The mouse cortico-basal ganglia-thalamic network.

The cortico-basal ganglia-thalamo-cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1-4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico-basal ganglia-thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.

Anti-inflammatory effects of an ethanol extract of Aster glehni via inhibition of NF-κB activation in mice with DSS-induced colitis.

Although Aster glehni has been reported to prevent diabetes mellitus, hypercholesterolemia, insomnia, and cardiovascular disease, the anti-inflammatory effect of Aster glehni in colonic tissue remains unclear. In this study, we investigated the anti-inflammatory effects and the underlying molecular mechanism of an ethanol extract of Aster glehni (AG) in mice with dextran sulfate sodium (DSS)-induced colitis. AG significantly attenuated DSS-induced DAI scores, which implied that it suppressed diarrhea, gross bleeding, and the infiltration of immune cells. AG administration also effectively prevented shortening of the colon length and enlargement of the spleen size. Histological examinations indicated that AG suppressed colonic damage and the thickness of the muscle layer induced by DSS. In addition, AG inhibited the production of pro-inflammatory cytokines, such as TNF-α, IL-1ß, and IL-6, and the protein expression of COX-2 and iNOS in mice with DSS-induced colitis. Administration with AG suppressed the activation of nuclear factor-κB (NF-κB) including the nuclear translocation of the p65 NF-κB subunit, phosphorylation and degradation of IκB-α. Taken together, these findings suggest that the anti-inflammatory effects of AG are mainly related to the inhibition of the expressions of inflammatory mediators via NF-κB inactivation, and support its possible therapeutic application in colitis.

Suppression of LPS-induced inflammatory activities by Rosmarinus officinalis L.

Rosemary (Rosmarinus officinalis L.) has been used in folk medicine to treat headaches, epilepsy, poor circulation, and many other ailments. It was found that rosemary could act as a stimulant and mild analgesic and could reduce inflammation. However, the mechanisms underlying the anti-inflammatory effects of rosemary need more study to be established. Therefore, in this study, the effects of rosemary on the activation of nuclear factor kappa beta (NF-kB) and mitogen-activated protein kinases (MAPKs), the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)), and cytokine in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were investigated. A methanol extract of rosemary and its hexane fraction reduced NO generation with an IC(50) of 2.75 and 2.83 µg/ml, respectively. Also, the methanol extract and the hexane fraction inhibited LPS-induced MAPKs and NF-kB activation associated with the inhibition of iNOS or COX-2 expression. LPS-induced production of PGE(2) and tumour necrosis factor-alpha (TNF-α) were blocked by rosemary. Rosemary extract and its hexane fraction are important for the prevention of phosphorylation of MAPKs, thereby blocking NF-kB activation, which in turn leads to decreased expression of iNOS and COX-2, thus preventing inflammation.