Figure 3: Dendritic afterdepolarization may represent the associative signal for LTP induction during post–presynaptic pairing.

(a) Dendritic recording from apical (top) and basal CA3 pyramidal neuron dendrites (bottom). Infrared-DIC videomicrographs (photomontage for top graph) taken under experimental conditions. Arrows indicate dendritic recording sites. (b) The ADP has comparable amplitude at soma and dendrite. Dendritic recording sites 218 μm (top) and 54 μm (bottom) from the soma. Somatic (black) and dendritic AP (red), evoked by somatic current injection. (c) ADP amplitude remains constant as a function of distance from soma. Positive and negative distance values represent apical and basal recordings, respectively. Black, somatic ADP; red, dendritic ADP. Inset shows procedure to measure the ADP in the dendrite (at 294 μm). Note that the ADP amplitude shows a slight, but insignificant increase as a function of distance (26 simultaneous dendritic-somatic recordings, Spearman rank correlation coefficient r=0.26; P=0.065). (d) Similar plot as shown in c, but for ADP decay time constant. Note that the ADP becomes faster with increasing distance (r=0.72; P<0.001). (e) Properties of synthetic EPSPs, evoked by dendritic current injection. Top, schematic illustration of the recording configuration. Bottom, dendritic EPSPs (red) and somatic EPSPs (black). (f) Summary bar graph of peak amplitudes of synthetic EPSPs at the soma (top) and the dendrite (bottom). I₀, I₁ and I₂ correspond to peak current amplitudes of 123, 306 and 610 pA, respectively (three simultaneous dendritic-somatic recordings). Right bar, top shows peak amplitudes of EPSPs evoked by extracellular stimulation (163 cells). (g) Summation of synthetic EPSPs with preceding ADPs. APs were evoked by somatic current injection, and synthetic EPSPs were generated by dendritic current injection (amplitudes I₀, I₁ and I₂; Δt=−10 ms). (h) Similar traces as shown in g, but for dendritic current injection amplitude I₁ and Δt=5 ms (black), –10 ms (red), –15 ms (green) and –20 ms (blue). (i) Plot of peak amplitude of the summated signal in the dendrite against AP–EPSP pairing interval Δt (3 simultaneous dendritic-somatic recordings). (j) Conversion of the ADP into an afterhyperpolarization during a post–presynaptic sequence abolishes LTP. Top, post–presynaptic pairing protocol (Δt=–10 ms) combined with hyperpolarizing somatic current injection and corresponding membrane potential trace. Bottom, plot of mean compound EPSP peak amplitude against experimental time before and after post–presynaptic pairing (Δt=−10 ms) with afterhyperpolarization (9 cells).