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This review article entitled ＂Physiological approaches to understanding molecular actions on dorsolateral prefrontal cortical neurons underlying higher cognitive processing＂ examines the relationship between neurotransmitters and prefrontal cognitive function. The authors of this article are leading the field in such research.

旨在探讨甘氨酸对大鼠视皮层神经元突触后不同亚型NMDA受体功能的调制作用。采用脑片标本的全细胞膜片钳技术，记录大鼠视皮层Ⅱ／Ⅲ层锥体神经元的微小兴奋性突触后电流（mEPSC）；灌流不同浓度甘氨酸和D-丝氨酸后，观察其对突触后NMDA受体电流的影响，之后使用NR2A—NMDAR和NR2B-NMDAR拮抗剂，观察其对突触后NMDA受体电流（NMDAR-mEPSC）的影响。结果表明：甘氨酸和D-丝氨酸均能增强mEPSC的NMDA受体成分，并呈现一定的浓度依赖性；

Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin （CCK）. Local infusion of CCK in the auditory cortex of anesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCKB antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCKB antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical olasticitv via CCK-vositive cortical projection neurons in the entorhinal cortex.

Alpha-synuclein （a-syn） deposition in Lewy bodies （LB） is one of the main neuropathological hallmarks of Parkinson＇s disease （PD）. LB accumulation is considered a causative factor of PD, which suggests that strategies aimed at reducing a-syn levels could be relevant for its treatment. In the present study, we developed novel nanocarriers suitable for systemic delivery of small interfering ribonucleic acid （siRNA） that were specifically designed to reduce neuronal α-syn by RNA interference. Anionic liposomes loaded with an siRNA-protamine complex for α-syn gene silencing and decorated with a rabies virus glycoprotein （RVG）-derived peptide as a targeting agent were prepared. The nanoparticles were characterized for their ability to load, protect, and deliver the functional siRNA to mouse primary hippocampal and cortical neurons as well as their efficiency to induce gene silencing in these cells. Moreover, the nanocarriers were evaluated for their stability in serum. The RVG-decorated liposomes displayed suitable characteristics for future in vivo applications and successfully induced α-syn gene silencing in primary neurons without altering cell viability. Collectively, our results indicate that RVG-decorated liposomes may be an ideal tool for further studies aimed at achieving efficient in vivo α-syn gene silencing in mouse models of PD.

Receptor for activated C kinase 1（RACK1）is an evolutionarily conserved scaffolding protein within the tryptophan-aspartate（WD）repeat family of proteins.RACK1 can bind multiple signaling molecules concurrently,as well as stabilize and anchor proteins.RACK1 also plays an important role at focal adhesions,where it acts to regulate cell migration.In addition,RACK1 is a ribosomal binding protein and thus,regulates translation.Despite these numerous functions,little is known about how RACK1 regulates nervous system development.Here,we review three studies that examine the role of RACK1 in neural development.In brief,these papers demonstrate that（1）RACK-1,the C.elegans homolog of mammalian RACK1,is required for axon guidance;（2）RACK1 is required for neurite extension of neuronally differentiated rat PC12cells;and（3）RACK1 is required for axon outgrowth of primary mouse cortical neurons.Thus,it is evident that RACK1 is critical for appropriate neural development in a wide range of species,and future discoveries could reveal whether RACK1 and its signaling partners are potential targets for treatment of neurodevelopmental disorders or a therapeutic approach for axonal regeneration.

In the central nervous system, Asiaticoside has been shown to attenuate in vitro neuronal damage caused by exposure to β-amyloid. In vivo studies demonstrated that Asiaticoside could attenuate neurobehavioral, neurochemical and histological changes in transient focal middle cerebral artery occlusion animals. In addition, Asiaticoside showed anxiolytic effects in acute and chronic stress animals. However, its potential neuroprotective properties in glutamate-induced excitotoxicity have not been fully studied. We investigated the neuroprotective effects of Asiaticoside in primary cultured mouse cortical neurons exposed to glutamate-induced excitotoxicity invoked by N-methyl-D-aspartate. Pretreatment with Asiaticoside decreased neuronal cell loss in a concentration-dependent manner and restored changes in expression of apoptotic-related proteins Bcl-2 and Bax. Asiaticoside pretreatment also attenuated the upregulation of NR2B expression, a subunit of N-methyl-D-aspartate receptors, but did not affect expression of NR2A subunits. Additionally, in cultured neurons, Asiaticoside significantly inhibited Ca^2＋ influx induced by N-methyl-D-aspartate. These experimental findings provide preliminary evidence that during excitotoxicity induced by Nmethyl-D-aspartate exposure in cultured cortical neurons, the neuroprotective effects of Asiaticoside are mediated through inhibition of calcium influx. Aside from its anti-oxidant activity, down-regulation of NR2B-contalning N-methyl-D-aspartate receptors may be one of the underlying mechanisms in Asiaticoside neuroprotection.

Membrane depolarization induces the release of the serine proteinase tissue-type plasminogen activator（t PA） from the presynaptic terminal of cerebral cortical neurons.Once in the synaptic cleft this t PA promotes the exocytosis and subsequent endocytic retrieval of glutamate-containing synaptic vesicles,and regulates the postsynaptic response to the presynaptic release of glutamate.Indeed,t PA has a bidirectional effect on the composition of the postsynaptic density（PSD） that does not require plasmin generation or the presynaptic release of glutamate,but varies according to the baseline level of neuronal activity.Hence,in inactive neurons t PA induces phosphorylation and accumulation in the PSD of the Ca~（2＋）/calmodulin-dependent protein kinase IIα（pCa MKIIα）,followed by pCa MKIIα-induced phosphorylation and synaptic recruitment of Glu R1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid（AMPA） receptors.In contrast,in active neurons with increased levels of pCa MKIIα in the PSD t PA induces pCa MKIIα and p Glu R1 dephosphorylation and their subsequent removal from the PSD.These effects require active synaptic N-methyl-D-aspartate（NMDA） receptors and cyclin-dependent kinase 5（Cdk5）-induced phosphorylation of the protein phosphatase 1（PP1） at T320.These data indicate that t PA is a homeostatic regulator of the postsynaptic response of cerebral cortical neurons to the presynaptic release of glutamate via bidirectional regulation of the pCa MKIIα/PP1 switch in the PSD.

Huntington＇s disease （HD） is an autosomal-dominant neurodegenerative disease characterized by the selec- tive loss of neurons in the striatum and cortex, leading to progressive motor dysfunction, cognitive decline and behavioral symptoms. HD is caused by a trinucleotide （CAG） repeat expansion in the gene encoding for huntingtin. Several studies have suggested that inflammation is an important feature of HD and it is already observed in the early stages of the disease. Recently, new molecules presenting anti-inflammatory and/or immunomodulatory have been investigated for HD. The objective of this review is to discuss the data obtained so far on the immune-based therapeutic strategies for HD.

Flavonoids from the stems and leaves of Scutellaria baicalensis Georgi, an antioxidant, markedly improve memory impairments and neuronal injuries. In the present study, primary cortical neurons of rats were exposed to potassium cyanide to establish a model of in vitro neural cell apoptosis. Inhibition of apoptosis by flavonoids from the stems and leaves of Scutellaria baical- ensis Georgi at concentrations of 18.98, 37.36, and 75.92 gg/mL was detected using this model. These flavonoids dramatically increased cell survival, inhibited cell apoptosis and excessive pro- duction of malondialdehyde, and increased the activities of superoxide dismutase, glutathione peroxidase, and Na＋-K＊-ATPase in primary cortical neurons exposed to potassium cyanide. The flavonoids from the stems and leaves of Scutellaria baicalensis Georgi were originally found to have a polyhydric structure and to protect against cerebral hypoxia in in vitro and in vivo models, including hypoxia induced by potassium cyanide or cerebral ischemia. The present study suggests that flavonoids from the stems and leaves of Scutellaria baicalensis Georgi exert neuroprotective effects via modulation of oxidative stress, such as malondialdehyde, superoxide dismutase, glutathione peroxidase and Na＋-K＋-ATPase disorders induced by potassium cyanide.

Microcephaly is a clinical characteristic for human nijmegen breakage syndrome （NBS, mutated in NBS1 gene）, a chromosomal instability syndrome. However, the underlying molecular pathogenesis remains elusive. In the pres- ent study, we demonstrate that neuronal disruption of NBS （Nbn in mice） causes microcephaly characterized by the reduction of cerebral cortex and corpus callosum, recapitulating neuronal anomalies in human NBS. Nbsl-deficient neocortex shows accumulative endogenous DNA damage and defective activation of Ataxia telangiectasia and Rad3- related （ATR）-Chkl pathway upon DNA damage. Notably, in contrast to massive apoptotic cell death in Nbsl- deficient cerebella, activation of p53 leads to a defective neuroprogenitor proliferation in neocortex, likely via specific persistent induction of hematopoietic zinc finger （Hzf） that preferentially promotes p53-mediated cell cycle arrest whilst inhibiting apoptosis. Moreover, Trp53 mutations substantially rescue the microcephaly in Nbsl-deficient mice. Thus, the present results reveal the first clue that developing neurons at different regions of brain selectively respond to endogenous DNA damage, and underscore an important role for Nbsl in neurogenesis.