Amygdalo-hypothalamic circuit allows learned cues to override satiety and promote eating

Abstract

Organisms eat not only in a response to signals related to energy balance. Eating also occurs in response to "extrinsic," or environmental, signals, including learned cues. Such cues can modify feeding based on motivational value acquired through association with either rewarding or aversive events. We provide evidence that a specific brain system, involving connections between basolateral amygdala and the lateral hypothalamus, is crucial for allowing learned cues (signals that were paired with food delivery when the animal was hungry) to override satiety and promote eating in sated rats. In an assessment of second-order conditioning, we also found that disconnection of this circuitry had no effect on the ability of a conditioned cue to support new learning. Knowledge about neural systems through which food-associated cues specifically control feeding behavior provides a defined model for the study of learning that may be informative for understanding mechanisms that contribute to eating disorders and more moderate forms of overeating.

Fig. 1.

Histology. A, The extent of the largest (enclosed black area) and smallest (filled black area) acceptable lesions at several rostrocaudal levels for all rats in the contralateral and ipsilateral groups. Except for minor mechanical damage along the injector tracks, no damage was evident in any of the sham-lesioned brains. Plates adapted from the atlas of Swanson (1992). B, Representative photomicrographs of lesion and sham histology.Arrows denote lesion borders. Scale bar, 0.5 mm. Amygdala: BLA, Basolateral area (includesBL, BMA, and LA);BL, basolateral (basal); BMA, basomedial (accessory basal); CEA, central; LA, lateral nuclei. Hypothalamus: DMH, Dorsomedial nucleus;fx, fornix; LHA, lateral area;mtt, mammillothalamic tract; VMH, ventromedial nucleus.

Fig. 2.

First-order conditioning. Acquisition of discrimination between the CS+ and CS− auditory stimuli during the initial phase of training in rats with contralateral (▪), ipsilateral (▴), or sham (●) lesions of the BLA and LHA. Conditioned responses to the CS+ are represented by filled symbols, and conditioned responses to the CS− are represented by open symbols. Conditioned responses are expressed as the mean ± SEM percentage of time expressing food cup behavior.

Fig. 3.

Food consumption tests.A, Food consumption of sham, ipsilateral, and contralateral rats during the potentiated eating tests. Black bars show food consumption during the tests with CS+, andwhite bars show consumption during the tests with CS−.B, Mean difference between the consumption during the tests with CS+ and consumption during the tests with CS− presentations. Consumption of sham, ipsilateral, and contralateral rats is shown with white, gray, andblack bars, respectively. The error bars indicate the SEM.

Fig. 4.

Second-order conditioning. Acquisition of second-order conditioned responses (food cup behavior) to the light CS2 during the second phase of training in rats with contralateral (▪), ipsilateral (▴), or sham (●) lesions of the BLA and LHA. Rats that received paired CS2–CS+ presentations are represented by filled symbols, and rats that received unpaired presentations of CS2 and CS+ are represented by open symbols. SessionP refers to the pretest of the light at the beginning of training. Conditioned responses are expressed as the mean ± SEM percentage of time expressing food cup behavior.