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Disruption of glycine transporter 1 restricted to forebrain neurons is associated with a procognitive and antipsychotic phenotypic profile.

The NMDA receptor is thought to play a central role in some forms of neuronal plasticity, including the induction of long-term potentiation. NMDA receptor hypofunction can result in mnemonic impairment and has been implicated in the cognitive symptoms of schizophrenia. The activity of NMDA receptors is controlled by its endogenous coagonist glycine, and a local elevation of glycine levels is expected to enhance NMDA receptor function. Here, we achieved this by the generation of a novel mouse line (CamKIIalphaCre;Glyt1tm1.2fl/fl) with a neuron and forebrain selective disruption of glycine transporter 1 (GlyT1). The mutation led to a significant reduction of GlyT1 and a corresponding reduction of glycine reuptake in forebrain samples, without affecting NMDA receptor expression. NMDA (but not AMPA) receptor-evoked EPSCs recorded in hippocampal slices of mutant mice were 2.5 times of those recorded in littermate controls, suggesting that neuronal GlyT1 normally assumes a specific role in the regulation of NMDA receptor responses. Concomitantly, the mutants were less responsive to phencyclidine than controls. The mutation enhanced aversive Pavlovian conditioning without affecting spontaneous anxiety-like behavior in the elevated plus maze and augmented a form of attentional learning called latent inhibition in three different experimental paradigms: conditioned freezing, conditioned active avoidance, conditioned taste aversion. The CamKIIalphaCre;Glyt1tm1.2fl/fl mouse model thus suggests that augmentation of forebrain neuronal glycine transmission is promnesic and may also offer an effective therapeutic intervention against the cognitive and attentional impairments characteristic of schizophrenia.

Animals↗

Development of an ethanol model using social insects: III. Preferences for ethanol solutions.

Experiments are designed to assess whether free-flying honey bees have an aversion to an ethanol solution when given a choice between targets containing an ethanol solution in sucrose or sucrose only. Animals given a choice between a 1% ethanol solution and sucrose only show no aversion to the ethanol solution either in acquisition or extinction. Honey bees given a choice between a 5% ethanol solution and sucrose only show no differences in the initial choice of targets but some ees do switch over to the sucrose-only target. Performance during extinction indicates that bees landed on the previously reinforced sucrose-only target more than the target previously containing the 5% ethanol solution. An experiment in which bees were given a single 5%, ethanol target showed that of 20 bees, 11 returned for the entire 12 trials of the experiment. All bees returned at least 6 times to the 5% ethanol target. Additional experiments were run on harnessed foragers in a palatability study of alcoholic beverages consumed by humans. The results of the palatability experiment indicate that in general, bees prefer more sweet drinks with less alcohol.

Alcohol Drinking↗

Effects of marbling and shear force on consumers' willingness to pay for beef strip loin steaks.

Experimental economic procedures were used to measure the effects of changes in marbling score and Warner-Bratzler shear force (WBSF) value on consumer purchasing behavior and willingness to pay for beef strip loin steaks (n = 541). Consumers were more likely to bid on a steak during the experimental auction if the steak had a high marbling score or low WBSF value. Averaging across all consumers in the study (n = 489), the predicted odds that consumers would submit a nonzero bid were favorable for steaks with a marbling score greater than Modest(50) or a WBSF value less than 3.9 kg. Bid prices for steaks were analyzed with respect to changes in steak marbling score, WBSF value, quality grade marketing category classification (Select, Low Choice, Premium Choice, and Prime), and WBSF marketing category classification (very tender, 5.40 kg). The percentage of bids that were zero was highest (P < 0.05) for Select steaks, intermediate (P < 0.05) for Low Choice steaks, and lower (P <0.05) for Premium Choice or Prime steaks. Steaks in the very tender category had the lowest (P < 0.05) percentage of zero bids, and steaks in the slightly tough and very tough categories had the highest (P < 0.05) percentage of zero bids submitted from "buyers" in the auction. Premium Choice and Prime steaks were valued higher (P < 0.05) than Select steaks by consumers. On average, Premium Choice steaks received a 0.89 dollars/kg premium, and Prime steaks received a 2.47 dollars/kg premium over the mean bid price for Select steaks. Predicted mean bid prices for steaks decreased by 1.02 dollars/kg for each 1 kg increase in WBSF value. On average, steaks in the very tender marketing category received a higher (P < 0.05) bid price than the bid price for steaks in the slightly tender, slightly tough, and very tough categories (+0.83 dollars/kg, +2.09 dollars/kg, and +2.55 dollars/kg, respectively). Mean bid prices for steaks from the slightly tough and very tough categories did not differ (P = 0.184). Compared with the mean bid price for steaks in the slightly tender category, steaks from the slightly tough and very tough categories were discounted (P < 0.05) by 1.26 dollars/kg and 1.72 dollars/kg, respectively. Results suggest that marbling score and WBSF influence both the probability that consumers will purchase and the price they are willing to pay for strip loin steaks.

Animals↗

Fitting mixture distributions to phenylthiocarbamide (PTC) sensitivity.

A technique for fitting mixture distributions to phenylthiocarbamide (PTC) sensitivity is described. Under the assumptions of Hardy-Weinberg equilibrium, a mixture of three normal components is postulated for the observed distribution, with the mixing parameters corresponding to the proportions of the three genotypes associated with two alleles A and a acting at a single locus. The corresponding genotypes AA, Aa, and aa are then considered to have separate means and variances. This paper is concerned with estimating the parameters of the model, and their standard errors, by using an application of the EM algorithm. This technique also caters for the fact that the sensitivity measurements are only known to lie between the endpoints of certain intervals and that the exact measurement of the attribute is not possible.

Algorithms↗

Animal models of infantile amnesia, benign senescent forgetfulness, and senile dementia.

The Jacksonian principle of hierarchical development and dissolution of function was applied to infantile amnesia and memory loss in senescence. When the Jacksonian model is generalized to include life-span changes in memory it predicts a last-in, first-out appearance and disappearance of memory processes. Those memory capacities that are the last to appear in ontogeny should be the first to be compromised in aging. To evaluate this proposition in a specific context, the rodent literature on long-term memory in infant, adult, and aged animals was surveyed. Three types of memorial processes that emerged sequentially in development were identified and then examined in adult and aged rats. Although strong support of the Jacksonian principle did not emerge from this analysis, the data were sufficiently positive to suggest that the theory was still viable and even vigorous enough to guide future research on both the normal and pathological processes of development and aging.

Aging↗

Involvement of the anterior insular gustatory neocortex in taste-potentiated odor aversion learning.

When an odor conditioned stimulus (CS) precedes illness (unconditioned stimulus; UCS), rats acquire relatively weak odor aversions. Conversely, when a compound odor-taste (flavor) CS precedes illness, rats acquire robust aversions both to the odor and to the taste components of a compound flavor CS. Thus, tastes potentiate odor-illness aversions during toxiphobic conditioning. Such conditioning effects have been referred to as taste-potentiated odor aversion learning (POA). Previous neurobehavioral experiments have shown that the anterior insular gustatory neocortex contributes to conditioned taste aversion (CTA) learning. The present experiment examined the involvement of the anterior insular gustatory neocortex in CTA learning and POA learning. To that end, four distinct groups of rats received bilateral electrolytic lesion placements in the orbitofrontal neocortex, the "somatic" gustatory neocortex, the anterior insular gustatory neocortex or the posterior insular neocortex. Control animals received anesthesia only. Subgroups of animals thereafter received aversion conditioning using either an odor (almond) CS or a compound odor-taste (almond-saccharin) CS. Aversions to the almond odorant and/or saccharin tastant were evaluated during extinction. Results indicated that animals lacking orbitofrontal neocortex or posterior insular neocortex acquired normal CTAs and POAs. Animals lacking somatic gustatory neocortex exhibited impaired CTA learning, yet those animals showed normal POA learning. Lesions centered in the anterior insular neocortex impaired both CTA learning and POA learning. These results demonstrate that the insular gustatory neocortex is uniquely involved in the higher-order integration of odors, tastes and illness.

Animals↗

Temporal properties of the human taste system.

An attempt to apply linear systems methods to the temporal properties of the human taste system is described. The percentage modulation in concentration required to detect a fluctuation in intensity was measured as a function of frequency of modulation. Both a sine-wave and a square-wave input were used. The sensitivity of the taste system at its maximum, and also at the low frequencies, was greater than expected from previous work based on classical methodology. The sensitivity of the taste system at its maximum, and also at the low frequencies, was greater then expected from previous work base on classical methodology. The sensitivity of the taste system to the various qualities was, in decreasing order, salty, sweet, sour, and bitter. The taste system in insensitive to frequencies above about 5 Hz. Except for bitter, representatives of the various taste qualities yielded similar functions within qualities.

Adaptation, Physiological↗

Electrophysiology of Necturus taste cells.

Taste buds are sensory end organs that detect chemical substances occurring in foodstuffs and relay the relative information to the brain. The mechanisms by which the chemical stimuli are converted into biological signals represent a central issue in taste research. Our understanding of how taste buds accomplish this operation relies on the detailed knowledge of the biological properties of taste bud cells-the taste cells-and of the functional processes occurring in these cells during chemostimulation. The amphibian Necturus maculosus (mudpuppy) has proven to be a very useful model for studying basic cellular processes of vertebrate taste reception, some of which are still awaiting to be explored in mammals. The main advantages offered by Necturus are the large size of its taste cells and the relative accessibility of its taste buds, which can therefore be handled easily for experimental manipulations. In this review, I summarize the functional properties of Necturus taste cells studied with electrophysiological techniques (intracellular recordings and patch-clamp recordings). My focus is on ion channels in taste cells and on their role in signal transduction, as well as on the functional relationships among the cells inside Necturus taste buds. This information has revealed to be well suited to outline some of the general physiological processes occurring during taste reception in vertebrates, including mammals, and may represent a useful framework for understanding how taste buds work.

Action Potentials↗

Multiple remote-US preexposures and the blocking effect produced by a proximal-US.

Weanling, young-adult, and old-age Wistar albino rats were used to determine whether number of unconditioned stimulus (US) presentations, given 24 h or more (remote preexposure) prior to conditioning, alters the blocking effect of a single-US preexposure given 2 h before (proximal) taste aversion conditioning. As the number of remote-US preexposures increased from 0 to 6, the ability of the proximal-US preexposure to block conditioning initially increased then decreased for all age groups. Of the models put forth to explain US preexposure effects on conditioned taste aversion (CTA), only Wagner's information processing model adequately explained the reduction of the blocking effect of the proximal-US preexposure produced as a result of increasing remote-US preexposures.

Aging↗

From small sweeteners to sweet proteins: anatomy of the binding sites of the human T1R2_T1R3 receptor.

The sweet taste receptor, a heterodimeric G protein coupled receptor (GPCR) protein, formed by the T1R2 and T1R3 subunits, recognizes several sweet compounds including carbohydrates, amino acids, peptides, proteins, and synthetic sweeteners. Its similarity with the metabotropic glutamate mGluR1 receptor allowed us to build homology models. All possible dimers formed by combinations of the human T1R2 and T1R3 subunits, modeled on the A (closed) or B (open) chains of the extracellular ligand binding domain of the mGluR1 template, yield four ligand binding sites for low-molecular-weight sweeteners. These sites were probed by docking a set of molecules representative of all classes of sweet compounds and calculating the free energy of ligand binding. These sites are not easily accessible to sweet proteins, but docking experiments in silico showed that sweet proteins can bind to a secondary site without entering the deep cleft. Our models account for many experimental observations on the tastes of sweeteners, including sweetness synergy, and can help to design new sweeteners.

Binding Sites↗

Biology of taste buds and the clinical problem of taste loss.

Taste buds are the anatomical structures that mediate the sense of taste. They comprise taste cells and nerve fibers within specialized epithelial structures. Taste cells are traditionally described by histologic methods as basal, dark, intermediate, and light cells, with the nerve fibers surrounding and infiltrating the taste buds. By means of immunohistochemical methods, taste cells and gustatory nerve fibers can be classified in functional groups based on the expression of various cell adhesion molecules and other proteins. When taste buds become damaged, the loss of the ability to taste results. This loss is not uncommon and can impact health and quality of life. Patients who receive radiation therapy for head and neck cancer often experience taste loss, which leads to compromised nutritional intake and a worse outcome than patients who do not experience taste loss. The mode of radiation damage to taste cells and nerve fibers has been investigated using cell adhesion molecules, synaptic vesicle proteins, and other cell markers. The light and intermediate cells are preferentially affected by ionizing radiation, whereas the nerve fibers remain structurally intact. Experimental studies of radiation-induced taste loss are performed via a unique animal/human model.

Ageusia↗

Neural substrates for conditioned taste aversion in the rat.

Conditioned taste aversions (CTAs) are well known to be robust and long-lasting instances of learning induced by a single CS (taste)-US (malaise) pairing. CTA can be taken as a general model to search for neural mechanisms of learning and memory. In spite of extensive research on CTAs using a variety of approaches during the last three decades, the neural mechanisms of taste aversion learning still remain unsolved. In this article we propose a model of neural substrates of CTAs on the basis of our recent studies incorporating previous findings by other workers. Our studies mainly included experiments using ibotenic acid injections into various parts of the rat brain as a lesion technique, and c-fos immunohistochemistry in naive and CTA trained rats. CTAs were established by pairing the ingestion of saccharin (CS) with an ip injection of LiCl (US). Behavioral studies have shown that the parabrachial nucleus (PBN), medial thalamus, and basolateral nucleus of the amygdala are essential for both acquisition and retention of CTAs. C-fos studies suggested that association between gustatory CS and visceral US takes place in the PBN. The gustatory cortex (GC) may modify the strength of this association depending on the nature of the CS, viz., novel or familiar. The amygdala is indispensable for the expressions of CTAs. Tastes with hedonic values are stored in the GC in a long-term manner.

Animals↗

Role of taste and calories in the selection of ethanol by C57BL/6NHsd and Hsd:ICR mice.

The C57BL/6 mouse (C57) is used as a model for the human consumption of ethanol. Previous studies on the taste preferences of the C57 mouse indicate that ethanol drinking by this animal is for calories and not for a pharmacological effect. The purpose of this study, therefore, was to further determine the role of calories and taste in the selection of ethanol by the C57 mouse. C57 and outbred Hsd:ICR (ICR or CD-1) mice were housed two per cage with three drinking tubes. A standard 10-day preference test of 3-30% ethanol (v/v) vs. water was performed: the mean maximally preferred concentrations of ethanol were 17.9% for C57 and 6.8% for ICR mice. Once drinking of the preferred concentration for each cage had stabilized at 13.2 and 0.9 g/kg/day, respectively, the third tube was filled with water, 0.5% aspartame, isocaloric dextrose, or diluted chocolate Ultra Slim-Fast plus dextrose. Five days of dextrose or chocolate drink reduced the amount of ethanol consumed by 41% and 44% by C57 mice, but aspartame did not affect their drinking. Additional groups of C57 and ICR mice were habituated to a 2-h limited access to water. When offered a 0.5 mM quinine solution as the only fluid, both strains consumed the same volumes as water. Presentation of a saccharin solution was followed by an i.p. injection of either 0.5 M LiCl or NaCl. When given the saccharin solution 48 h later, the LiCl-treated mice of both strains drank less saccharin. The C57 mouse did not exhibit a LiCl-induced taste aversion when ethanol was the novel solution. As a test of response to novelty, a cork stopper was placed in each cage. The ICR mice gnawed much more of the cork than did the C57 mice. Thus, both C57 and ICR mice learned a taste aversion, but the C57 mouse altered its large consumption of ethanol based on more palatable sources of calories. These data support the earlier concept that the consumption of ethanol represents a preferred source of calories for the C57 mouse. Extrapolation of genetic or biochemical differences between these mice to differences between the human alcoholic and the nonalcoholic should thus be made with caution.

Alcohol Drinking↗