ABSTRACT
@#【Objective】To unmask the effect of Orexin B on the synaptic transmission between feed-forward projection from the lateral geniculate nucleus（LGN）to orexin-sensitive neurons in layer 6b（L6b）of visual cortex（VC）.【Methods】C57 mice at P25-P30 were used for micro-injection of CTB555 and ChR2-EGFP into LGN to label the neurons feedback projection to LGN from L6b and the feed-forward projection from LGN to the neurons in L6b of VC respectively. The EPSC in L6b cells was intracellularly recorded from the neurons labeled by CTB555.【Results】The neurons feedback projection to LGN in L6b are mainly pyramidal neurons, and the most of these cells are activated by orexin B，called orexin- sensitive neurons. Orexin B enhanced the NMDAR-mediated postsynaptic current in orexin-sensitive neurons in L6b by electrical or optical stimulation on the LGN projection to VC［electrical stimulation：（125.1 ± 3.7）%，optical stimulation：（123.8 ±3.8）%. In the case of OX2R′s blocker，the effect of Orexin B on EPSC amplitude disappeared with significant statistical significance，P < 0.05］，thus，strengthening the synaptic transmission between LGN and orexin-sensitive neurons in L6b.【Conclusions】Orexin B enhances the synaptic transmission between LGN to pyramidal neurons in L6b of VC.
ABSTRACT
The blood brain barrier can selectively block the uptake of xenobiotics from peripheral blood into the brain. Although this is important for maintaining the stability of the brain environment and normal function of the central nervous system, it presents a challenge for delivery of therapeutic drugs to the brain. Passive brain-targeting drug carrier is able to increase the drug concentration in the brain by enhancing the affinity to blood-brain barrier and/or inhibiting the efflux absorbed drug via P-glycoprotein. The active brain-targeting drug carrier can be obtained by linking specific ligands or antibodies onto passive target carriers to achieve precise delivery of drugs to the brain. Dual targeting drug carriers obtained by combining tumor cell targeting with brain targeting have shown their advantages for treatment of brain tumors. The targeted drug delivery to brain will provide a unique manner for the treatment of brain diseases such as Alzheimer's, Parkinson's, brain tumors, and stroke. Among the drug delivery systems of passive brain-targeting, active brain-targeting and dual brain-targeting, we evaluated the strategies to improve brain drug delivery efficiency, such as by reducing carrier size, opening tight junctions between cells at the blood-brain barrier, incorporating hydrophilic groups on the surface of the carrier, and alternative intranasal drug administration.