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The central nervous system has been implicated in the age-induced reduction in adipose tissue lipolysis. However, the underlying mechanisms remain unclear. Here, we show the expression of SLC7A14 is reduced in proopiomelanocortin (POMC) neurons of aged mice. Overexpression of SLC7A14 in POMC neurons alleviates the aging-reduced lipolysis, whereas SLC7A14 deletion mimics the age-induced lipolysis impairment. Metabolomics analysis reveals that POMC SLC7A14 increased taurochenodeoxycholic acid (TCDCA) content, which mediates the SLC7A14 knockout- or age-induced WAT lipolysis impairment. Furthermore, SLC7A14-increased TCDCA content is dependent on intestinal apical sodium-dependent bile acid transporter (ASBT), which is regulated by intestinal sympathetic afferent nerves. Finally, SLC7A14 regulates the intestinal sympathetic afferent nerves by inhibiting mTORC1 signaling through inhibiting TSC1 phosphorylation. Collectively, our study suggests the function for central SLC7A14 and an upstream mechanism for the mTORC1 signaling pathway. Moreover, our data provides insights into the brain–gut–adipose tissue crosstalk in age-induced lipolysis impairment. The underlying mechanisms of central nervous system regulation of age-dependent obesity remain unclear. Here, the authors show hypothalamic SLC7A14 plays a role in age-induced lipolysis impairment by the brain–gut–adipose tissue axis. [ABSTRACT FROM AUTHOR]

An important role for liver in the regulation of adipose tissue thermogenesis upon cold exposure has been suggested; however, the underlying mechanisms remain incompletely defined. Here, we identify elevated serum bradykinin levels in response to acute cold exposure in male mice. A bolus of anti-bradykinin antibodies reduces body temperature during acute cold exposure, whereas bradykinin has the opposite effect. We demonstrate that bradykinin induces brown adipose tissue thermogenesis and white adipose tissue browning, and bradykinin increases uncoupling protein 1 (UCP1) expression in adipose tissue. The bradykinin B2 receptor (B2R), adrenergic signaling and nitric oxide signaling are involved in regulating bradykinin-increased UCP1 expression. Moreover, acute cold exposure inhibits hepatic prolyl endopeptidase (PREP) activity, causing reduced liver bradykinin degradation and increased serum bradykinin levels. Finally, by blocking the breakdown of bradykinin, angiotensin-converting enzyme inhibitors (ACEIs) increase serum bradykinin levels and induce brown adipose tissue thermogenesis and white adipose tissue browning via B2R. Collectively, our data provide new insights into the mechanisms underlying organ crosstalk in whole-body physiology control during cold exposure and also suggest bradykinin as a possible anti-obesity target. Adipose tissue thermogenesis plays a role in appropriate response to cold exposure through incompletely understood mechanisms. Here the authors report that acute cold exposure increases the serum levels of bradykinin, which induces brown adipose tissue thermogenesis and white adipose tissue browning in male mice. [ABSTRACT FROM AUTHOR]

Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr2+. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABAA receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions. [ABSTRACT FROM AUTHOR]

Microglia are important immune cells in the central nervous system (CNS) that undergo turnover throughout the lifespan. If microglial debris is not removed in a timely manner, accumulated debris may influence CNS function. Clearance of microglial debris is crucial for CNS homeostasis. However, underlying mechanisms remain obscure. We here investigate how dead microglia are removed. We find that although microglia can phagocytose microglial debris in vitro, the territory-dependent competition hinders the microglia-to-microglial debris engulfment in vivo. In contrast, microglial debris is mainly phagocytosed by astrocytes in the brain, facilitated by C4b opsonization. The engulfed microglial fragments are then degraded in astrocytes via RUBICON-dependent LC3-associated phagocytosis (LAP), a form of noncanonical autophagy. Interference with C4b-mediated engulfment and subsequent LAP disrupt the removal and degradation of microglial debris, respectively. Together, we elucidate the cellular and molecular mechanisms of microglial debris removal in mice, extending the knowledge on the maintenance of CNS homeostasis.Microglia are professional phagocytes in the CNS. However, which cells scavenge corpses of microglia is largely neglected. Peng and colleagues found that nonprofessional phagocytes (astrocyte) phagocytose the debris of professional phagocytes (microglia). [ABSTRACT FROM AUTHOR]

The basal ganglia play a key role in integrating a variety of human behaviors through the cortico–basal ganglia–thalamo–cortical loops. Accordingly, basal ganglia disturbances are implicated in a broad range of debilitating neuropsychiatric disorders. Despite accumulating knowledge of the basal ganglia functional organization, the neural substrates and circuitry subserving functions have not been directly mapped in humans. By direct electrical stimulation of distinct basal ganglia regions in 35 refractory epilepsy patients undergoing stereoelectroencephalography recordings, we here offer currently the most complete overview of basal ganglia functional characterization, extending not only to the expected sensorimotor responses, but also to vestibular sensations, autonomic responses, cognitive and multimodal effects. Specifically, some locations identified responses weren't predicted by the model derived from large-scale meta-analyses. Our work may mark an important step toward understanding the functional architecture of the human basal ganglia and provide mechanistic explanations of non-motor symptoms in brain circuit disorders. Direct electrical stimulation of the basal ganglia using implanted SEEG electrodes produced a variety of motor and non-motor effects in human participants, providing insight into the functional architecture of this key brain region. [ABSTRACT FROM AUTHOR]

Biologically, there exist two kinds of syntheses: photosynthesis and ATP-driven biosynthesis. The light harvesting of photosynthesis is known to achieve an efficiency of ∼ 95% by the quantum energy transfer of photons. However, how the ATP-driven biosynthesis reaches its high efficiency still remains unknown. Deoxynucleotide triphosphates (dNTPs) in polymerase chain reaction (PCR) adopt the identical way of ATP to release their energy, and thus can be employed to explore the ATP energy process. Here, using a gold nanoparticle (AuNP) enhanced PCR (AuNP-PCR), we demonstrate that the energy released by phosphoanhydride-bond (PB) hydrolysis of dNTPs is in form of photons (PB-photons) to drive DNA replication, by modulating their resonance with the average inter-AuNP distance (D). The experimental results show that both the efficiency and yield of PCR periodically oscillate with D increasing, indicating a quantized process, but not simply a thermal one. The PB-photon wavelength is further determined to 8.4 µm. All these results support that the release, transfer and utilization of bioenergy are in the form of photons. Our findings of ATP-energy quantum conversion will open a new avenue to the studies of high-efficiency bioenergy utilization, biochemistry, biological quantum physics, and even brain sciences. [ABSTRACT FROM AUTHOR]

Polaritons are arousing tremendous interests in physics and material sciences for their unique and amazing properties, especially including the condensation, lasing without inversion and even room-temperature superfluidity. Herein, we propose a cell vibron polariton (cell-VP): a collectively coherent mode of a photon and all phospholipid molecules in a myelin sheath formed by glial cells. Cell-VP can be resonantly self-confined in the myelin sheath under physiological conditions. The observations benefit from the specifically compact, ordered and polar thin-film structure of the sheath, and the relatively strong coupling of the mid-infrared photon with the vibrons of phospholipid tails in the myelin. The underlying physics is revealed to be the collectively coherent superposition of the photon and vibrons, the polariton induced significant enhancement of myelin permittivity, and the resonance of the polariton with the sheath. The captured cell-VPs in myelin sheaths may provide a promising way for super-efficient consumption of extra-weak bioenergy and even directly serve for quantum information. These findings further the understanding of nervous system operations at cellular level from the view of quantum mechanics. [ABSTRACT FROM AUTHOR]

Inhibitory GABAergic interneurons are fundamental elements of cortical circuits and play critical roles in shaping network activity. Dysfunction of interneurons can lead to various brain disorders, including epilepsy, schizophrenia, and anxiety. Based on the electrophysiological properties, cell morphology, and molecular identity, interneurons could be classified into various subgroups. In this study, we investigated the density and laminar distribution of different interneuron types and the co-expression of molecular markers in epileptic human cortex. We found that parvalbumin (PV) and somatostatin (SST) neurons were distributed in all cortical layers except layer I, while tyrosine hydroxylase (TH) and neuropeptide Y (NPY) were abundant in the deep layers and white matter. Cholecystokinin (CCK) neurons showed a high density in layers IV and VI. Neurons with these markers constituted ~7.2% (PV), 2.6% (SST), 0.5% (TH), 0.5% (NPY), and 4.4% (CCK) of the gray-matter neuron population. Double- and triple-labeling revealed that NPY neurons were also SST-immunoreactive (97.7%), and TH neurons were more likely to express SST (34.2%) than PV (14.6%). A subpopulation of CCK neurons (28.0%) also expressed PV, but none contained SST. Together, these results revealed the density and distribution patterns of different interneuron populations and the overlap between molecular markers in epileptic human cortex. [ABSTRACT FROM AUTHOR]

Patch-clamp recording requires direct accessibility of the cell membrane to patch pipettes and allows the investigation of ion channel properties and functions in specific cellular compartments. The cell body and relatively thick dendrites are the most accessible compartments of a neuron, due to their large diameters and therefore great membrane surface areas. However, axons are normally inaccessible to patch pipettes because of their thin structure; thus studies of axon physiology have long been hampered by the lack of axon recording methods. Recently, a new method of patch-clamp recording has been developed, enabling direct and tight-seal recording from cortical axons. These recordings are performed at the enlarged structure (axonal bleb) formed at the cut end of an axon after slicing procedures. This method has facilitated studies of the mechanisms underlying the generation and propagation of the main output signal, the action potential, and led to the finding that cortical neurons communicate not only in action potential-mediated digital mode but also in membrane potential-dependent analog mode. [ABSTRACT FROM AUTHOR]

The vast majority of synaptic connections onto neurons in the cerebral cortex arise from other cortical neurons, both excitatory and inhibitory, forming local and distant 'recurrent' networks. Although this is a basic theme of cortical organization, its study has been limited largely to theoretical investigations, which predict that local recurrent networks show a proportionality or balance between recurrent excitation and inhibition, allowing the generation of stable periods of activity. This recurrent activity might underlie such diverse operations as short-term memory, the modulation of neuronal excitability with attention, and the generation of spontaneous activity during sleep. Here we show that local cortical circuits do indeed operate through a proportional balance of excitation and inhibition generated through local recurrent connections, and that the operation of such circuits can generate self-sustaining activity that can be turned on and off by synaptic inputs. These results confirm the long-hypothesized role of recurrent activity as a basic operation of the cerebral cortex. [ABSTRACT FROM AUTHOR]

Autapses are synaptic contacts of a neuron’s axon onto its own dendrite and soma. In the neocortex, self-inhibiting autapses in GABAergic interneurons are abundant in number and play critical roles in regulating spike precision and network activity. Here we examine whether the principal glutamatergic pyramidal cells (PCs) also form functional autapses. In patch-clamp recording from both rodent and human PCs, we isolated autaptic responses and found that these occur predominantly in layer-5 PCs projecting to subcortical regions, with very few in those projecting to contralateral prefrontal cortex and layer 2/3 PCs. Moreover, PC autapses persist during development into adulthood. Surprisingly, they produce giant postsynaptic responses (∼5 fold greater than recurrent PC-PC synapses) that are exclusively mediated by AMPA receptors. Upon activation, autapses enhance burst firing, neuronal responsiveness and coincidence detection of synaptic inputs. These findings indicate that PC autapses are functional and represent an important circuit element in the neocortex. [ABSTRACT FROM AUTHOR]

Arising from: B. Naundorf, F. Wolf & M. Volgushev 440, 1060–1063 (2006); Naundorf et al. replyAction potentials in cortical neurons show a variable threshold and a sudden rise in membrane potential at initiation. Naundorf et al. fail to explain these features using single- or double-compartment Hodgkin–Huxley-style models, suggesting instead that they could arise from cooperative opening of Na+ channels, although there is no direct biological evidence to support this. Here we show that these so-called unique features are to be expected from Hodgkin–Huxley models if the spatial geometry and spike initiation properties of cortical neurons are taken into account — it is therefore unnecessary to invoke exotic channel-gating properties as an explanation. [ABSTRACT FROM AUTHOR]