The Regulation Of Lrp4 In Hippocampal DG Area Inhibitory Mircocircuit

Synaptic transmission and plasticity,associated with learning and memory,has always been the topic of interest to scientists.Lrp4 is a member of the low density lipoprotein receptor(LDLR)family,and reports have shown that Lrp4 plays a key role in the neuromuscular junction(NMJ)formation and maintenance.It has reported that Lrp4 is also expressed in the central nervous system(CNS).The function of Lrp4 in the brain,however,has been rarely reported,as Lrp4-/-mice die at birth.Our Lab found that Lrp4 is expressed in the hippocampus and regulate glutamate transmission.And Lrp4 mutant astrocytes would impair locomotor activity and spatial memory of mice.GABA can not be ignored on the regulation of learning memory,but it has not been known about the function of Lrp4 in the inhibitory information delivery.In this study,we use Lrp4-Lacz report mice to confirm the expression of Lrp4 in the brain.Then through the Cre-loxp system and western blot,we establish the central nervous system Lrp4 knockout mice(hGfap-Lrp4-/-).The whole cell recording on Dentate gyrus granule cells in mutant showed that spontaneous inhibitory postsynaptic current(s IPSC)frequency and amplitude are reduced and the tonic GABA current(I-tonic current)is decreased.And qRT-PCR showed that the expression of GABA_α5 subunit is suppressed on DG region in mutant.Our data suggest that Lrp4 may be expressed in some neurons of mammalian central system,and play a regulatory role in inhibitory information transmission.