Thomas R. Scott

Taste in the monkey cortex.

The sense of taste in humans differs substantially from that of rodents, from which a preponderance of gustatory electrophysiology derives. To establish a more appropriate neural model for human gustation, we recorded the activity of single neurons in the primary taste cortex in 11 alert cynomolgus macaques. Taste cells composed 6% of all neurons encountered. Another 24% responded during mouth and jaw movements, and 4% were sensitive to tactile stimulation of the mouth. Smaller numbers responded during olfactory or visual stimulation, or when the monkey extended his tongue. Taste cells could be divided into four statistically independent groups, corresponding to those most responsive to glucose (38%), NaCl (34%), quinine (22%), or HCI (5%). The location of a taste cell did not predict its response profile, i.e., there was no clear topographic organization of taste sensitivity. We established neural thresholds and intensity-response functions to the basic stimuli and determined that-with the exception of HCl, to which the macaque is relatively insensitive-they were similar to those reported by human subjects. We then turned to the coding of taste quality, as inferred in macaques from the patterns of neural activity elicited by each of greater than 100 stimuli. The results proved generally faithful to human reports of the perceived qualities of these same tastants. Finally, an investigation of taste mixtures revealed a degree of mixture suppression and interaction among basic qualities similar to those reported by humans. We conclude that the alert macaque offers a reliable neural model for human gustation.

Taste as a factor in the management of nutrition.

The sense of taste lies at the interface between the external and internal milieux, at the point at which the animal must decide which chemicals from the environment to incorporate into itself. Accordingly, taste is organized along a neural dimension of nutrients versus toxins, which corresponds to a behavioral dimension of acceptance versus rejection, and to a hedonic dimension of appetitive versus aversive qualities. Reflexive responses, cognitive analyses, and hedonic reactions appear to be managed at different levels of the nervous system. At the first central relay, the nucleus of the solitary tract, somatic reflexes for acceptance or rejection, and autonomic reflexes anticipating digestion are orchestrated. At the second, the parabrachial nucleus of the rodent, associative mechanisms important to the development of conditioned aversions and sodium appetite are manifested. In the thalamic taste relay, gustatory memories associated with non-visceral events may be formed. Primary taste cortex appears to be the site for a cognitive evaluation of gustatory quality and intensity. Finally, a hedonic assessment of the chemical may be made in secondary taste cortex and in the ventral forebrain sites to which it projects. With this assessment comes integration of the gustatory signal with those from other senses, perhaps to create a perception of flavor. Therefore, a sequence that begins with an analysis of the molecular structure of a chemical in the mouth serves to incorporate that gustatory component into an appreciation of flavor, and to participate in the control of motivational processes that guide dietary selection.

Memory-dependent c-Fos expression in the nucleus accumbens and extended amygdala following the expression of a conditioned taste aversive in the rat

Retrieving the memory of a conditioned taste aversion involves multiple forebrain areas. Although the amygdala clearly plays a role in the expression of a conditioned taste aversion, critical regions, downstream from the amygdala remain to be defined. To this end, Fos immunoreactivity was used in the rat to explore forebrain structures associated with retrieval that have an anatomical relationship with the amygdala. The results showed that expression of a conditioned taste aversion to 0.5 M sucrose elicited neuronal activation in the nucleus accumbens and in a complex of structures collectively referred to as the extended amygdala. The posterior hypothalamus and parasubthalamic nucleus, which receive inputs from the extended amygdala, were also activated upon re-exposure to the sucrose conditioned stimulus. Fos immunoreactivity did not increase in these regions in response to an innately aversive tastant, quinine hydrochloride (conditioned stimulus control), nor to LiCl-induced visceral stimulation in unconditioned animals (unconditioned stimulus control). In addition, these regions did not respond to the sucrose conditioned stimulus in sham-conditioned animals. These results suggest that conditioned and innately aversive tastes are differentially processed in the forebrain circuitry that includes the nucleus accumbens and extended amygdala.

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.

Differential activation of anterior and midline thalamic nuclei following retrieval of aversively motivated learning tasks

Two thalamic nuclear groups, the anterior thalamic nuclei (ATN) and midline and intralaminar thalamic complex (MITC) have connections to the prefrontal cortex, amygdala, hippocampus and accumbens that are important for learning and memory. However, the anatomical proximity between the ATN and MITC makes it difficult to reveal their roles in memory retrieval of aversive conditioned behavior. To address the issue, we explored the activation of the ATN and MITC, as represented by the expression of the immediate early gene c-fos, following either the retrieval of a conditioned taste aversion (CTA) induced by taste-LiCl pairing (visceral aversion) or of inhibitory avoidance (IA) induced by context-foot shock pairing (somatic aversion) in rats. The anterodorsal (AD) nucleus in the ATN was activated by foot shock and the recall of IA, but not by i.p. injection of LiCl or the recall of CTA. No significant elevation was observed in the other ATN following these treatments. Among nuclei of the MITC, the paraventricular thalamic nucleus (PVT) was activated by the delivery of shock or LiCl and by the recall of both CTA and IA, while the mediodorsal thalamus (MD) and central medial and intermediate thalamus (CM/IMD) were not. The innately aversive taste of quinine did not elevate c-fos expression in either the ATN or MITC. These results suggest that the PVT in the MITC is involved in the processing and retrieval of both taste-malaise and context-shock association tasks, while the AD in the ATN is involved in those of context-shock association only. The difference of the activity between the ATN and MITC demonstrates their functional and anatomical heterogeneity in neural substrates for aversive learning tasks.

The Role of the Parabrachial Nucleus in Taste Processing and Feeding

The parabrachial nucleus (PBN) was identified as a taste relay in rodents in 1971. Early recordings suggested that the PBN transmitted a faithful representation of taste activity from the nucleus of the solitary tract (NTS). However, its role assumed greater significance as its subnuclei were shown to deal with different aspects of taste, visceral sensations, hedonics, and conditioned aversions. The discovery of parallel projections from PBN to the thalamus and to ventral forebrain, and evidence that the former carried sensory information while the latter signaled hedonics, conferred on PBN a central role in guiding feeding. Thus, it was surprising to discover that the PBN is not a taste relay in primates. So arose a distinction between rodents, in which parallel processing of taste and hedonic information is the rule, and primates, where serial processing through the cortex precedes a hedonic assessment. Where does the integration of taste and hedonics occur, and how does this affect feeding? Neurons in both NTS and PBN of rodents are modified by changing physiological conditions. That altered activity parallels and perhaps directs the rodents feeding behavior. Information from primate NTS implies no such modification. These interactions are reserved for orbitofrontal cortex and ventral forebrain. The implication is that in rodents, hindbrain alterations not only control the reflexes associated with taste, but also direct food selection through the PBN–ventral forebrain projections. In primates, the apparatus is in place for an independent cognitive analysis unaltered by physiological state, upon which a hedonic assessment is subsequently overlaid.

Learning through the taste system

Taste is the final arbiter of which chemicals from the environment will be admitted to the body. The action of swallowing a substance leads to a physiological consequence of which the taste system should be informed. Accordingly, taste neurons in the central nervous system are closely allied with those that receive input from the viscera so as to monitor the impact of a recently ingested substance. There is behavioral, anatomical, electrophysiological, gene expression, and neurochemical evidence that the consequences of ingestion influence subsequent food selection through development of either a conditioned taste aversion (CTA) (if illness ensues) or a conditioned taste preference (CTP) (if nutrition). This ongoing communication between taste and the viscera permits the animal to tailor its taste system to its individual needs over a lifetime.

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 3.1u2003spikes/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.

Involvement of the supramammillary nucleus in aversive conditioning

Mechanisms for the retention and retrieval of conditioned taste aversions (CTAs) have yet to be fully defined. The authors explored relevant subcortical forebrain regions by tracking the expression of immediate early genes, c-fos and zif268. The supramammillary nucleus (SuM) was activated following both viscerally based CTA and somatically based inhibitory avoidance (IA). Excitotoxic lesions of the SuM before conditioning caused no disruption of acquisition but accelerated the extinction of both the CTA and IA. In contrast, lesions after CTA conditioning did not impair retention or retrieval. The present study indicates that the SuM is activated by memory-elicited discomfort during retrieval, suggesting that it plays a role in resisting the extinction of a long-term aversive memory.

Neuroscience may supersede ethics and law.

Advances in technology now make it possible to monitor the activity of the human brain in action, however crudely. As this emerging science continues to offer correlations between neural activity and mental functions, mind and brain may eventually prove to be one. If so, such a full comprehension of the electrochemical bases of mind may render current concepts of ethics, law, and even free will irrelevant.