Article Figures & Data
Figures
- Fig. 1.
A, A KAR-mediated EPSP, recorded in the presence of GYKI 53655 and APV, was elicited in an interneuron recorded in area CA1 by stimulation in stratum radiatum (black trace). A lognormal fit to the EPSP is shown also (gray trace). B, A dual-component AMPAR- and KAR-mediated EPSP was elicited by stimulation (solid line). The late component of the EPSP was fit with a lognormal distribution (dotted line) to account for the KAR component of the EPSP. The inset shows the AMPAR EPSP isolated by subtraction of the lognormal distribution from the dual-component EPSP. C, The AMPAR-mediated EPSP shown in the inset of B is shown with a faster time base (black trace). A fit that uses the ADC distribution is shown also (gray trace).D, ADC and lognormal distributions with experimentally determined average parameter values were used to generate a model EPSP mediated by AMPARs (black trace) or KARs (gray trace). Scaling was determined by the relative sizes of the AMPAR and KAR components of the dual-component EPSPs. In this and all subsequent figures, all EPSPs that are shown are averages of 5–50 EPSPs. Calibration: A, 0.75 mV, 210 msec; B, 3.1 mV, 130 msec; C, 2 mV, 40 msec; D, 0.25 mV, 170 msec.
- Fig. 2.
A, A dual-component EPSP is shown.B, A dual-component EPSC from the same cell as inA is shown. Note that the late component of the EPSC, relative to the peak of the EPSC, is smaller than the late component of the EPSP, relative to the peak of the EPSP. C, A summary of data is shown, comparing the size of the late component, measured at 200 msec after stimulation, relative to the peak of the synaptic signal. The late component of the EPSP is significantly larger, relative to the peak, than the late component of the EPSC. A passive membrane model with a membrane time constant of 20 msec reproduced this increase (see below). D, A simulated EPSP has been generated by using the EPSC in B in a passive membrane model. Calibration: A, 1.3 mV, 100 msec;B, 10 pA, 100 msec; C, 1.1 mV, 100 msec. In this and all other figures, error bars signify SEM.
- Fig. 3.
A, The simulated AMPAR- and KAR-mediated EPSPs were used in simulations in which a single afferent fiber is stimulated at a single constant frequency. The AMPAR-mediated response (left) caused little summation at firing frequencies, whereas the KAR-mediated response (right) caused substantial summation. B, The tonic depolarization, defined as the minimum depolarization once steady state is reached, is shown for AMPARs (filled circles) and KARs (open circles). C, The peak depolarization, defined as the maximum depolarization once steady state is reached, is shown for AMPARs (filled circles) and KARs (open circles).
- Fig. 4.
A, EPSPs in response to trains of stimuli at different frequencies are shown (left). EPSPs predicted by a simple model of depletion and facilitation in response to the same train are shown also (right). EPSPs and model EPSPs were scaled to the same peak amplitude for the first EPSP in the train. Scale bar is 300 msec for traces at 20 and 10 Hz, 640 msec for traces at 2 Hz, and 1.1 sec for traces at 1 Hz.B, The late component of the EPSPs during the train at 10 Hz is shown at a higher gain (black trace), along with the response predicted by the model (gray trace). The model, using parameters defined by the early component, accurately predicted the behavior of the late component, indicating that short-term plasticity is similar for AMPARs and KARs.C, There is a strong correlation between the EPSP amplitudes predicted by the model and the measured EPSP amplitudes. The model accounted for 75% of the total variability in EPSP amplitude during stimulus trains over a wide range of frequencies.
- Fig. 5.
A, AMPAR-mediated (left) and KAR-mediated (right) EPSPs were modeled in response to a single afferent fiber firing randomly at the indicated frequency. Neither response generated a depolarization exceeding 2 mV over 20 sec of simulated firing. B, The average peak depolarization for a fiber over the 20 sec of the simulation is shown (n = 50 fibers) for AMPARs (filled circles) and KARs (open circles). C, The mean depolarization under the same conditions as B is shown for AMPARs (filled circles) and KARs (open circles).
- Fig. 6.
A, AMPAR-mediated (left) and KAR-mediated (right) EPSPs were modeled in response to 50 afferent fibers, firing randomly and asynchronously at the indicated frequency. The AMPAR-mediated response was variable with little tonic depolarization, whereas the KAR-mediated response was relatively invariant with a large tonic depolarization.B, The average tonic (circles) and peak (triangles) depolarizations are shown as a function of the frequency of afferent firing for 1 sec blocks of the model, run for 20 sec. In this and subsequent figures the first second of the EPSP simulation was excluded from population statistics because it had not yet reached steady state. AMPARs (filled symbols) had little tonic depolarization and a large peak depolarization, whereas KARs (open symbols) had a large tonic depolarization and a peak depolarization that was not much larger (n = 19). C, The CV of the membrane potential is shown as a function of the frequency of afferent firing, as in B. The AMPAR-mediated depolarization (filled circles) had a much larger CV than the KAR-mediated depolarization did (open circles;n = 19).
- Fig. 7.
A, The modeled depolarizations mediated by synapses with only AMPARs (left), only KARs (center), or both AMPARs and KARs (right) are shown. The synapses with both AMPARs and KARs led to a large tonic depolarization, similar to the response mediated by synapses with only KARs, but with a larger variability, similar to the response mediated by synapses with only AMPARs. B, The characteristics of depolarization mediated by synapses with AMPARs, KARs, or both are shown for 1 sec blocks of the model (n = 19).B1, The tonic (filled bars), mean (light gray bars), and peak (dark gray bars) depolarizations are shown for each population of modeled synapses. B2 , The CV of the membrane depolarization is shown for synapses with AMPARs, KARs, or both. C, The modeled depolarizations are shown for 50 fibers synapsing onto AMPARs added to 50 independent fibers synapsing onto KARs (top) and 50 fibers synapsing onto colocalized AMPARs and KARs (bottom). There was little difference between the two conditions. D, The tonic, mean, and peak depolarizations are shown, as is the CV of the depolarization, for synapses in which AMPARs and KARs were colocalized (filled bars) or segregated to different synapses (open bars).
- Fig. 8.
A, A raster plot is shown for a model of five afferent fibers firing at a loosely synchronized theta rhythm (see Results). B, A model is shown for the AMPAR-mediated depolarization in response to 25 afferent fibers firing at the theta rhythm illustrated in A. C, A model is shown for the KAR-mediated depolarization in response to the same 25 fibers as shown in B. D, The average tonic depolarization and oscillation amplitude were compared for AMPARs (open bars) and KARs (filled bars) in the model (n = 15). AMPARs generated a large oscillation with little tonic depolarization, whereas KARs generated the opposite.
- Fig. 9.
A, Interneuronal spiking was elicited by injecting currents that simulate EPSCs generated by 50 independent afferent fibers firing at 5 Hz. The current injections simulated synapses that have only AMPARs (top), only KARs (middle), or AMPARs and KARs (bottom), all examined in the same cell. The simulated responses mediated by AMPARs elicited less spiking than did the responses simulating KARs, and the responses simulating both AMPARs and KARs generated the most spiking. B, The results from the simulations in seven cells are shown. C, The CV of the interspike interval, an assay for rhythmicity, indicated that KARs elicit more rhythmic spiking than AMPARs in six of seven cells, resulting in significantly more rhythmic firing when the whole population of cells was considered. In contrast, the CV of the interspike interval for synapses with both AMPARs and KARs was more variable and did not elicit significantly more rhythmic firing than synapses with either AMPARs or KARs.
- Fig. 10.
A, Interneuronal spiking was elicited by injecting currents that simulate EPSCs, generated by 25 independent afferent fibers firing in a loosely synchronized theta rhythm. The current injections simulating AMPAR-mediated EPSCs (top) generated spiking at the theta rhythm, whereas current injections simulating KAR-mediated EPSCs (middle) did not. Current injections simulating dual-component EPSCs with both AMPARs and KARs (bottom) generated periodic spiking that was correlated with the theta rhythm, although the correlation was weaker than that obtained by using only AMPARs. B, Autocorrelations of spike timing were averaged for six cells in which all three current injections were applied.
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