Determining the activation time course of synaptic AMPA receptors from openings of colocalized NMDA receptors

Excitatory postsynaptic currents (EPSCs) in most mammalian central neurons have a fast alpha-amino-3-hydroxy-5-methyl-4-isoazole-proprionic acid (AMPA ) receptor-mediated component, lasting a few milliseconds, and a slow N-met hl-(D-aspartic acid (NMDA)-receptor-mediated component, lasting hundreds of milliseconds. The time course of the AMPA phase is crucial in the integrat ive function of neurons, but measuring it accurately is often confounded by cable filtering between the recording electrode and the synapse. We descri be a method for recovering the AMPA phase of individual EPSCs by determinin g the impulse response of the cable filter from single NMDA channel transit ions in the slow tails of the same EPSC, then deconvolving the measured AMP A current. Using simulations, we show that filtering of an AMPA conductance transient in a voltage-clamped dendrite behaves in an almost perfectly lin ear fashion. Expressions are derived for the time course of single channel transitions and the AMPA phase filtered through a voltage-clamped cable or a single exponential filter, using a kinetic model for AMPA receptor activa tion. Fitting these expressions to experimental records directly estimates the underlying kinetics of the AMPA phase. Example measurements of spontane ous EPSCs in cultured nonpyramidal rat cortical neurons yielded rising time constants of 0.2-0.8 ms, and decay time constants of 1.3-2 ms at 23-25 deg rees C.