Dopamine production in neurotensin receptor 1 neurons is required for diet-induced obesity and increased day eating on a high-fat diet.

OBJECTIVE: This study aimed to determine a dopaminergic circuit required for diet-induced obesity in mice. METHODS: We created conditional deletion mutants for tyrosine hydroxylase (TH) using neurotensin receptor 1 (Ntsr1) Cre and other Cre drivers and measured feeding and body weight on standard and high-fat diets. We then used an adeno-associated virus to selectively restore TH to the ventral tegmental area (VTA) Ntsr1 neurons in conditional knockout (cKO) mice. RESULTS: Mice with cKO of Th using Vglut2-Cre, Cck-Cre, Calb1-Cre, and Bdnf-Cre were susceptible to obesity on a high-fat diet; however, Ntsr1-Cre Th cKO mice resisted weight gain on a high-fat diet and did not experience an increase in day eating unlike their wild-type littermate controls. Restoration of TH to the VTA Ntsr1 neurons of the Ntsr1-Cre Th cKO mice using an adeno-associated virus resulted in an increase in weight gain and day eating on a high-fat diet. CONCLUSIONS: Ntsr1-Cre Th cKO mice failed to increase day eating on a high-fat diet, offering a possible explanation for their resistance to diet-induced obesity. These results implicate VTA Ntsr1 dopamine neurons as promoting out-of-phase feeding behavior on a high-fat diet that could be an important contributor to diet-induced obesity in humans.

Light affects the prefrontal cortex via intrinsically photosensitive retinal ganglion cells.

The ventromedial prefrontal cortex (vmPFC) is a part of the limbic system engaged in the regulation of social, emotional, and cognitive states, which are characteristically impaired in disorders of the brain such as schizophrenia and depression. Here, we show that intrinsically photosensitive retinal ganglion cells (ipRGCs) modulate, through light, the integrity, activity, and function of the vmPFC. This regulatory role, which is independent of circadian and mood alterations, is mediated by an ipRGC-thalamic-corticolimbic pathway. Lack of ipRGC signaling in mice causes dendritic degeneration, dysregulation of genes involved in synaptic plasticity, and depressed neuronal activity in the vmPFC. These alterations primarily undermine the ability of the vmPFC to regulate emotions. Our discovery provides a potential light-dependent mechanism for certain PFC-centric disorders in humans.

Alkali metal doped crystalline g-C3N4 with an enriched cyano group for visible-light photocatalytic degradation of methylamine.

In this study, alkali-metal-doped crystalline g-C3N4 with an enriched cyano group was synthesized using the molten salt method and used for the visible-light photocatalytic degradation of methylamine (MA), a common organic amine compound with a low odor threshold. Different types and proportions of melting salts (Li, K, and Na) were added during secondary calcination to regulate the morphology, crystallinity, and surface defects of graphitic carbon nitride (g-C3N4). With molten salt treatment matched the melting point of the binary salt system, a cyano group and alkali metal co-doped crystalline g-C3N4 with a high surface area and good crystallinity were prepared. Co-decorating the alkali metal and cyano groups on crystalline g-C3N4 facilitated the adsorption of MA, realized an excellent photo-charge transfer efficiency, and generated more superoxide radicals. Compared with pristine g-C3N4 (PCN), the apparent rate constant of LiK15 : 5-CCN for the degradation of MA increased by 10.2 times and the degradation efficiency of 1000 ppm MA gas was 93.1% after 90 min of irradiation with visible light, whereas the degradation efficiency of PCN was 19.2%.

Leptin receptor neurons in the dorsomedial hypothalamus input to the circadian feeding network.

Salient cues, such as the rising sun or availability of food, entrain biological clocks for behavioral adaptation. The mechanisms underlying entrainment to food availability remain elusive. Using single-nucleus RNA sequencing during scheduled feeding, we identified a dorsomedial hypothalamus leptin receptor-expressing (DMHLepR) neuron population that up-regulates circadian entrainment genes and exhibits calcium activity before an anticipated meal. Exogenous leptin, silencing, or chemogenetic stimulation of DMHLepR neurons disrupts the development of molecular and behavioral food entrainment. Repetitive DMHLepR neuron activation leads to the partitioning of a secondary bout of circadian locomotor activity that is in phase with the stimulation and dependent on an intact suprachiasmatic nucleus (SCN). Last, we found a DMHLepR neuron subpopulation that projects to the SCN with the capacity to influence the phase of the circadian clock. This direct DMHLepR-SCN connection is well situated to integrate the metabolic and circadian systems, facilitating mealtime anticipation.

A leptin-responsive hypothalamic circuit inputs to the circadian feeding network.

Salient cues, such as the rising sun or the availability of food, play a crucial role in entraining biological clocks, allowing for effective behavioral adaptation and ultimately, survival. While the light-dependent entrainment of the central circadian pacemaker (suprachiasmatic nucleus, SCN) is relatively well defined, the molecular and neural mechanisms underlying entrainment associated with food availability remains elusive. Using single nucleus RNA sequencing during scheduled feeding (SF), we identified a leptin receptor (LepR) expressing neuron population in the dorsomedial hypothalamus (DMH) that upregulates circadian entrainment genes and exhibits rhythmic calcium activity prior to an anticipated meal. We found that disrupting DMHLepR neuron activity had a profound impact on both molecular and behavioral food entrainment. Specifically, silencing DMHLepR neurons, mis-timed exogenous leptin administration, or mis-timed chemogenetic stimulation of these neurons all interfered with the development of food entrainment. In a state of energy abundance, repetitive activation of DMHLepR neurons led to the partitioning of a secondary bout of circadian locomotor activity that was in phase with the stimulation and dependent on an intact SCN. Lastly, we discovered that a subpopulation of DMHLepR neurons project to the SCN with the capacity to influence the phase of the circadian clock. This leptin regulated circuit serves as a point of integration between the metabolic and circadian systems, facilitating the anticipation of meal times.

Food-induced dopamine signaling in AgRP neurons promotes feeding.

Obesity comorbidities such as diabetes and cardiovascular disease are pressing public health concerns. Overconsumption of calories leads to weight gain; however, neural mechanisms underlying excessive food consumption are poorly understood. Here, we demonstrate that dopamine receptor D1 (Drd1) expressed in the agouti-related peptide/neuropeptide Y (AgRP/NPY) neurons of the arcuate hypothalamus is required for appropriate responses to a high-fat diet (HFD). Stimulation of Drd1 and AgRP/NPY co-expressing arcuate neurons is sufficient to induce voracious feeding. Delivery of a HFD after food deprivation acutely induces dopamine (DA) release in the ARC, whereas animals that lack Drd1 expression in ARCAgRP/NPY neurons (Drd1AgRP-KO) exhibit attenuated foraging and refeeding of HFD. These results define a role for the DA input to the ARC that encodes acute responses to food and position Drd1 signaling in the ARCAgRP/NPY neurons as an integrator of the hedonic and homeostatic neuronal feeding circuits.

Dopamine systems and biological rhythms: Let's get a move on.

How dopamine signaling regulates biological rhythms is an area of emerging interest. Here we review experiments focused on delineating dopamine signaling in the suprachiasmatic nucleus, nucleus accumbens, and dorsal striatum to mediate a range of biological rhythms including photoentrainment, activity cycles, rest phase eating of palatable food, diet-induced obesity, and food anticipatory activity. Enthusiasm for causal roles for dopamine in the regulation of circadian rhythms, particularly those associated with food and other rewarding events, is warranted. However, determining that there is rhythmic gene expression in dopamine neurons and target structures does not mean that they are bona fide circadian pacemakers. Given that dopamine has such a profound role in promoting voluntary movements, interpretation of circadian phenotypes associated with locomotor activity must be differentiated at the molecular and behavioral levels. Here we review our current understanding of dopamine signaling in relation to biological rhythms and suggest future experiments that are aimed at teasing apart the roles of dopamine subpopulations and dopamine receptor expressing neurons in causally mediating biological rhythms, particularly in relation to feeding, reward, and activity.

A building block-based beam-break (B5) locomotor activity monitoring system and its use in circadian biology research.

Locomotor activity is one of the most commonly assayed animal behaviors. It is the gold standard for assessing behavioral circadian rhythmicity. Here, we develop a flexible and affordable locomotor activity monitoring system that does not interfere with the behavior of animals. We validate the reliability of the system in multiple circadian biology research scenarios. This device is customizable and can be used for many animal species.

Boosted CO2 photoreduction performance on Ru-Ti3CN MXene-TiO2 photocatalyst synthesized by non-HF Lewis acidic etching method.

Photocatalytic CO2 reduction to produce value-added products is considered a promising solution to solve the global energy crisis and the greenhouse effect. In this study, Ti3CN MXene was synthesized using a Lewis acidic etching method without the usage of toxic hydrofluoric acid (HF). Ti3CN MXene was then used as a support for the in situ hydrothermal growth of TiO2 and Ru nanoparticles. In the presence of 0.5 wt% Ru, Ru-Ti3CN-TiO2 shows CO and CH4 production rates of 99.58 and 8.97 µmol/g, respectively, in 5 h under Xenon lamp irradiation, more than 20.5 and 9.3 times that of commercial P25. The enhancement in photocatalytic activity was attributed to the synergy between the in-situ growth of TiO2 on Ti3CN MXene and Ru nanoparticles. It was proven experimentally that Ti3CN MXene can provide abundant pathways for electron transfer. The separation and transfer of the photo-induced charge were further increased with the help of Ru and Ti3CN MXene, leaving more electrons to participate in the subsequent CO2 reduction reaction. We believe that this work will encourage more attention to designing environment-friendly MXene-based photocatalysts for CO2 photoreduction using the non-HF method.

Long-term high fat diet consumption reversibly alters feeding behavior via a dopamine-associated mechanism in mice.

Obesity is a costly, global epidemic that is perpetuated by an unhealthy diet. A significant factor in the initial consumption and maintenance of an unhealthy diet is the abundance of highly palatable, calorically dense foods. The aim of the present study is to better understand the effects of high fat diet (HFD) consumption on food valuation and preference, and to elucidate the neurobiological mechanisms mediating these effects. By using a novel food preference assay, we found that prolonged consumption of a HFD diminishes preference for and consumption of the more calorically dense food choice when two lab diets are presented. Additionally, we demonstrated that prolonged HFD consumption dampens ventral tegmental c-fos induction during hedonic feeding, implicating the mesolimbic dopamine signaling pathway as a target of HFD. Notably, both the changes in food preference and this reduced c-fos induction were reversed during withdrawal from HFD. Further, HFD-induced alterations in food preference were attenuated by exercise. Our findings suggest that prolonged HFD consumption leads to anhedonia and altered feeding choices, and this is associated with changes in mesolimbic dopamine signaling.

Dopamine Signaling in the Suprachiasmatic Nucleus Enables Weight Gain Associated with Hedonic Feeding.

The widespread availability of energy-dense, rewarding foods is correlated with the increased incidence of obesity across the globe. Overeating during mealtimes and unscheduled snacking disrupts timed metabolic processes, which further contribute to weight gain. The neuronal mechanism by which the consumption of energy-dense food restructures the timing of feeding is poorly understood. Here, we demonstrate that dopaminergic signaling within the suprachiasmatic nucleus (SCN), the central circadian pacemaker, disrupts the timing of feeding, resulting in overconsumption of food. D1 dopamine receptor (Drd1)-null mice are resistant to diet-induced obesity, metabolic disease, and circadian disruption associated with energy-dense diets. Conversely, genetic rescue of Drd1 expression within the SCN restores diet-induced overconsumption, weight gain, and obesogenic symptoms. Access to rewarding food increases SCN dopamine turnover, and elevated Drd1-signaling decreases SCN neuronal activity, which we posit disinhibits downstream orexigenic responses. These findings define a connection between the reward and circadian pathways in the regulation of pathological calorie consumption.

Decorating g-C3N4 with alkalinized Ti3C2 MXene for promoted photocatalytic CO2 reduction performance.

Photocatalytic reduction of carbon dioxide (CO2) under visible light irradiation for producing high-value fuel has attracted tremendous attention in recent years. In this study, titanium carbide MXene (Ti3C2) was used as a noble metal-free co-catalyst by simply mixing graphitic carbon nitride (g-C3N4) and alkalized Ti3C2. The carbon monoxide evolution rate of the optimized composite (5%TCOH-CN) from photocatalytic reduction of CO2 was 5.9 times higher than that of pure g-C3N4. Alkalized Ti3C2 was responsible for the superior photocatalytic activity due to its excellent electrical conductivity and large CO2 adsorption capacity. Furthermore, the separation of the photo-induced electron-hole pairs was greatly enhanced because of the large Fermi level difference between alkalized Ti3C2 and pure g-C3N4. This work demonstrates the potential of MXenes as noble metal-free co-catalyst for photocatalysis processes such as carbon dioxide reduction reaction and nitrogen reduction reaction.

A direct Z-scheme Bi2WO6/NH2-UiO-66 nanocomposite as an efficient visible-light-driven photocatalyst for NO removal.

To explore an efficient photocatalyst for NO pollution, a direct Z-scheme photocatalytic system is successfully fabricated by coupling Bi2WO6 with NH2-UiO-66 via a simple hydrothermal synthesis technique. The Z-scheme system promotes the NO photocatalytic oxidation activity with an optimum NO removal rate of 79%, which is 2.7 and 1.2 times that obtained by using only pristine Bi2WO6 and NH2-UiO-66, respectively. Simultaneously, superior selectivity for converting NO to NO3 -/NO2 - is observed. The enhanced photocatalytic performance of the Bi2WO6/NH2-UiO-66 hybrids is attributed to the following two aspects: (i) large specific area of NH2-UiO-66, which exposes more active sites and is beneficial to the adsorption and activation of NO; (ii) outstanding Z-scheme structure constructed between BiWO6 and NH2-UiO-66, which can improve the efficiency of the separation of electron-hole pairs and preserves the strong oxidation ability of hybrids. ESR analysis shows that ·O2 - and ·OH contribute to NO removal. A possible photocatalytic mechanism of NO oxidation on the direct Z-scheme photocatalyst (BWO/2NU) under visible light irradiation is proposed. This work displays the BWO/2NU hybrid's potential for treating low-concentration air pollutants, and the proposed Z-scheme photocatalyst design and promotion mechanism may inspire more rational synthesis of highly efficient photocatalysts for NO removal.

The feature-specific propagation of orientation and direction adaptation from areas 17 to 21a in cats.

Adaptation plays a key role in visual information processing, and investigations on the adaptation across different visual regions will be helpful to understand how information is processed dynamically along the visual streams. Recent studies have found the enhanced adaptation effects in the early visual system (from LGN to V1) and the dorsal stream (from V1 to MT). However, it remains unclear how adaptation effect propagates along the form/orientation stream in the visual system. In this study, we compared the orientation and direction adaptation evoked by drifting gratings and stationary flashing gratings, as well as moving random dots, in areas 17 and 21a simultaneously of cats. Recorded by single-unit and intrinsic signal optical imaging, induced by both top-up and biased adaptation protocols, the orientation adaptation effect was greater in response decline and preferred orientation shifts in area 21a compared to area 17. However, for the direction adaptation, no difference was observed between these two areas. These results suggest the feature-specific propagation of the adaptation effect along the visual stream.