Feeding is known to be profoundly affected by stress-related emotional states and eating disorders are comorbid with psychiatric symptoms and altered emotional responses. The neural basis underlying feeding regulation by stress-related emotional changes is poorly understood. Here, we identify a novel projection from the paraventricular hypothalamus (PVH) to the ventral lateral septum (LSv) that shows a scalable regulation on feeding and behavioral changes related to emotion.
View Article and Find Full Text PDFThe paraventricular hypothalamus (PVH) regulates stress, feeding behaviors and other homeostatic processes, but whether PVH also drives defensive states remains unknown. Here we showed that photostimulation of PVH neurons in mice elicited escape jumping, a typical defensive behavior. We mapped PVH outputs that densely terminate in the ventral midbrain (vMB) area, and found that activation of the PVH→vMB circuit produced profound defensive behavioral changes, including escape jumping, hiding, hyperlocomotion, and learned aversion.
View Article and Find Full Text PDFAnimals must consider competing information before deciding to eat: internal signals indicating the desirability of food and external signals indicating the risk involved in eating within a particular environment. The behaviors driven by the former are manifestations of hunger, and the latter, anxiety. The connection between pathologic anxiety and reduced eating in conditions like typical depression and anorexia is well known.
View Article and Find Full Text PDFAbnormal feeding often co-exists with compulsive behaviors, but the underlying neural basis remains unknown. Excessive self-grooming in rodents is associated with compulsivity. Here, we show that optogenetically manipulating the activity of lateral hypothalamus (LH) projections targeting the paraventricular hypothalamus (PVH) differentially promotes either feeding or repetitive self-grooming.
View Article and Find Full Text PDFDiet-induced obesity (DIO) represents the major cause for the current obesity epidemic, but the mechanism underlying DIO is unclear. β-Adrenergic receptors (β-ARs) play a major role in sympathetic nervous system-mediated (SNS-mediated) diet-induced energy expenditure (EE). Rbc express abundant β-ARs; however, a potential role for rbc in DIO remains untested.
View Article and Find Full Text PDFLeptin receptors (LepRs) expressed in the midbrain contribute to the action of leptin on feeding regulation. The midbrain neurons release a variety of neurotransmitters including dopamine (DA), glutamate and GABA. However, which neurotransmitter mediates midbrain leptin action on feeding remains unclear.
View Article and Find Full Text PDFThe hypothalamus is critical for feeding and body weight regulation. Prevailing studies focus on hypothalamic neurons that are defined by selectively expressing transcription factors or neuropeptides including those expressing proopiomelanocortin (POMC) and agouti-related peptides (AgRP). The Cre expression driven by the pancreas-duodenum homeobox 1 promoter is abundant in several hypothalamic nuclei but not in AgRP or POMC neurons.
View Article and Find Full Text PDFLesions of the lateral hypothalamus (LH) cause hypophagia. However, activation of glutamatergic neurons in LH inhibits feeding. These results suggest a potential importance for other LH neurons in stimulating feeding.
View Article and Find Full Text PDFATP6V0C is the bafilomycin A1-binding subunit of vacuolar ATPase, an enzyme complex that critically regulates vesicular acidification. We and others have shown previously that bafilomycin A1 regulates cell viability, autophagic flux and metabolism of proteins that accumulate in neurodegenerative disease. To determine the importance of ATP6V0C for autophagy-lysosome pathway function, SH-SY5Y human neuroblastoma cells differentiated to a neuronal phenotype were nucleofected with non-target or ATP6V0C siRNA and following recovery were treated with either vehicle or bafilomycin A1 (0.
View Article and Find Full Text PDFAccumulation of α-synuclein (α-syn) in the brain is a core feature of Parkinson disease (PD) and leads to microglial activation, production of inflammatory cytokines and chemokines, T-cell infiltration, and neurodegeneration. Here, we have used both an in vivo mouse model induced by viral overexpression of α-syn as well as in vitro systems to study the role of the MHCII complex in α-syn-induced neuroinflammation and neurodegeneration. We find that in vivo, expression of full-length human α-syn causes striking induction of MHCII expression by microglia, while knock-out of MHCII prevents α-syn-induced microglial activation, antigen presentation, IgG deposition, and the degeneration of dopaminergic neurons.
View Article and Find Full Text PDFRotenone, which selectively inhibits mitochondrial complex I, induces oxidative stress, α-synuclein accumulation, and dopaminergic neuron death, principal pathological features of Parkinson's disease. The autophagy-lysosome pathway degrades damaged proteins and organelles for the intracellular maintenance of nutrient and energy balance. While it is known that rotenone causes autophagic vacuole accumulation, the mechanism by which this effect occurs has not been thoroughly investigated.
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