Local glutamate-mediated dendritic plateau potentials change the state of the cortical pyramidal neuron

In cortical pyramidal neurons, we recorded glutamate-mediated dendritic plateau potentials with voltage imaging and created a computer model that recreated experimental measures from dendrite and cell body. Our model made new predictions, which were then tested in experiments. Plateau potentials profoundly change neuronal state: a plateau potential triggered in one basal dendrite depolarizes the soma and shortens membrane time constant, making the cell more susceptible to firing triggered by other afferent inputs.

Local Glutamate-Mediated Dendritic Plateau Potentials Change the State of the Cortical Pyramidal Neuron

Dendritic spikes in thin dendritic branches (basal and oblique dendrites) of pyramidal neurons are traditionally inferred from spikelets measured in the cell body. Here, we used laser-spot voltage-sensitive dye imaging in cortical pyramidal neurons (rat brain slices) to investigate the voltage waveforms of dendritic potentials occurring in response to spatially-restricted glutamatergic inputs. Local dendritic potentials lasted 200–500 ms and propagated to the cell body where they caused sustained 10-20 mV depolarizations. Plateau potentials propagating from dendrite to soma, and action potentials propagating from soma to dendrite, created complex voltage waveforms in the middle of the thin basal dendrite, comprised of local sodium spikelets, local plateau potentials, and back-propagating action potentials, superimposed on each other. Our model replicated these experimental observations and made predictions, which were tested in experiments. Dendritic plateau potentials occurring in basal and oblique branches put pyramidal neurons into an activated neuronal state (“prepared state”), characterized by depolarized membrane potential and faster membrane responses. The prepared state provides a time window of 200-500 ms during which cortical neurons are particularly excitable and capable of following afferent inputs. At the network level, this predicts that sets of cells with simultaneous plateaus would provide cellular substrate for the formation of functional neuronal ensembles.New & NoteworthyIn cortical pyramidal neurons, we recorded glutamate-mediated dendritic plateau potentials using voltage imaging, and created a computer model that recreated experimental measures from dendrite and cell body. Our model made new predictions, which were then tested in experiments. Plateau potentials profoundly change neuronal state -- a plateau potential triggered in one basal dendrite depolarizes the soma and shortens membrane time constant, making the cell more susceptible to firing triggered by other afferent inputs.

Spatiotemporally Graded NMDA Spike/Plateau Potentials in Basal Dendrites of Neocortical Pyramidal Neurons

Glutamatergic inputs clustered over ∼20–40 μm 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 ∼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 an approximately sevenfold 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 NMDA receptor (NMDAR) conductance-dominated at all locations. Large Ca2+ transients accompanied spike/plateaus over a ∼10- to 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.