Distinct Quantal Features of AMPA and NMDA Synaptic Currents in Hippocampal Neurons: Implication of Glutamate Spillover and Receptor Saturation
Overview
Authors
Affiliations
Excitatory postsynaptic currents (EPSCs) were studied in the CA1 pyramidal cells of rat hippocampal slices. Components mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) and by N-methyl-D-aspartate (NMDA) receptors were separated pharmacologically. Quantal parameters of AMPA and NMDA receptor-mediated EPSCs were obtained using both maximal likelihood and autocorrelation techniques. Enhancement of transmitter release with 4-aminopyridine caused a significant increase in quantal size of NMDA EPSC. This was accompanied by a slowing of the EPSC decay. The maximal number of quanta in the NMDA current was unchanged, while the probability of quantal event dramatically enhanced. In contrast, neither the quantal size nor the kinetics of AMPA EPSC was altered by 4-aminopyridine, while the maximal number of quanta increased. These changes in the quantal parameters are consistent with a transition to multivesicular release of the neurotransmitter. Spillover of excessive glutamate on the nonsynaptic areas of dendritic spines causes an increase in the quantal size of NMDA synaptic current. The difference in quantal behavior of AMPA and NMDA EPSCs implies that different mechanisms underlie their quantization: the additive response of nonsaturated AMPA receptors contrasts with the variable involvement of saturated intrasynaptic and nonsaturated extrasynaptic NMDA receptors.
Impact of Autophagy Impairment on Experience- and Diet-Related Synaptic Plasticity.
Lalo U, Nezis I, Pankratov Y Int J Mol Sci. 2022; 23(16).
PMID: 36012495 PMC: 9408861. DOI: 10.3390/ijms23169228.
Optical analysis of glutamate spread in the neuropil.
Matthews E, Sun W, McMahon S, Doengi M, Halka L, Anders S Cereb Cortex. 2022; 32(17):3669-3689.
PMID: 35059716 PMC: 9433421. DOI: 10.1093/cercor/bhab440.
Wang Q, Wang Y, Wang B, Chen Y, Lu S, Yao J PLoS Biol. 2021; 19(7):e3001323.
PMID: 34228711 PMC: 8284830. DOI: 10.1371/journal.pbio.3001323.
Functional organization of postsynaptic glutamate receptors.
Scheefhals N, MacGillavry H Mol Cell Neurosci. 2018; 91:82-94.
PMID: 29777761 PMC: 6276983. DOI: 10.1016/j.mcn.2018.05.002.
Theis A, Rozsa B, Katona G, Schmitz D, Johenning F Front Cell Neurosci. 2018; 12:109.
PMID: 29755321 PMC: 5932410. DOI: 10.3389/fncel.2018.00109.