These experiments examined the sufficiency of pairing an odor with either intrabulbar activation of noradrenergic beta-receptors or pharmacological stimulation of the locus coeruleus to support learned odor preferences in Postnatal Day 6-7 rat pups. The results showed that pups exposed to odor paired with beta-receptor activation limited to the olfactory bulb (isoproterenol, 50 microM) displayed a conditioned approach response on subsequent exposure to that odor. Furthermore, putative stimulation of the locus coeruleus (2 microM idazoxan or 2 mM acetylcholine) paired with odor produced a subsequent preference for that odor. The effects of locus coeruleus stimulation could be blocked by a pretraining injection of the beta-receptor antagonist propranolol (20 mg/kg). Together these results suggest that convergence of odor input with norepinephrine release from the locus coeruleus terminals within the olfactory bulb is sufficient to support olfactory learning.

Lemon, Christian H., Susan M. Brasser, David V. Smith. Alcohol activates a sucrose-responsive gustatory neural pathway. J Neurophysiol 92: 536 -544, 2004. First published February 25, 2004 10.1152/jn.00097.2004. A strong positive association exists between the ingestion of alcohol and sweet-tasting solutions. The neural mechanisms underlying this relationship are unknown, although recent data suggest that gustatory substrates are involved. Here, we examined the role of sweet taste receptors and central neural circuits for sugar taste in the gustatory processing of ethanol. Taste responses to ethanol (3, 5, 10, 15, 25, and 40% vol/vol) and stimuli of different taste qualities (e.g., sucrose, NaCl, HCl, and quinine-HCl) were recorded from neurons of the nucleus of the solitary tract in anesthetized rats prior to and after oral application of the sweet receptor blocker gurmarin. The magnitude of ethanol-evoked activity was compared between sucroseresponsive (n ϭ 21) and sucrose-unresponsive (n ϭ 20) neurons and the central neural representation of ethanol taste was explored using multivariate analysis. Ethanol produced robust concentration-dependent responses in sucrose-responsive neurons that were dramatically larger than those in sucrose-unresponsive cells. Gurmarin selectively and similarly inhibited ethanol and sucrose responses, leaving NaCl, HCl, and quinine responses unaltered. Across-neuron patterns of response to ethanol were most similar to those evoked by sucrose, becoming increasingly more so as the ethanol concentration was raised. Results implicate taste receptors for sucrose as candidate receptors for ethanol and reveal that alcohol and sugar taste are represented similarly by gustatory activity in the CNS. These findings have important implications for the sensory and reward properties of alcohol.

Based on the molecular findings that many bitter taste receptors (T2Rs) are expressed within the same receptor cells, it has been proposed that bitter taste is encoded by the activation of discrete neural elements. Here we examined how a variety of bitter stimuli are represented by neural activity in central gustatory neurons. Taste responses (spikes/s) evoked by bathing the tongue and palate with intensity-matched concentrations (in M) of 2 sugars (0.32 sucrose and 0.5 D-fructose), ethanol (40%), 4 salts (0.01 NaCl, 0.008 NaNO(3), 0.01 MgCl(2), and 0.05 KCl), 2 acids (0.003 HCl and 0.005 citric acid), and 10 bitter ligands (0.007 quinine-HCl, 0.015 denatonium benzoate, 0.003 l-cysteine, 0.001 nicotine, 0.005 strychnine-HCl, 0.04 tetraethylammonium chloride, 0.03 atropine-SO(4), 0.005 brucine-SO(4), 0.03 papaverine-HCl, and 0.009 sparteine) were recorded from 51 neurons in the nucleus of the solitary tract of anesthetized rats. Cluster analysis was used to categorize neurons into types based on responses to sucrose, NaCl, HCl, and quinine-HCl. Three groupings emerged: type S (responded optimally to sweets), type N (sodium-optimal), and type H/Q (responded robustly to bitters, acids, and salts). Multivariate analyses revealed that across-neuron patterns of response among bitter stimuli were strongly correlated. However, neural type H/Q, which was most responsive to bitter tastants, was not differentially sensitive to bitter stimuli and Na(+) salts, which rats perceive as distinct. Thus central neurons most responsive to bitter substances receive significant input from receptors that mediate other tastes, indicating that bitter stimuli are not represented by activity in specifically tuned neurons.

Taste and somatosensation both mediate protective behaviors. Bitter taste guides avoidance of ingestion of toxins while pain sensations, such as noxious heat, signal adverse conditions to ward off harm. Although brain pathways for taste and somatosensation are typically studied independently, prior data suggest that they intersect, potentially reflecting their common protective role. To investigate this, we applied electrophysiologic and optogenetic techniques in anesthetized mice of both sexes to evaluate relationships between oral somatosensory and taste activity in the parabrachial nucleus (PbN), implicated for roles in gustation and pain. Spikes were recorded from taste-active PbN neurons tested with oral delivery of thermal and chemesthetic stimuli, including agonists of nocisensitive transient receptor potential (TRP) ion channels on somatosensory fibers. Gustatory neurons were also tested to follow electrical pulse stimulation of an oral somatosensory region of the spinal trigeminal subnucleus caudalis (Vc), which projects to the PbN. Neurons composed classic taste groups, including sodium, electrolyte, appetitive, or bitter cells. Across groups, most neurons spiked to Vc pulse stimulation, implying that trigeminal projections reach PbN gustatory neurons. Among such cells, a subpopulation responsive to the bitter taste stimuli quinine and cycloheximide, and aversive concentrations of sodium, cofired to agonists of nocisensitive TRP channels, including capsaicin, mustard oil, and noxious heat. Such neurons populated the lateral PbN. Further, nociceptive activity in PbN bitter taste neurons was suppressed during optogenetic-assisted inhibition of the Vc, implying convergent trigeminal input contributed to such activity. Our results reveal a novel role for PbN gustatory cells in cross-system signaling related to protection.

Changes in oral temperature can influence taste perception, indicating overlap among mechanisms for taste and oral somesthesis. Medullary gustatory neurons can show cosensitivity to temperature, albeit how these cells process combined taste and thermal input is poorly understood. Here, we electrophysiologically recorded orosensory responses (spikes) from 39 taste-sensitive neurons in the nucleus tractus solitarii of anesthetized mice during oral delivery of tastants adjusted to innocuous cool (16 and 18°C), room (22°C, baseline), and warm (30 and 37°C) oral temperatures. Stimuli included (in mM) 100 sucrose, 30 NaCl, 3 HCl, 3 quinine, an umami mixture, and water. Although cooled water excited few cells, water warmed to 30 and 37°C significantly excited 33% and 64% of neurons, respectively. Warmth induced responses of comparable magnitude to room temperature tastants. Furthermore, warming taste solutions influenced the distribution of gustatory responses among neurons and increased (P < 0.05) neuronal breadth of tuning across taste qualities. The influence of warmth on response magnitude was stimulus specific. Across neurons, warming facilitated responses to sucrose and umami in a superadditive manner, as these responses exceeded (P < 0.05) the arithmetic sum of activity to warming alone and the taste stimulus tested at room temperature. Superadditive increases (P < 0.05) in responding were also noted in some cells for warmed HCl. Yet warming induced only simple additive or subtractive effects on responses to quinine and NaCl. Data show temperature is a parameter of gustatory processing, like taste quality and concentration, in medullary circuits for taste.