This study addresses the fundamental principle of inter-synaptic interactions in synaptic cross-talk through homosynaptic and heterosynaptic plasticity by studying the intrinsic calcium signaling dynamics in spines. B...This study addresses the fundamental principle of inter-synaptic interactions in synaptic cross-talk through homosynaptic and heterosynaptic plasticity by studying the intrinsic calcium signaling dynamics in spines. Beyond the calcium influx into synapse through voltage gated calcium channels （VGCCs） and N-methyl-D-aspartate （NNMDA） receptors, the function of calcium released from internal store in mediating inter-synaptic cross-talk has barely been modeled. This work investigates how different sources of calcium contribute to inter-synaptic cross-talk and synaptic clustering. Based on experimental observations, we developed a mathematical model in one dimensional system with uniform distribution of spines with the connected dendrite. We modeled the biophysical process of calcium induced calcium release （CICR） in the dendritic smooth endoplasmic reticulum （SER）. Our model compared distinct roles of calcium diffusion, back propagated action potentials （bAPs） and CICR played in synaptic clustering and inter-synaptic cross-talk. The simulation result demonstrated that calcium signal extruded from spine into dendrite requires amplification by CICR before invading neighboring spines to induce plasticity. Our model predicted that initial calcium concentration in SER may discriminate between different types of neuronal activity and induce completely different synaptic potentiation and depression.展开更多
In researches that examine neuroplasticity, many studies that are performed directly on isolated neurons in the pyramidal cells of CA1 area (CA1) and slices of the hippocampus indicate that changes occur at the molecu...In researches that examine neuroplasticity, many studies that are performed directly on isolated neurons in the pyramidal cells of CA1 area (CA1) and slices of the hippocampus indicate that changes occur at the molecular and cellular levels during long-term synaptic potentiation (LTP), and these changes are dependent on N-methyl-D-aspartate (NMDA) acid receptors and/or purinergic receptors. Electrophysiological studies and the chemical induction of LTP of synaptic neurotransmissions provide key evidence that LTP is dependent on the volume of Ca2+ influx through postsynaptic NMDA receptors, in addition to the subsequent activation and autophosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and the increase in the density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on postsynaptic neuronal membranes. The primary peculiarity of LTP in the central nervous system (CNS) excitatory synapses is the synthesis of additional AMPA receptors in the postsynaptic elements. Furthermore, the proteolysis of the extracellular matrix (ECM) has an important role in the synaptic neuroplasticity of the CNS. Proteases from the serine family and metalloproteinases of the extracellular matrix are localized within the synapses and are released into the extracellular space in proportion to the degree of neuronal excitation. These enzymes cause changes in the morphology, shape and size, as well as the overall number of synapses and synthesize new synaptic connections. The proteinases also change the function of receptors, and consequently, the secretions of neurotransmitters from the presynaptic elements are strengthened or weakened.展开更多
基金We would like to thank Prof. Florentin Woergoetter, Dr. Christian Tetzlaff and Dr. Tomas Kulvicius for helpful discussions. This work is supported by Chinese Natural Science Foundation with 31601145, the Fundamental Research Funds for the Central Universities, and the Federal Ministry of Education and Research （BMBF） Germany to the Goettingen Bernstein Center for Computational Neuroscience Project D1. Y.L. conceived the experiment（s）, Z.Z. and Y.L. conducted the experiment（s）, Y.L. and Z.Z. analyzed the results, Y.L. wrote the paper. All authors reviewed the manuscript. The authors declare no competing interest.
文摘This study addresses the fundamental principle of inter-synaptic interactions in synaptic cross-talk through homosynaptic and heterosynaptic plasticity by studying the intrinsic calcium signaling dynamics in spines. Beyond the calcium influx into synapse through voltage gated calcium channels （VGCCs） and N-methyl-D-aspartate （NNMDA） receptors, the function of calcium released from internal store in mediating inter-synaptic cross-talk has barely been modeled. This work investigates how different sources of calcium contribute to inter-synaptic cross-talk and synaptic clustering. Based on experimental observations, we developed a mathematical model in one dimensional system with uniform distribution of spines with the connected dendrite. We modeled the biophysical process of calcium induced calcium release （CICR） in the dendritic smooth endoplasmic reticulum （SER）. Our model compared distinct roles of calcium diffusion, back propagated action potentials （bAPs） and CICR played in synaptic clustering and inter-synaptic cross-talk. The simulation result demonstrated that calcium signal extruded from spine into dendrite requires amplification by CICR before invading neighboring spines to induce plasticity. Our model predicted that initial calcium concentration in SER may discriminate between different types of neuronal activity and induce completely different synaptic potentiation and depression.
文摘In researches that examine neuroplasticity, many studies that are performed directly on isolated neurons in the pyramidal cells of CA1 area (CA1) and slices of the hippocampus indicate that changes occur at the molecular and cellular levels during long-term synaptic potentiation (LTP), and these changes are dependent on N-methyl-D-aspartate (NMDA) acid receptors and/or purinergic receptors. Electrophysiological studies and the chemical induction of LTP of synaptic neurotransmissions provide key evidence that LTP is dependent on the volume of Ca2+ influx through postsynaptic NMDA receptors, in addition to the subsequent activation and autophosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and the increase in the density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on postsynaptic neuronal membranes. The primary peculiarity of LTP in the central nervous system (CNS) excitatory synapses is the synthesis of additional AMPA receptors in the postsynaptic elements. Furthermore, the proteolysis of the extracellular matrix (ECM) has an important role in the synaptic neuroplasticity of the CNS. Proteases from the serine family and metalloproteinases of the extracellular matrix are localized within the synapses and are released into the extracellular space in proportion to the degree of neuronal excitation. These enzymes cause changes in the morphology, shape and size, as well as the overall number of synapses and synthesize new synaptic connections. The proteinases also change the function of receptors, and consequently, the secretions of neurotransmitters from the presynaptic elements are strengthened or weakened.
