Spatio-temporally Graded NMDA Spike/Plateau Potentials in Basal Dendrites of Neocortical Pyramidal Neurons. Abbreviated Title: Graded Basal Dendritic NMDA Spike/Plateaus

Glutamatergic inputs clustered over ~20-40 μm can elicit local 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 ~100-200 μm 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 a ~7fold spatial gradient in average spike/plateau amplitude measured at the soma, from ~3 mV for distal inputs to ~23 mV for proximal inputs. Spike/plateaus were NMDAR conductance-dominated at all locations. Large Ca transients accompanied spike/plateaus over a ~10-40 μm zone around the input site; smaller Ca transients extended approximately uniformly to the dendritic tip. Spike/plateau duration grew with increasing glutamate and depolarization; high Ca zone size grew with spike/plateau duration. The minimum high Ca zone half-width (just above NMDA spike threshold) increased from distal (~10 μm) to proximal locations (~25 μm), 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 cooperating 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. Page 2 of 70