Paradoxical roles of inhibitory autapse and excitatory synapse in formation of counterintuitive anticipated synchronization

Different from the common delayed synchronization(DS)in which response appears after stimulation,anticipated synchronization(AS)in unidirectionally coupled neurons denotes a counterintuitive phenomenon in which response of the receiver neuron appears before stimulation of the sender neuron,showing an interesting function of brain to anticipate the future.The dynamical mechanism for the AS remains unclear due to complex dynamics of inhibitory and excitatory modulations.In this article,the paradoxical roles of excitatory synapse and inhibitory autapse in the formation of AS are acquired.Firstly,in addition to the common roles such that inhibitory modulation delays and excitatory modulation advances spike,paradoxical roles of excitatory stimulation to delay spike via type-II phase response and of inhibitory autapse to advance spike are obtained in suitable parameter regions,extending the dynamics and functions of the excitatory and inhibitory modulations.Secondly,AS is related to the paradoxical roles of the excitatory and inhibitory modulations,presenting deep understandings to the AS.Inhibitory autapse induces spike of the receiver neuron advanced to appear before that of the sender neuron at first,and then excitatory synapse plays a delay role to prevent the spike further advanced,resulting in the AS as the advance and delay effects realize a dynamic balance.Lastly,inhibitory autapse with strong advance,middle advance,and weak advance and delay effects induce phase drift(spike of the receiver neuron advances continuously),AS,and DS,respectively,presenting comprehensive relationships between AS and other behaviors.The results present potential measures to modulate AS related to brain function.

Leucine-rich repeats containing 4 protein(LRRC4)in memory,psychoneurosis,and glioblastoma

Leucine-rich repeats containing 4(LRRC4,also named netrin-G ligand 2[NGL-2])is a member of the NetrinGs ligands(NGLs)family.As a gene with relatively high and specific expression in brain,it is a member of the leucine-rich repeat superfamily and has been proven to be a suppressor gene for gliomas,thus being involved in gliomagenesis.LRRC4 is the core of microRNA-dependent multi-phase regulatory loops that inhibit the proliferation and invasion of glioblastoma(GB)cells,including LRRC4/NGL2-activator protein 2(AP2)-microRNA(miR)182-LRRC4 and LRRC4-miR185-DNA methyltransferase 1(DNMT1)-LRRC4/specific protein 1(SP1)-DNMT1-LRRC4.In this review,we demonstrated LRRC4 as a new member of the partitioning-defective protein(PAR)polarity complex that promotes axon differentiation,mediates the formation and plasticity of synapses,and assists information input to the hippocampus and storage of memory.As an important synapse regulator,aberrant expression of LRRC4 has been detected in autism,spinal injury and GBs.LRRC4 is a candidate susceptibility gene for autism and a neuro-protective factor in spinal nerve damage.In GBs,LRRC4 is a novel inhibitor of autophagy,and an inhibitor of protein–protein interactions involving in temozolomide resistance,tumor immune microenvironment,and formation of circular RNA.

Structure,function,and pathology of Neurexin-3

Neurexin-3 is primarily localized in the presynaptic membrane and forms complexes with various ligands located in the postsynaptic membrane.Neurexin-3 has important roles in synapse development and synapse functions.Neurexin-3 mediates excitatory presynaptic differentiation by interacting with leucine-rich-repeat transmembrane neuronal proteins.Meanwhile,neurexin-3 modulates the expression of presynapticα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors andγ-aminobutyric acid A receptors by interacting with neuroligins at excitatory and inhibitory synapses.Numerous studies have documented the potential contribution of neurexin-3 to neurodegenerative and neuropsychiatric disorders,such as Alzheimer's disease,addiction behaviors,and other diseases,which raises hopes that understanding the mechanisms of neurexin-3 may hold the key to developing new strategies for related illnesses.This review comprehensively covers the literature to provide current knowledge of the structure,function,and clinical role of neurexin-3.