Parabrachial coding of sapid sucrose: relevance to reward and obesity

Abstract

Cumulative evidence in rats suggests that the pontine parabrachial nuclei (PBN) are necessary for assigning hedonic value to taste stimuli. In a series of studies, our laboratory has investigated the parabrachial coding of sapid sucrose in normal and obese rats. First, using chronic microdialysis, we demonstrated that sucrose intake increases dopamine release in the nucleus accumbens, an effect that is dependent on oral stimulation and on concentration. The dopamine response was independent of the thalamocortical gustatory system but was blunted substantially by lesions of the PBN. Similar lesions of the PBN but not the thalamic taste relay diminished cFos activation in the nucleus accumbens caused by sucrose ingestion. Recent single-neuron recording studies have demonstrated that processing of sucrose-evoked activity in the PBN is altered in Otsuka Long Evans Tokushima Fatty (OLETF) rats, which develop obesity due to chronic overeating and express increased avidity to sweet. Compared with lean controls, taste neurons in OLETF rats had reduced overall sensitivity to sucrose and altered concentration responses, with decreased responses to lower concentrations and augmented responses to higher concentrations. The decreased sensitivity to sucrose was specific to NaCl-best neurons that also responded to sucrose, but the concentration effects were carried by the sucrose-specific neurons. Collectively, these findings support the hypothesis that the PBN enables taste stimuli to engage the reward system and, in doing so, influences food intake and body weight regulation. Obesity, in turn, may further alter the gustatory code via forebrain connections to the taste relays or hormonal changes consequent to weight gain.

Fig. 1

Dopamine release from the nucleus accumbens shell before, during, and after licking 0.3 M sucrose expressed as a percentage of prestimulus baseline. Dopamine was collected by microdialysis in 20-min samples and measured with high performance liquid chromatography. The dotted lines indicate the sample taken during sucrose licking. Only one solution was tested per day. Statistically significance differences from baseline (p < 0.05) are indicated by asterisks. A. Concentration-response functions using 0.03 M, 0.1 M, and 0.3 M sucrose during sham feeding. B. Sham feeding a fixed volume of either 0.03 M or 0.3 M sucrose. The volume was 75% of the average that the rats ingested of the 0.03 M stimulus during a 20 min sham feeding session. C. The effect of central gustatory lesions on dopamine release in nucleus accumbens while ingesting 0.3 M sucrose. Abbreviations: PBNx – Bilateral lesions of the parabrachial nuclei; Sham. Op. - Combined data from 2 groups of full surgical controls; TTAx –Bilateral lesions centered on the thalamic taste relay. The figure is published elsewhere (Norgren et al. 2006) and reprinted with the permission of Publisher.

Fig. 2

The number c-fos positive neurons in the nucleus accumbens elicited by 1-h sham drinking of distilled water (dH₂O) or 0.6 M sucrose (SUC). CTRL, sham-operated controls; TTAx, lesions in the thalamic taste relay; mPBNx, lesions in the medial (gustatory) PBN; lPBNx, lesions in the lateral PBN. * P <0.05, ** P < 0.01, *** P < 0.001; SUC vs. dH₂O.

Fig. 3

Spontaneous firing activity (spikes/sec) of PBN taste neurons in obese OLETF and lean LETO rats. Numbers indicate number of recorded neurons; Ts, “specialist” units; Tx, “generalist” units. * P < 0.05

Fig. 4

Mean corrected neuronal response magnitudes (5-s minus prestimulus water baseline, spike/sec) to various concentrations of sucrose. A, sucrose-specific units (Ss); B, NaCl-best neurons also responding to sucrose (NS) $, statistical differences between strains based on overall ANOVA; * statistical differences between strains for a particular concentration; # statistical difference between the actual and the former sucrose response magnitude within the same strain. First significant response concentration: the lowest sucrose concentration that results in a significant neuronal taste response determined by significant t-test (p < 0.05) compared to the 5-s prestimulus water baseline. Maximum response concentration: the stimulus (sucrose) concentration that causes the highest magnitude taste response in the neuronal activity (one response magnitude is higher than the other if there is at least a 10% increase in the normalized firing rate). Maximum effective concentration: the highest applied sucrose concentration that results in significant taste response. Dynamic sucrose concentration range: a particular range within the tested sucrose concentrations (0.01, 0.03, 0.1, 0.3, 1 and 1.5 M), in which the consecutive higher concentrations are potent to cause at least 10% increase in the normalized neuronal firing rate over the effect of the one lower concentration. Non-dynamic sucrose concentration range or “plateau”: a particular range within the tested increasing sucrose concentrations, in which the consecutive higher concentrations do not cause increase in the normalized neuronal firing rate. The figure is published elsewhere (Kovacs and Hajnal, 2008) and reprinted with the permission of Publisher.

Fig. 5

Concentration effects on mean response magnitude in all sucrose-responsive PBN neurons. For definitions of measures, see the text. * P < 0.05. The data are published elsewhere in a different form (Kovacs and Hajnal, 2008).