Author
Chian Ping Ye
Bio: Chian Ping Ye is an academic researcher from Harvard University. The author has contributed to research in topics: Neuron & Energy homeostasis. The author has an hindex of 2, co-authored 2 publications receiving 1468 citations.
Papers
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TL;DR: Using designer receptors exclusively activated by designer drugs (DREADD) technology to provide specific and reversible regulation of neuronal activity in mice, it is demonstrated that acute activation of AgRP neurons rapidly and dramatically induces feeding, reduces energy expenditure, and ultimately increases fat stores.
Abstract: Several different neuronal populations are involved in regulating energy homeostasis. Among these, agouti-related protein (AgRP) neurons are thought to promote feeding and weight gain; however, the evidence supporting this view is incomplete. Using designer receptors exclusively activated by designer drugs (DREADD) technology to provide specific and reversible regulation of neuronal activity in mice, we have demonstrated that acute activation of AgRP neurons rapidly and dramatically induces feeding, reduces energy expenditure, and ultimately increases fat stores. All these effects returned to baseline after stimulation was withdrawn. In contrast, inhibiting AgRP neuronal activity in hungry mice reduced food intake. Together, these findings demonstrate that AgRP neuron activity is both necessary and sufficient for feeding. Of interest, activating AgRP neurons potently increased motivation for feeding and also drove intense food-seeking behavior, demonstrating that AgRP neurons engage brain sites controlling multiple levels of feeding behavior. Due to its ease of use and suitability for both acute and chronic regulation, DREADD technology is ideally suited for investigating the neural circuits hypothesized to regulate energy balance.
1,170 citations
TL;DR: These mice with an AgRP neuron–specific deletion of vesicular GABA transporter are lean, resistant to obesity and have an attenuated hyperphagic response to ghrelin, indicating that GABA release from AgRP neurons is important in regulating energy balance.
Abstract: The physiologic importance of GABAergic neurotransmission in hypothalamic neurocircuits is unknown. To examine the importance of GABA release from agouti-related protein (AgRP) neurons (which also release AgRP and neuropeptide Y), we generated mice with an AgRP neuron-specific deletion of vesicular GABA transporter. These mice are lean, resistant to obesity and have an attenuated hyperphagic response to ghrelin. Thus, GABA release from AgRP neurons is important in regulating energy balance.
577 citations
Cited by
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TL;DR: A change in the efficiency of energy expenditure based upon diet is suggested, such that SPA during HFD burns fewer calories compared to SPA on a standard chow diet.
1,444 citations
TL;DR: This work constructed a cellular taxonomy of one cortical region, primary visual cortex, in adult mice on the basis of single-cell RNA sequencing and identified 49 transcriptomic cell types, including 23 GABAergic, 19 glutamatergic and 7 non-neuronal types.
Abstract: Nervous systems are composed of various cell types, but the extent of cell type diversity is poorly understood. We constructed a cellular taxonomy of one cortical region, primary visual cortex, in adult mice on the basis of single-cell RNA sequencing. We identified 49 transcriptomic cell types, including 23 GABAergic, 19 glutamatergic and 7 non-neuronal types. We also analyzed cell type-specific mRNA processing and characterized genetic access to these transcriptomic types by many transgenic Cre lines. Finally, we found that some of our transcriptomic cell types displayed specific and differential electrophysiological and axon projection properties, thereby confirming that the single-cell transcriptomic signatures can be associated with specific cellular properties.
1,388 citations
TL;DR: Using designer receptors exclusively activated by designer drugs (DREADD) technology to provide specific and reversible regulation of neuronal activity in mice, it is demonstrated that acute activation of AgRP neurons rapidly and dramatically induces feeding, reduces energy expenditure, and ultimately increases fat stores.
Abstract: Several different neuronal populations are involved in regulating energy homeostasis. Among these, agouti-related protein (AgRP) neurons are thought to promote feeding and weight gain; however, the evidence supporting this view is incomplete. Using designer receptors exclusively activated by designer drugs (DREADD) technology to provide specific and reversible regulation of neuronal activity in mice, we have demonstrated that acute activation of AgRP neurons rapidly and dramatically induces feeding, reduces energy expenditure, and ultimately increases fat stores. All these effects returned to baseline after stimulation was withdrawn. In contrast, inhibiting AgRP neuronal activity in hungry mice reduced food intake. Together, these findings demonstrate that AgRP neuron activity is both necessary and sufficient for feeding. Of interest, activating AgRP neurons potently increased motivation for feeding and also drove intense food-seeking behavior, demonstrating that AgRP neurons engage brain sites controlling multiple levels of feeding behavior. Due to its ease of use and suitability for both acute and chronic regulation, DREADD technology is ideally suited for investigating the neural circuits hypothesized to regulate energy balance.
1,170 citations
TL;DR: A primer on DREADDs is provided highlighting key technical and conceptual considerations and identify challenges for chemogenetics going forward.
1,145 citations
TL;DR: This work takes an alternative approach and tests whether first-order neurons are inhibitory (GABAergic, VGAT⁺) or excitatory (glutamatergic, VGLUT2⁺), which mediates the vast majority of leptin's antiobesity effects.
993 citations