Taste is a primary channel controlling feeding behavior. Taste substances are first recognized by taste receptor cells (TRCs) on the epithelium of the tongue and palate. Activated TRCs then transmit their signals synaptically to the taste cortex. Previously, the authors identified the cells mediating all five basic taste modalities (sweet, bitter, umami, salty, and sour) and showed that each taste is mediated by its own class of TRCs expressing dedicated receptors. The taste system triggers predetermined behaviors through labeled lines, independent of learning or experience (such as attraction to sweetness and aversion to bitterness), but it is highly modulated by internal states and nutritional needs. For example, sweet stimuli become more attractive when the animal is hungry. Notably, despite tremendous progress in sensory biology, it remains unknown how Sugars drive consummatory feeding behavior.
On November 26, 2025, a team led by Charles S. Zuker from Columbia University published an article in Cell titled "A brain center that controls consummatory responses." The authors dissected the neural circuitry driving responses to sweetness and showed that amygdala neurons connect to the bed nucleus of the stria terminalis (BNST) to promote sweet-induced feeding behavior. Next, the authors demonstrated that the BNST acts as a central brain region that translates appetitive signals into feeding behavior, linking sensory input with internal states to flexibly regulate consummatory behavior. Using single-cell functional imaging, the authors found that the collective activity of the BNST encodes both the stimulus modality and the animal's internal state.
Finally, the authors demonstrated that manipulating BNST activity can bidirectionally alter feeding responses. In summary, these findings illustrate how internal states modulate sensory responses and provide new insights into the site of action of GLP1R Agonists and strategies to help promote weight gain in pathological conditions.
The authors explored the mechanisms of value encoding of sensory stimuli within the central amygdala (CEA). Using Act-seq single-cell RNA sequencing (scRNA-seq), the authors analyzed 12,000 CEA neurons and found that cluster 15 neurons specifically responded to sweet stimuli, while cluster 5 and 13 neurons specifically responded to bitter stimuli. Further analysis revealed that neurons in cluster 15 expressed the Pdyn gene, and over 90% of Fos-positive sweet-responsive neurons co-expressed Pdyn. Fiber photometry confirmed that Pdyn-positive CEA neurons were indeed specifically activated by sweet stimuli. Optogenetic activation of Pdyn-positive CEA neurons made water more attractive, leading animals to actively seek out this activation, while optogenetic inhibition of these neurons eliminated the preference for Sweetness. In summary, Pdyn-expressing neurons in the CEA are a key neuronal population that encodes the value signal of sweetness and promotes corresponding feeding behavior.
The authors further explored how Pdyn neuron signaling in the CEA is translated into appetitive feeding behavior through downstream regions. Tracing experiments revealed that CEA Pdyn neurons primarily project to the BNST region, which is mainly composed of GABAergic neurons. Fiber photometry experiments showed that GABAergic neurons in the BNST region do respond to sweet taste stimuli. Optogenetic activation of the projection from CEA Pdyn neurons to the BNST made previously unattractive water stimuli attractive, inducing the animals to actively lick the water. However, this activation did not induce active consumption behavior without water stimuli, indicating a specific feeding behavior. Conversely, direct optogenetic activation of the CEA Pdyn neuron cell bodies resulted in more widespread rewarding self-stimulation behavior. Finally, optogenetic inhibition of GABAergic neurons in the BNST completely blocked the animals' feeding behavior in response to sweet stimuli. In summary, these results indicate that Pdyn neurons in the CEA project sweet taste value signals to the BNST, and GABAergic neurons in the BNST are a crucial intermediate link in translating this signal into a specific feeding behavior response.
Fig. 1 Projections of CEA Pdyn-expressing neurons to the BNST drive sweet consumption. (Canovas, et al. 2025)
The authors used single-neuron retrograde viral tracing techniques to discover that neurons in the BNST region receive input signals from the CEA and the arcuate nucleus of the hypothalamus (ARC). Further experiments revealed that optogenetic activation of AGRP neurons in the ARC projecting to the BNST in a satiated state enhanced the response of BNST neurons to sweet stimuli. Optogenetic activation of the AGRP neuron projection to the BNST caused satiated animals to exhibit strong sweet-seeking behavior similar to that of hungry animals. Conversely, chemogenetic silencing of AGRP neuron activity in a hungry state inhibited the enhanced sweet-seeking behavior, reducing it to the level observed in a satiated state. These results indicate that in a hungry state, AGRP neurons in the ARC, through their projection to the BNST, enhance the response of BNST neurons to sweet stimuli, thereby promoting the expression of sweet-seeking behavior.
The authors found that chemogenetic activation of GABAergic neurons in the BNST can enhance feeding behavior independently of internal state. In mice treated with the chemotherapy drug cisplatin, which induces severe anorexia and weight loss, chemogenetic activation of BNST GABAergic neurons effectively inhibited weight loss. Conversely, chemogenetic inhibition of BNST neuron activity caused significant weight loss in a High-Fat Diet-Induced Obesity Model, even surpassing the effect of a GLP-1 receptor agonist. In summary, BNST neurons may be a crucial center for regulating feeding behavior and body weight balance, and activating BNST GABAergic neurons could be a novel therapeutic strategy for preventing and treating Metabolic Diseases accompanied by severe anorexia.
In summary, this article elaborates on the crucial role of the BNST in regulating feeding behavior. Pdyn neurons in the CEA project to the BNST, and GABAergic neurons in the BNST receive this sweetness signal and translate it into specific ingestive behaviors. AGRP neurons in the arcuate nucleus (ARC) of the hypothalamus project to the BNST, and under starvation conditions, they can enhance the response of BNST neurons to sweet stimuli, thereby driving strong ingestive behavior towards sweetness. Furthermore, the response patterns of BNST neurons can encode the animal's internal state (satiety, hunger, salt deficiency) and external sensory stimuli (sweetness, saltiness), providing evidence for the role of the BNST as a center for integrating internal and external environmental information. Manipulating the activity of BNST neurons, such as chemogenetic activation of GABAergic neurons or inhibition of PKCδ neurons, can effectively regulate the animal's feeding behavior and body weight, providing new strategies for treating related diseases. Overall, this study reveals the BNST as a critical node that integrates information from internal states and external sensory stimuli, thereby coordinating corresponding feeding behaviors. This provides important clues for understanding how the central nervous system regulates energy balance. However, the work described here focuses on the sweet taste sensory input to the BNST and assumes that similar inputs will occur for other signals, such as salt and fat. Future research should focus on identifying the sources of these signals.
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