Spatiotemporally graded NMDA spike/plateau potentials in basal dendrites of neocortical pyramidal neurons

Glutamatergic inputs clustered over similar to 20-40 mu m can elicit local N-methyl-D-aspartate (NMDA) spike/plateau potentials in terminal dendrites of cortical pyramidal neurons, inspiring the notion that a single terminal dendrite can function as a decision-making computational subunit. A typical terminal basal dendrite is similar to 100-200 mu m long: could it function as multiple decision-making subunits? We test this by sequential focal stimulation of multiple sites along terminal basal dendrites of layer 5 pyramidal neurons in rat somatosensory cortical brain slices, using iontophoresis or uncaging of brief glutamate pulses. There was an approximately sevenfold spatial gradient in average spike/plateau amplitude measured at the soma, from similar to 3 mV for distal inputs to similar to 23 mV for proximal inputs. Spike/plateaus were NMDA receptor (NMDAR) conductance-dominated at all locations. Large Ca2+ transients accompanied spike/plateaus over a similar to 10- to 40-mu m zone around the input site; smaller Ca2+ transients extended approximately uniformly to the dendritic tip. Spike/plateau duration grew with increasing glutamate and depolarization; high Ca2+ zone size grew with spike/plateau duration. The minimum high Ca2+ zone half-width (just above NMDA spike threshold) increased from distal (similar to 10 mu m) to proximal locations (similar to 25 mu m), as did the NMDA spike glutamate threshold. Depolarization reduced glutamate thresholds. Simulations exploring multi-site interactions based on this demonstrate that if appropriately timed and localized inputs occur in vivo, a single basal dendrite could correspond to a cascade of multiple co-operating dynamic decision-making subunits able to retain information for hundreds of milliseconds, with increasing influence on neural output from distal to proximal. Dendritic NMDA spike/plateaus are thus well-suited to support graded persistent firing.