Biology subjects

Liu, Z.-W.

Publications and source records attributed to Liu, Z.-W..

4 recordsLinked to original sources

bioRxiv2026

A hypothalamic circuit links hunger to mesolimbic dopamine to drive feeding

Hunger enhances the motivational value of food, but the neural circuits linking homeostatic hunger neurons to dopamine systems remain poorly understood. Here, we identify a hypothalamic-midbrain neural circuit through which AgRP neurons engage the mesolimbic dopamine system. We demonstrate that AgRP neuron activity is both necessary and sufficient for the potentiated dopamine response to food by hunger, and that they achieve this by reducing inhibitory drive onto midbrain dopamine neurons. Importantly, this AgRP neuron-evoked dopamine signaling is required for subsequent food intake. Mechanistically, we find that AgRP neuron projections to NPY-sensitive paraventricular hypothalamic neurons selectively amplify food-evoked dopamine release to promote feeding behavior. These findings reveal a circuit mechanism through which hunger recruits dopamine signaling to transform physiological need into motivated feeding behavior.

neuroscience↗

bioRxiv2025

Mitofusin 2 controls mitochondrial and synaptic dynamics of suprachiasmatic VIP neurons and related circadian rhythms including sleep

Sustaining the strong rhythmic interactions between cellular adaptations and environmental cues has been posited as essential for preserving the physiological and behavioral alignment of an organism to the proper phase of the daily light/dark cycle. Here, we show that mitochondria and synaptic input organization of suprachiasmatic (SCN) vasoactive intestinal peptide (VIP)-expressing neurons show circadian rhythmicity. Perturbed mitochondrial dynamics achieved by conditional ablation of the fusogenic protein mitofusin 2 (Mfn2) in VIP neurons cause disrupted circadian oscillation in mitochondria and synapses in SCN VIP neurons leading to desynchronization of entrainment to the light/dark cycle in Mfn2 deficient mice that resulted in advanced phase angle of their locomotor activity onset, alterations in core body temperature and sleep-wake amount and architecture. Our data provide direct evidence of circadian SCN clock machinery dependence on high-performance Mfn2-regulated mitochondrial dynamics in VIP neurons for maintaining the coherence in daily biological rhythms of the mammalian organism.

neuroscience↗

bioRxiv2021

LINE-1 activation in the cerebellum drives ataxia

Previous studies have revealed that dysregulation of long interspersed nuclear element 1 (LINE-1), a dominant class of transposable elements in the human genome, correlates with neurodegeneration1-3. Yet whether LINE-1 dysregulation is causal to disease pathogenesis has not been proven directly. Here, we demonstrate that expression of evolutionarily younger LINE-1 families is elevated in the cerebella of ataxia telangiectasia (AT) patients, which was correlated with extensive downregulation of epigenetic silencers. To examine whether LINE-1 activation causes neurologic disease, we established an approach to directly target and activate the promoter of a young family of LINE-1 in mice. LINE-1 activation in the cerebellum was sufficient to lead to robust progressive ataxia. Purkinje cells in the diseased mice exhibited marked electrophysiological dysfunctions and degeneration with a significant accumulation of cytoplasmic ribonucleoprotein LINE-1Orf1p aggregates, endoplasmic reticulum (ER) stress, and DNA damage. Treatment with lamivudine, a nucleoside reverse transcriptase inhibitor, blunted the disease progression by reducing DNA damage, attenuating gliosis and interferon gene signature, and recovering the loss of key functional molecules for calcium homeostasis in Purkinje cells. This study provides direct evidence that young LINE-1 activation drives ataxia phenotype, and points to its pleiotropic effects leading to DNA damage, inflammation, and dysfunction and degeneration of neurons.

neuroscience↗

bioRxiv2020

DRP1 IS REQUIRED FOR AGRP NEURONAL ACTIVITY AND FEEDING

The hypothalamic orexigenic Agouti-related peptide (AgRP)-expressing neurons are crucial for the regulation of whole-body energy homeostasis. Here, we show that fasting-induced AgRP neuronal activation is associated with dynamin-related peptide 1 (Drp1)-mediated mitochondrial fission and mitochondrial fatty acid utilization in AgRP neurons. In line with this, mice lacking Drp1 in adult AgRP neurons (Drp1AgRPKO) show decrease in fasting-or ghrelin-induced AgRP neuronal activity and feeding and exhibited a significant decrease in body weight, fat mass, and feeding accompanied by a significant increase in energy expenditure. In support of the role for mitochondrial fission and fatty acids oxidation, Drp1AgRPKO mice showed attenuated palmitic acid-induced mitochondrial respiration. Altogether, our data revealed that mitochondrial dynamics and fatty acids oxidation in hypothalamic AgRP neurons is a critical mechanism for AgRP neuronal function and associated behavior.

physiology↗