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1 Molecular Biology and Physics, Princeton University, Princeton, New Jersey, United States; Biosciences, Cardiff University, Cardiff, Wales, United Kingdom
2 Physiology, Technion Medical School, Haifa, Israel
3 Biomedical Optics, Max-Planck-Institut for Medical Research, Heidelberg, Germany
4 Molecular Biology and Physics, Princeton University, Princeton, New Jersey, United States
* To whom correspondence should be addressed. E-mail: majorg{at}cardiff.ac.uk.
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 ~7-fold 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 Ca2+ transients accompanied spike/plateaus over a ~10-40 µm 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 (~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 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.
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