Opioidergic signaling contributes to food-mediated suppression of AgRP neurons.

Opioids are generally known to promote hedonic food consumption. Although much of the existing evidence is primarily based on studies of the mesolimbic pathway, endogenous opioids and their receptors are widely expressed in hypothalamic appetite circuits as well; however, their role in homeostatic feeding remains unclear. Using a fluorescent opioid sensor, deltaLight, here we report that mediobasal hypothalamic opioid levels increase by feeding, which directly and indirectly inhibits agouti-related protein (AgRP)-expressing neurons through the μ-opioid receptor (MOR).

AgRP neurons encode circadian feeding time.

Food intake follows a predictable daily pattern and synchronizes metabolic rhythms. Neurons expressing agouti-related protein (AgRP) read out physiological energetic state and elicit feeding, but the regulation of these neurons across daily timescales is poorly understood. Using a combination of neuron dynamics measurements and timed optogenetic activation in mice, we show that daily AgRP-neuron activity was not fully consistent with existing models of homeostatic regulation.

Adrenergic modulation of melanocortin pathway by hunger signals.

Norepinephrine (NE) is a well-known appetite regulator, and the nor/adrenergic system is targeted by several anti-obesity drugs. To better understand the circuitry underlying adrenergic appetite control, here we investigated the paraventricular hypothalamic nucleus (PVN), a key brain region that integrates energy signals and receives dense nor/adrenergic input, using a mouse model. We found that PVN NE level increases with signals of energy deficit and decreases with food access.

Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits.

Objective: Serotonin (5HT) is a well-known anorexigenic molecule, and 5HT neurons of dorsal raphe nucleus (DRN) have been implicated in suppression of feeding; however, the downstream circuitry is poorly understood. Here we explored major projections of DRN neurons for their capacity to modulate feeding.

Methods: We used optogenetics to selectively activate DRN axonal projections in hypothalamic and extrahypothalamic areas and monitored food intake.

Distinct properties of Ca efflux from brain, heart and liver mitochondria: The effects of Na, Li and the mitochondrial Na/Ca exchange inhibitor CGP37157.

Mitochondrial Ca transport is essential for regulating cell bioenergetics, Ca signaling and cell death. Mitochondria accumulate Ca via the mitochondrial Ca uniporter (MCU), whereas Ca is extruded by the mitochondrial Na/Ca (mtNCX) and H/Ca exchangers. The balance between these processes is essential for preventing toxic mitochondrial Ca overload.

Loss of tau and Fyn reduces compensatory effects of MAP2 for tau and reveals a Fyn-independent effect of tau on calcium.

Microtubule-associated protein tau associates with Src family tyrosine kinase Fyn and is tyrosine phosphorylated by Fyn. The presence of tyrosine phosphorylated tau in AD and the involvement of Fyn in AD has drawn attention to the tau-Fyn complex. In this study, a tau-Fyn double knockout (DKO) mouse was generated to investigate the role of the complex.

Deletion of mitochondrial calcium uniporter incompletely inhibits calcium uptake and induction of the permeability transition pore in brain mitochondria.

Ca influx into mitochondria is mediated by the mitochondrial calcium uniporter (MCU), whose identity was recently revealed as a 40-kDa protein that along with other proteins forms the mitochondrial Ca uptake machinery. The MCU is a Ca-conducting channel spanning the inner mitochondrial membrane. Here, deletion of the MCU completely inhibited Ca uptake in liver, heart, and skeletal muscle mitochondria.

Nerve growth factor (NGF) regulates activity of nuclear factor of activated T-cells (NFAT) in neurons via the phosphatidylinositol 3-kinase (PI3K)-Akt-glycogen synthase kinase 3β (GSK3β) pathway.

The Ca(2+)/calcineurin-dependent transcription factor nuclear factor of activated T-cells (NFAT) plays an important role in regulating many neuronal functions, including excitability, axonal growth, synaptogenesis, and neuronal survival. NFAT can be activated by action potential firing or depolarization that leads to Ca(2+)/calcineurin-dependent dephosphorylation of NFAT and its translocation to the nucleus. Recent data suggest that NFAT and NFAT-dependent functions in neurons can also be potently regulated by NGF and other neurotrophins.