP cells.

Iontophoretic microlesions with kainate or 6-hydroxidopamine in ventromedial prefrontal cortex result in deficit in conditioned taste avoidance to palatable tastants

Effects of kainate or 6-hydroxidopamine (6-OHDA) lesions in the ventromedial prefrontal cortex (vmPFC) on taste-related learning and memory processes were examined. Neurotoxins were applied by iontophoretic method to minimize the extent of lesion and the side effects. Acquisition and retention of conditioned taste avoidance (CTA) was tested to different taste stimuli (0.05u2009M NaCl, 0.01u2009M saccharin, 0.01u2009M citrate and 0.00025u2009M quinine). In the first experiment, palatability index of taste solutions with these concentrations has been determined as strongly palatable (NaCl, saccharin), weakly palatable (citrate) and weakly unpalatable (quinine) taste stimuli. In two other experiments vmPFC lesions were performed before CTA (acquisition) or after CTA (retrieval). Our results showed that both kainate and 6-OHDA microlesions of vmPFC resulted in deficit of CTA acquisition (to NaCl, saccharin and citrate) and retrieval (to NaCl and saccharin). Deficits were specific to palatable tastants, particularly those that are strongly palatable, and did not occur for unpalatable stimulus. The present data provide evidence for the important role of vmPFC neurons and catecholaminergic innervation of the vmPFC in taste related learning and memory processes.