FACTORS DETERMINING THE EFFICACY OF DISTAL EXCITATORY SYNAPSES IN RATHIPPOCAMPAL CA1 PYRAMIDAL NEURONS

1. A new preparation of the in vitro rat hippocampal slice has been de veloped in which the synaptic input to the distal apical dendrites of CA1 pyramidal neurones is isolated. This has been used to investigate the properties of distally evoked synaptic potentials. 2. Distal paire d-pulse stimulation (0.1 Hz) evoked a dendritic response consisting of a pair of EPSPs, which showed facilitation. The first EPSP had rise t ime (10-90 %) of 2.2 +/- 0.05 ms and a half-width of 9.1 +/- 0.13 ms. The EPSPs were greatly reduced by CNQX (10 mu M) and the remaining com ponent could be enhanced in Mg2+-free Ringer solution and blocked by A P5 (50 mu M). In 70 % of the dendrites, the EPSPs were followed by a p rolonged after hyperpolarization (AHP) which could be blocked by a sel ective and potent GABA(B) antagonist, CGP55845A (2 mu M). These result s indicate that the EPSPs are primarily mediated by non NMDA receptors with a small contribution from NMDA receptors, whereas the AHP is a G ABA(B) receptor-mediated slow IPSP. 3. With intrasomatic recordings, t he rise time of proximally generated EPSPs (3.4 +/- 0.1 ms) was half t hat of distally generated EPSPs (6.7 +/- 0.5 ms), whereas the half-wid ths were similar (19.6 +/- 0.8 ms and 23.8 +/- 1 ms, respectively). Th ese results indicate that propagation through the proximal apical dend rites slows the time-to-peak of distally generated EPSPs. 4. Distal st imulation evoked spikes in 60 % of pyramidal neurones. At threshold, t he distally evoked spike always appeared on the decaying phase of the dendritic EPSP, indicating that tile spike is initiated at some distan ce proximal to the dendritic recording site. Furthermore, distally and proximally generated threshold spikes had a similar voltage dependenc y These results therefore suggest that distally generated threshold sp ikes are primarily initiated at the initial segment. 5. At threshold, spikes generated by stimulation of distal synapses arose from the deca ying phase of the dendritic EPSPs with a latency determined by the tim e course of the EPSP at the spike initiation zone. With maximal stimul ation, however, the spikes arose directly from the peak of the EPSPs w ith a time-to-spike similar to the time-to-peak of subthreshold dendri tic EPSPs. Functionally: this means that the effect cf dendritic propa gation can be, overcome by recruiting more synapses, thereby ensuring a faster response time to distal synaptic inputs. 6. In 42 % of the ne urones in which distal EPSPs evoked spikes, the relationship between E PSP amplitude and spike latency could be accounted for by a constant d endritic modulation of the EPSP. In the remaining 58 %, the change in latency was, greater than can be accounted for by a constant dendritic influence. This additional change in latency is best explained by a s udden shift in the spike initiation zone to the proximal dendrites. Th is would explain the delay observed between the action of somatic appl ication of TTX (10 mu M) on antidromically evoked spikes and distally evoked suprathreshold spikes. 7. The present results indicate that ful l compensation for the electrotonic properties of the main proximal de ndrites is not achieved despite the presence of Na+ and Ca2+ currents. Nevertheless, distal excitatory synapses are capable oi initiating sp iking in most pyramidal neurones, and changes in EPSP amplitude can mo dulate the spike latency. Furthermore, even though the primary spike i nitiation zone is in the initial segment, the results suggest that it can move into the proximal apical dendrites under physiological condit ions, which was the effect of further shortening the response time to distal excitatory synaptic inputs.