Thomas C. Pritchard

Mode of action of OB protein (leptin) on feeding

OB protein (leptin) decreases food intake in a variety of species. Here we investigated the effects of the intracerebroventricular administration of recombinant murine OB protein on food consumption and meal parameters in Wistar rats maintained ad libitum. The intracerebroventricular administration of OB protein (0.56-3.5 μg/rat) decreased feeding in a dose-dependent manner. Computer analysis of meal parameters demonstrated that OB protein (3.5 μg/rat, n = 10) decreased nighttime meal size by 42%, whereas meal frequency and meal duration were unaffected. Derived analyses for the nighttime also showed that OB protein decreased the feeding rate (meal size/meal duration) by 30%, whereas the satiety ratio (intermeal intervals/meal size) increased by 100%. A similar profile was observed during the daytime and total daily periods. The intracerebroventricular administration of heat-inactivated OB protein (3.5 μg/rat, n = 10) had no effect on any meal parameter. The results show that OB protein administered intracerebroventricularly inhibits feeding through a specific reduction of meal size.

Projections of the Parabrachial Nucleus in the Old World Monkey

The efferent projections of the pontine parabrachial nucleus (PBN) were examined in the Old World monkey (Macaca fascicularis) using tritiated amino acid autoradiography and horseradish peroxidase histochemistry. Parabrachiofugal fibers ascended to the forebrain along three pathways: the central tegmental tract, the ventral ascending catecholaminergic pathway, and a pathway located on the midline between the medial longitudinal fasciculi. The PBN projected heavily to the central nucleus of the amygdala and the lateral division of the bed nucleus of the stria terminalis and moderately to the ventral tegmental area and the substantia nigra. Light terminal label also was present within the dorsomedial, ventromedial, lateral, supramammillary, and infundibular nuclei of the hypothalamus and the annular nucleus and the dorsal raphe nucleus within the brain stem. The overall pattern of terminal label was similar to that previously reported for nonprimate species, but several differences were notable. In monkey the projection to the ventrobasal thalamus did not coincide with the region that contains gustatory-responsive neurons. In rats, these parabrachiothalamic fibers convey gustatory activity but in the monkey these fibers may carry visceral afferent information. The projections from the PBN to the hypothalamus in the monkey were neither as widespread nor as intense as in the rat, and the monkey lacks a projection from the PBN to the frontal and insular cortices.

Gustatory thalamus lesions in the rat: II. Aversive and appetitive taste conditioning

The learning capacities of rats with electrolytic lesions of the gustatory thalamus (GT) were investigated in 3 experiments. In Experiment 1, the presence of a taste cue failed to overshadow odor aversion learning in the lesioned rats, yet these same animals acquired normal taste and odor aversions. Thalamic lesions had no discernible effect on the acquisition of a conditioned flavor preference in Experiment 2. Finally, GT lesions completely reversed the anticipatory contrast effect shown by control subjects in Experiment 3. These results suggest that damage to the GT spares taste detection and recognition and simple associative learning but interferes with learning that involves more complex gustatory information processing.

Gustatory neural responses in the medial orbitofrontal cortex of the old world monkey

The primary taste cortex has widespread and occasionally dense projections to the orbitofrontal cortex (OFC) in the macaque. Nonetheless, electrophysiological studies have revealed that only 2-8% of the cells in the OFC are activated by taste stimuli on the tongue. We describe an area centered in Brodmanns area 13m of the medial OFC (mOFC) where taste neurons are more concentrated. It consists of a 12 mm2 core, where gustatory neurons constituted 20% of the population, and a 1 mm perimeter in which 8% of the cells responded to taste. Data were collected from three awake cynomolgus monkeys (Macaca fascicularis) prepared for chronic recording. Single neurons were isolated with epoxylite-coated tungsten microelectrodes and tested for responsiveness to 1.0 m glucose, 0.3 m NaCl, 0.03 m HCl, and 0.001 m QHCl. These stimuli elicited responses that were 96% excitatory and ranged from 5.2 to 5.9 spikes/s. Cells were broadly tuned (H = 0.79), similar to those in the anterior insula (H = 0.70), and decidedly unlike the narrowly tuned taste neurons in the caudolateral OFC (clOFC; H = 0.39). Whereas 82% of the taste cells in the clOFC respond to glucose, in the mOFC, HCl-responsive (56%), glucose-responsive (50%), NaCl-responsive (43%), and QHCl-responsive (40%) cells were almost evenly represented. The mOFC taste area appears to comprise a major gustatory relay that lies anatomically and functionally between the anterior insula and the clOFC.

Satiety-responsive neurons in the medial orbitofrontal cortex of the macaque.

Feeding-related gustatory, olfactory, and visual activation of the orbitofrontal cortex (OFC) decreases following satiety. Previous neurophysiological studies have concentrated on the caudolateral OFC (clOFC). We describe satiety-induced modulation of 23 gustatory, 5 water, and 15 control neurons in the medial OFC (mOFC), where gustatory neurons represent a much larger percentage of the population. For 15 of the 23 gustatory neurons (65%), every significant taste response evoked during pre-satiety testing decreased following satiety (X=70%). Responses evoked by the ineffective taste stimuli during pre-satiety testing were unchanged following satiety. The graded response decrements of the mOFC gustatory neurons stand in marked contrast to the clOFC responses, which are almost completely suppressed by satiety. Two other novel findings are reported here. First, all significant pre-satiety taste responses of four gustatory neurons increased following satiety (X=51%). Second, post-satiety emergent taste responses were observed in 7 of 15 neurons (47%) classified as non-responsive during pre-satiety testing. The presence of increased responsiveness and emergent gustatory neurons in the mOFC suggests that meal termination may require active processes as well as the passive loss of hedonic value.

Gustatory thalamus lesions in the rat: I. Innate taste preferences and aversions.

Two experiments examined the innate taste preferences and aversions of rats with electrolytic lesions of the gustatory thalamus (GT). Contrary to previous research, GT lesions had only a minor influence on intake of the 4 basic tastes as assessed with the 24-hr, 2-bottle preference test in Experiment 1. The same lesioned rats, when tested with the same stimuli in the 15-min, single-bottle procedure in Experiment 2, showed normal consumption patterns except for sucrose intake, which was attenuated. The conflicting findings of previous and present research are considered to result from differences in lesion size. The current data suggest that the GT has a relatively minor functional role in the unconditioned acceptance or rejection of sapid stimuli.

Gustatory Thalamus Lesions in the Rat: III. Simultaneous Contrast and Autoshaping

The performance of rats with electrophysiologically guided electrolytic lesions of the gustatory thalamus (GT) was compared to that of control subjects in two experiments. In Experiment 1, the lesioned rats showed normal simultaneous contrast effects (both positive and negative) during brief, alternating access to 0.15% saccharin and 1.0 M sucrose. There was, however, a substantial lesion-induced impairment in the level of conditioned stimulus-directed maintenance responding on the autoshaping procedure of Experiment 2. These findings are discussed with respect to the anticipatory contrast deficit recently reported in GT-lesioned rats.

A new gustometer for testing taste discrimination in the monkey

A fully automated, 10-channel gustometer for use with nonhuman primates is described. The system, constructed primarily from commercially available components, includes an intelligence panel (containing sample spout, reward spout, and two operant response keys) that attaches to the door of a standard primate cage. The novel feature of the gustometer is a sample delivery spout that can be flushed, rinsed, and refilled within a specially designed rinsing chamber. All wetted surfaces of the gustometer are either Teflon, glass, or stainless steel. Flame photometric analysis confirmed the absence of cross-contamination between trials. Behavioral data collected from one rhesus monkey using a shock-suppression procedure demonstrates the detection threshold for sodium chloride. Improvements to the design, including the addition of pressurized sample delivery triggered by a lickometer circuit, are discussed.

Taste in the Medial Orbitofrontal Cortex of the Macaque

Abstract: Taste activates about 6% of the neurons in the anterior insula (primary taste cortex) of the macaque. The anterior insula has many direct and indirect projections to the orbitofrontal cortex (OFC), including the caudolateral OFC (clOFC), where only 2% of the neurons respond to taste. We have identified a 12‐mm2 region in the medial OFC (mOFC) where taste represents 7–28% of the population. This rich trove of taste cells has functional characteristics typical of both the insular cortex that projects to it and the clOFC to which it projects. Mean spontaneous rate was 3.1 spikes/s, nearly identical to that in the insula, but double that of the clOFC. In the mOFC, 19% of the taste cells also responded to other modalities, most commonly olfaction and touch, slightly less than the 27% in the clOFC. The distribution of best stimulus neurons was almost even across the four prototypical stimuli in the mOFC, as in insula, but discrepant from the clOFC, where sugar responsiveness dominated. The broadly tuned taste neurons in the mOFC were similar to those in the insula and strikingly different from the more specialized cells of the clOFC. Whereas the responsiveness to the taste of a satiating stimulus declines among the narrowly tuned clOFC cells, satiety has much less impact on the responsiveness of mOFC neurons. The mOFC is a robust area worthy of exploration for its involvement in gustatory coding, the amalgamation of sensory inputs to create flavor, and the hedonics that guide feeding.

CHAPTER 31 – Gustatory System

This chapter describes the human gustatory system and integrates the clinical and experimental literature. When the clinical reports contradict the experimental literature, the chapter has weighed the likelihood of a species difference versus the possibility that the disagreement reflects differences in the quality of the data. This chapter deals primarily with the central organization of the gustatory system and emphasizes its cortical organization, where most of the research over the last decade has been done. The human peripheral gustatory apparatus is described. On the anterior tongue, taste buds occur in fungiform papillae. The density of taste buds on the anterior tongues of adult cadavers varies by two orders of magnitude, and the differences are not attributable to age or race. These differences in the number of taste buds per papilla are more than an anatomical curiosity. The number of fungiform papilla correlates positively with taste intensity, the inherited ability to taste bitterness, and the intensity of the “burn” produced by capsaicin, the active ingredient in chili peppers. Furthermore, functional issues such as transduction, coding, and behavior are also covered in this chapter.