Xiaobing Zhang

Research topics

Matched from this investigator's NIH project titles and abstracts.

• Developmental Cognitive Neuroscience
• Decision Making and Reward

Active NIH awards

• Dopamine neurons in the zona incerta regulate feeding motivation

  5R01DK131474-02

  NIDDK · FY 2024 · $376K

  PROJECT SUMMARY Zona incerta (ZI), a brain region located between the ventral thalamus and the hypothalamus, has been revealed to regulate food intake by latest findings. We reported that g-aminobutyric acid (GABA) neurons in the ZI regulate food intake through inhibitory projections to paraventricular thalamus (PVT). In addition to GABA neurons, dopamine (DA) neurons have been found in the ZI for decades. However, little is known about their function in the behavioral regulation. In our pilot studies, we used TH-Cre mice to target ZI DA neurons and found that chemogenetic activation of ZI DA neurons potently increased motivation to obtain food reward. Based on our pilot data, we hypothesize that: 1) ZI DA neurons regulate feeding motivation to control food consumption. 2) ZI DA neurons encode feeding behaviors and respond to metabolic hunger signals. 3) the PVT serves as one of the important postsynaptic areas for ZI DA neurons to exert the functional control on feeding. To test our hypothesis, we will use adeno-associated viral vectors (AAVs) to induce Cre-dependent expression of excitatory hM3Dq, inhibitory hM4Di, or ChR2 selectively in ZI DA neurons of TH-Cre mice. Chemogenetic activation and silencing will be employed to selectively manipulate ZI DA neurons for testing their role in the control of food motivation using progressive ratio (PR) schedule of reinforcement and real-time food consumption and meal pattern using Feeding Experimental Devices (FED). We will also use optogenetics to selectively activate ZI DA projections to determine the role of PVT neurons in feeding regulation induced by ZI DA neurons. In addition to the behavioral studies, we will perform slice electrophysiology in combination with optogenetics to dissect functional ZI DA pathways. In vivo fiber photometry will be applied to examine how ZI DA neurons encode feeding behaviors including food seeking and consumption and slice electrophysiology will be used to study the activity response of ZI DA neurons to metabolic hunger signals. Together, the proposed studies in this application will reveal novel ZI DA pathways in feeding control. The expected outcome from the proposed studies will significantly expand our view of how ZI and central DA signaling regulate feeding motivation and food consumption.

• Serotonin Signaling in Zona Incerta and Paraventricular Thalamus Regulate Feeding Behavior

  5R01DK131441-03

  NIDDK · FY 2024 · $332K

  PROJECT SUMMARY Increasing evidence indicates that both zona incerta (ZI) and paraventricular thalamus (PVT) play important roles in the regulation of feeding. Our previous study reported that activation of ZI GABA neurons and their projections to PVT rapidly evokes binge-like eating. Food deprivation activates ZI GABA neurons and selective ablation of ZI GABA neurons suppresses daily food intake and body weight gain in mice, supporting the importance of ZI GABA neurons in the physiological feeding control. However, it remains largely unknown how the ZI-PVT pathway is innervated and controlled by other brain areas for the feeding regulation. In this application, we propose to study how central serotonin (5-HT) signaling targeting both ZI and PVT for the feeding control. Although the importance of central 5-HT signaling in the satiety regulation is well-known, little is known what raphe 5-HT projections regulate feeding motivation. Our pilot data show that both ZI and PVT receive dense 5-HT projections from raphe nuclei, including both dorsal and medial raphe. Food deprivation depressed the activity of dorsal raphe neurons that project to ZI and PVT. In addition, 5-HT excited PVT neurons but inhibited ZI neurons as well as ZI-PVT GABA transmission. Based on the significant role of the ZI- PVT neural pathway in feeding control, we hypothesize that: 1) raphe neurons send 5-HT signaling to modulate both ZI and PVT neurons, and inhibit ZI-PVT GABA transmission. 2) raphe 5-HT projections to ZI and PVT regulate feeding motivation and food intake. 3) chronic high-fat high-sugar (HFHS) diet alters 5-HT inhibition on PVT-projecting ZI neurons and ZI-PVT GABA transmission. Aim 1 of the proposal is focused on the study about the functional 5-HT neural projections from raphe to both ZI and PVT, and the modulatory effects of 5- HT signaling on ZI and PVT neurons. Using slice electrophysiology in combination with optogenetics to target specific neurons in brain slices, we will corroborate the differential modulation of 5-HT signaling on ZI and PVT neurons as well as ZI-PVT GABA transmission. In Aim 2, we will examine how raphe 5-HT projections to both ZI and PVT regulate feeding motivation and food intake. In the proposed experiments for the behavioral study, we will use optogenetic tools to manipulate raphe 5-HT neurons and their projections to ZI and PVT. We will also use slice electrophysiology and c-fos immunoreactivity to study how ZI- and PVT-projecting 5-HT neurons respond to the metabolic states, revealing the role of raphe 5-HT projections to ZI and PVT in the physiological feeding regulation. In Aim 3, we will study how chronic HFHS diets alter 5-HT inhibition on PVT-projecting ZI neurons and ZI-PVT GABA transmission. Together, the proposal in this application will elucidate a novel role of 5-HT signaling in the regulation of food intake by targeting both ZI and PVT. Also, the findings from this project will help further understand how dysfunctional brain 5-HT signaling is involved in overeating and obesity.

• Dopamine neurons in the zona incerta regulate feeding motivation

  1R01DK131474-01A1

  NIDDK · FY 2023 · $414K

  PROJECT SUMMARY Zona incerta (ZI), a brain region located between the ventral thalamus and the hypothalamus, has been revealed to regulate food intake by latest findings. We reported that g-aminobutyric acid (GABA) neurons in the ZI regulate food intake through inhibitory projections to paraventricular thalamus (PVT). In addition to GABA neurons, dopamine (DA) neurons have been found in the ZI for decades. However, little is known about their function in the behavioral regulation. In our pilot studies, we used TH-Cre mice to target ZI DA neurons and found that chemogenetic activation of ZI DA neurons potently increased motivation to obtain food reward. Based on our pilot data, we hypothesize that: 1) ZI DA neurons regulate feeding motivation to control food consumption. 2) ZI DA neurons encode feeding behaviors and respond to metabolic hunger signals. 3) the PVT serves as one of the important postsynaptic areas for ZI DA neurons to exert the functional control on feeding. To test our hypothesis, we will use adeno-associated viral vectors (AAVs) to induce Cre-dependent expression of excitatory hM3Dq, inhibitory hM4Di, or ChR2 selectively in ZI DA neurons of TH-Cre mice. Chemogenetic activation and silencing will be employed to selectively manipulate ZI DA neurons for testing their role in the control of food motivation using progressive ratio (PR) schedule of reinforcement and real-time food consumption and meal pattern using Feeding Experimental Devices (FED). We will also use optogenetics to selectively activate ZI DA projections to determine the role of PVT neurons in feeding regulation induced by ZI DA neurons. In addition to the behavioral studies, we will perform slice electrophysiology in combination with optogenetics to dissect functional ZI DA pathways. In vivo fiber photometry will be applied to examine how ZI DA neurons encode feeding behaviors including food seeking and consumption and slice electrophysiology will be used to study the activity response of ZI DA neurons to metabolic hunger signals. Together, the proposed studies in this application will reveal novel ZI DA pathways in feeding control. The expected outcome from the proposed studies will significantly expand our view of how ZI and central DA signaling regulate feeding motivation and food consumption.

• Serotonin Signaling in Zona Incerta and Paraventricular Thalamus Regulate Feeding Behavior

  5R01DK131441-02

  NIDDK · FY 2023 · $346K

  PROJECT SUMMARY Increasing evidence indicates that both zona incerta (ZI) and paraventricular thalamus (PVT) play important roles in the regulation of feeding. Our previous study reported that activation of ZI GABA neurons and their projections to PVT rapidly evokes binge-like eating. Food deprivation activates ZI GABA neurons and selective ablation of ZI GABA neurons suppresses daily food intake and body weight gain in mice, supporting the importance of ZI GABA neurons in the physiological feeding control. However, it remains largely unknown how the ZI-PVT pathway is innervated and controlled by other brain areas for the feeding regulation. In this application, we propose to study how central serotonin (5-HT) signaling targeting both ZI and PVT for the feeding control. Although the importance of central 5-HT signaling in the satiety regulation is well-known, little is known what raphe 5-HT projections regulate feeding motivation. Our pilot data show that both ZI and PVT receive dense 5-HT projections from raphe nuclei, including both dorsal and medial raphe. Food deprivation depressed the activity of dorsal raphe neurons that project to ZI and PVT. In addition, 5-HT excited PVT neurons but inhibited ZI neurons as well as ZI-PVT GABA transmission. Based on the significant role of the ZI- PVT neural pathway in feeding control, we hypothesize that: 1) raphe neurons send 5-HT signaling to modulate both ZI and PVT neurons, and inhibit ZI-PVT GABA transmission. 2) raphe 5-HT projections to ZI and PVT regulate feeding motivation and food intake. 3) chronic high-fat high-sugar (HFHS) diet alters 5-HT inhibition on PVT-projecting ZI neurons and ZI-PVT GABA transmission. Aim 1 of the proposal is focused on the study about the functional 5-HT neural projections from raphe to both ZI and PVT, and the modulatory effects of 5- HT signaling on ZI and PVT neurons. Using slice electrophysiology in combination with optogenetics to target specific neurons in brain slices, we will corroborate the differential modulation of 5-HT signaling on ZI and PVT neurons as well as ZI-PVT GABA transmission. In Aim 2, we will examine how raphe 5-HT projections to both ZI and PVT regulate feeding motivation and food intake. In the proposed experiments for the behavioral study, we will use optogenetic tools to manipulate raphe 5-HT neurons and their projections to ZI and PVT. We will also use slice electrophysiology and c-fos immunoreactivity to study how ZI- and PVT-projecting 5-HT neurons respond to the metabolic states, revealing the role of raphe 5-HT projections to ZI and PVT in the physiological feeding regulation. In Aim 3, we will study how chronic HFHS diets alter 5-HT inhibition on PVT-projecting ZI neurons and ZI-PVT GABA transmission. Together, the proposal in this application will elucidate a novel role of 5-HT signaling in the regulation of food intake by targeting both ZI and PVT. Also, the findings from this project will help further understand how dysfunctional brain 5-HT signaling is involved in overeating and obesity.

Earlier awards

• Dopamine neurons in the zona incerta regulate feeding motivationFY 2025 · $387K
• Serotonin Signaling in Zona Incerta and Paraventricular Thalamus Regulate Feeding BehaviorFY 2025 · $346K